LaSalle University
The Welfare State and the Paradoxical Shift
of Coronary Artery Disease Risk
Associated with Socioeconomic Status
A Dissertation Submitted to the Faculty of the Division of
the Nutritional Sciences
in Candidacy for the Degree of
Doctor of Philosophy
Department of Nutrition
By
Steven P. Petrosino
Columbus, Ohio
September 30, 1994
Acknowledgements
This author is indebted to the invaluable assistance of my friend and mentor,
Neurocardiologist Robert S. Eliot, M.D., F.A.C.C., one of the world's foremost
experts on stress, the heart, and human physiology, and upon whose important
research much of this paper is based.
I am also indebted to my friend Ever D. Grech, M.D., M.R.C.P. for assisting me in
my research in free radical theory, and for providing me access to his own unique
clinical research in the field.
And to Hari M. Sharma, M.D., F.R.C.P.C., expert in nutritional preventative
medicine and free radical theory, who has offered helpful insights and who has
shared his own important research on nutrition and degenerative disease with me.
Special thanks:
To my wife Lynn and my children Angela and Aaron for their constant love,
support and patience.
My gratitude to my friend Tate Antrim for computer technical support and
assistance during the course of my research, to Janet K. Bixel, M.D., endocrinologist
and authority in psychoendocrinology for her assistance in my research, and to my
friend Virgil C. Dias, Pharm D. for his support and valuable assistance.
ii
Preface
The decade of the sixties was characterized by radical and sweeping changes in
the United States. These alterations encompassed not only social aspects, but also
American lifestyle and nutrition. The early years of the decade of the sixties saw the
assassination of a President, the opening of the Vietnam war, the prohibition of
prayer in public schools, and a general moral and spiritual decline in America. The
early 1960s also ushered in Lyndon Johnsons' "Great Society" social welfare
programs, and set the stage for the Surgeon General of the United States' warning
against the health risks associated with smoking, and the American Heart
Association's well-publicized recommendation that Americans should limit their fat
and cholesterol intake.
There is one great paradox which occurred in this decade: Prior to the 1960s,
black Americans and other members of lower socioeconomic status displayed a
resistance to ischemic heart disease. Whites and members of the upper
socioeconomic strata more frequently fell prey to ischemic heart disease. After the
decade of the sixties, this situation was (and remains) reversed.
This paper will address the following Hypothesis: The American Social Welfare
System, which was designed to benefit the poor, is indirectly responsible for a
detrimental effect on the cardiovascular health of the American indigent who
depend upon the system. These consequences became evident in the decade of the
1960s and were exerted through modifications of lifestyle, environment, diet, and
family structure which were shaped and influenced by the American social welfare
system. The urban poor reacted differently and more slowly to consumer education
on diet, exercise and smoking than did the affluent. Both this factor and the inherent
stress, demoralization, hopelessness, and despair, engendered by the dependency of
the impoverished upon the social welfare system, were responsible for the
paradoxical and rapid shift in heart disease risk.
Stress exerts its detrimental cardiovascular effects more rapidly than does poor
diet, smoking, or lack of exercise, while further potentiating their destructive effects.
Stress contributed to the rapid development of adverse cardiovascular effects and
increased susceptibility to cardiovascular disease experienced by the indigent in the
decade of the sixties.
iii
Table of Contents
Acknowledgements.....................................................................................
ii
Preface.........................................................................................................
iii
Table of Contents.......................................................................................
iv
List of Abbreviations..................................................................................
vii
Chapter:
I.
Introduction.....................................................................................
Goal of this paper.............................................................................
2
6
II.
Method.............................................................................................
7
III.
Background: The Clinical Data....................................................
Risk Factors for CAD .......................................................................
The Paradox of SES as a CAD risk factor..........................................
Diet and the Geographical Paradox of CAD among Populations......
9
9
15
21
IV.
Historical Background and Demographics...............................
23
Population Studies on CAD Mortality and American Longevity.......
Population Studies which Examined Acute versus Chronic CAD....
Historical Events Effecting CAD Risk of Populations......................
Historical Changes in Infant Mortality, Human Lifespan and SES....
Race and Historical Changes in Life Expectancy............................
A History of Pharmacologic Secondary Intervention Trials..............
Population Studies which Examined Racial Differences in CAD......
Racial Differences in the American Rural to Urban Migration..........
Race and Demographics and Their Effect on SES..............................
23
25
27
32
33
34
39
49
50
V.
Demographic Theory and Discussion...........................................
52
Access to Medical Services and Quality of Care: Their Relationship to
SES and CAD Risk....................................................................... 52
Exercise, Daily Activity Levels, SES, and CAD Risk....................... 56
Diet and Demographics: Sources of Dietary Fat............................... 60
Page 1
VI.
Physiology and CAD Risk.............................................................
Resting Heart Rate, Blood Pressure, Vasospasm, Left Ventricular
Mass and Function, Platelet Aggregation, Plasma Fibrinogen,
Catecholamines and CAD Risk.................................................. 90
Atherogenesis, Lipids, Abdominal Fat Deposition and Their
Relation to Stress, Hostility, and CAD Risk..................................
iv
90
96
Table of Contents (continued)
VII. SES Associated Behaviors............................................................
103
Abdication of Responsibility, Loss of Traditional Family Structure,
and Father Absence as an Influence on SES................................. 103
Supportive Social Relationships, the Intact Nuclear Family and
CAD Risk....................................................................................
116
The Decline of Faith, Abandonment of Personal Responsibility, and
increased CAD Risk.................................................................... 118
Stress, Hostility, Rage and CAD Risk Factors.................................
120
Stress, Coping Skills, Environment and CAD................................... 123
Unemployment, Frustration, Fatalism, and CAD Risk....................
138
Eating Habits, Family Gathering Traditions, and CAD Risk...........
142
Dietary Fat and Cholesterol Consumption......................................
144
Changes in Carbohydrate Consumption..........................................
148
Transfats and Hydrogenated Oil Consumption...............................
149
Obesity and Fat Consumption........................................................
152
Obesity, Race, SES, and CAD Mortality........................................
153
Diabetes, Fat Consumption.............................................................
155
Dietary Fiber Consumption, SES and CAD Risk............................
158
Prevalence of Smoking, Attitudes to Smoking, and Access to Tobacco
Products by Adolescents............................................................. 163
Excessive Alcohol Consumption and SES.......................................
175
Destructive Personal Behaviors and their relationship to SES........
180
VIII. Dietary Electrolyte, Mineral and Anti-Oxidant Vitamin and
Flavonoid Consumption and SES................................................
Dietary Antioxidants, Recommended Daily Allowance, and SES...
Ratio of Dietary Sodium to Magnesium and Potassium in
Hypertension..............................................................................
Dietary Calcium Intake, Hypertension, and CAD.............................
Dietary Iron Intake and CAD..........................................................
Dietary Selenium Intake and CAD..................................................
Page 2
182
182
183
185
187
191
Antioxidant Vitamins and CAD: Epidemiology.................................
Laboratory and Clinical Studies of Vitamin E....................................
Laboratory and Clinical Studies of Vitamin C...................................
Laboratory and Clinical Studies of Beta Carotene.............................
Antioxidants and Their Effect on Serum Lipids................................
Free Radical Theory.......................................................................
Antioxidants and Prevention of Oxidative Modification of LDL...
Laboratory and Clinical Studies of Folate and the B Vitamins.......
Laboratory and Clinical Studies of Flavonoids...............................
IX.
Summary, Conclusions and Recommendations.........................
229
The Legacy of the Welfare State......................................................
The Probable Cause of the Paradoxical Shift of SES associated
Risk............................................................................................239
Working Hypothesis.........................................................................
Recommendations to Reduce CAD risk associated with
Lower SES....................................................................................
195
196
203
207
211
211
216
221
225
229
243
256
X.
Appendix A (List of Figures)........................................................
262
XI.
Appendix B (List of Tables)..........................................................
264
XII. References.......................................................................................
265
XIII. Index................................................................................................
344
Page 3
INDEX
An Exhaustive Index is available on
WPWIN\Steve\Welfare3.rpt
software disc:
Access Word Perfect, Install Disc, and Use Word Perfect
Edit/Search function.)
Page 4
List of Abbreviations
AFDC.................................................
AHA...................................................
AMI...................................................
CAD...................................................
CHD...................................................
CHF...................................................
COPD................................................
CVD...................................................
CI.......................................................
D........................................................
DL.....................................................
DNA..................................................
ECG...................................................
EDRF.................................................
EMS...................................................
EPA....................................................
G.........................................................
HDL...................................................
HG.....................................................
HUD..................................................
IU.......................................................
L.........................................................
LDL....................................................
LDLOX.................................................
LV......................................................
MDA.................................................
MG....................................................
MI......................................................
ML.....................................................
MMOL...............................................
MUFA...............................................
NIDDM.............................................
NRC...................................................
PUFA.................................................
PVD...................................................
RDA...................................................
Aid to families with dependent children
American heart association
Acute myocardial infarction
Coronary artery disease
Coronary heart disease
Congestive heart failure
Chronic Obstructive Pulmonary Disease
Cardiovascular disease
Confidence interval
Day
Deciliter
Deoxyribonucleic acid
Electrocardiogram
Endothelium derived relaxing factor
Emergency Medical Service
Eicosapentaenoic acid
Gram
High density lipoprotein cholesterol
Mercury
Housing and urban development
International units
Liter
Low density lipoprotein cholesterol
Oxidized low density lipoprotein
Left ventricle
Malondialdehyde
Milligram
Myocardial infarction
Milliliter
Millimole
Monounsaturated fatty acid
Non insulin-dependent diabetes mellitus
National research council
Polyunsaturated fatty acid
Peripheral vascular disease
Recommended daily allowance
Page 5
REDOX..............................................
SES.....................................................
SOD...................................................
SSI......................................................
TBARS..............................................
μG......................................................
μM.....................................................
Oxygen reduction system or reactant
Socioeconomic status
Superoxide Dismutase
Supplemental Security Income
Thiobarbituric acid reactive substances
Microgram
Micromole
Page 6
I. Introduction
Observations by researchers in the first half of this century regarding dramatic
differences in Coronary Artery Disease (CAD) mortality between different
geographic areas raised questions about the possible association of mortality with
differing dietary habits or other environmental factors which are unique to certain
populations.1,2 Prior to Sir Alexander Fleming's discovery of a penicillinproducing mold in 1928 and the first clinical use of penicillin in 1941, (and prior
to the subsequent proliferation of other widely-available antibiotic compounds by
1948, and vaccines in the 1950s), the major cause of death in the United States
was infectious disease. Currently, those diseases account for fewer than 3% of
deaths. In 1900, chronic degenerative diseases including cancer and CAD
accounted for only fourteen percent of deaths, while today they account for over
75 percent.3
Because CAD accounts for the vast majority of the chronic
degenerative disease-associated deaths, numerous clinical and epidemiological
studies have been conducted during the past four decades with the hope that these
diseases would respond as dramatically to medical interventions as did the
infectious diseases. The results of most of these medical intervention studies have
been disappointing,62 which, together with contemporary market pressures for
sweeping health care cost containment, has shifted the current investigational
emphasis to the realm of prevention through dietary and life-style modifications.
Research has identified at least nine risk factors for developing CAD, and most
of these cardiovascular risk factors can be altered through changes in diet or in
life-style [See Table 1].
A.
B.
Table 1: Risk Factors For Atherosclerosis
Not Reversible
1. Aging
2. Male sex
3. Positive family history of premature atherosclerosis
Potentially reversible
Page 7
1. Cigarette smoking
2. Physical inactivity
3. Hypertension*
4. Obesity*
5. Hyperlipidemia, hypercholesterolemia and/or
hypertriglyceridemia.*
6. Low levels of high-density lipoprotein (HDL)*
C. Other possible factors
1. Body build
2. Emotional stress
3. Personality type
* Influenced by diet
______________________________________________________________________
Adapted From: Bierman EL, Chait A. Nutrition and Diet in Relation to Hyperlipidemia and Atherosclerosis,
in: Shils ME, Modern Nutrition in Health and Disease, 7th ed., 1988:1285.
There is, however, a historical paradox facing researchers attempting to structure
clinical studies to evaluate the effects of these preventative modifications.
Clearly, coronary artery disease has historically increased in populations who
increasingly use tobacco products, have become sedentary, and who have adopted
diets rich in saturated animal fats and cholesterol. These increases in the
incidence of CAD and other chronic degenerative diseases typically parallel the
degree to which a population has adopted these at-risk practices. The United
States population suffered a dramatic increase in CAD mortality during the six
decades between 1900 and 1964 during which Americans increasingly embraced
these practices, and has been enjoying a consistent decline since widespread
changes in smoking and diet were adopted in the mid 1960s [see Fig. 1].
Indicative of the significant dietary changes which have occurred in the United
States within the last three decades, one recent survey reported that 13.5% of all
American households currently claim to have at least one vegetarian member.
This number represents an eight-fold increase from 1979 to 1992.890
Figure 1. Death Rate Due to Coronary Artery Disease, 1900-1988
Pooled data using early un-adjusted data and age-adjusted data, deaths per 100,000.
Page 8
_________________________________________________________________________________________________
Sources: Vital Statistics of the United States, Volume II Mortality, Part A; 1988; Moriyama IM, Grover M. Statistical studies
of heart diseases I. Heart diseases and allied causes of death in relation to age changes in the population. Public Health Rep
1948;63:537-545; Heart Disease and Tuberculosis. Public Health Reports 1946;61:1425; National Center for Health Statistics;
American Heart Association.
Dietary and lifestyle changes do not immediately yield discernable effects upon
CAD morbidity and mortality. A plateau of coronary artery disease mortality
occurred in the mid to late 1960s, and the sweeping dietary and lifestyle changes
instituted by a significant portion of the American population within this decade
became evident within the following decade. While death from noncardiovascular diseases (non-CVD) have remained steady, age-adjusted mortality
due to stroke and coronary heart disease (CHD) has declined rapidly and
consistently since 1972 [see Fig. 2].
Figure 2: Decline in Age-Adjusted Mortality From All Causes Since 1972
__________________________________________________________________
From: Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure, Arch Int Med 1993;153:158.
National Center for Health Statistics data calculated by the National Heart, Lung, and Blood Institute.
These results, however, have not been consistent for all subgroups of Americans.
Page 9
Enigmatically, during the period of 1900 through 1964, blacks and poor
Americans of all ethnic groups had a lower risk of CAD than the wealthy [see Fig.
3], however in the mid 1960s, as the CAD mortality rate of the rest of the nation
reached a plateau and subsequently began to plummet, the CAD mortality rate of
indigent Americans surpassed that of the affluent, and the gap has subsequently
been widening [see Fig. 7].4,393,394,395,396,397
A study conducted by Cassel et al49 is noteworthy because it examined the
incidence of coronary heart disease by ethnic group, social class, and sex from
1960 to 1962, [see Fig. 3], and conducted a follow-up in 1967 through 1969.
During the initial period of observation, researchers were able to document the
"excess prevalence found in the high social class," but noted that during the course
of the study the class differences were disappearing in favor of a lower trend of
CAD among the high social class.
Figure 3. Prevalence of Coronary Artery Disease, 1960-1962
Age-adjusted prevalence rates per 1,000 population
Prevalence By Race and Sex
Prevalence by Social Class
_______________________________________________________________
Cassel JC. Review of 1960 through 1962 Cardiovascular Disease Prevalence Study. Arch Intern Med 1971;128:890-895
The Goal of this Paper
Page 10
This paper will attempt to identify the risk factors for CAD and the forces which
differentially altered them within the last three decades, causing a "risk factor
shift" between members of low and high socioeconomic status (SES). This paper
will also attempt to identify those risk factors for CAD which are more prevalent
among young members of lower SES, and those which are more prevalent among
older members of higher SES, and investigate their potential impact on the
established paradoxical shift of SES-associated CAD mortality which occurs
between age groups. This paper will further examine the span of influence of the
American social welfare system and other contemporary sociological influences
upon these forces of alteration and will attempt to demonstrate a cause and effect
relationship using previous epidemiologic and clinical data.
II. Method
In Phase I, an initial group of studies potentially relevant to the question of the
association between SES, stress, and the incidence CAD was retrieved through
computer searches of the following databases (1960 through 1994): Medline, BRS
Colleague, Catline, Dissertation Abstracts International, and government
document indices. A maximally broad keyword scheme was used ("cardiac,"
"cardiovascular," "coronary heart disease," or "coronary artery disease;" "blacks"
or "minority;" "psychological factors," "stress," and the word stem "psych;" and
"socioeconomic status," "social class," "indigent," "poverty," or "poor"). Library
searches were conducted using Index Medicus for additional references between
1890 and 1960. Computer and manual searches were then augmented with a
bibliographic review of retrieved manuscripts.
In Phase II, a broad database search was conducted for the nine generally
accepted risk factors for CAD, and these sources were also augmented by a
bibliographic review of the manuscripts. Factors with the potential to magnify the
deleterious effects of these known risk factors were identified through exhaustive
Page 11
literature review, and these factors were subsequently indexed, searched, and
cross-referenced.
In Phase III, a database search (Social Work, Psychological Abstracts), and
extensive library searches were conducted for review articles on the American
social welfare system and upon welfare reform recommendations. These reviews
were cross-referenced using retrieved bibliographies, and were augmented using
current data bases from the Vital Statistics of the United States.
In Phase IV, a casual-comparative research methodology was utilized to
demonstrate a cause-and-effect relationship between identified CAD risk factors
specific to blacks or to the indigent and exacerbating environmental factors
potentially influenced by or documented to have been influenced by the American
social welfare system. This comparison was accomplished using the retrieved
epidemiologic, statistical, and clinical data.
III. Background: The Clinical Data
Risk Factors for Coronary Artery Disease
Coronary artery disease remains the number one cause of death in the United
States, regardless of race,14,17,21,37,217 and mortality rates from cardiovascular
diseases in the United States are among the highest in the world. 35,61,294
Approximately 20% of American men and 5% of women will have symptomatic
CAD by age 60,17,21 and of all Americans who died in 1989, CAD was listed as the
cause of death in 43% of the cases.217
The recognized risk factors for coronary artery disease include
hypertension,14,17,21,32,35 hyperlipidemia,5,14,17,28,32,35,36,400,401
smoking,6,14,17,21,32,33,35,53,79,81,95,96,97 diabetes,14,17,21,32,34,80,81,82 family history of
premature CAD,14,17,21,32,34 a sedentary lifestyle with minimal aerobic
Page 12
exercise,13,14,17,21,34,35,80,87,291,292,293,385,386,466,511,512,513,514,515,516,517
stress,10,14,17,21,34,35,57,80,145,148,149,164,165,166,168,169,225,226,229,230,231,232,351,493,494,495,496,688,689,6
90,692, 693, 701,709,714,734,735,736,738,739,740
aggressive personality,10,14,17,21,34,35,57,698 and
obesity.14,17,21,34,145,172,181 According to epidemiologic studies, these risk factors
influence only about 50% of overt cases of coronary heart disease.274 Only
recently has lower socioeconomic status, (SES), been recognized as a potential
risk factor for coronary artery disease among Americans.4,112,113,114,115,725,726,727
Race as a CAD Risk Factor
Some researchers have postulated that the association between lower SES and
heart disease is due to inherent racial CAD risk factors,14,16,225 since blacks
comprise the largest segment of the American minority population,11,42 have lower
average incomes than whites,11 are more likely to live in the most impoverished
areas,11 are at greater risk for developing hypertension, CAD, renal failure, stroke,
left ventricular hypertrophy, cardiac arrest, and sudden cardiac
death,14,15,16,19,20,37,38,39,40,41,178,314,942 experience more rapid disease
progression,14,15,16,19,20,37,38,39,40,41 have been shown to have more underlying
disease,175,180,182,942 and are more likely to succumb to
CAD.14,15,16,19,20,37,38,39,40,41,178,179,313 Other theories attempt to link socioeconomic
risk factors with dietary inadequacies or environmental differences, such as
limited access to health care,47,177,358,359,360,361 that more frequently accompany
lower socioeconomic status. While the latter theories may have validity, the
assumption that minority racial status is a causative factor for CAD (especially
among blacks) lacks scientific basis. A genetic basis for increased CAD
susceptibility of blacks has not been identified to date,35,38,442,444 nor have older
post-mortem416,419,427,444,450,451,456 or recent angiographic
studies135,362,363,364,365,366,367,368 demonstrated greater prevalence of detectable
coronary artery lesions in blacks compared to white persons. Blanche and
Page 13
Handler,427 in discussing the lower incidence of CAD in American blacks in
contrast to whites in 1950, noted that degenerative changes in the coronary vessels
developed more slowly in blacks, and Gilbert and Gillman812 in their discussion of
diet and disease in the African Bantu in 1944, cautioned against "attributing a
racial factor to any differences in the incidence of disease amongst the black and
white people," and suggested that diet was the major contributor to the observed
differences.
The current correlation with increased incidence of CAD in blacks does not
establish causality, and particularly in light of the inconsistencies involving this
correlation, and the existence of numerous confounding variables. Black men and
women with four or less years of grade school education have an age-adjusted
mortality rate 75% higher than blacks with five or more years of college[see Fig.
4].4,129
Figure 4. All Cause Mortality by Education and Race
A mortality study of 1.3 million persons 25 years of age and older, 1979-1985.
__________________________________________________________
From: Rogot E, Sorlie P, et al. A mortality study of 1.3 million persons by demographic, social and economic factors:
1979-1985 follow-up. National Institutes of Health. 1992. NIH Publication No. 92-3297:1-5.
After 14 years of follow-up, black men of high socioeconomic status who
participated in the Charleston Heart Study had CAD and infarction rates half those
of black or white men of lower socioeconomic status.142
Page 14
In a prospective analysis of over 4,000 blacks and whites living in the Piedmont
region of North Carolina,114 a subgroup of black women who had the highest
education levels was found to have the highest total life expectancy and a
widening advantage over similarly educated white women with increasing age.
The authors, citing previous scholarship,346 concluded that educational level and
socioeconomic status are alterable risk factors, and that at least part of the
disadvantage associated with lower SES relates to poorer health practices in this
group.114 Several additional studies have demonstrated that men with the lowest
annual incomes have a mortality rate as much as twice that of men in the highest
income categories studied, regardless of race[see Fig. 5].143,144
Figure 5: All Cause Mortality by Income in Subjects Age 25 Years and Older
______________________________________________________
Adapted from Rogot et al.143
Unemployment, Residence in Poverty Areas, and CAD Risk
Living in areas of high unemployment has been proposed as an accurate
identifier for members of lower socioeconomic status,120,125 however this method
of identification is not consistently reliable. In one study by Berkman and coworkers,238 which compared an area of poverty with an affluent area, the
incidence of hypertension was 50% higher in the poor area, regardless of social
interaction, medical care, smoking or other identified CAD risk factors. Among a
group of more affluent people who chose to live in the poverty area, the pattern of
Page 15
hypertension was more closely related to that seen within the poor area rather than
to that of a high SES group with a similar income living in an affluent area.
Because relatively few members of high SES groups, (regardless of race), choose
to live in poverty areas, this data suggests that the increased mortality generally
seen among lower socioeconomic classes may be related to greater exposure to
certain environmental factors within poverty areas which are more common to
members of low SES, rather than to risk factors associated with race.114,225,346
The finding that hostile environment and material deprivation predict CAD
mortality more accurately than social class has been validated by several
additional researchers.182,382,629
Although more blacks than whites are unemployed per capita, there is evidence
that it is stress associated with unemployment, rather than risk factors associated
with race, lack of income, or the availability of affordable medical care which
increases CAD mortality among the unemployed. Unemployed workers are up to
fifty percent more likely to suffer sudden cardiac death, and are more likely to die
from any cause than their employed counterparts [see Fig. 6] regardless of
race.4,10,49,70,116,117,118,119,140,143,144
Figure 6. All Cause Mortality by Employment Status of Subjects
Age-adjusted mortality rates per 1,000 population, ages 25 to 64 years.
_____________________________________________________________
From: Rogot E, Sorlie P, et al. A mortality study of 1.3 million persons by demographic, social and economic factors:
1979-1985 follow-up. National Institutes of Health. 1992. NIH Publication No. 92-3297:1-5.
Page 16
In addition to an increased risk of death, the unemployed are significantly more
likely to be depressed122,123,124 or be hospitalized for serious mental illness,120,121
independent of their racial status.
In the Rancho-Bernardo Study, Kritz-Silverstein and associates380 examined the
relationship between employment status and CAD risk factors in middle-aged
women, and found an increased risk of CAD which was associated with
unemployment. These researchers noted that women who were employed smoked
less cigarettes, drank less alcohol, had significantly lower total cholesterol and
fasting plasma glucose levels, and exercised more than unemployed women.
The association of unemployment with increased CAD risk in both men and
women has not only been seen in America, but also has been demonstrated across
diverse cultures in nine industrialized countries.116 Education, income, place of
residence, and employment status seem to overcome or modify the "risk factor"
associated with race.
The Paradox of Socioeconomic Status as a CAD Risk Factor
The indigent clearly were not always the highest at-risk group for developing or
dying from heart disease. Prior to 1960, the affluent had a significantly greater
risk for sudden coronary death and CAD mortality than did the
poor.4,129,132,301,369,377,378,379 In fact, the late-nineteenth century surgeon, Sir William
Osler described angina pectoris as being an "affliction of the wealthy". 377 As
early as 1937, White418 stated "race, temperament, social and economic status, and
occupation appear to have some slight bearing on the incidence of coronary
disease," and observed that blacks and members of lower socioeconomic status
rarely developed CAD. In 1939, Burch and Voorhies419 stated that "coronary
occlusion and angina pectoris, along with other cardiovascular states such as
hypertension, have been associated with high tension living conditions and
occupations requiring considerable responsibility and intelligence, e.g., the
Page 17
physician, banker, and lawyer." The following year, Crile,458 writing on
"Diseases Peculiar to Civilized Man," argued that the existence of a racial or class
distribution of hypertension suggested that urban stress may induce hypertension
because the highest known prevalence is among "those who struggle with the
complexities and pressures of civilization," and the lowest prevalence is among
aboriginal natives. Similarly in Europe, the 1950 decennial Occupational
Mortality statistics of England and Wales449 demonstrated a susceptibility of the
professional and executive social class and a resistance of the unskilled lower
class to the development of CAD and subsequent cardiovascular mortality.
Examining CAD prevalence data gathered from 1962 to 1964, Cassel and
colleagues49 stated: "It is clear from these analyses that black males are definitely
protected in some fashion from coronary heart disease..." As late as 1964, upward
mobility was still being associated with an increased risk of heart disease. 459 After
1960 and through the present, a steady increase in mortality among members of
lower SES has been coinciding with reductions in upper SES mortality in both
Europe301,457 and the United States.4,112,301,379 By the mid to late 1960s, mortality
from CAD in both the United States and the United Kingdom was more common
in the lower socioeconomic classes than in the higher,4,301,379 and there is
significant evidence that this inverse relationship between SES and cardiovascular
disease has subsequently been widening [see Fig.7].4,393,394,395,396,397
Cassel et al49 were some of the first researchers to document a paradoxical shift
of socioeconomic status-associated CAD risk factors in the rural Evans County
Georgia Heart Study, a biracial cohort study which examined the incidence of
CAD in rural Georgians from 1960 to 1967.
Figure 7: A Graphic Representation of the Paradoxical 1964 Risk Factor
Shift
Comparative Mortality Per 100,000 Due to Diseases of the Heart
Page 18
_____________________________________________________________
Adapted from Keil,4 and Vital Statistics of the United States.216,217
Analyzing this same data, Kaplan and associates510 concluded that in 1960 the
more affluent upper-half of the socioeconomic class range was found to have ageadjusted rates of CAD which were more than twice as high as those who where in
the lower-half of the socioeconomic class range. By 1967, however, this social
class difference had disappeared, and this equalizing of the CAD rates for the two
social class groups was primarily "achieved by an increase in the rates for the
"lower" social class men (particularly the younger men), rather than a decrease in
the "higher" social class." Furthermore, the researchers noted that these changes
in CAD risk associated with those of lower SES occurred primarily during a rapid
transition in rural Evans County Georgia from a rural agrarian society to a more
modern, urbanized, and industrialized economy.510 High-coronary risk patterns of
living which were previously "characteristic of the more favored segments of
white society" were being adopted by low SES whites, and to a lesser extent by
low SES blacks. Specifically, Cassel et al49 noted that changes in lifestyle were
occurring more slowly in lower class blacks than in lower class whites while both
groups were living in rural areas, but adverse lifestyle changes among blacks
accelerated following the black migration to urban centers, and resulted in an
increased incidence of CAD within this group which was detected by the
researchers by 1967. Kaplan, Cassel et al510 stated that although no evidence of
major changes in diet among blacks was detected prior to 1967, increases in
Page 19
tobacco consumption, the adoption of a more sedentary lifestyle, and
"psychosocial factors" which accompanied social mobility and urbanization might
be implicated in the shift of coronary risk. Building upon previous research, the
authors hypothesized that powerlessness,948 role and value conflicts,948 disruption
of relationships,949 reduction in family ties,949 anomie (or the breakdown of social
norms and values),952 alienation,950 the loss of social support,951 and social
isolation951 are powerful stressors which have been associated with social
mobility, and that these factors have the potential for eliciting adverse
"neuroendocrine changes".510 Kaplan, Cassel, and their co-workers further
suggested that these alterations might be responsible for the selective adverse
cardiovascular changes in the health status within the lower socioeconomic class
which was socially more vulnerable to these effects of change. The authors
concluded that migration and upward social mobility among those of higher SES
did not increase cardiovascular risk within this group because of an inherently
greater degree of social support and stability which resulted in a "comfortable
acculturation" following the "successful acquisition of new lifestyles."
Subsequent reanalysis of the Evans County data in 1980 by Morgenstern379
affirmed the conclusions of previous researchers, and also attributed the reversal
of risk associated with socioeconomic status to changes in certain urban
populations "following a period of rapid socioeconomic change or
"modernization"."
Figure 8: Incidence of CAD per 1,000 in White Males by Age and Social
Class, 1960 through 1962 and 1967 through 1969.
Page 20
_____________________________________________________________
From: Cassel et al.173
This reanalysis by Morgenstern further revealed that the association of CAD risk
and lower socioeconomic status demonstrated an age-related cross-over effect and
was reversed with increasing age [see Fig. 8]. When incidence rates were
stratified by age, it became evident that younger men of high socioeconomic status
had lower CAD rates than their poorer counterparts, but older men of high
socioeconomic status had a higher incidence of CAD than similarly aged men of
lower status. A similar crossover trend was seen in a Piedmont region of North
Carolina study by Guralnik and co-workers114 of over 4,000 blacks and whites. In
this study, researchers found that through the age of 65, black men had a lower
total life expectancy than white men, however both black men and women 75
years of age and older had greater total life expectancy than whites, and these
differences were larger after adjusting for education.
In a population-based, ten-year study of 1.5 million northwestern American
whites, blacks, urban American Indians and Alaskan natives by Grossman and
co-workers,302 average death rates per 100,000 were 120% higher among urban
blacks between the ages of 25 to 44 years than urban whites, however this
negative trend seemed to slow with increasing age and disappeared by age 65.
There was only a 4% increase in all-cause death rate per 100,000 for urban blacks
over the age of 65 versus urban whites (who were of somewhat higher average
SES) within the same age group. U.S. Census Data confirms that age reverses the
Page 21
risk associated with CAD among blacks and whites. Elderly black males and
females demonstrate a lower mortality rate per 100,000 population than whites for
both acute and chronic heart disease, but only after age 85. Similarly, mortality
from all forms of ischemic heart disease is lower among blacks after age 65, and
mortality from acute myocardial infarction is lower after age 54 in black males,
and after age 84 in black females than among whites of similar ages.216 Clearly,
environmental factors exist which have the potential to increase CAD risk. There
is evidence that these factors may vary in their prevalence, intensity, or effect
between socioeconomic groups as well as between age groups.
These data indicate that although socioeconomic status and race may currently
be associated risk factors for CAD, since this association has not remained
constant, they cannot be recognized as causative risk factors.
Diet and the Geographical Paradox of CAD Mortality among Population
Groups
The relationship of diet and CAD mortality is complex. Traditionally, the
influence of diet on CAD risk factors has been attributed to alterations in serum
low density lipoprotein (LDL) cholesterol concentrations moderated by dietary
cholesterol, saturated fatty acids, and soluble fiber.819,891 Animal and plant foods,
however, are highly complex "chemical cocktails" which contain many other
natural or additive substances which may positively or negatively impact upon
CAD risk, including flavonoids, isoflavones, phytosterols, tocotrienols, arginine,
folacin, phytochemicals, phytoestrogens, antioxidant vitamins and minerals,
antioxidant co-factors, electrolytes and other essential minerals, transfats, heme
iron and chemical additives and contaminants.
Saturated fat consumption has been the single dietary variable which has been
most studied by previous research. Increases in the incidence of CAD and other
chronic degenerative diseases within large population groups typically parallel the
Page 22
degree to which a population has adopted certain at-risk practices, including a diet
high in saturated animal fat and cholesterol.528,529,530,531,532 Numerous
epidemiologists have successfully linked the dietary fat and saturated fat
consumption of entire populations to the incidence of CAD within that
population.2,35,36,53,376,444,451,476,522,526,527
The Paradox of Finland, France, and Greenland
The associations between dietary fat consumption and CAD are typically strong,
however there are three notable exceptions which constitute a paradox. Finland
consistently demonstrates the highest level of CAD mortality, and France and
Greenland are among the countries with the lowest, despite having comparably
high intakes of dietary fat [see Figures 11 and 15].35,61,476,527,528,529,608 Because
Finland is an industrialized nation whose population generally enjoys better
economic conditions than the countries of Poland, Romania, and Yugoslavia
(which are countries that enjoy significantly lower rates of CAD mortality,61,476,527
and whose populations consume less fat,476) this further sheds doubt on SES as a
causative risk factor for CAD.
IV. Historical Background and Demographics
Population Studies on CAD Mortality and American Longevity
A gradual rise in the rate of death from CAD between 1900 and 1940 was first
documented in a series of U.S. Public Health Service reports published between
1946 and 1951.315,316,317,407,408,409 Many of the early statistical studies of CAD were
predominantly conducted with white subjects, and were rarely stratified for SES.
In the first of these reports, a 1946 Public Health Report editorial409 briefly
mentioned that total deaths reported due to heart disease in the United States had
increased from 303,724 in 1934 to 418,062 in 1944--an (unadjusted) escalation of
38 percent. In 1948, Moriyama and Grover315 documented a rise in age-adjusted
CAD mortality from 168 deaths per 100,000 in 1900 to 239 in 1920; and
Page 23
subsequently climbing to 339 per 100,000 in 1940. From 1950 through 1963, ageadjusted mortality from CAD increased an additional 19 percent.371,372 After six
decades of consistent increases,36,376,388,389,390 Epstein318 reported in 1965 that
overall CAD mortality was leveling. Borhani and Hechter319 showed in 1964
that for the first time in this century, ischemic heart disease mortality in California
had begun a sudden decline as sharp as its abrupt rise after 1920. This same
phenomenon which was first seen in California, subsequently was documented to
have occurred throughout the rest of the nation about a decade later. From 1960
through 1970, the rate of death from heart disease in the United States began to
slow and plateau, and since 1970 it has been declining. 3,62,63,325 In subsequent
analyses of the onset of this decline in CAD mortality at the state level rather than
at the national level, it became evident that states with the poorest socioeconomic
conditions (in terms of income, education, and occupation) were from two to ten
times more likely to have experienced a later onset in this decline [see Fig.
9].398,399
In a recent population study by Davis and associates,347 the authors
noted that between 1973 and 1987, CAD mortality decreased by 42% in
Americans less than 54 years of age, and decreased by 33% in Americans aged 55
to 84 years. This decline has been variously attributed to changes in smoking
habits,320 lifestyle,321,725,819,820, 821,822 the environment,322 dietary habits,323 gradual
improvements in diagnosis over time,62 and shifts in mortality from other
diseases.324
Figure 9: Percent of State Economic Areas with Late Onset (Occurring After
1968) of Decline in Cardiovascular Mortality.
Page 24
_________________________________________________________
From: Wing et al.399
The actual cause of this decline may be a combination of many of these factors.
Indeed, Stallones63 argued in 1980 that no single one of these factors could
account for the early rise, then fall of CAD mortality in the United States.
Although reductions in CAD mortality were recorded for affluent Americans in
the mid 1960s, epidemiologic studies have shown that decreases in CAD mortality
among American blacks and the poor occurred much later and have been
significantly less.37,43 In 1970, the life expectancy of blacks in the United States
was a significant 7.6 years less than that of whites.216 By 1988, the gap had
narrowed slightly to 6.4 years.214,216 It is possible that the adoption of beneficial
changes in diet, lifestyle and environment occurs more quickly among affluent
populations who have more formal education, and greater access to health-related
information and guidance. This may explain the lag in CAD mortality reduction
among indigent population groups.
Population Studies which Examined Acute versus Chronic CAD: The 20th
Century Epidemic
A recent analysis by Slater and associates325 of acute (predominantly thrombotic
or arrhythmic) and chronic (predominantly atherosclerotic) CAD death rates
between 1931 and 1980 indicated that an epidemic of acute ischemic heart disease
occurred with dramatic rises in acute CAD deaths among (predominantly white)
males between 1931 and 1968, with a rapid decline thereafter [see Fig. 10].
Figure 10: Life Table Proportions of Men Dying From Acute and Chronic
CAD
1931-1980.
Page 25
_______________________________________________________________________________
From: Slater et al.325
A similar trend in acute CAD mortality was seen throughout this 50-year period
among women, but to a lesser degree than men. Compared to men, females
enjoyed an increasing margin of benefit from 1931 through 1950, and a narrowing
margin since 1960. In contrast, these investigators noted fairly stable and
comparable rates for chronic CAD mortality for both men and women during this
period. Robertson884 found that the incidence of chronic CAD (atherosclerosis)
was as extensive in inhabitants of Jamaica as in urban American inhabitants of
New Orleans, but that the incidence of acute CAD (acute myocardial infarction, or
AMI) was 2.4% in Jamaica versus 16.1% in New Orleans. This differential
suggests factors present in, or common to urbanized and Westernized population
groups which increase the probability of thrombosis or vasospasm when
superimposed upon fixed atherogenic plaques in population groups with similar
levels of atherosclerotic disease. These factors may have been more common to
whites and members of upper SES prior to the 1960s, but currently are more
common to blacks and members of lower SES (at least until the 6th or 7th decade
of life). This hypothesis is supported by current U.S. census data on mortality
from all forms of heart disease which shows that black males and females (who are
significantly more likely than whites to reside in major urban inner-city areas)
Page 26
have higher death rates from acute CAD for most of their adult lives. Black males
and females consistently demonstrate a higher mortality rate per 100,000
population than whites for all forms of heart disease (both acute and chronic) from
birth through age 84 (but not after age 85). Similarly, black males and females die
more frequently per 100,000 of population from all forms of ischemic heart
disease from birth through age 64 (but not from age 65 and beyond); of acute
myocardial infarction from birth through age 54 in males (but not after age 54);
and of acute myocardial infarction from birth through age 84 in females (but not
after age 85).216
Historical Events Effecting Populations and Their Impact on CAD Risk
The Surgeon General, the Heart Association, and the 1960 CAD Risk Shift
Since early 1964, there has been a documented decline in the American per
capita consumption of tobacco, animal fats and oils, butter, milk, cream and
eggs.375 Historically, two significant forces for change can be identified which
occurred during the early 1960s and which were probably responsible for this
decline. In January, 1964, the Surgeon General of the United States Public Health
Service warned of the health hazards of tobacco consumption, with a particular
emphasis on cigarette smoking.370 Several months later, the American Heart
Association recommended a change in the American diet, with the goal of
reducing heart attacks and strokes by limiting the intake of saturated fat and
cholesterol.371 A decline in mortality from CAD began the same year these
warnings were issued.318,319,372 A possible explanation for the narrowing margin
of acute CAD mortality between women and men since 1960 which was
documented by Slater et al325 is the significant reduction in smoking among men
beginning in the early 1960s and the increase in smoking among women
subsequent to the aggressive tobacco advertising campaigns for women's cigarette
brands during the same decade. This increase in smoking among women may
Page 27
have offset any potential benefits from reduction of dietary fat and cholesterol
consumption, and may have been more predominant among members of lower
SES. Similarly, the greater prevalence of smoking and higher saturated fat
consumption among blacks since the 1960s may have contributed to rapid
increases in acute CAD seen among this group beginning in the 1960s and
subsequently.
Wartime Dietary Restrictions and CAD Risk
Populations which are subject to dietary restrictions which invariably include
reduced intake of fat, have been shown to have reduced blood cholesterol levels.
During the World War II, extremely low serum cholesterol values were observed
among the inmates of numerous European concentration camps.442,452,453,454
During war-time, it is common for diets of entire populations to fall in energy
value, animal protein content, and in fat and cholesterol content while
simultaneously increasing in carbohydrate and crude fiber (high-residue) content.
The consumption of meat, milk and dairy foods, eggs, animal fat, highly processed
low-residue carbohydrates, and sugar usually decreases during war-time, while
significantly more cereals, cereal products, whole grain breads, vegetables, and
legumes are consumed.442 A decline in CAD mortality was reported in several
Scandinavian countries after comparable changes in dietary habits which were the
result of such deprivation (including shortages of tobacco and sources of dietary
saturated fats), rather than the voluntary adoption of a healthy lifestyle, during
World War II.373,374,442 Conversely, a significant rise in mean blood cholesterol
levels and an increase in CAD risk occurred in German subjects who experienced
profound "improvements" in their diet, including increased intake of fat, between
1947 to 1949 following the war.455
Other Population Studies on Demographic Change, Effects on Diet, and CAD Risk
Nationwide reductions in the intake of animal fat and cholesterol, 1,2,36 and a
Page 28
concomitant reduction in the percentage of male smokers,2,99,102,103 during the last
three decades clearly have been primary contributors to the substantial decline in
American CAD morbidity and mortality since 1964.3,33,99,100,371 Epidemiologic
studies among populations of other developed countries experiencing a decline in
the rate of CAD, [see Fig. 11], have partially attributed these improvements to
increased popular awareness of the benefits of the adoption of a healthier
lifestyle.273,725,819,820,821,822
Figure 11: Death Rates From CAD by Country
in 35 to 74 Year-Old Males
_____________________________________________________________
_
From: Levy RI. Atherosclerosis 1981;1:312.
Conversely, other industrialized nations, including Russia, Bulgaria, Poland,
Romania,Yugoslavia, Crete, and Italy, have adopted poor dietary habits with
increased consumption of animal fat, and have increased their use of tobacco
Page 29
products. These increasingly urbanized populations have demonstrated
escalations in cardiovascular disease and associated cardiovascular mortality
during this same period, thereby further verifying the positive association between
these risk factors and CAD [see Fig. 11].6,273
Case-control studies have verified epidemiologic findings among population
groups. In both the Western Electric Study,205 and the Ireland-Boston Diet Heart
Study,554 dietary cholesterol consumption and saturated animal fat intake
significantly predicted 20-year CAD mortality. In a 20-year follow-up of Seventh
Day Adventists by Snowdon and Associates,555 it was observed that meat
consumption was associated with an increased risk of CAD for both men and
women, and risk increased as the frequency of meat consumption increased.
Animal protein consumption, and its associated high levels of saturated fat, is
probably highest among lower SES populations in contemporary America. A
nutritional study conducted among blacks, Hispanics, and other lower SES
minorities and whites in East Harlem, found nutritional deficiencies in many
categories, with the exception of animal protein.969 Increased saturated animal fat
intake by the indigent may increase the risk of CAD morbidity and mortality in
this population.
Historical Changes in Infant Mortality, Human Lifespan and SES
Lifespan has increased greatly for children in the twentieth century. A white
male infant born in 1900 had a life expectancy of 48 years. By 1988, the life
expectancy of a similar infant increased to over 72 years.216 Increases in infant
and early childhood life-expectancy realized during the last nine decades were
primarily due to significant reductions in infant and early childhood deaths from
infectious disease and other causes.3,5,7,8,216,371 However, research suggests that
these declines may be occurring predominantly in white versus minority subgroups. Data published by Grossman et al302 demonstrates that while urban white
Page 30
infant mortality rates in the northwest Unites States declined between 1981 and
1990, the infant mortality rates of urban blacks and other minority groups rose
alarmingly during the same 10-year period. Alexander and colleagues404 recently
published a study which indicates that, similar to the trends seen with CAD
mortality among the urban poor, the increased infant mortality among the indigent
is probably due to certain environmentally-associated risks, and not due to risk
factors associated with race. The researchers examined the pregnancy outcomes of
married adult black, Filipino, or non-Hispanic white women who all were
residents of Hawaii, whose spouses were on active duty in the military, and who
had similar availability and access to comparable prenatal care and hospital
delivery services. Despite persistent ethnic differences in birth weight, no
significant ethnic differences were seen in neonatal or post-neonatal infant
mortality rates.
Race and Historical Changes in Human Life Expectancy Among Adults
The average life-expectancy of a 65-year old white male increased by only 3.39
years from 1900 to 1988 (lifespan, or the age at which he would expect to die
increased from 76.51 years to 79.9 years),3,7,8,216 with virtually no increase (0.39
years) in the decade between 1979 and 1988.216 The average life expectancy for a
65-year old black male has increased by only 3.02 years from 1900 to 1988 (from
75.38 years to 78.4 years); with virtually no increase (0.11 years) between 1979
and 1988.216 Average life expectancy data for blacks during this period is more
limited and was not consistently stratified by race, was combined into a broad
category as "all other," or in some cases was not even tabulated for blacks in
certain years prior to 1970.216
Since birth and one year life expectancies have increased markedly by 25.7 and
19.5 years respectively between 1900 and 1988, (24 and 17.4 years respectively
for white males; 32.4 and 22.7 years respectively for black males) and because
Page 31
most of these gains occurred between 1900 and 1959,216 which was prior to the
wide availability of antibiotics and vaccines, this gain probably reflects
improvements in pediatric care, reductions in childbirth mortality, and
improvements in infectious disease control rather than advancements in the
treatment of CAD. Because the current life expectancy of a black male is 7.4
years less than that of a white male at birth but differs only by 1.5 years at age
65,216 this suggests that early mortality from causes other than CAD (such as
higher infant mortality due to lack of prenatal care, prenatal drug, alcohol or
tobacco abuse, drug related childhood deaths, and increased adolescent deaths due
to urban violence) may also be compounding the factors resulting in shorter
lifespan among blacks.
A History of Pharmacologic Secondary Intervention Trials: Their Effect upon
Lifespan
The emphasis of traditional medicine has typically been upon secondary
prevention, which is the treatment of manifest coronary heart disease (CHD),
rather that upon primary prevention, which is the method of disease prevention
directed towards changing lifestyle or habits among presently healthy patients.
Within the last decade, however, this emphasis appears to be slowly changing.
Figure 12: Mortality in Secondary Prevention Trials
Trials With Objectives of Serum Cholesterol Reduction and Their Effect on Mortality
Treatment versus control all-cause mortality differences are not significant (p=ns)
_________________________________________________________
From: LaRosa JC. Cholesterol lowering, low cholesterol, and mortality. Am J Cardiol 1993;72:778
Page 32
Diagnosis and treatment of heart disease in the United States has significantly
improved during the last three decades. These advancements have led to
pharmaceutical and medical interventions which have demonstrated benefits when
they have been evaluated using disease-specific endpoints (i.e. coronary events,
cardiac death, progression of atherosclerosis) in secondary prevention trials when
disease is manifested [see Fig. 12].904 In patients without evidence of CHD,
however, pharmacologic treatment of established risk factors such as
hypertension, coronary atherosclerosis, or elevated blood cholesterol has not
significantly influenced CAD morbidity or mortality, 5,18,22,23,24,25,26,27,28,29,30,31,33,65,76,
77,78,92,93,94,98,99,100,101,902,903,905
and in some trials has even resulted in increased risk
of death or morbidity among patients receiving treatment versus those who
remained untreated, [see Fig. 13].74,75,76,77,78,98,906,908
Figure 13: Mortality in Primary Prevention Trials
Increased mortality from non-cardiovascular causes (NON-CVD);
All-cause mortality not significantly different between control and treatment groups (p=ns)
________________________________________________________________
From: LaRosa JC. Cholesterol lowering, low cholesterol, and mortality. Am J Cardiol 1993;72:778
There is no data which indicates that reduction, or eradication of CAD would
necessarily increase lifespan or life-expectancy. To the contrary, there is evidence
that another major degenerative or infectious disease might supplant CAD, if it
were eliminated, as the major cause of death. Most pharmacologic intervention
trials have not succeeded in extending lifespan, and many have only modified the
Page 33
ultimate cause of death (i.e. fatal arrythmia or cancer as a mortality end-point
versus infarction, stroke, or heart failure).5,74,75,76,77,78,98,99,349,677,908 The results of
these intervention trials may reflect the potential long-term toxicity of the
pharmacologic therapies which have been studied to date, and do not necessarily
exclude benefits that might be associated with newer classes of agents for CAD
risk factor reduction, or benefits which might be associated with aggressive
lifestyle and dietary interventions. In a secondary prevention trial of aggressive
lifestyle and dietary interventions by Ornish et al,909 41 patients with significant
CAD were followed for one year. Patients who were placed on an austere fatrestricted diet, and who were enrolled in an exercise and stress modification
program experienced significant regressions of angiographically-evident coronary
atherosclerosis. This trial was too small and too short in duration to detect
significant differences in total mortality, but the results of larger and longer diet
and lifestyle trials have shown trends toward reduced all-cause mortality.
Life expectancy is not necessarily inversely proportionate to CAD mortality. It
is interesting that Sweden, Denmark, Canada, and the United States, which boast
some of the highest life expectancies, are among the countries with the highest
CAD mortality rates. Japan, France, and Italy are notable exceptions with low
CAD mortality rates and high life expectancies,62 although the Japanese have a
high incidence of hypertension,476 and hemorrhagic stroke, and the French have a
high incidence of smoking-associated cancers and alcoholic cirrhosis.
Some minimal gains in over-all mortality rates in the United States, and the
modest increase in life expectancy of an older adult over the last several decades
may have been due to significant reductions of in-hospital mortality (e.g. those
reductions resulting from new treatment approaches including coronary bypass
surgery, angioplasty, and thrombolysis) occurring within the last two decades
among patients suffering from acute myocardial infarction.33,72,73,99 Declines in
Page 34
CAD death rates within the United States, however, are primarily related to
prevention, or the reduction in the percentage of people who are at risk for
developing the disease.3,99,100,371 Clearly, changes in diet, exercise patterns, and
the reduction of smoking and stress are among the best methods of reducing this
risk. In fact, the disparate results in stroke and CAD mortality reduction in
numerous hypertension trials may be due to confounding factors which may be
reducing cardiovascular risk within the control groups of these studies. These
factors include a reduction in tobacco use,102,103 increased exercise, greater
potassium and anti-oxidant vitamin intake resulting from increased fruit and
vegetable consumption67,68,69,105,106 improved blood pressure control,183 resolution
of Type II diabetes80,115,253,271 (secondary to weight loss or dietary fat reduction),
reduction in dietary sodium intake,99,105,184,185,186,187,188,189 and improvements in
maternal health (the health of the mother is the most important determinant of
stroke risk among offspring).107 These improvements in cardiovascular morbidity
and mortality manifested by heterogeneous populations may not exist to the same
degree within specific sub-populations, and particularly those sub-groups largely
comprised of members of the lower socioeconomic class.
Primary Intervention and Human Lifespan
Although data from both primary and secondary intervention trials of
pharmacologic treatments (aimed at reducing known risk factors such as
hypertension or hyperlipidemia) are suggestive of reduced coronary events and
cardiac death [see Figures 12 and 13], neither have demonstrated consistent and
significant reductions in all-cause mortality,5,75,76,77,902,903,904 certain
pharmacologic primary prevention trials have demonstrated increased mortality
when performed in subjects without clinical manifestations of coronary artery
disease,5,14,18,65,75,76,77,348,904,906 and no trial has demonstrated an ability to increase
human lifespan. For these reasons, most researchers use improved quality of life,
Page 35
or various cardiac endpoints as markers of successful outcome in these trials.
In 1988, the United States Public Health Service estimated that the average
length of life for a male was 71.5 years, and for a female, 75.6 years.216 It is
interesting to note that Psalm 90, written between 1450 and 1410 BC, quotes a
similar statistic: "As for the days of our life, they contain 70 years, or if due to
strength, eighty years." The patriarchal statistician quoting the latter figures
however, probably did not adjust for early infant mortality.
Population Studies Which Examined Racial Differences in CAD
Surveys conducted in the United States in the first six decades of this century
(primarily from the rural South), in the Caribbean, and from the African medical
literature report an extremely low incidence of CAD, including morbidity and
mortality resulting from ischemic heart disease and coronary atherosclerotic
disease,44,416,419,420,421,422,425,427,428,429,430,431,433,434,438,439,440,441,443,444,445,446,450,451,817,954,95
5,956,
thrombosis and myocardial
infarction,44,388,416,417,418,419,420,423,427,430,434,435,436,437,441,443,444,
445,446,451,456,953,955,958,959,960,961,962,963,964
and
angina,44,388,416,418,419,421,422,423,425,427,432,434,451, 953,955,958,959,960,961,962,963,964 in blacks as
compared to whites [see Table 2].
Table 2: Death Rate per Hundred Thousand from CAD
1940 and 1945
Year
White
Black
1940............................... 81.8 ............................ 34.6
1945................................ 106.5 .......................... 41.3
_______________________________________________________
Adapted from: Federal Security Agency, United States Public Health Service,
Office of Vital Statistics: Vital Statistics, in Special Report 1948;27:295.
In a study of rural Southern blacks published in 1924, Woody506 became one of
the first researchers to document a difference in the incidence of heart disease
Page 36
between blacks and whites. Brock and Bronte-Stewart spoke of "the remarkable
immunity of the [African] Bantu people to myocardial infarction,"444 and studies
conducted among rural Africans in the early decades of this century consistently
reported a lower incidence of CAD416,417,442,443,444,445,446 and hypertensive heart
disease in blacks as compared to whites.412,413,414,415,424,425,426 In 1927, Stone and
Vanzant434 concluded that the incidence of coronary atherosclerosis was between
two to four times more common among whites than among blacks, and in 1950,
Blanche and Handler427 in a pathological comparison of the coronary arteries of
47 black patients to white controls, reported "that coronary artery disease and
coronary thrombosis occur with considerable less frequency" in the black versus
the white population, and that the rate of development of coronary atherosclerosis
was slower in blacks than in whites by approximately a decade. Blanche and
Handler found evidence of coronary thrombosis in 16% to 23% of 1,961
necropsies performed upon whites, versus 1% to 2% of 2,963 necropsies
performed on blacks. In an analysis of the 1960-1962 Evans County, Georgia
heart study database, Bartel et al965 determined that electrocardiographic (ECG)
abnormalities were significantly less common among blacks as compared to
whites in this rural population study, and that abnormal ECG manifestations were
less predictive of the subsequent development or presence of CAD in blacks.
Hypertensive Heart Disease and Race
Many of these early researchers, however, noted that the incidence of
hypertension or hypertensive heart disease was more common among Eastern and
Southern American blacks and among American Virgin Island blacks than among
rural African blacks or among whites.411,413,419,424,425,426 In 1937, Nye811 reported
that blood pressures among Australian Aboriginals were characteristically normal
or subnormal by European standards, and a large study among native South
African blacks by Donnison415 showed that until the age of 40, blood pressures of
Page 37
native blacks and Europeans were similar, but between the ages of 40 and 60, the
average blood pressure of the native declined, whereas the pressure of the
European rose steadily. Saunders and Bancroft413 postulated that the difference
observed in the prevalence of hypertension between American Virgin Island
blacks and African blacks may have been due to the poorer diet of the American
Virgin Island black as compared to his African counterpart, citing the
unavailability of "agricultural products in any quantity," and that the general
Virgin Island diet was found to be "inadequate," with deficiency diseases
occurring on a relatively common basis. The researchers concluded that among
the study participants, "poverty, with its associated vitamin deficiencies, may tend
to raise blood pressure." Supporting these early observations of an association
between hypertension and reduced vegetable intake, Melby et al,931 in a study of
blood pressure and blood lipids among 167 black vegetarians, semi-vegetarians,
and non-vegetarians, found serum cholesterol levels to be 13% lower among
vegetarians than among non-vegetarians, and that the incidence of hypertension
among black vegetarians was half that of the non-vegetarians (16% versus 31.1%),
despite significantly greater use of antihypertensives among the non-vegetarians.
Urbanization, Migration, Race, and CAD Risk.
Kesilman411 in a study of 2,230 blacks, concluded that transplantation of blacks
from rural environments and the subsequent stress associated with urbanization
was responsible for disparate results seen among higher blood pressures of eastern
black males versus those recorded previously among primitive blacks, among rural
black agricultural workers, or among whites. In support of this hypothesis,
Kesilman cited statistics from the Metropolitan Life Insurance Company for 1936
which showed that the lowest mortality for cardiovascular-renal disease among
blacks occurred among agricultural workers, and the highest death rate occurred in
the densely populated urban centers. Similarly, Dahl941 stated in 1958 that
Page 38
hypertensive disease was rare among primitive populations, and Schwab and
Schulze hypothesized in 1932 that "stress and strain" incidental to urbanization
and "acculturation" were responsible for the development of hypertension among
urban blacks. Examining indexes of deprivation among 18,930 subjects living in
rural, small town, and urban areas in 1993, Reading et al940 concluded that there
was a "substantial disadvantage to living in urban areas compared with rural
areas". This disadvantage was the consequence of poorer health that resulted from
certain social or environmental factors which were unrelated to the subjects'
current level of material deprivation. The authors further concluded that "there is
a consistent association between increasingly urban environments and poorer
measures...of child and adult health."
In a report based on observations made in the early 1960s, Kuller957 determined
that sudden death in patients with atherosclerotic disease occurred less frequently
in black males than in whites, however studies of predominantly urban
populations in Nashville,966 New Orleans,967 and in South Carolina968 which were
published in the following two decades, reported higher rates of cardiac arrest in
blacks than in whites. A large urban population study by Becker and
associates,178 which examined 6,451 patients experiencing out-of-hospital cardiac
arrest between 1987 and 1988, found that blacks were at significantly higher risk
for cardiac arrest and sudden death than whites, and were significantly less likely
to survive the event. The survival rate of blacks was less than one third that of
whites, (p<0.001), even after controlling for other potentially confounding
variables. In the Pre-Hospital Arrest Survival Evaluation Study which examined
the circumstances surrounding 3,243 consecutive cardiac arrests occurring in
metropolitan New York City between October 1990 and April 1991, Lombardi et
al175 found a higher cardiac arrest mortality rate among individuals living in urban
New York City than among more suburban or rural settings, irrespective of race,
Page 39
and concluded that residence in a major urban area was a risk factor for cardiac
arrest mortality.
It is interesting to note that in 1956, Roberts et al962 reported a lower incidence
and prevalence of CAD among black males residing in urban inner-city Baltimore,
than among whites (no comparison was made, however, to rural blacks). Since
most major American urban areas currently report higher rates of CAD mortality
among blacks than among whites, urban living per se is probably not a risk factor
for CAD, but rather factors which are currently associated with urban living, are
more common to the black community, and which were less common to blacks
prior to 1960 may be implicated.
Numerous contemporary reviews have documented low incidences of CAD
among blacks within the early decades of this century, 10,37,44,45,225,304,305,369 and as
late as 1971, Cassel, Bartel, and co-workers, who examined data gathered in rural
Georgia in the early 1960s, wrote: "It is clear from these analyses that black males
are definitely protected in some fashion from CHD..."49,965
Some clinicians theorized that a genetic resistance to CAD might exist among
blacks due to the low incidence and prevalence of the disease among black
Africans and among American blacks in the early decades of the twentieth
century.4,129,132,301,369,377,378,379,418,419,444,965 After 1940, however, an increase in the
incidence of CAD mortality among American blacks occurred,4,46,301,379,818 but
even with this increase, CAD and myocardial infarctions continued to be more
prevalent among whites than blacks for several decades.47,48,49,818
This slight increase in the incidence of CAD among American blacks
accompanied the rural to urban black migrations which began at the end of the
second World War, but significant increases in CAD morbidity and mortality
among blacks were not recorded until the decade of the 1960s.
In 1960, Evans County study researchers determined that the age-adjusted rate of
Page 40
CAD was significantly less among blacks than whites, but at 20-year follow-up,
all racial differences were lost.49,50 By the 1980s, most epidemiologic studies
revealed significantly higher CAD mortality rates in blacks than in
whites.4,37,51,313,314
A 1929 study by Donnison415 demonstrated that among 1,000 healthy adult
African male Kenyan natives, the mean systolic pressure was very low (123 mm
hg during the later teen years and decreasing to 106 mm hg by the age of 60). In a
1938 publication, Crile stated that hypertension rarely occurs among primitive
blacks.414 Surveys in South Africa within the last fifteen years, however, have
shown a high prevalence of hypertension among the Zulu and Xhosa. 279,308,309,310 In
these surveys, the highest prevalence of hypertension has been seen in urban
versus rural groups, among males, and among the elderly. Demographic risk
factors for hypertension and CAD in these populations include residence in cities
and low income.279 Similarly, a Public Health Report published in 1951,408 stated
that higher urban than rural CAD mortality was observed for both black males and
females in the United States. The authors also noted that CAD mortality was
significantly higher in the more highly urbanized Northern United States than in
the predominantly rural South. Acculturation, (and especially that involving
Westernization or migration to urban areas), has been shown to be associated with
increases in blood pressure.279,311,327 In contemporary rural equatorial Africa,
blacks typically succumb to stroke more frequently than to CAD. Some clinicians
have postulated that more aggressive treatment of hypertension in the United
States, and improved patient compliance due to the availability of pharmacologic
agents possessing fewer side effects or adverse metabolic effects have reduced the
incidence of stroke to such a degree that American blacks are now living long
enough to develop and succumb to CAD.4,371 Indeed, major reductions in
cerebrovascular deaths have been reported among treated patients with
Page 41
hypertension,22 however, mortality rates for strokes in the United States actually
began to fall before the availability of effective antihypertensive therapy, and as
long ago as 1940.4, 99,104,371,372 Most recent surveys examining CAD mortality
among ethnic subgroups are adjusted for age as well as other risk factors, yet still
demonstrate an increasing incidence of CAD among the black population within
the last three decades. Current death rates per 100,000 in 1989 for all forms of
cardiovascular disease (including stroke, hypertensive disease, peripheral vascular
disease, CAD, and organic heart disease) were 39% higher for black men than for
whites, and 68% higher for black women than for white women.313 This same
survey demonstrated that black men were about one third more likely to die of
CAD than their white counterparts.
Social Mobility, Dietary Changes, Lifestyle Changes, and CAD Risk
Current and previous research demonstrates that blacks in industrialized nations
(as opposed to rural areas in Africa) become hypertensive earlier in life, at higher
levels, and twice as often as whites,10,226 and that blacks who migrate from rural to
urban areas tend to experience greater increases in blood lipids,442,444 and a greater
incidence of hypertensive disease with more rapid onset than blacks who remain in
rural areas.225,234
Similar differences in CAD risk within homogeneous ethnic
population groups have been seen between low CAD risk populations such as the
native Japanese and their higher risk counterparts who have emigrated to the
United States. Japanese who emigrate to America and who become acculturized
in both lifestyle and diet demonstrate rapid and significant increases in CAD risk
and begin to experience incidences of CAD similar to that of the general United
States population.212,213,225,236,237 Kafatos et al273 postulated that the adoption of a
sedentary lifestyle and a Western diet among modern urban inhabitants of the
Greek island of Crete was responsible for the significant increases in CAD
mortality from those low rates observed in earlier studies conducted in the late
Page 42
1950s and early 1960s of predominantly rural Cretan populations. Primarily
farmers, the rural Cretans had rates of heart disease and cancer that were among
the lowest in the world, despite their consumption of a relatively high-fat diet and
their daily consumption of four times as much wine as Americans. Forty percent of
daily calories consumed by these rural inhabitants of Crete were supplied by fat.
This is similar to American consumption levels, however the primary source of the
fat in the Cretan diet, olive oil, is very different from the primary American fat
source, animal fat. Kafatos and co-workers found that the abandonment of this
protective diet and the adoption of a high-stress sedentary lifestyle resulted in
significant increases of CAD among the urban Cretans. Snapper558 reported low
serum cholesterol levels among indigent Chinese in Peiping, yet high values
among the more prosperous commercial Chinese dwelling in Indonesia. Similarly,
Verhoef559 reported low serum cholesterol values among indigenous Javanese,
compared to normal values occurring in Javanese who emigrated to, and had been
resident in Holland for some time. Connor and co-workers538 reported low serum
cholesterol and a lack of hypertension or death from CVD among a primitive
group of 523 Tarahumara Indians of the Sierra Madre Occidental Mountains of
Mexico whose diet consists primarily of beans, corn, and squash and supplies only
2% of total calories as saturated fat and only 5% of total fat from animal sources.
By comparison, the more urbanized Pima Indians, who migrated to Arizona and
who eat a diet which is more similar to the American diet (which supplies 66% of
its total fat intake from animal sources, and 15% of total calories as saturated fat),
have significantly higher serum cholesterol levels (148 mg/dl versus 116 mg/dl,
or a difference of 28%). Brock and Bronte-Stewart444 and Walker and
Arvidsson442 reported significant differences in mean cholesterol values of urban
Bantu (or Cape Blacks) consuming a high-fat Westernized diet providing 35% of
calories derived from fat, versus the cholesterol levels of the rural South African
Page 43
Bantu (Becuanas and Basutos) consuming diets of maize, wheat, sorghum, beans
and legumes and providing only 17% of calories from fat. An analysis of African
ethnic groups which were subdivided on the basis of income by Brock and BronteStewart444 revealed that economic privilege and upward mobility resulted in
increased serum cholesterol and increased consumption of saturated fat (which
resulted primarily from the substitution of more expensive animal fat for vegetable
fat during cooking).
These disparate results among homogeneous populations implicate
environmental differences such as diet, exercise or stress as potential causative
factors for CAD risk increases which have been associated with social mobility,
rather than genetic or racial factors.237,273,442,464,918
Racial Differences in the American Rural to Urban Migration
At the turn of this century, 60 percent of all Americans lived in rural areas. By
1960, only 37 percent of Americans remained in rural areas, and currently rural
Americans comprise only 20 percent of the population. With 80 percent of
Americans living in metropolitan areas or their suburbs, and more than 50 percent
living in cities of over one million in population, American demographics have
radically changed within this century.64
The white majority migration to the cities occurred predominantly in the early
decades of the twentieth century through the 1950s, as they began to abandon the
less predictable, less lucrative and more labor-intensive agricultural jobs and
pursued the higher paying industrial, service, and manufacturing jobs available
within the major metropolitan areas. This white majority migration took place
prior to the black and other minority urban migrations occurring in the late 1940s
through the 1960s. Data from the Evans County Study clearly documents this
minority migration from 1960-1969, indicating that the rural South was the origin
and the urban North the destination for the black migration. 49 As the blacks
Page 44
migrated to the cities, property values fell, the higher SES whites and the affluent
withdrew to private enclaves in the suburbs, and the inner cities became the
primary domain of minorities and members of the lower socioeconomic groups. 11
Race and Demographics and their Effect on Socioeconomic Status
According to the 1992 Current population survey,160 black and Hispanic
Americans were about three times more likely to be poor than whites. The poverty
rate for blacks was 33.3 percent, and the corresponding rate for Hispanics was
29.3 percent. Recently (1990 census) poverty rates for black families with
children was reported to be about 37% [see Fig. 14].
In a population-based study by Grossman and co-workers,302 the unemployment
rate of urban African Americans was over three times as great as urban whites, and
the percentage of blacks below the federal poverty level was over 3.5 times as
great as urban whites.
Figure 14: Poverty Rates of Families With Children Under Age 18
By Race and Hispanic Origin: 1959-1990
___________________________________________________________________________________
Households, Families and Children: A 30-year Perspective215
The authors noted that the urban black adults in this study were less than half as
likely to have achieved a high school diploma compared to urban whites. The
Page 45
unemployment rates, poverty rates and health-risk behaviors of the urban blacks in
this study closely resembled the prevalence of these same factors in two other
minority groups, the urban American Indians and urban Alaskan natives, who
were also included in the study.
According to a recent survey, poverty rates were highest in the south (16.9%),
followed by the West (14.4%), the Midwest (13.1%), and the Northeast (12.3%).
Unemployment rates in 1992, which tend to vary from region to region on an
annual basis, were highest in the West (8.1%), followed by 7.6% in the Northeast,
7.5% in the south and 6.6% in the Midwest.161 Mortality rates in 1988 were
highest in the Middle Atlantic (10.0 per 1,000) and East South Central states (9.5),
and lowest in the Mountain (7.1) and pacific states (7.6).216
V. Demographic Theory and Discussion
Access to Medical Services and Quality of Care: Their Relationship to
Socioeconomic Status and CAD Risk
Unemployment, living in poverty, and lack of formal education have been
associated with likelihood of poor health, increased hospital stays, and an
increased number of reported physician contacts per year.218 According to the
most recent census data, 37.4 million (14.7% of the U.S. population) reported that
they were without health insurance at some time between 1991 and 1992. 160 The
majority of these respondents without adequate insurance were members of lower
socioeconomic groups, however the lack of adequate insurance, or lower total
government spending on medical coverage for the poor does not necessarily
correlate with the inability to access health care. In 1984, Congress, dismayed by
the low ranking of the United States with regard to infant mortality, mandated an
expansion of state-administered Medicaid coverage for low-income women and
their children, and in 1988 passed catastrophic amendments to medicare. Despite
$350 billion of expenditures over the decade, access to health care for these
Page 46
groups actually declined.627
A recent study of a relatively affluent group of employees of a major corporation
who were all covered by adequate health insurance (with 100% reimbursement for
pediatric immunizations with no deductible) demonstrated that despite availability
of services, preschool immunization rates did not reach public health goals.
Higher SES, greater parental formal education, and knowledge of when to initiate
immunization was associated with higher immunization rates. 628
The poor, and especially African-Americans, may have inadequate access or
certainly difficulties in access to medical care and may receive poorer quality of
care, according to several studies.133,134,135,136,182,381,382 The Medicaid Access Study
Group557 recently reported that Medicaid recipients in urban areas receive
outpatient care primarily from emergency departments. One recent study
published by Marmot et al, however, demonstrated that the strong association
between poverty and increased mortality was independent of the availability of
easy access to medical care and was "not amenable to medical care."132 Becker
and co-workers,178 in a population study of the incidence of sudden cardiac arrest
among 6,451 inner city black and white patients, stated that "the quality of the
EMS services does not appear to explain the lower survival rates among blacks."
A third large population study with a nine-year follow-up conducted by Berkman
and Syme238 demonstrated that the association of hypertension and increased
mortality with areas of poverty was independent of "considerations of...medical
care,"225 and Goldman and co-workers argued that improved hospital care cannot
account for the decline in CAD mortality which was observed in the late 1970s. 326
These studies suggest that access to and quality of care alone do not explain this
association of the poor with increased risk of death.
Haan et al130 demonstrated that residence in a poverty area is associated with
increased risk of death from all causes, regardless of the socioeconomic status of
Page 47
the resident. In fact, the researchers found that affluent residents who chose to
reside in poverty areas demonstrated CAD risk almost equal to that of poor
residents. This finding has been supported in recent studies conducted by
Lombardi et al175 and by Becker and co-workers 176 which demonstrated that
survival from out-of-hospital cardiac arrest in major urban areas was significantly
less than in rural or suburban areas, irrespective of the socioeconomic status of the
patient. Although as many as twenty-five percent of the inhabitants of major
American cities live below the federal poverty level,174 Lombardi concluded that
minority status and poverty may contribute to substandard baseline health, but he
stated that these factors alone could not account for the magnitude of the inner city
increased risk of death. Becker et al178 questioned race as a risk factor for acute
cardiovascular events, and suggested that race might be a "marker" for other
coexisting or underlying factors which compromise health including environment,
poor understanding of good health practices, genetics, occult disease, and drug
abuse. These markers, which tend to be significantly more common among the
young, may provide an additional explanation for the racial differences involving
increased risk among younger blacks, and decreased risks among elderly blacks
[see Fig. 38]. Berkman and Syme238 found that the increased risk of hypertension
in a poverty area versus an area of affluence was independent of the
socioeconomic status of the inhabitants, or the presence of various accepted CAD
risk factors. The only positive correlation was an increased incidence of
hypertension with the increased number of fire department, ambulance, or police
calls. Conversely, Bright's finding in the Baltimore Study demonstrated that "outmigration among whites tends to be selective of those with lower mortality," and
may reflect the benefits of the migration of upper SES individuals out of the city to
the suburbs and away from certain factors contributing to increased risk of
coronary death in the inner city.173,507,508,509
Page 48
A strong association between socioeconomic status and risk of death has been
found in studies conducted in Norway,137 the Netherlands,138 England and
Wales,139 Finland,140 and Canada.141 Many of these countries have extensive
socialized medicine programs which should guarantee equal access to comparable
levels of medical care regardless of income, education, or social status.
Studies conducted in the late 1950s and early 1960s found that rates of
neoplastic and cardiovascular disease were among the lowest, and the life
expectancies of the rural mediterranean Cretan islanders were among the highest
in the world, despite a lack of sophisticated medical technology and an extremely
limited access to medical services.
These studies suggest that certain environmental factors which may be more
common to the urban poor, and not the ability to afford or access quality health
care may have the greatest effect on CAD, survival of a cardiovascular event, and
all cause mortality.
Exercise, Daily Activity Levels, Socioeconomic Status, and CAD Risk
Factors
In 1929, Levine and Brown462 stated that physical effort was conducive to CAD
by inducing coronary thrombosis. Although strenuous physical exercise in
habitually sedentary individuals carries an increased risk of acute myocardial
infarction,466 research has documented the protective or beneficial cardiovascular
effects of regular aerobic exercise.13,14,17,21,34,35,80,87,259,291,292,293,385,386,466,511,512,513,514,
515,516,517,626,719,947
The magnitude of CAD risk reduction associated with exercise
has varied from study to study, however a conservative estimate places the risk at
40-50% lower than that of sedentary individuals.
Both leisure and occupational physical activity are frequently directly
proportional to SES. Members of lower SES typically tend to be less active than
the affluent [seeTable 3],261,262,263,384,385,387 however Cassel et al947 determined that
Page 49
higher SES whites were less active and suffered from more CAD than lower SES
blacks during an early 1960s prevalence study in rural Georgia. The authors
attributed the higher risk of CAD observed among whites to the high prevalence of
sedentary occupations among whites, and to the active, manual-labor occupations
prevalent among blacks during this period. The single exception which Cassel
noted was that low SES white share-croppers who engaged in as much hard
physical labor as did blacks, had lower CAD mortality per 1,000 than did
sedentary white farm owners, and equal mortality from coronary artery disease as
compared to black share croppers.947 The researchers blamed "increasing
mechanization" for making low-SES jobs less physically demanding and
subsequently increasing the risk of CAD among blacks by the end of the
observation period in the late 1960s. The authors further concluded that increased
recreational and leisure-time physical activity may have been responsible for the
reduction of CAD-risk associated with more sedentary, upper-SES jobs [see Table
3].
Table 3: Reported Exercise by Americans, 1977
Stratum
College educated
High School
Who exercises?
59%
47%
Who jogs?
17%
11%
Grade School
30%
3%
Professional and business
56%
13%
Clerical and sales 57%
Manual labor
45%
16%
12%
______________________________________________________________________________________
Adapted from: Stamler35
These changes may have contributed to the paradoxical SES-associated CAD
prevalence gradient disappearance which was observed by these researchers in
1967.
Page 50
The Alameda County Study387 similarly documented a nine-year decline in
physical activity occurring primarily among members of lower-SES in the late
1960s and into the decade of the 1970s. One possible exception may be the
physical activity status of employed blue-collar workers. Salonen et al386 found
that lower-SES men in Finland had higher levels of occupational physical activity
than their more wealthy counterparts.
Exercise influences nutritional status and body fat composition, delays ageassociated degeneration of the cardiovascular system, maintains muscle function,
and may extend active lifespan.279 In a review of the approximately 2.1 million
deaths in the United States which occurred in 1990, McGinnis and associates115
identified inadequate exercise as a major contributing factor. Regular exercise has
been associated with a decreased risk of death from CAD,87,290,291,292,293,511,
512,513,514,515,516,517,626
and secondary prevention trials have demonstrated significant
reduction in mortality rates (from 24% to 32%) in patients who exercise regularly,
or who maintain regular regimens of moderate, self-directed leisure time
activities.80, 86, 87 An analysis of the Framingham study by Kannel and
associates626 suggested that the probability of ischemic heart disease was reduced
25% in those with higher physical activity. Similarly, only 16.9% of the
approximately two million adults who died in 1986 were reported to have
exercised vigorously and regularly in the decade prior to their death. 214
Levels of physical activity and their relationship to SES may vary depending on
whether leisure or occupational physical activity is measured, however in general,
members of lower SES are less active. If unemployment or joblessness is used as
a marker for low SES, the prevalence of a sedentary lifestyle is even more likely
than among the working poor.
In the 1985 Health Interview Survey, there was a direct and consistent
relationship between level of education and income and the level of physical
Page 51
activity.261 Millar and associates262 found that the prevalence of physical
inactivity in Canadian adults decreased with increasing educational level. The
rate of inactivity in those with an elementary school education was more than
twice the rate in those who attended at least one year of college or more. The
German Cardiovascular Prevention Study found that those in the lowest social
class had an increased risk of being physically inactive (exercising less than 1 hour
per week) that was four and a half to five times that of subjects in the highest
class.263
Regular exercise improves cardiac function,80 reduces blood pressure,252 helps
maintain weight control,3 improves glucose tolerance,88 increases joint mobility,89
reduces stress and resting heart rate,3,111 increases the sense of well-being,
improves HDL to LDL subfraction ratios,3,90,111,253,254,511 decreases plasma
fibrinogen levels,719,511 triglycerides,511 and apolipoprotein B,511 and decreases the
frequency of exercise induced ventricular arrhythmias.91
Whether exercise is accomplished through leisure or occupational activities, it is
equally beneficial in reducing cardiovascular risk.87,385,386,511 Members of lower
SES, however, are significantly less likely to achieve this goal through either
occupational or leisure activities.261,262,263,384,385,387
Diet and Demographics: Sources of Dietary Fats
The relationship between diet and physical health has been explored for
centuries. In the 6th century BC, Pythagoras argued in favor of a meatless diet for
improved physical health. Numerous studies within the last several decades have
investigated the relationship between diet and disease, and more recently the
interrelationships between diet, disease, and poverty. There is little doubt that
mortality from CAD is not only related to the socioeconomic conditions of
adulthood, but that it is also mediated by the current and changing dietary and
health-related behaviors of populations.275,276,299,391,522 As early as 1948, Ansel
Page 52
Keys proposed a link between the increased consumption of dietary saturated fat
and cholesterol which occurred during the previous decades of the twentieth
century and the increased incidence of CAD during this same period.275,276,391 The
pioneering Seven Country Study by Keys was initiated in 1960 and confirmed an
increased incidence of coronary artery disease in populations consuming diets
higher in saturated fats and cholesterol.522,600 Subsequent follow-up and reanalysis
of the Seven Country Study continues to validate the original findings. 526,527,546
In 1992, de Lorgeril and Renaud,872 citing a substantial body of previous
research, reported that epidemiologic evidence has demonstrated that diet has a
direct and quantifiable effect upon hemostatic factors involved in thrombosis and
acute coronary events. This includes effects upon fibrinogen, factor VII,
leukocytes, and platelets. This observation may explain the significant increases
of acute thrombotic events observed by various authors in populations increasing
their consumption of saturated animal fats.
Dietary Fat and CAD Risk of Populations
Increased CAD risk and CAD mortality is not consistently associated with
indigent populations. In fact, men living in countries such as Greece, Crete, Italy,
Yugoslavia, Romania, Poland, and Portugal have significantly lower CAD
mortality rates than do their more affluent counterparts in Finland, The United
States, and the United Kingdom, possibly due to significant differences in
lifestyle and diet which were prevalent in the past few decades [see Figure
11].300,392,522 The change in the trends of the mortality rates of these previously
low-risk populations is directly associated with the adoption of adverse dietary
and lifestyle changes which are more in conformance with the lifestyles and
dietary habits of high-risk populations. For instance, immigrants from Poland and
Japan experience a rapid increase in mortality from cancer, CAD, and other
degenerative diseases upon coming to the Unites States.847,848 Lopes-S and co-
Page 53
workers376 stated that the Finnish population has undergone great dietary changes
in the last half-century including a marked reduction in the consumption of
vegetables, cereals, and complex carbohydrates, and significant increases in the
consumption of refined sugars and animal fat, including milk and butter. At over
one quart per day, the Finnish per capita daily milk consumption is 37% higher
than the United States, and is probably one of the highest of any population in the
world.660 The Adventist Health Study,851 a prospective cohort investigation of
31,208 white men and women, found that whole milk intake in this population was
associated with an increased incidence of coronary events (relative risk 1.33;
p=0.07) when the highest tertile of milk intake (in this study, "high" intake was
one or more eight ounce glasses per day) was compared to individuals consuming
no whole milk.891 Based on these findings, the Finnish consumption of over one
quart per day of whole milk (four times the intake designated as "high" in the
Adventist study) might partially explain the extremely high incidence of CAD in
that country [see Fig. 17].
Aldercreutz, Markkanen and Watanabe607 compared the serum levels of several
types of flavonoids (supplied by dietary vegetable sources) of 14 healthy, middleaged Japanese men and 14 Finnish men and found that average blood levels of
these nutrients were seven to 110 times higher among the Japanese men. Finnish
fat intake is as high as 45% of total calories and is supplied largely by meat and
milk.476,660,828 Although Finnish cholesterol and saturated fat intake is similar to
France (which enjoys CAD mortality levels one fifth that of Finland), the Fins
consume 3.4 times more milk and milk fat and 1.5 times more butter fat while
consuming one thirtieth the amount of monounsaturated fat (from olive oil,
peanuts and peanut oil), and one quarter as many vegetables as do the French.476
Interestingly, Finland also leads the world in coffee consumption at 37.5 pounds
per person per year, which represents about three times the per capita consumption
Page 54
of the United States.
New Zealand, which ranked fourth among 30 countries in the incidence of
CAD,61 and fourth among 27 countries in adult CAD mortality392 [see Figures 11
and 15], leads the world in per capita red meat consumption with 230 pounds
consumed in 1970. Several researchers469,641,644,648 have examined the dietary
habits of the Scotch, who demonstrated the third highest death rate from CAD
among 27 countries studied in 1977392 [see Fig. 11]. These studies revealed that
middle-aged Scottish men had a high saturated fat intake supplied primarily by
meat and milk, low consumption of polyunsaturated oils and cereal fiber, 641,644 and
ate very little fruit or green vegetables.648 Snowdon, Phillips and Fraser829 found
a 60% increased risk of fatal coronary disease among Seventh Day Adventists
consuming meat at least six times per week compared with those consuming meat
less than once weekly.
Much lower CAD mortality rates are consistently found in most European
countries, especially the rural areas of eastern Europe, the Mediterranean
countries, the Pacific rim countries, and Japan. Sub-population analyses obtained
in many countries indicate that upper socioeconomic classes that have adopted the
culture and diet of Western industrialized countries have far more CAD than lower
socioeconomic classes within the same countries.392
Epidemiologic studies have demonstrated that among the populations of the Far
East, animal products contribute only about 20% of the per capita food protein,
and may contribute significantly less in certain rural areas (10.8% has been
reported for the rural Chinese). On a global basis, animal products contribute
about 35% of protein, however in industrialized and urbanized North America, the
figure approaches 70%.874 These high protein intakes parallel dietary animal fat
consumption within these population groups.
The Ni-Hon-San study of men of Japanese descent in Hawaii, California, and
Page 55
Japan demonstrated that differences in the incidence of CAD closely paralleled the
substantial difference in fat consumption. Residents in Japan had the lowest risk,
Hawaii was intermediate, and residents of California had the highest risk. 212,213,553
Among the most consistent and obvious differences between these sub-groups are
total daily calories consumed, fat content of the diet, the source and type of fat in
the diet, the amount of flavonoids in the diet, and the amount of physical work.
Eicosapentaenoic Acid and The Dietary Fat Paradox
Eicosapentaenoic acid, or EPA, is an omega-3 C20:5 polyunsaturated fatty acid
with 20 carbons and 5 double bonds. With the exception of human breast milk, the
dietary sources of EPA are almost exclusively marine, and include salmon, tuna,
mackerel, anchovy, herring, trout, sardines and shellfish. The most effective way
of obtaining EPA is directly from foods. Given sufficient dietary linolenic acid,
however, the body can synthesize EPA,253,910 but the conversion process is slow.253
Consumption of omega-3 fatty acids decrease serum triglyceride levels, reduce
platelet aggregation, and may elevate HDL cholesterol.891,914,922 The native
Japanese, who have a high intake of EPA from marine sources also have a high
rate of hemorrhagic stroke. It has been suggested that the high prevalence of
hemorrhagic stroke among the Japanese may be due to anti-platelet effects
mediated by EPA and the omega-3 fatty acids,5,914 however a study of 80 Yupik
Eskimos in rural southwestern Alaska by Parkinson et al,929 found no increase in
bleeding time (but did not examine differences in platelet aggregation) versus nonnative controls even though the serum EPA and omega-3 fatty acid levels of the
Eskimos averaged 13 and 4.3 times higher, respectively, than controls. Fatty fish
and marine mammals high in EPA and omega-3 fatty acids are the major source of
subsistence food among the rural Alaskan Eskimo population. The serum levels of
omega-3 fatty acids and EPA may be significant in view of the fact that the annual
age-adjusted death rate from circulatory diseases, including CAD, among the
Page 56
Alaskan Eskimo population is 69 deaths per 100,000, which represents only onethird the rate of the U.S. white population.929,930
In 1981, Dyberg and Bang608 examined the epidemiologic data of Greenlanders,
who have a historically low incidence of CAD and myocardial infarction although
they have a diet which is highest in fat of any major population group, and
determined that the primary source of fat in their diet was supplied by fish, seal
and other marine sources, and was characterized by a high intake of marine
omega-3 fatty acids. These Eskimos exhibited low levels of LDL and VLDL,
increased HDL, reduced platelet aggregation, and a high degree of physical
activity as compared to that of Danes who were also studied.392,608
In the
Zuthphen Elderly Study,467,556 Dutch investigators found an inverse association of
fish consumption and 20-year CAD mortality.556 Recent research conducted by
Mori et al922 suggests that the beneficial lipid effects associated with omega-3
fatty acids are best achieved in association with a reduced fat diet (30% of calories
supplied by fat). These authors recommended one fish meal daily as a dietary
source of omega-3 fatty acids, but similar beneficial lipid effects were achieved by
equivalent levels of EPA supplementation. At lease nine other research groups
have noted beneficial effects associated with fish consumption and the reduced
risk of CAD morbidity or mortality.551,861,862,863,864,865,866,867,868
Linolenic Acid and Linoleic Acid
Linolenic acid is an omega-3, C18:3 polyunsaturated fatty acid supplied by nuts,
walnuts, purslane, wheat germ, and seeds, or vegetable oils produced from canola,
soybean, walnut, nuts, seeds, flaxseed, vegetables, and wheat germ. There is no
linolenic acid, however, in olive oil. Animal fat is a rich source of linolenic acid,
but not linoleic acid.605 Dietary linolenic acid increases serum EPA,253,910 and
flaxseed oil supplementation has been associated with a 2.5- fold increase in
plasma EPA, which is a level comparable to that achieved by fish oil
Page 57
supplementation, or by the daily consumption of fish.910 Linolenic acid reduces
platelet aggregation and stickiness,891 and may reduce the incidence of ventricular
arrhythmias. In both epidemiologic and clinical studies, it has been associated
with a reduced risk of CAD.270,850 Elevated post-prandial triglycerides may be
predictive of increased CAD risk. A diet containing a high percentage of fat as an
omega-3 PUFA (such as linolenic acid), or an omega-6 PUFA (such as linoleic
acid) is associated with increased triglyceride clearance, and lower serum
triglycerides, and may therefore reduce the risk of CAD.891
Linoleic acid is an omega-6, C18:2 polyunsaturated fatty acid supplied by olive
oil, and vegetable oils produced from cereals and seeds such as canola, corn,
sunflower seed, safflower, soybean, cottonseed, and sesame.253,483 Corn,
sunflower seed, safflower, soybean, cottonseed, and sesame oils contain only 13%
to 28% monounsaturated fat, but supply from 50% to 77% polyunsaturated fats.
Olive oil contains 77% monounsaturated fat, and only 8% polyunsaturated fats. 253
Linoleic acid reduces serum cholesterol levels,891 probably reduces platelet
aggregation,891 and has been associated with a reduced risk of CAD.469,630,643,849
Linolenic Acid Research and the Mediterranean Diet
When comparing the diets and serum levels of EPA, alpha-linolenic acid, and
linoleic acid of 51,000 physicians, Giovannucci and co-workers605,606 found that
three hundred physicians who had developed cancer of the prostate had lower
levels of linoleic acid and EPA than a comparable group of healthy controls. An
association of linolenic acid and prostate cancer was probably due to the fact that
it is supplied by animal fat as well as by vegetable sources. This explanation is
further strengthened by the researchers' observations that only fat from animal
sources, and especially that supplied by cooked meat, was related to the risk of
cancer. Alpha-linolenic acid, like the antioxidant vitamins, may under certain
conditions act as a pro-oxidant and increase the formation of free radicals.477,605
Page 58
while reducing serum levels of antioxidant beta carotene and vitamin E. 478 The
researchers noted that alpha linolenic acid itself may not be the culprit, but rather
the oxidation by-products of alpha linolenic acid formed during the cooking of
meat. This is further supported by the fact that those with active disease reported
consuming more cooked red meat, which was the strongest dietary risk factor in
the study. These patients also consumed more butter, mayonnaise, and creamy
salad dressings, and less fish (a source of EPA) and vegetables (a source of
linoleic acid) than controls. The authors noted that consumption of vegetable fat
was not associated with increased incidence of disease.
There is strong epidemiologic evidence of benefit of vegetable sources of
linolenic acid and EPA in reducing the risk of CAD. Japanese Kohama islanders,
who demonstrate the lowest incidence of CAD among population groups, have
diets which are high in marine sources of EPA supplied by a rural diet including
liberal amounts of seafood.476,551 Additionally, these islanders eat a large amount
of soybean products such as Tofu, and consume highly monounsaturated rapeseed,
or canola oil, (all are high in alpha linolenic acid).605,483
Rural Cretans from the eastern Mediterranean Greek island of Crete have the
second lowest incidence of heart disease of all major population groups and one of
the highest life expectancies in the world. They also consume a diet rich in alphalinolenic acid from plant sources such as purslane and walnuts.
This strong epidemiologic evidence is supported by the results of a major
secondary prevention trial. Michel de Lorgeril270,850 and a group of French
researchers set out to determine if a diet similar to the rural Cretans or Japanese
islanders would provide better protection against a second myocardial infarction
than the low cholesterol diet promoted by the American Heart Association.
Researchers followed the progress of 605 survivors of a first myocardial infarction
for an average of 27 months. Of these patients, 303 were randomized to an
Page 59
experimental group and instructed to consume a typical rural Cretan diet, and 302
patients were assigned to be the control group and were placed on the American
Heart Association low fat diet.
The experimental group ate a "Mediterranean" diet of whole-grain bread, ample
grains, root vegetables, pasta, rice, bulgar, green vegetables, and fruit, and
moderate amounts of fish, poultry, and cheese [see Fig. 39 and Table 6]. Beef,
lamb, and pork, other red meats, deli meats, butter, and cream were discouraged
(limited to a few times per month), and the patients were instructed to substitute
fish for red meat, or moderate and limited amounts of poultry. Total fat was
limited principally to highly monounsaturated olive oil, with monounsaturated
canola as an alternative. Eggs were limited to four per week, including those used
in cooking, and sweets, sugar and honey were limited to a few times per week.
Total fat ranged from 25% to more than 35% of total calories, however saturated
fat constituted no more than 6-7% of calories. Regular daily physical activity was
recommended, and daily wine consumption was encouraged in moderation (1-2
glasses per day). Emphasis was placed upon eating seasonally fresh and locally
grown foods.
The experimental patients ate 83% less butter and cream than controls
(p<0.001), 33% less red meat (p=0.009), and 19% more fish (p=ns). The
experimental patients used only olive oil or canola oil for cooking, and consumed
3.7 times more margarine (p<0.001) than controls, which was supplied by the
researchers as a non-hydrogenated blend of olive and canola oils rich in alpha
linolenic acid, (Linolenic 18:3 N3/ Linoleic 18:2 N6 PUFA ratio of 1:6).270
The control patients were placed on a diet restricting cholesterol and saturated
fats, and were told to increase their consumption of polyunsaturated fats. Total fat
in this group was reduced to just over 30% of calories, of which 10% was
saturated.
Page 60
Over the course of the study, blood cholesterol levels, blood pressures, smoking,
and average body weights were similar between the two groups. Differences in
SES were not reported. Intake of vitamin C was 27% higher and intake of
linolenic acid was 160% higher in the experimental group, (p<0.001). At the end
of the study, blood levels of alpha linolenic acid of those on the Mediterranean
diet were similar to those recorded among natives of Crete or Kohama.534 Plasma
levels of vitamin C and E increased significantly (p<0.05), and platelet
aggregation decreased (p<0.05) in the experimental group.
After a mean follow-up of 27 months, there were 33 major coronary events
(cardiac death or non-fatal AMI) in the controls versus only 8 in the experimental
group, a risk reduction of 76% (p<0.0001). The risk of all major cardiovascular
events (death,non fatal AMI, unstable angina, stroke, and heart failure) was
reduced by 79%, (p<0.0001), [see Table 4]. This reduced risk of acute events may
reflect the anti-thrombotic potential of increasing linolenic acid.
Table 4: Mortality and Cardiovascular Events Among Patients with First
Myocardial Infarction on Mediterranean versus American Heart Association (AHA)
Diet
Cardiovascular Event
Total in group:
A.H.A. Diet
302
Repeat Myocardial Infarction: 33 (10.9%)
Mediterranean Diet
303
8 (2.6%)
Fatal Myocardial Infarction:
Sudden Death:
16 (5.3%)
8 (2.6%)
3 (1%)
0 (0%)
Linolenic Acid Intake
.30%
.78% (p<0.001)
Linoleic Acid Intake
5.2% (p<0.001)
3.5%
_________________________________________________________________
Adapted from de Lorgeril850
The Mediterranean or Cretan diet is similar to the diet eaten in much of Greece
and southern Italy four decades ago, and was followed with certain variations in
Page 61
parts of Spain and Portugal, southern France, North Africa (particularly Morocco
and Tunisia), Turkey, and the Balkan region in the Middle East (especially
Lebanon and Syria).
Fraser et al851 conducted research using the extensive Adventist Health Study
database of 31,208 non-hispanic white California Seventh-Day Adventists, whose
religious beliefs encourage strict adherence to a lacto-ovovegetarian diet. These
researchers found that eating nuts, (relative risk 0.49, p=0.0001) whole grain
breads, (relative risk 0.63, p=0.006) and vigorous exercise (relative risk 0.61, p=
0.0001) lowered the risk of fatal coronary events and myocardial infarction.851 ,891
Those eating nuts, (which are an excellent source of linolenic acid) once weekly
reduced their risk of nonfatal and fatal CHD by 25 percent, and those who ate nuts
five or more times weekly lowered their risk by almost 50 percent, (Non-fatal
AMI: relative risk 0.49; 95% CI, 0.28 to 0.85; Fatal CHD: relative risk 0.52; 95%
CI, 0.36 to 0.76). Those eating whole wheat bread (wheat germ and whole wheat
kernels are an excellent source of linolenic acid) had a 55% reduction in non-fatal
AMI (p<0.01, relative risk 0.45; 95% CI, 0.28 to 0.71), and a 20% reduction in
fatal CHD (p<0.01, relative risk 0.78 to 0.82; 95% CI, 0.55 to 1.21). These
findings persisted on covariate adjustment and were seen in all of 16 different subgroups of the population. One of the most frequently eaten nuts in this study was
walnuts, one of the best and most concentrated vegetable sources of linolenic
acid.
With the exception of olive oil as a primary source of fat, the rural
Mediterranean diet, (including the increased consumption of plant sources of
alpha linolenic acid, whole grain breads, and the rural Mediterranean pattern of
physical activity) was more closely followed by blacks in the first four or five
decades of this century rather than whites.
Linoleic Acid Research
Page 62
Wood and colleagues630 reported an inverse relation between adipose linoleic
acid and platelet EPA content and the risk of angina pectoris in a population casecontrol study of 110 angina patients and 394 controls selected from a sample of
6,000 men aged 35 to 64 years. Riemersma et al determined that increased
linoleic acid in adipose tissue (p<0.001), platelet EPA (p<0.01), and plasma
vitamin E concentrations (p=0.09) were associated with reductions in the
incidence of angina pectoris.469,643 Roberts, Wood Riemersma, and Gallagher 849
measured adipose linoleic acid in 102 women with CAD as compared to 181
healthy controls, and found that linoleic acid was inversely related to the risk of
CAD in women. These researchers found an adjusted odds ratio of 3.9 (95%
confidence interval 1.3-12.0) for CAD when comparing those women with the
lowest levels of tissue linoleic acid with those with the highest levels.
Western Diet and CAD Epidemiology
The rural diets of many agrarian populations are substantially richer in foods of
plant origin when compared with diets consumed in more industrialized, Western
societies. The Western, urbanized lifestyle is associated with significant increases
in plasma cholesterol (p<0.01) versus rural, predominantly vegetarian groups
within homogeneous populations. Blood plasma cholesterol concentration is
significantly associated with the consumption of meat, total fat, and foods of
animal origin, and inversely associated with the intake of legumes and cereal
fiber.855
Numerous epidemiological studies have determined that Japanese who emigrate
to America and who become acculturized demonstrate rapid and significant
increases in CAD risk conforming more to the known risk of their adoptive
country than their country of origin.212,213,225,236,237
Native Japanese, who
consume a diet low in fat and who possess one of the lowest CAD mortality rates
and one of the highest life expectancies of all population groups, consume more
Page 63
salt and smoke more than do Americans. The Japanese have a high incidence of
hypertension, higher average blood pressures, and higher rates of hemorrhagic
stroke than Americans, which suggests that diet may play a greater role in the
pathogenesis of CAD than does smoking or hypertension.476,914
Examining the nutritional transition in China, Popkin272 noted that wealthy urban
Chinese who have become Westernized, suffer from significantly higher rates of
CAD and other degenerative diseases than do the rural Chinese. Similarly,
Campbell and Junshi855 observed a geographic clustering of diseases among the
Chinese, [see Table 5] one primarily of infectious and associated with poverty, the
second primarily degenerative, and associated with wealth.
Table 5: Diseases of Wealth And Poverty
Degenerative diseases Associated with Westernization versus Infectious diseases of Rural Poverty
Diseases of Wealth
Diseases of Poverty
(Primarily degenerative)
(Primarily infectious)
1. Coronary heart disease
1. Pneumonia
2. Diabetes
2. Pulmonary tuberculosis
3. Colon cancer
3. Other infectious diseases
4. Liver cancer
4. Rheumatic heart disease
5. Lung cancer
5. Parasitic diseases
6. Breast cancer
6. Nephritis
7. Stomach cancer
7.
Eclampsia
8. Brain cancer, ages 0-14 years
8. Other diseases of pregnancy
9. Leukemia
9. Metabolic and endocrine disorder
10. Intestinal obstructions
11. Peptic ulcer
12. Other digestive disorders
______________________________________________________________________
Adapted from: Campbell and Junshi,855 Diet and chronic degenerative diseases: perspectives from China.
Mortality rates in Yugoslavia, Hungary, Romania, Poland, and Bulgaria,
although lower than more industrialized nations, increased significantly between
1969 and 1977392 probably due to a trend towards Westernization which occurred
in urban areas during this period [see Fig. 11].
Large Epidemiologic Studies on Diet and CAD
In a review by McGinnis and associates115 of articles published between 1977
Page 64
and 1993 which identified factors contributing to death in the United States,
inadequate diet and exercise were identified as the second most prominent
contributor to mortality, after use of tobacco products. The Western Electric
Study205 showed evidence of the effect of diet on lowering the death rate from
CAD, even though emphasis on prevention was minimal and was not stressed until
late in the study.525 Using a dietary scoring system for saturated fat intake
developed by Keys et al892 and Hegsted et al,893 the Western Electric Study
researchers found that after adjusting for serum cholesterol levels, fat intake and
serum concentrations of polyunsaturated fatty acids (PUFA) were still predictive
of CAD risk in this population. Similarly, the Boston Irish Diet-Heart Study554
found that both the Keys and Hegsted dietary scores and saturated fat consumption
were predictive of CAD morbidity and mortality even after adjusting for serum
cholesterol, and Salonen et al585 reported that the ratio of serum PUFA to saturated
fatty acids is predictive of coronary events after adjustment for serum cholesterol.
Additionally, the Diet-Heart Study researchers found that both a vegetable intake
score and an estimation of consumption of fiber were predictive of coronary
deaths during 20-years of follow-up. These findings suggest that vegetable and fat
consumption may have important physiological and biochemical effects beyond
their effects of raising or lowering serum cholesterol.
The China Study
The largest study conducted to date, the China Study269,272 ,601,855 examined the
eating habits and health of the rural Chinese who rarely suffer from the major
chronic degenerative diseases common to Americans. As has been demonstrated
within other populations including the Japanese, the Cretans, the Javanese,
Africans, and American blacks, rural to urban migration in China was associated
with an increased risk of death from CAD. In particular, Chinese members of the
upper socioeconomic class, particularly in urban areas, consumed diets which
Page 65
were higher in fat, and subsequently were more obese than their rural
counterparts.272 Because urban and wealthier Chinese who have adopted more
"Western" eating practices suffer from rates of CAD and cancer approaching those
of the United States, these people were excluded from the China Study. Baseline
data collection demonstrated that the rate of colo-rectal cancer among the rural
Chinese is one-half that of Americans; the rate of breast cancer one fifth that of
American women; and the rate of CAD is one seventeenth that of American men.
On the average, the Chinese are leaner than Americans, and engage in
significantly more aerobic exercise, largely because of the use of bicycles as their
primary mode of transportation.
There were several striking differences between the diets of the rural Chinese
and the typical American diet. Only 14.5% of the calories that the Chinese
consumed came from fat, compared to about 40% in the American diet, according
to recent observations.602,855 The Chinese consume three times as much dietary
fiber (33.3 g/d) and significantly more vegetables, complex carbohydrates and
dietary sources of antioxidant vitamins, including vitamin C and beta carotene.
Intake of animal protein in China constitutes only 10.8% of total protein intake,
whereas in the United States it is 69% of total protein intake and 30% of total
caloric intake.2,538,855 This finding is accordance with previous research which
demonstrated that population groups in developed countries consume six times as
much animal protein per person per day as do those in undeveloped countries. 660
Although they consumed relatively little red meat and animal protein, iron intake
in China was surprisingly high, averaging about 37g/d, especially when compared
to a U.S. intake of only 18g/d. Mean plasma iron levels among Chinese men and
women were significantly higher than levels common to the United States.
Approximately 95% of the iron intake of the Chinese, however, was in the nonheme form and was supplied by plant sources.855
Page 66
Previous scholarship has demonstrated that as much as 80% of total calories
consumed by the rural Chinese is supplied by complex carbohydrate sources,
primarily from rice, [see Table 6].376
Similar to the findings of the China Study, Connor et al538 reported that the
Tarahumara Indians of Mexico, among whom hypertension, obesity, and death from
CVD are relatively unknown, consume only 12% of their total caloric intake as fat, of
which 95% is derived from vegetable sources, and is primarily monounsaturated or
polyunsaturated. The Tarahumara Indians consume almost twice as much dietary
fiber as Americans, (19 g/d) and their intake of animal fat in this rural primitive
population constitutes only 5% of total fat consumption. Over 96% of the protein in
the Tarahumara diet was derived from vegetable sources, and only 2% of calories was
derived from saturated fat. Sugar and refined carbohydrate consumption by the
Tarahumaras constitutes less than 3% of total calories compared to an average of 51%
of total calories in the American diet, [see Table 6].
__________________________________________________________________________________________________________________
Table 6: Composition of Three Low CAD Risk Diets
Versus the High Risk Western Diet
Component
Tarahumara Diet
Chinese Diet
9-12%
14.5%
FAT
SOURCE*
95% V; 5% A; 2% S
CARBOHYDRATES
SOURCE*
PROTEIN
SOURCE*
90% V; 10% A; 4% S
75-80%
97% Complex; 3% Refined
8-13%
96% V; 4% A
FIBER
19gr/d
*A=animal V=vegetable; S= saturated
American Diet
38-40%
Mediterranean Diet
25-35%
34% V; 66% A; 15% S
75-80%
45%
83% V; 17% A; 7%S
47-57%
80% Complex 49% Complex; 51% Refined
5.5-10%
89% V; 11% A
33gr/d
15-17%
32% V; 68% A
11gr/d
90-95% Complex
18%
>80% V
19g/d
____________________________________________________________________________________________________________________
Adapted from: Connor et al538 de Lorgeril et al,270,534,850,970and Campbell et al.855
Total carbohydrate consumption, consisting almost exclusively of unprocessed
Page 67
complex carbohydrates and starches, was 75-80% of total calories. In contrast,
grains, fruits, and vegetables comprised approximately 50% of American daily caloric
intake between 1909 and 1913, when significantly more Americans lived in rural
areas. Paralleling swift trends in urbanization, grain, fruit, and vegetable
consumption fell to only 30% of daily caloric intake in the United States by 1959, and
remained approximately at that level through 1980.2 Currently, consumption of these
foods is increasing (primarily among the upper socioeconomic class).
It is interesting to note, however, that population groups such as the rural
Chinese and the Mexican Tarahumara Indians who consume diets high in
carbohydrate and low in fats generally have lower HDL cholesterol levels and
higher triglycerides than populations that eat diets high in saturated fat.538,742 In
several clinical studies, low fat diets were consistently associated with a mild
reduction of HDL cholesterol.549,891 This suggests that diets which lower LDL
cholesterol or increase its resistance to oxidation may be preferable to dietary,
lifestyle, or pharmacologic interventions which primarily increase plasma HDL
levels without reducing the potential for oxidative stress and the oxidation of
LDL.
There are numerous similarities between the rural Chinese diet, the Pacific Rim
diet of Japan,212,540,541 the rural Eastern European diet of Poland, Romania and
Yugoslavia,392 the diet of the Tarahumara Indians of Mexico,538 the diet of the
Ugandans of East Africa,539 and the Mediterranean diet of southern Italy, Greece,
Crete, and other Mediterranean islands.270 These diets are primarily based on the
liberal consumption of fruits, whole grains, vegetables, beans, cereals, legumes,
other complex carbohydrates, and dairy products with little use of red meat, and
moderate use of fish or poultry, and have consistently been associated with low
plasma cholesterol levels.476,855 According to Ansel Keys: "Fruits and vegetables
other than roots and tubers are much more prominent in the average diets in Italy
Page 68
and Greece than in those of Finland, the Netherlands, and the United States.526"
The greatest similarity is the fact that all six of these dietary regimens offer
significant protection against the risk of developing CAD in these
populations.212,269,270,392,476
Saturated Fat and Sugar Intake of Populations
Examining the increases in serum cholesterol associated with changes in the
United States civilian diet between 1909 and 1965, Khan attributed a significant
part of the historical increase in blood lipids to changes in diet which occurred
during this period, which included a 5% increase in meat consumption, a 132%
increase in poultry consumption, a 7% increase in egg consumption, and a 34%
increase in dairy product consumption (excluding butter). 36 The author stated that
"beef in 1909 was leaner than the average beef referred to in the current handbook
of nutrient values." Examining the relationship between diet and CAD mortality
in Europe, Lopez-S and associates similarly noted increases in animal fat
consumption between 1934 and 1959, stating that the profile of the high risk
coronary patient involves, (in addition to hypertension, obesity, and elevated
blood lipids), "the luxurious consumption of high fat foods rich in cholesterol,
reduced exercise and activity patterns, and certain psychological and emotional
stresses associated with continued striving for success." 376 These authors further
stated that increases in CAD morbidity and mortality observed
during the twenty-five year period were manifested to a greater degree in
technically advanced countries, and may be "the price of affluence and
advancement."
Armstrong and associates61 examined the effect of certain dietary practices on
CAD mortality in England and Wales from 1950 to 1967 and compared these
results to those of thirty other countries. These authors found that total green
vegetable consumption consistently was inversely correlated with CAD mortality
Page 69
in both men and women. Per capita sugar (refined carbohydrate) consumption
however was directly proportional to the incidence of CAD in England and Wales
and in the 30 country comparison populations [see Fig. 15]. This may be due in
part to the effect of hyperglycemia on increased lipoprotein oxidation, 823,834,835,836
increases in plasma triglycerides,742 and decreases in plasma HDL cholesterol that
may accompany high carbohydrate diets,742 and the lack of sufficient antioxidant
vitamins and other nutrients in these urban diets due to processing and refining.
Figure 15: Incidence of CAD in Males and Females Plotted Against
Sugar Consumption in 30 Countries.
____________________________________________________
From: Amrstrong et al.61
Several other researchers518,519,520 previously noted a strong association between
increased consumption of sugar and refined carbohydrates and the increased
consumption of saturated fats in study populations. In his review of research
related to CAD risk factors in twenty countries, Stamler35 cited sociocultural,
dietary, and lifestyle factors and argued against a population genetic susceptibility
Page 70
in the etiology of CAD.
Figure 16: Per Capita Calories Available From Principal Animal Sources
and Age-Standardized CAD Mortality For 20 Countries in 1973.
________________________________________________________________________________________
From: Stamler35
Stamler stated that per capita saturated fat and cholesterol consumption (Dairy,
eggs, meat and poultry consumption as a percent of total calories consumed) was
directly proportional to CAD mortality per 100,000 in 20 countries [see Fig. 16].
Artaud-Wild and associates476 examined milk intake (in addition to saturated fat
and cholesterol intake) in 40 countries to explain the French and Finnish
deviations from expected CAD mortality rates and postulated that higher milk and
butterfat consumption in Finland and greater vegetable consumption in France
may be the cause of the apparent paradox [see Fig. 17]. Similarly, Turpeinen532
documented a correlation between dairy fat consumption and CAD mortality rates
for 22 industrialized countries, and Renaud and de Lorgeril533,534 found a strong
correlation between CAD mortality rates and the consumption of dairy fat
(excluding fat from cheese) in 19 countries. Interestingly, Renaud and de Lorgeril
found no increased risk of CAD associated with cheese consumption, and this was
similar to the earlier finding of Ansel Keys in his pioneering Seven countries
Study,522,526,527,534,546 and to the subsequent findings of the Adventist Health Study,
Page 71
which showed that the highest tertile of cheese intake (3 times per week or greater)
among a cohort of 26,473 non-diabetic white men and women was associated with
a decreased risk (p=ns) of fatal coronary events.851,891
Figure 17: Death Rate from CAD Correlated With Daily Dietary Intake of
Saturated Fat/Cholesterol and Milk Products in 40 Countries, 1976-1978.
__________________________________________________________________________________
From: Artaud-Wild et al.476
Both de Lorgeril and Keys postulated that the fermentation process of cheese, and
possibly other fermented milk products, may modify and render the milk fat less
bioavailable.534
Joossems and colleagues535 found significantly higher CAD mortality in
northern Belgium than in southern Belgium. These researchers noted that butterfat
consumption was far greater in northern Belgium. Even France has a contrasting
pattern of cultures regarding diet. Butterfat consumption is high in the north
where the incidence of CAD is higher.533
Monounsaturated fat
In southern France, which enjoys low CAD incidence rates, olive oil is the
Page 72
primary dietary fat.536 It is noteworthy that in the Seven Countries Study, Keys
and colleagues546 demonstrated that the CAD death rate was inversely
proportional to the percentage of dietary calories derived from monounsaturated
fats such as olive oil. Barradas et al895 fed 21 healthy volunteers 21g of olive oil
daily for eight weeks and found a pronounced decrease in platelet aggregation
when platelet rich plasma and whole blood samples of these volunteers were
stimulated by adenosine diphosphate (ADP) or adrenalin, which suggests a
protective effect of olive oil during conditions of stress. In metabolic studies,
monounsaturated fatty acids possess a beneficial low density lipoprotein-lowering
effect without significantly lowering desirable high density lipoprotein
cholesterol levels,476,547,548,549,550,742,891 and in-vitro studies have demonstrated that
diets rich in monounsaturated fatty acids reduce the oxidation of LDL
cholesterol.742,891
The associations noted in these population studies are complex and must be
interpreted with care. Many of these population cohorts are and have traditionally
been industrialized and highly urbanized in their demographics, and Westernized
in their dietary practices. Others are less urbanized and are predominantly rural in
demographics. Interestingly, Armstrong and associates presented an example
which emphasizes the need for interpretive caution when dealing with
demographics of large populations. These authors noted a strong association
"between ischemic heart disease mortality and the number of telephones in a
population, which in turn is related to dietary saturated fat..." 61
Addressing epidemiological studies linking CAD to sugar consumption,
Keys522,523,524 noted that dietary sucrose is probably not a major factor for the
development of CAD because the association between dietary fat and CAD is not
markedly reduced when controlling for sucrose intake. However, Antar and
coworkers,277 examining dietary changes between 1889 and 1961 in relation to the
Page 73
incidence of CAD, found the principal change to be decreased consumption of
total carbohydrates with a greater progressive decline in the intake of complex
carbohydrates and a concurrent increase in refined simple sugars. A subsequent
analysis of this and other data by Armstrong et al61 noted that the
hypocholesterolemic properties of fiber in unrefined complex carbohydrates may
be partially responsible for the strong negative association between increased
complex carbohydrate consumption in selected populations and CAD. The lack
of fiber, vitamins, and antioxidants in a refined high carbohydrate diet, however,
might result in adverse lipid changes including decreases of serum HDL and
increases in plasma triglycerides, and the hyperglycemic effect of refined sugars in
conjunction with a low-fiber diet may increase susceptibility of LDL to
oxidation.834,835,836 Artaud Wild and co-workers,476 in their epidemiologic study
of CAD mortality in 40 countries, similarly suggested that soluble fiber, as well as
saponins and antioxidants, might be the factors present in unrefined complex
carbohydrates and other natural antioxidant compounds which confer a CADprotective effect through their inherent hypocholesterolemic properties and by the
prevention of LDL oxidation.. Both the Boston Irish Diet Heart Study554 and the
Western Electric Company Study205 demonstrated that certain components of, or
dietary properties common to vegetables which were not related to their effects on
serum cholesterol, were associated with reduced CAD risk.891 Antar and
associates277 suggested that a 75% reduction in apple consumption over the 70year period of their study may have been partially responsible for the increase in
CAD mortality due to a loss of dietary pectin, a significant source of soluble
dietary fiber. Additionally, these authors cited previous scholarship demonstrating
that ingestion of large quantities of sugar increased serum lipids, and that high
intakes of starch and grain products had the opposite effect.355,356,357 These effects
may be due to the differential effect of fiber versus dietary sucrose on insulin
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sensitivity.
Slattery and coworkers2 examined trends in CAD mortality and food
consumption in the United States between 1909 and 1980, and found that national
dietary changes preceded CAD mortality changes in the American population by
10 to 20 years. These authors further noted that in the years between 1909 and
1913, three times more calories were consumed in the form of grain products
(38% of total calories) than calories consumed of animal products (12% of total
calories). By 1957 through 1959, the consumption of grain products and animal
products (meat, poultry, fish) were equal, with each supplying approximately 20%
of calories. Consumption of fats and oils increased from 12% of calories in 19091913 to 17% of calories in 1957-1959. By the mid 1960s, consumption of meat
products and dairy products began to decline, and by 1975, the consumption of
grain products began to increase.
There has been one consistent theme in each of the major population studies
(especially those conducted prior to 1960) which have been reviewed: As the
standard of living of these study populations increased, a concomitant increase in
the consumption of animal fat and refined carbohydrates and a reduction in the
consumption of complex carbohydrates generally occurred, with increases in CAD
mortality following shortly thereafter.
VI. Physiology and CAD Risk
Resting Heart Rate, Blood Pressure, Vasospasm, Left Ventricular Mass and
Function, Platelet Aggregation, Plasma Fibrinogen, and Serum
Catecholamines and Their Relationship to Stress, Diet, Smoking, Exercise,
and SES.
The revolutionary fields of neurobiology and neurocardiology seek to define the
complex manner in which the brain communicates with the heart and various other
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organs of the body, and how the brain plays an active role in physical
disease.10,225,494,761 The physiological effects of the brain's interaction with the
sympathoadrenal and pituitary-adrenal response systems, include effects on heart
rate, blood pressure, hemostasis, vascular reactivity, left ventricular mass, immune
function, and possibly atherogenesis.10,225,351,492,494,496,699,701,709,734,740
Heart Rate and CAD Risk
The effects of acute and chronic stress on heart rate are well
documented.10,225,493,736,740 Elevated heart rate may be an independent risk factor
for cardiovascular death, especially in persons with hypertension. 110 Numerous
epidemiologic studies have demonstrated that elevated resting heart rate is
associated with increased incidence of CAD and death from all causes, and a
recent analysis of the Framingham database of 5,209 men and women followed for
36 years has supported this negative association of increased heart rate with
cardiovascular mortality and death from all causes.110
Exercise and CAD Risk
Over 66% of the approximately 2 million Americans who died in 1986 were
reported to have exercised rarely,214 and this lack of aerobic exercise may be
responsible, in part, for elevated resting heart rates frequently seen among the
sedentary. Physical training and regular exercise, which is more prevalent among
members of upper socioeconomic groups, has been shown to reduce levels of
plasma fibrinogen, (an essential protein for the clotting of blood), 719 and resting
heart rate and blood pressure,253,259 and these reductions may be associated with
beneficial changes in plasma lipids,3,111 a reduction in the incidence of
atherosclerosis,225, 239 and reduced CAD risk.3,111,225,724 Research conducted with
50 sedentary hypertensive men259 suggested that regular aerobic exercise may be
as effective as drug therapy in controlling mild hypertension. A recent study by
Massie260 indicated that the higher the baseline blood pressure and hypertension,
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the greater the likelihood that exercise would be effective in reducing blood
pressure.
Fibrinogen Levels, Platelet Aggregation and CAD Risk
French researchers de Lorgeril and Renaud872 reported that numerous hemostatic
factors including fibrinogen, factor VII, leukocytes and platelets have been
demonstrated by epidemiology to be closely related to thrombosis and acute
coronary events. Kimura and colleagues610 demonstrated that smoking was
associated with significant (p<0.01) increases in resting heart rate, fibrinogen
generation, and plasma thrombin. Numerous other researchers have demonstrated
a relationship between smoking and plasma fibrinogen concentrations in large
epidemiological studies,719,730,731,732 and Rosengren and associates719 found
smoking to be the most powerful determinant of plasma fibrinogen levels of all
factors studied.
Diet effects hemostatic factors, including fibrinogen levels and platelet
aggregability. Barradas et al895 showed that a diet rich in monounsaturated olive
oil prevented catecholamine-induced platelet aggregation in vitro, which suggests
one possible explanation for the protective effect associated with a Mediterranean
diet. Palmer et al898 showed that the non-essential amino acid arginine (supplied
in the diet by nuts, and vegetable foods) is a precursor to the beneficial
endothelium derived relaxing factor (EDRF) nitric oxide. Flavahan896 determined
that nitric oxide is a potent endogenous vasodilator that also inhibits platelet
adhesion and aggregation, monocyte adherence, and chemotaxis. Humans with
CAD have reduced concentrations of EDRF and nitric oxide in their arteries, as do
hypercholesterolemic subjects.897 The beneficial effect of a low fat diet rich in
vegetables may be due, in part, to vegetable sources of arginine which may
increase serum arginine levels above those capable of being synthesized by the
body, and increase EDRF.
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Wilson et al131 and Rosengren et al719 demonstrated that levels of plasma
fibrinogen were higher among members of lower socioeconomic groups, possibly
increasing the risk of atherosclerosis, myocardial infarction, and cerebrovascular
events among the poor. Additionally, high plasma concentrations of fibrinogen
have been found to be independently associated with increased risk of CAD in
longitudinal studies,720,721,722,723 and fibrinogen has been implicated in the inverse
relationship between social class and heart disease724 that has been documented in
Sweden719,725 and other Western industrialized countries.726,727
Reduced dietary
intake of antioxidant vitamins C and E, a dietary status more prevalent among
lower socioeconomic groups, may adversely effect hemostasis and coagulation by
increasing plasma fibrinogen500,504 and platelet adhesiveness,501,502,503,504 which
may additionally place the indigent at greater risk of an acute thrombotic event.
Physiologic Effects of Stress
Research has demonstrated that acute or chronic emotional stress may increase
myocardial oxygen demand,712 adrenaline, norepinephrine and thromboxane B2
levels,495,699,717 shorten the clotting time,447,495,619,620 increase heart rate,495,712,717 and
blood pressure,171,495,701,702,703,710,712,717 increase vasospasm, coronary vascular
resistance,712 transient ischemia and silent myocardial ischemia,692,714,718 perfusion
defects, and wall motion abnormalities in the presence of underlying coronary
disease,692,716,718 suppress production of hepatic LDL receptors leading to
increased serum LDL,739,750 increase platelet count and
aggregability,495,691,694,695,696,697 serum cholesterol,225,226,227,354,464,465 plasma
fibrinogen,724 left ventricular mass,701,703 coronary atherosclerosis,688,689,690,709 risk
of myocardial infarction688,689,690,706,707,711,713 and sudden death,715 and may
decrease left ventricular function in patients with underlying cardiovascular
disease.693
Serum Catecholamines and CAD
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It is postulated that many of these early physiological responses to acute stress
are mediated by increased activation of both the sympathoadrenal and pituitaryadrenal response systems,494,699 and were designed to provide the necessary energy
for self-defense or rapid escape from danger, to protect against the loss of blood
through vasoconstriction and hemostasis, and to conserve metabolites through
sodium retention.10,492 In situations where danger or perceived danger is
chronically present, persistent elevation of these stress chemicals can greatly
increase CAD risk. Chronically elevated norepinephrine levels have been
associated with significant cardiovascular pathophysiology, 699 including
congestive heart failure (CHF),793,794 severity of myocardial infarction,795,796
hypertension,798 hypertrophic cardiomyopathy,792 orthostatic hypotension,797 and
ventricular ectopic activity.799
Several studies have demonstrated that sociocultural factors may influence
catecholamine levels, and that these levels are useful as measures of chronic stress.
Women generally excrete lower levels of epinephrine than men,800 however
women in stressful, high-achievement occupations excrete epinephrine in the
"male range" of values.801 As subjects move from more rural and traditionally
organized living conditions to more urban and chaotic conditions, their daytime
urinary catecholamine levels increase.802 Individuals living in the immediate
vicinity of the Three Mile Island nuclear reactor in central Pennsylvania continued
to excrete elevated levels of norepinephrine five years after the reactor
catastrophically failed in 1979.803
Caffeine, nicotine and salt may potentiate the effects of stress by increasing
plasma catecholamines.699 Research suggests that stress and its associated
catecholamine increases may selectively induce detrimental cardiovascular effects
in patients with CAD as compared to normal controls.495,716,735,747,740 The
destructive effects of stress may be greatest among the indigent, who are at
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increased risk due to a greater prevalence of underlying cardiovascular disease,
increased exposure to environmental stressors, and greater consumption of
nicotine and salt.
Stress and Sodium Sensitivity
Data suggests that there is an interaction between stress and sodium sensitivity
which may be more prevalent among members of low SES. Serum catecholamine
levels may mediate the interaction between stress and sodium sensitivity.
Dimsdale and Ziegler699 stated that dietary salt can increase plasma catecholamine
levels. Blacks and the elderly are most likely to exhibit salt-sensitive
hypertension,253 however black children on high salt diets who were exposed to
stress exhibited higher than anticipated increases in blood pressure. 235
Atherogenesis, Lipids, and Abdominal Fat Deposition: Their Relationship to
Stress, Hostility and CAD.
Stress and Atherogenesis.
Stress intensifies the atherogenic potential of a high-fat diet, and increased
activity of the sympathetic nervous system influences lipid metabolism.225,739 As
early as 1952, Keys464 and Groen and co-workers465 concluded that stress,
emotional tension, and mental over-exertion directly influence serum cholesterol
levels and are involved in the etiology of hypercholesterolemia. Several primate
and human studies suggest that not only does stress potentiate the atherogenic
effect of a high-fat diet, but it also may contribute to atherogenesis regardless of
the fat content of the diet. In animal studies involving stressed and unstressed
primates, little disease was seen in unstressed monkeys on low-fat diets. In
unstressed primates which were placed on high-fat atherogenic diets, the dominant
animals showed minimal atherosclerotic lesions, while subordinate animals
showed moderate extent of disease. Conversely among monkeys subjected to
considerable levels of stress, (by frequent disruptions of social groupings), the
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dominant animals in unstable social conditions developed more atherosclerotic
lesions than the subordinate animals irrespective of diet; however all animals who
were stressed while on the high fat diets developed 30-fold more atherosclerotic
lesions.60,225,740
Stress and its Effect upon Lipids.
In human studies, serum cholesterol and blood lipid levels have been observed
to increase as much as 159% during periods of stress prior to student
examinations, military training with demolitions, and anticipated surgery. 225,227,744
Similar results have been observed among military aviators demonstrating high
levels of blood cholesterol after being subjected to the high stress levels of tactical
jet carrier-landings and who ate essentially the same foods in similar quantities,
and in the same dining facilities as lower-stress transport aviators demonstrating
lower serum cholesterol levels.
Sympathetic activation of the nervous system by stress inhibits lipoprotein lipase
activity and impairs LDL hepatic clearance leading to elevated low density
lipoprotein (LDL), elevated very low density lipoprotein (VLDL), elevated
triglycerides, and decreased high density lipoprotein (HDL) cholesterol levels. 354
It therefore appears that cholesterol levels are not solely dependent on diet and
genetics, but that stress may be a significant factor.225,226,227
Hostility, Suppressed Anger, Low Decision Latitude and Depression:
Their Effect upon Lipids, Hypertension and CAD Risk.
Stress may be external or internal. When poor coping skills are involved,
depression, hostility and emotional instability may be markers for internalized
stress, and these factors have been associated with adverse effects on blood
pressure, lipids and other CAD risk factors. Stressors capable of producing
pressor reactivity or inducing hypertension include inadequate anger coping styles,
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interpersonal conflicts, anxiety, and aversive environmental stimuli. 351,781,782,783,784
Individuals who make active yet unsuccessful coping attempts may be predisposed
to hypertension . James785 suggested that studies measuring active coping
attempts of individuals with low education and socioeconomic status, and
epidemiologic studies measuring blood pressure in modernizing third world
populations support the concept that stress resulting where material aspirations are
discordant with resources produces hypertension. Light782 noted that studies have
confirmed a positive relationship between hypertension and both inhibited anger
expression and excessive anger expression.
In one clinical study, van Doornen and Orlebeke228 found that cholesterol levels
were directly related to the degree of depression, hostility and emotional
instability, while they were inversely correlated with motivation and happiness.
According to data from a Duke University study of 4,700 students which was
presented at the 1994 Society of Behavioral Medicine meetings in Boston, a
hostile personality during college years predicts coronary risk as long as 23 years
later in both men and women. Those college students who were classified as the
most hostile and angry at the beginning of the study were most likely to be
smokers with high cholesterol levels as middle aged adults.
In addition to its effects on blood lipids, recent research has shown that stress
and low decision latitude are correlated with increased 24-hour ambulatory blood
pressure, even during sleep. Schnall et al701 found that hypertension found among
men screened at several work-sites was associated with high psychological job
demands combined with low employee decision latitude, and Frankenhauser759
documented that high job demands and low decision latitude resulted in increased
sympathetic tone and catecholamine release. Theorell et al758 demonstrated that
young men in high strain occupations who had a history of stress-related
hypertension were more hypertensive during working hours than other groups, and
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Suarez and Williams760 found that hostile men had a greater pressor response to
harassment than in men with low hostility scores on a psychological questionnaire.
Low decision latitude and suppressed anger seem to further increase the risk of
CAD in persons with hostile personalities, and these factors tend to be more
prevalent among those of lower SES.
Type A Behavior and CAD Risk.
Numerous studies have suggested that subjects displaying type-A behavior
patterns (characterized by time urgency, explosive speech patterns, hostility and
competitiveness), may have a pathologic response to stress. These individuals
frequently display larger than normal increases in blood pressure, heart rate,
cortisol, and catecholamines when confronted by challenging or stressful
tasks.493,740 Krantz and Raisen740 stated that elevated or heightened physiologic
reactivity typical of type-A behavior is the most consistent finding in patients
displaying overt symptoms of CAD such as angina, acute myocardial infarction, or
hypertension, and Specchia and co-workers735 suggested that CAD patients with a
positive response to mental stress have a higher sympathetic drive, heart rate, and
blood pressure, reduced ischemic threshold and exercise tolerance, and poorer
prognosis and quality of life
The Western Electric Study found a correlation between type-A behavior and
increased incidence of coronary atherosclerosis, and twenty-year risk of death
from CAD.241 In the Western Collaborative Group Study242 and other studies
involving middle-class American men,225 individuals with extreme type-A
behavior demonstrated a CAD risk which was two to four times that of
individuals with non-hostile type-B behavior. Results from the Framingham Heart
Study indicate that type-A behavior is an independent predictor of the eight-year
incidence of both CAD and myocardial infarction among high-SES men.493,763
The French-Belgian Cooperative Study found type-A behavior to be an
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independent predictor of CAD, infarction, and sudden death.762 Results from a
study of 3,750 middle-aged Finnish men suggest that hostility and type-A behavior
patterns may exacerbate existing cardiovascular disease to increase mortality
risk.493
Suppressed anger, particularly with regard to one's spouse, was directly related
to the increased incidence of CAD associated mortality in the 12-year Tecumseh
follow-up study.243 Increased hostility has been associated with increased
cigarette and alcohol consumption,493 suggesting that the increased CAD risk and
mortality due to cynical hostility may be partially attributable to the effects of
excessive smoking and drinking. Clearly, depression, hostility and emotional
instability are correlated with an increased risk of CAD and cardiovascular
mortality, and these psychological conditions are more prevalent among the poor
and less-educated. In fact, Naura and Goldstein351 suggested that hostility may be
one of the causative factors behind the association of poverty, race, poor diet, and
lack of social support with increased CAD risk.
Abdominal Fat, Race and CAD
The effects of chronic stress may be observed in human physiology and
pathophysiology as well as in psychological reactions. There is data which
indicates that stress increases the likelihood of weight gain in the abdominal
region,226 and that this type of weight gain is associated with an increased risk of
hypertension, diabetes and CAD in blacks.932,939 Obesity is seen twice as often in
black women as in white women,932,933,934,935 and the distribution pattern is more
abdominal in black women than in white women.937,938 In 1987, Gillum936 found
that abdominal adiposity appeared to increase the risk for CAD among both blacks
and whites, but after adjusting for other risk factors, the increased risk fell short of
full statistical significance.
In 1993, research conducted by Bengtsson et al943 of 1,462 women living in
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Gothenburg, Sweden who were followed for twenty years beginning in 1968,
established the importance of abdominal fat as a significant predictor of heart
disease in women. These authors found that a high waist-to-hip ratio among these
female subjects, (indicative of excessive abdominal fat), was highly predictive
(p=0.0002) of total mortality and death from AMI within the ensuing 20 years of
follow up. Subsequent research has demonstrated that abdominal fat is associated
with coronary atherosclerosis,946 CAD,932 angiographically determined CAD,932,945
and risk of cardiovascular death in both men and women.944,945, Risk factors for
CAD including elevated serum triglycerides,943 high blood pressure,932,936,938,939
and adult-onset diabetes52,253,932,936,939 have been associated with excessive
abdominal fat in numerous studies and reviews. A recent study by Clark et al932 of
200 black women found that angiographically or electrocardiographically evident
CAD was significantly more prevalent (p<0.001) among black women with the
highest percentage of abdominal fat. These authors stated that "body fat
distribution as measured by waist-to-hip circumference is an important risk factor
for CAD that is easily determined." Subsequent researchers have postulated that
this risk may be associated with the accumulation of abdominal fat around the
internal organs which produces the larger waist-to-hip ratio more commonly seen
in men, and this accumulation may be caused or accelerated by chronic stress. 226
Although this physiologic trait is more commonly associated with males, it is
interesting to note that several studies of females who possess large waist-to-hip
ratios indicative of abdominal fat storage, have suggested an increased risk of
CAD, and this risk may be associated with, or secondary to chronic stress. For
instance, the study conducted by Clark et al932 examined black women at an urban
medical center in Brooklyn, New York who may have been under greater levels of
stress than similar women in a suburban or rural setting.
Pathophysiology of Abdominal Fat Deposition
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Chronic stress, or the long-term endurance or vigilance response, results in the
release of cortisol which stimulates and facilitates visceral fat storage. 492,740 In
addition to chronic stress, poor coping skills, inactivity, smoking, over-eating and
excessive alcohol consumption are all more prevalent among the indigent, and
contribute to visceral obesity and increased CAD risk.10,52,740
VII. SES Associated Behaviors.
Abdication of Responsibility, Loss of Traditional Family Structure, and
Father Absence as an Influence on Crime and Socioeconomic Status
Abdication of Responsibility and Fragmentation of the Family
In 1993, Bennett published an assessment of the moral, social, and behavioral
condition of modern American society entitled The Index of Leading Cultural
Indicators.405 Consisting of nineteen social indicators, it provides the most
comprehensive statistical portrait available of American behavioral and social
trends over the last three decades, and documents a steady decline in social
responsibility, morality, and the traditional American family. According to the
Index, Since 1960, the total social spending by all levels of government
(measured in constant 1990 dollars) has risen more than a five-fold, yet during
this same thirty-year period, there has been an exponential disintegration of the
American family as evidenced by almost a seven-fold increase in violent crime;
more than a five-fold increase in illegitimate births, a quadrupling in divorce rates;
a tripling of the number of American children living in single-parent homes; and
more than a tripling of the teenage suicide rate. 405
Traditional and Non-Traditional Family Structure
A strong, supportive and stable marriage relationship has been identified as one
of the two factors reducing CAD risk and beneficially effecting human
longevity.10,225,238 Being unmarried, however, may be preferable to an unstable
and non-supportive marriage relationship. Suppressed anger in regard to one's
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spouse was directly related to the increased incidence of CAD-associated mortality
in the 12-year Tecumseh follow-up study,243 although traditional married couples
who reside with their spouse typically report suffering from significantly fewer
acute medical conditions.218 Forty-five percent of the approximately 2 million
American adults, aged twenty-five years or older, who died in 1986 were married
at the time of their deaths, while only 41 percent of adults who died at the
youngest age (25 to 44 years) were married at the time of their death.214
The Report of the National Commission on America's Urban Families224 lists
nine characteristics of strong families [see Table 7].
Table 7: Characteristics of Strong Families
(1) Open and honest communication;
(2)Encouragement which is marked by mutual support and respect for family members;
(3)Commitment through which family members feel valued and a sense of being part of a team;
(4)Appreciation which is characterized by love, warmth, and humor;
(5)Religious orientation, or adherence to a belief system;
(6) Adaptability and stress coping skills;
(7) Clear well-defined roles;
(8) Quality time together; and
(9)Participation in a support network of relatives, friends, neighbors and community
organizations.
________________________________________________________________________________________
From: The Report of the National Commission on America's Urban Families 224
The family is the principal institution in society which teaches children to respect
and obey those societal norms which are unenforceable by law: The basic values
of morality, civility, citizenship, civic responsibility, compassion, and
trustworthiness.224,405
There are significantly fewer traditional families in the United States than there
were three decades ago, even though the population and total number of American
households have increased markedly during the same period. American
households which contain "traditional" families of husband, wife and children
declined by 60% between 1960 and 1990 [see Fig. 18].215
In 1960, eighty-three percent of the 53 million census households were traditional
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families consisting of married couples with one or more children. By 1990, only
28% of the 93 million census households represented traditional families. 215 This
alarming trend is continuing as more Americans are choosing to live in solitude or
in one-parent families, and this trend has been three times more prevalent among
blacks than whites [see Fig. 18].160,215
Figure 18: Household Composition: 1960-1990
________________________________________________________________________________
From: Households, Families and Children: A 30-Year Perspective215
In major cities, this negative trend may be even more exaggerated. In Atlanta,
Washington D.C., and Detroit, from 49 to 55 percent of all children reside in
single parent homes, regardless of race.224 Certain low SES neighborhoods within
many of the major cities have appallingly large percentages of single-parent
homes. The decline of the nuclear family is the combined result of several
sweeping demographic changes occurring primarily within the last four to five
decades. Families began to migrate from rural farming areas where both parents
and their offspring worked together sharing in the financial support of the family.
This exodus was from extended families, close-knit communities and small towns
where social pressure was a great deterrent to divorce or to bearing children out of
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wedlock. Once in the cities, people experienced greater anonymity, declining
church and religious affiliation, less social support, and less societal and family
pressure to remain married. The government replaced the extended family as the
source of "social welfare", and the structure of the American social welfare system
placed incentives on single-parenthood.
According to the New York Times, over 70 percent of all children of the lower
east side of Manhattan, New York are from single-parent families.
Figure 19: Married-Couple Families With Wives
in the Labor Force: 1960-1990.
________________________________________________________________________________
From: Households, Families and Children: A 30-Year Perspective215
In ninety percent of these homes, the father is the absent parent, and in some
neighborhoods there are almost no fathers living with their children. In the
remaining traditional two-parent families, approximately 60% of wives were in the
work force and away from their children in 1990, compared with 30% of working
wives in 1960 [see Fig. 19].215 These statistical facts are even more sobering in
light of recent clinical evidence linking men who are employed and who are liveat-home fathers with reduced CAD risk, and employed mothers with increased
risk. A study presented at the 1994 Society of Behavioral Medicine convention in
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Boston demonstrated that fathers' stress hormone levels drop when they return
home from work in the evenings, however the catecholamine levels of mothers
who are employed as managers by day are reported to be unchanged or higher than
those levels measured during working hours.
Children of single working parents may be subjected to higher levels of stress
than children in traditional families. Children in single parent families are 50%
more likely to feel that they have insufficient time with their mothers than children
in families in which both biological or adoptive parents are present [see Fig.
20].224
The forty years between 1950 and 1990 saw declines in annual average
employment of over 12% among men, while employment of women increased by
70%.161 The structure and the role of the traditional family has been remarkably
altered by changing societal "norms" and employment-related absences of the
mother from the home within the last three decades.
Figure 20: Percentage of Children Wishing They Had
More Time With Their Mothers
________________________________________________________________________________
From: Households, Families and Children: A 30-Year Perspective215
Page 90
A Wirthlin Group poll commissioned by the Family Research Council asked its
respondents "[In] which setting would [a] child fare best?" An overwhelming
majority said that two parent households were the most beneficial to the welfare of
the child, including 80% of all single mothers who responded.56 According to a
recent statistical analysis, more than half of all single-parent households headed by
women in America live below the poverty line[see Fig. 21].
Unmarried persons and single parents are significantly more likely to be
unemployed.128 Adolescents from fatherless families are more likely to be
sexually active, and daughters are more likely to become single-parent mothers.
Figure 21: Single Mother Families and Poverty
____________________________________________________________________________________
From: Families First: Report of the National Commission on America's Urban Families 224
Between 1970 and 1990, the percentage of unmarried teenage mothers has more
than tripled [see Fig. 22].224
Adolescents in fatherless families are more likely to commit acts of delinquency,
drop out of high school, divorce, and engage in drug and alcohol use. 54,56 The
Report of the National Commission on America's Urban Families states that eighty
percent of all repeat juvenile offenders in Knoxville, Tennessee, and 70% of
juvenile murderers in New York State live in single-parent or non-traditional
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families.224 Clearly, fatherless families are more likely to produce dysfunctional
children.
Figure 22: Percentage of Unmarried Teenage Mothers
1970 and 1990
_______________________________________________________________________________________
From: Families First: Report of the National Commission on America's Urban Families 224
Some researchers have found that crime victimization is directly effected by
family structure and lack of adult supervision in neighborhoods where single
parents live. Neighborhood standards may be set by mothers, but they are
typically enforced by fathers or at least by responsible adult males.224
Crime, Violence and Socioeconomic Status
Urban crime and community violence are increasing in America, both among
adults and children, and are disproportionately experienced by members of low
SES. According to a 1994 publication, Kids Count Data Book,971 four million
American children--84% of whom are black or Hispanic--are living in deeply
troubled neighborhoods where poverty, violence, unemployment, and school
truancy are endemic. Stress which is related to chronic exposure to social and
ecologic dangers associated with inner city living increases the risk of CAD, and
living in a poverty area is an independent risk factor for CAD. 238 Judicial system
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reform may therefore be a factor in urban CAD risk reduction. A report by the
National Center for Policy Analysis ("1992 Update: Why Does Crime Pay?", Dec
8, 1992) states that although sentences for capital crimes appear prohibitive, the
average time served for murder in the United States is only 1.8 years; for rape the
expected sentence is 60 days; for robbery, 23 days; and for aggravated assault, 6.4
days. Judicial reform aimed at increasing time served for crimes may ultimately
reduce crime in the inner city, preferentially benefitting the urban poor.
According to the 1994 Kids Count Data Book, the number of teenagers who died
violently rose from 62.8 per 100,000 in 1985 to 71.7 in 1991; the number of
juveniles arrested for violent crime rose from 305 to 407 per 100,000; while the
percentage of children graduating from high school fell from 71.6% to 68.8% and
the percentage of children born to single teenage mothers increased by 20% during
the same period. According to the Washington Post ("Girls as Violent Offenders,"
December 29, 1992), in the District of Columbia alone, the number of girls
arrested for assault and other violent crimes jumped 57% from 1990 to 1991.
A recent longitudinal study of injury morbidity by Schwartz et al,904 which
surveyed over 46,000 injury events among a black inner-city population,
determined that over 94% of black men aged 20 through 29 visited an emergency
room at least once during the four-year study period due to an injury, and almost
41% of the men in this age group sough treatment al least once for a personal
injury resulting from assault or violence. These authors stated that their
conservative definitions of assault or violence-related injury used in this study
may have led to an underestimation of the true rates of their incidence.
There are significant racial differences between contemporary American family
groups in regard to both family composition and crime victimization. Black males
born in 1987 are more likely to be raised in single parent and non-traditional
families, and are 7.3 times more likely to be murdered than white males. In 1986,
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44% of the victims of crime in the U.S. were black, and 95% of black murder
victims were slain by black offenders.12 In a 1994 population-based study of 1.5
million northwestern American whites, blacks, urban American Indians and
Alaskan natives who were followed for ten years, Grossman and co-workers302
similarly demonstrated that age-adjusted homicides per hundred-thousand were
7.5 times higher among urban blacks than among urban whites.
Father Absence, Poverty, and Crime
Father absence has been responsible for the "feminization of poverty" in
America. African-American families are the greatest at-risk group for father
absence, and single black mothers are more likely to live below the poverty level
in America than any other population group [see Fig. 23]. Census figures from
1992 indicate that approximately 70% of black women between the ages of 15 and
34 have their first child before marriage, compared to 21.6 percent of white
women in the same age group [see Fig. 24],215 and almost half of the poor in the
United States are single mothers and their children [see Fig. 23].55
Figure 23: Poverty Rates of Families With Children By Race
and Hispanic Origin: 1959-1990.
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_______________________________________________________________________________
From: Households, Families and Children: A 30-Year Perspective215
A 1994 population-based study by Grossman and co-workers302 indicated that
almost six times more urban black that urban white women become mothers
between the ages of 10 and 17, and over four times more urban blacks become
single mothers at any age. The 1990 census data indicates that 56% of black
female householders with absent husbands are living in poverty, compared to only
14% of married black householders [see Fig. 23].215
Figure 24: Premarital Births by Race and Hispanic Origin:
1960-64 and 1985-89
_______________________________________________________________________________
From: Households, Families and Children: A 30-Year Perspective215
The percentage of single-parent black households, and the percentage of black
households with an absent father has increased dramatically within the last three
decades, and to a considerably greater extent than comparable white households. 11,
215
Twenty-two percent of white households consist of a single, never-married
parent compared to 53% of black households.215
A poll conducted by Newsweek in 1993 has demonstrated an increasing public
Page 95
awareness of the problem of father absence. The poll asked "Which one can do
the most to improve the situation for black families today?" Forty-one percent of
the respondents said "black families themselves," 25 percent said "churches" and
only 14 percent said "government".57
Supportive Social Relationships, the Intact Nuclear Family, and CAD Risk.
Strong social relationships and intact traditional families seem to offer protection
against CAD, lessening the effects of its associated risk factors.
Hirdes et al,141 demonstrated the importance of supportive social relationships on
reducing mortality among healthy Canadian males. Similarly, Rosengren and coworkers719 found that a high degree of social interaction and support seems to
reduce fibrinogen levels and effect the human coagulation system in a way that
reduces CAD and premature death. Results of the Beta Blocker heart Attack
Trial765 of 2,320 men suffering a recent heart attack indicate that the presence of
high life-stress and high social isolation produced more than four times the risk of
death at three-year follow-up than low levels of stress and isolation, and that high
levels of stress and social isolation were more prevalent among the least-educated
men. Johnson and Hall767 investigated the relationship between social support
and CAD in a cross-sectional sample of 13,779 Swedish workers and found that
the combination of high job demands, low degree of control or decision latitude,
and low social support produced the greatest risk for CAD. The Israeli Ischemic
Heart Disease Study768 followed a cohort of 10,000 adult male Israeli civil service
employees and found that family problems and the lack of spousal support were
important predictors in the subsequent development of angina pectoris over a fiveyear period. In a study of patients undergoing coronary angiography, Blumenthal
and associates769 concluded that type-A subjects with low levels of social support
had more severe CAD than type-A individuals with high levels of social support.
Other authors have found death from CAD,633 and the prevalence of ischemic
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heart disease728 to be correlated with indices of social support, independent of the
baseline health state of individuals studied. 238,251,634,635,740 In a recent unpublished
clinical study, Malarkey and co-workers193 demonstrated that elevations in resting
blood pressure and pulse-rate were directly related to patients' perceptions of lack
of social support and empathy and to a low degree of personal interaction with
family members and close friends. Earlier studies have demonstrated that people
who maintain social contacts are less likely to develop chronic degenerative
illnesses10,225,237,238,351,766 and clinical depression122 than those who are loners. In a
recent study involving cardiac patients, Jefferson noted that CAD was most
prevalent among those patients who had been diagnosed as suffering from
depression and feelings of isolation.244
In another clinical study conducted by van Doornen and Orlebekle,228
cholesterol levels were directly related to the degree of depression, hostility and
emotional instability, while they were inversely correlated with motivation and
happiness. The effect of social contact can also be seen in animal studies. Rabbits
who were fondled or petted while on a high cholesterol diet had a markedly lower
rate of atherogenesis than a similar group which was not fondled or petted. 240 In
studies of non-human primates, tactile behaviors such as grooming are associated
lower heart rates, and this may have a protective effect against CAD since
increases in heart rate have been correlated with increased atherosclerosis. 225,239
An analysis of the extensive Framingham database by Gillman and associates110
demonstrated a correlation between increased heart rate and the risk of death from
cardiovascular disease and from all causes. Thus, social isolation may pose an
increased cardiovascular risk and supportive social relationships may confer a
benefit through complex psycho-social relationships. People who become socially
isolated through job changes, residential moves, or divorce would comprise a
group at increased risk of developing CAD.740 Social isolation is more prevalent
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among the indigent and the least-educated.765
The Decline of Faith, Abandonment of Personal Responsibility, CAD Risk
Religious faith, or strong religious conviction has been identified as one of the
two factors effecting human longevity.10,225 The Report of the National
Commission on America's Urban Families lists a strong religious orientation or an
adherence to a belief system as a characteristic of strong families,224 and the
contemporary decline of church and religious affiliation, especially within urban
areas, has been cited as one of the factors contributing to the decline of the
traditional family. Recently, a study verified the importance of religion on the
reduction of stress and associated CAD risk.238 Participants in this study were
evaluated on the basis of marital status, membership in clubs, and church or
synagogue attendance. Follow-up over nine years revealed that those with fewer
stable social connections, (such as lack of an identified religious faith), at the
beginning of the study had a cardiac and all-cause mortality rate which was two or
three times higher than those with a strong religious faith and regular church or
synagogue attendance, even when adjusting for all known CAD risk factors,
including reported poor health and low socioeconomic status. 225
There is a significant body of data of over fifty published clinical studies using
good scientific techniques of placebo control, investigator blinding, and random
selection which have demonstrated that religious faith evidenced by prayer may
have quantifiable benefits above and beyond the advantages of social interaction
and the establishment of relationships offered by regular church or synagogue
attendance.248 One of the most significant controlled clinical studies on the
positive therapeutic effects of intercessory prayer was carried out by Byrd in
1988.249 Three Hundred and ninety-three patients admitted to the coronary care
unit at San Francisco General Hospital were randomly divided into two groups. In
the first group, each patient's name, age, and general condition were recorded and
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given to prayer groups of devout Christians who agreed to pray for the patient's
recovery. The second group was the control. The method of evaluation included
the number of procedures, therapies delivered, over-all complications, and a global
score of whether the hospitalization was beneficial to the patient. When the
differences were submitted to multivariate analysis, the group who received prayer
fared significantly better, and the statistical odds that this difference occurred by
chance were one in 10,000.249
Stress, Hostility, Rage, SES and Cardiovascular Risk Factors
The relationship between psychological stress, anger, and the subsequent
development of hypertension or CAD has been a consistent focal point of
cardiovascular research during the past 50 years, and a growing body of scientific
evidence suggests that hostility can increase the risk of premature death from both
cardiovascular disease and cancer. Emotions such as anger or depression may
physiologically interact with other risk factors such as smoking, high blood
pressure, and elevated cholesterol to further increase the risk of CAD.496,736,755,756
Hostile individuals are significantly more likely to abuse alcohol, smoke, and
over-eat than are the more sedate personalities, all of which may contribute to the
increased risk of cardiovascular disease or death among persons exhibiting high
levels of hostility.742
Stress is the body's response to real or imagined events which are perceived as
requiring some immediate action or adaptive response.225,492 Stress causes
metabolic changes which can increase cardiovascular
risk,10,145,148,149,150,225,495,688,689, 690,691,692,693,694,695,696,697 and these changes are
mediated largely by increases in cortisol or serum catacholamines [see Fig.
26].225,351,492,493, 494,495,697,699,700,741 In the 1920s, Walter Cannon was the first to
describe the "fight or flight" response, and in the following decade, Wilhelm Raab,
demonstrated the effects of, and risks associated with adrenaline and cortisol
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during this response.10 In 1939, Alexander350 theorized that anger and anxious
emotional states could lead acutely to blood pressure elevations, and chronically to
established hypertension. In 1956, Hans Seyle popularized the term "stress" and
increased the general public awareness of the detrimental effects of stress on
human health in his widely-read book, The Stress of Life.58 Seyle called stress "the
salt of life", and defined it as the nonspecific response of the body to any
demand.145,146,147 He demonstrated that stress contributed to illness and death in
animals, and postulated that the same effects may occur in humans. Friedman and
Rosenbaum were some of the first researchers to demonstrate and publish proof of
this association in their 1974 work, Type-A Behavior and Your Heart.57 They
defined "Type-A behavior" as verbal and non-verbal behavior characterized by
impatience, anxiety, and hostility. In 1980, a scientific panel convened by the
National Institutes of Health concluded that Type-A behavior is a risk factor equal
to, or greater than any other risk factor for coronary artery disease.10 Eliot and coworkers148,149 demonstrated that "hot reactor" patients who had exaggerated
responses to mental stress (as evidenced by significant increases in total peripheral
vascular resistance, and accompanied by no change or a decrease in cardiac
output) were at high risk for severe cardiovascular disease. Verrier and
Dickerson741 have demonstrated in animal studies that in the presence of coronary
stenosis, heart rate acceleration secondary to psychological responses of fear or
anger is associated with substantial increases in coronary vascular resistance and a
decrease in coronary artery blood flow, and numerous other researchers have
identified subsets of patients suffering from CAD who display exaggerated heart
rate, blood pressure, cardiac output, and vasomotor responses to mental
stress.700,714,735,737,738 In an investigation of 63 patients with coronary artery
disease, L'Abbate and co-workers737 determined that psychological stress
significantly increased myocardial oxygen demand (by increasing heart rate and
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blood pressure), while simultaneously decreasing myocardial oxygen supply (by
increasing coronary vasomotor tone and reducing coronary blood flow at the level
of the microcirculation). Keys, in a 23-year prospective study,150 demonstrated
that an exaggerated hypertensive response to environmental stress (a cold-pressor
test) was the best single predictor for the future development of CAD.
Coronary artery disease may leave an individual more susceptible to the
damaging effects of uncontrolled rage and emotional stress. 495 In a recent study
reported in the American Journal of Cardiology, researchers asked patients
undergoing cardiac catheterization to recall incidents that angered them.
Researchers were angiographically able to document a significant narrowing of
diseased coronary arteries during the anger recall. Healthy arteries with
undamaged intima and without visible atherosclerotic narrowing showed no
significant response to anger. While stress can hasten the development of CAD,
unresolved anger may be one of the trigger mechanism which predisposes
atherosclerotic coronary vessels to vasospasm and possible myocardial infarction.
Thus, while smoking, lack of exercise, and the effect of a poor diet may take
decades to exert their detrimental effect on coronary health, unresolved anger has
the potential for more immediate and acute effects.
Family fragmentation, low levels of social interaction and support, and adverse
environmental or occupational settings (characterized by high psychological
demands and low levels of control or decision latitude) result in increased life
stress and unresolved anger, and may increase CAD risk.701,709,734,740 These
factors are more prevalent in poor urban environments,224 and are more frequently
associated with low socioeconomic status.740
Stress, Perceived Loss of Life-Control, Coping Skills, Environment, and CAD
Approximately 40% of Americans have hypertension14,16,162 and even after
thorough clinical examination, more than 90% of these patients are classified as
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having idiopathic or "essential" hypertension. 145 The highest prevalence of
hypertension occurs in blacks, in the elderly, and in men.14,16,19, 215,216
An
association between environmental and psychologic stress and the subsequent
development of essential hypertension has been demonstrated in numerous
studies.145,163,164,165,166,167,168,169,250,279,328,351,701,709,734
Coping Styles and Perceived Control.
Because individual differences in perception and coping skills vary greatly, it is
difficult to define any particular set of conditions as inherently stressful, and many
clinical studies structured to detect associations between stress and certain
cardiovascular risk factors have been unsuccessful due to differences in coping
styles among subjects.736 In a 1992 review of the clinical literature, Niaura and
Goldstein351 documented a strong correlation between poor anger coping styles
and the presence of hypertension. The authors concluded that these poor coping
styles were more frequently manifested among the young, the obese, and those of
lower SES. These researchers also noted a high degree of correlation between the
presence of hypertension and an individual's unsuccessful attempts to actively
cope with stressors not within his or her control. Sommers-Flannagan and
Greenburg, in their 1989 review353 of the relationship between psychosocial
variables and hypertension, reported a strong and consistent relationship between
the degree of anger and subsequent blood pressure elevation. Markovitz and coworkers250 examined a large cohort of men and women from the extensive
Framingham Heart Study database who were normotensive at baseline, and
followed this group for as long as two decades [see Fig. 25]. Their research
suggested that long-term anxiety, rather than a tendency to explosive anger per se,
was most predictive of the future development of hypertension .
Figure 25: Incidence of Hypertension by Level of Tension Among Men Aged
45 to 59 Years, From Multivariate Cox Model
Page 102
_________________________________________________________________________
From: Markovitz250
These findings are consistent with the observations of Eliot who states that a sense
of lack of control over life situations, (especially in patients with a hereditary
predisposition to hypertension, and who demonstrate non-assertive behavior), is
the most common finding in patients with essential hypertension. 352 Eliot further
suggests that loss of control, or a perception of loss of control may predispose an
individual to cardiovascular events.10,225 Cottington and associates328
demonstrated that men with low self-confidence and less perceived control over
their lives have higher systolic and diastolic blood pressures.
An interesting study on the subject of perceived control and health was recently
conducted among nursing home residents. One group was given increased
responsibility for making day-to-day decisions, while a second group was
encouraged to passively depend upon a competent staff for their needs. Six
months after beginning the study, the first group, (those who were more in control
of their lives), showed greater improvements in health according to a physician's
assessment. After 18 months, the survival rate for these residents was twice that
of the more dependent residents in the second group.631
Data from a study conducted at Cornell University and presented at the 1994
convention of the Society of Behavioral Medicine in Boston indicates that women,
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but not men, who assess themselves as "very involved" with their work have a
significantly reduced CAD risk. Researchers postulated that the differential in
CAD risk between the men and the women may have been due to different
reactions to similar environmental stressors, or different coping styles.
Interestingly, several studies have found that fathers' stress hormone levels drop
when they go home in the evenings, however the evening catecholamine levels of
mothers who are employed as managers by day are reported to be unchanged or
higher than those levels measured during working hours. Again, the dissimilarity
may be due to different styles of coping demonstrated by members of the opposite
sex.
Social Support, Stress, and CAD.
Social support within the context of the family or community has been
demonstrated to moderate or mitigate the impact of stress on CAD risk through a
buffering effect,122,193,237,251,351,632,633,634,635,637,638,734,751 however epidemiologic data
indicates that members of lower SES and the indigent are likely to experience less
social support than the affluent,351,765 probably due to greater fragmentation of
families.224 The epidemiologic evidence suggesting that social support may
mitigate the effect of stress may explain why women, who tend to have stronger
social relationships and intimate ties than men, experience lower CAD rates. A
study of Japanese migrants to the Bay area of California documented a five-fold
increase in CAD rates compared with Japanese who remained in Japan,212,213,225,236
however mobility per se was not the risk factor for the immigrants. There was a
sub-group among the Japanese migrants to California who exhibited the same low
risk of CAD as did their counterparts in Japan, and major CAD risk factors did not
account for the difference. The major difference between the Japanese migrant
high and low risk groups was the degree of social support. 237 The group with the
higher rate of CAD had become acculturated, had adopted American customs, and
Page 104
maintained fewer close family and social ties. The low risk group had close social
ties with other members of the Japanese ethnic group, and more closely
maintained Japanese language, diet, and family customs.
A more recent study of the general American population, conducted by Berkman
and Syme,238 verified the importance of social networks, religion and a stable
marriage on the reduction of stress and associated CAD risk. Participants in this
study were evaluated on the basis of marital status, membership in clubs, and
church or synagogue attendance. Follow-up over the ensuing nine years of the
study revealed that those with fewer stable social connections at the beginning of
the study had a cardiac and all-cause mortality rate two or three times higher than
those with the highest number of associations, even when adjusting for all known
CAD risk factors, including reported poor health, and low socioeconomic status.
Stress may be the single risk factor with the most immediate effect on health. A
study by Rosengren et al251 of 752 middle-aged men in Gothenberg, Sweden
demonstrated a distinct association between stress and premature death from CAD
or other causes. The men underwent detailed evaluations which included an
assessment of their psychological stress. During the subsequent seven years of
follow-up, stressful events were associated with an increased risk of death. The
risk of dying more than tripled if the men were divorced or separated from their
wives, or were in serious financial trouble during the previous year. Risk of death
increased 7.7-fold if they reported having been sued. Feelings of insecurity at
work were associated a 2.4-fold increase in risk. Of the men who had experienced
three or more stressful life events within the past year, 10.9% died compared with
3.3% among those reporting no stressful life events. The association between
recent stressful life events and mortality remained true even after controlling for
smoking, self-perceived health, occupational class, and indices of social support.
CAD was the most common cause of these deaths (32%), followed by alcohol
Page 105
abuse (27%), and cancer (20%). The authors reported that men with higher levels
of emotional support seemed to be protected. If this study had been constructed
to examine the effects of diet, exercise, smoking, or any other major risk factor for
CAD, it is unlikely that results of this magnitude would have been observed within
seven years.
Although hypertension, diabetes, smoking, obesity, and lack of exercise may
take decades to exert their detrimental effects on coronary health, acute stress can
exert its deleterious effects (i.e. sudden cardiac death) within moments, 225 and
certainly within a few years. Adequate social support seems to mitigate these
detrimental effects, and this support is less prevalent among those of lower SES
who are more likely to be a member of a fragmented or dysfunctional family.
Occupational Stress and CAD.
Occupational stress resulting from hectic and psychologically demanding work,
and low worker decision latitude can adversely influence cardiovascular
risk.171,701,704,705,706,707,709,734,739,740,743,744,745,746,747,748,749,751,752,753,754 Astrand, Hanson
and Isacsson734 concluded that job decision latitude, social network, and social
support were independent predictors of subsequent mortality in a Swedish pulp
and paper company. Cobb and Rose171 showed that air traffic controllers working
at busy airports had 5.6 times the incidence of hypertension of individuals
reporting low levels of occupational stress.
Siegrist and co-workers739 found an
increased atherogenic risk in men suffering from occupational stress characterized
by unsuccessful coping, defined by the authors as "high work demand and low
degree of control." The high-demand, low-control job-strain model and its
association with increased CAD risk has been advanced by numerous other
researchers.701,734,740 In a meta-analysis of five United States data bases, Pieper
and associates709 demonstrated a statistically significant correlation between
occupational stress, (defined as limited job decision latitude), increased systolic
Page 106
blood pressure, and prevalence of smoking. Taggart and Carruthers749
documented hyperlipidemia which was induced by emotional stress among racing
drivers. Kasl et al746 noted adverse changes in serum cholesterol among men
undergoing job loss, and Thomas and Murphy744 detected adverse changes in
cholesterol levels of Johns Hopkins medical students prior to examinations.
Numerous other researchers have documented the adverse effects of occupational
stress on various cardiovascular risk factors including blood lipids, 743,745,747,748
increased left ventricular mass,701 and increased use of tobacco496,736,755,756 and
alcohol.701
Environmental Stress and CAD.
Environmental stressors can also increase cardiovascular risk. 145,170,234,238
In
epidemiologic studies, an association between environmental noise (traffic noise,
aircraft take-offs and landings) and blood pressure elevations has been
demonstrated.145,170
Harburg et al234 found that hypertension was more prevalent among blacks
living in the most high-stress areas of urban Detroit than among blacks living in
areas with lower levels of crime and civil unrest. In a nine-year follow-up study
by Berkman and co-workers,238 which compared an area of poverty with an
affluent area, the incidence of hypertension was 50% higher in the poor area,
regardless of social interaction, availability of medical care, smoking or other
identified CAD risk factors. Among a group of more affluent people who chose to
live in the poverty area, the pattern of hypertension was more closely related to
that seen within the poor area, rather than to that of a high SES group with a
similar income living in the affluent area. Interviews with these individuals
revealed fears of robbery, injury and violence, and there was evidence that the
distribution of hypertension correlated directly with the number of police,
ambulance, and fire department calls.
Page 107
Life Changes and CAD.
Low social status, limited interactions with other people, and abrupt changes in
relationship factors such as divorce or bereavement produce stress and can directly
and rapidly impact on health.225,238,251,279,632,633,634,635,636,734,751 When people become
divorced, change jobs, move their place of residence, or make other major life
alterations, their risk of CAD may increase by two or three-fold, independent of
other known risk factors such as age, race, cigarette smoking, cholesterol,
hypertension, physical inactivity, and obesity.126,225,226,251 The life changes which
disrupt relationships such as the death of a spouse or family member, marital
separation or divorce, jail confinement, or loss of employment are some of the
most devastating life-events effecting individual stress levels,126 and therefore
have the greatest effect on CAD risk.225,236 Williams492 states that "one of the
primary qualities of stressful experiences or stressors is exposure to novel, strange,
or unfamiliar environments." Krantz and Raisen740 report that stressors are
typically viewed as "harmful, threatening, or noxious," and Eliot10 states that
stressful situations are accompanied by "fear, uncertainty and doubt." Survivors
of myocardial infarction reported more life-change units on a life-change scale in
the three years prior to the infarction than did a matched sample of normal
controls.740 Stressful life events occurring in the year before a baseline
examination were significantly associated with mortality from cardiac and all
causes in subsequent follow-up of seven years' duration of middle aged men in the
Gothenburg study.251
In community surveys conducted in the United States in the 1980s, Kessler et
al127 demonstrated that lack of income is the component of low socioeconomic
status that most strongly influences likelihood of exposure to these and to other
negative life events. Their findings, which have been corroborated by Eliot,10,225,226
further suggest that the extent to which an individual reacts negatively to these
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events is influenced by education and occupation, and this perceived degree of
stress becomes a biochemical reality, having a direct and deleterious effect on
cardiovascular health.
In the United States, many Americans define themselves in terms of their
occupation. Unexpected employment termination therefore can be one of the most
stressful life changes, can leave individuals with a feeling of extreme loss of
control, and can significantly increase the likelihood of severe
depression,120,121,122,123,124 sudden cardiac death, and death from any
cause.4,10,49,70,116,117,118,119,140,143,144
The Control Hypothesis.
Eliot225 has proposed that life stress involving a perceived outcome which
appears to be unmanageable, and not the stress itself, poses the true CAD risk [see
Fig. 26]. Stress does not reside in our environment, but in our reaction to our
environment. Chronic stress is associated with aversive situations or long-term
vigilance, and results in elevated cortisol levels.10,225,492,699,740 Cortisol elevates
blood pressure and increases total peripheral resistance, but decreases heart rate
and cardiac output. In humans, cortisol levels are indirectly proportional to the
perceived degree of control over psychological stressors.10,225
Fig. 26: The Control Hypothesis in Hypertension, CAD, and Sudden Death
Page 109
____________________________________________________________________________
From: Eliot RS. The Heart, Emotional Stress, and Psychiatric Disorders. In: Schlant RC, Alexander RW, eds. Hurst's The Heart, 8th Ed., New
York: McGraw Hill, 1994.
As an individual's perception of control decreases, cortisol increases causing
peripheral vascular resistance to increase and blood pressure to rise.
Subsequently, the incidence of myocardial ischemia increases, and cardiac output
falls.225,229
Research has confirmed that emotional stress is associated with
angina and silent myocardial ischemia,351,692,714,718,737,768,770,771,772,773 coronary
atherosclerosis,688,689,690,739 myocardial infarction,688,689,690,706,707,711,713 left
ventricular hypertrophy,701 transient left ventricular dysfunction,351,774
arrhythmias,225,351,493,700,738,775,776,777,778,779 and sudden death.225,351,493,738,776,777,780
In animal studies, plasma cortisol levels are consistently highest in submissive
animals with the least amount of control over their environments, intermediate in
subordinate animals, and lowest in dominant animals, while catecholamine levels
show the opposite patterns, being highest in dominant animals.225,741 Similar
patterns have been observed in human studies, and control or perceived control
over psychological demands seems to be a common factor in plasma cortisol
levels.225,505
Catecholamines (adrenaline and norepinephrine) and cortisol have been
associated with hypertension, clinical depression, left ventricular hypertrophy,
glucose intolerance (which may precipitate or aggravate diabetes), increased
cholesterol levels, increased platelet adhesion, increased platelet count, impaired
lipoprotein ratios, loss of serum potassium (increasing the potential for
arrhythmias), myocardial ischemia, acute rupture of heart muscle fibers
(contraction band necrosis), heart failure, and sudden cardiac death [see Fig.
26].10,80,83,84,225,245,353,735,737
Stress increases cortisol and adrenaline levels which increase the risk of both
Page 110
silent and symptomatic myocardial ischemia. Freeman and colleagues229
demonstrated that cardiac patients under stress experienced significantly more
asymptomatic ischemia, and those with higher levels of urinary cortisol and
norepinephrine had a significantly greater number of ischemic episodes.
Similarly, Rozanski and co-workers714 found that silent or painful myocardial
ischemia was easily induced by mental stress testing among patients with CAD.
Coumel and Leenhardt700 suggested that strong emotion and panic produce a
powerful adrenergic stimulation capable of producing cardiac arrhythmias in
patients with underlying heart disease. This finding has been supported by other
research.351,493,714,735,738 Even patients without underlying CAD may respond to
stress with increases in catacholamines, heart rate, and subsequent changes in the
electrical irritability of the heart which may predispose to sudden death.230 In
animal studies, vulnerability to ventricular arrythmia increased if the animal was
placed in a stressful situation, or was made angry.231 Animals administered large
infusions of catacholamines (mimicking conditions of anger, or acute stress)
exhibited myocardial contraction-band necrosis due to over-contraction of heart
muscle fibers during the resulting vigorous and rapid heart rate. Similarly, these
same lesions were observed in 86% of human sudden cardiac death victims,232 and
in cocaine-induced sudden death.233 In addition to causing contraction-band
necrosis, increases in heart rate have been associated with an increased incidence
of atherosclerosis in animal studies, and have been associated with increased risk
of death from all causes in human epidemiologic studies.110,239
Stress also has a direct effect on the initiation and continuance of other known
(and possible) coronary risk behaviors such as cigarette
smoking,225,246,493,496,736,755,756,764 poor nutrition,739 depression,225 inhibition of
immune system response,281 inability to schedule or avoidance of exercise,
excessive alcohol consumption (contributing to loss of critical electrolytes such as
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magnesium and potassium, alcoholic cardiomyopathies, and cardiac
arrhythmias),493,738,764 drug abuse, excessive coffee consumption (contributing to
increased risk of cardiac arrhythmias through increased catecholamine release and
electrolyte loss resulting from diuresis),207 and obesity.10,80
Although stress alone has not been clinically proven to lead to sustained
hypertension, in the presence of other potentiators such as genetic susceptibility or
salt-loading,235 stress might act as a trigger mechanism.225 Furthermore, both the
physiologic and metabolic effects of stress can aggravate the process of
atherosclerosis at any of its early phases739 [See Table 8].
Table 8: The Process of Atherosclerosis
(1) Hydraulic or oxidative injury to the vascular intima.
(2) Platelet adhesion and aggregation at the site of vascular injury.
(3) Chemical and mechanical stimulation of smooth muscle growth and
proliferation.
(4) Attraction of the macrophages.
(5) Ingestion of lipids by the macrophages and further thickening of
vascular tissue by smooth muscle proliferation and macrophage
invasion.
(6) Plaque enlargement by the secretion of fibrin.
_________________________________________________________________________________
From: Hurst225
Both increased blood pressure and heart rate may contribute to hydraulic
damage of the vascular intima. Free radical injury due to inadequate dietary intake
of antioxidant vitamins may accelerate vascular injury leading to CAD. 476,537
Lipid mobilization, and increased platelet aggregation (and the resulting increased
release of platelet-derived growth factors) which accompany stress, may accelerate
the growth of atherosclerotic plaque. Increased neurohormonal activity, including
elevated adrenaline and cortisol, contributes to vascular endothelial cell
dysfunction, and the resulting abnormal vascular endothelium may permit platelets
and monocytes to adhere to, and subsequently infiltrate into the blood vessel wall,
leading to an accelerated progression of the atherosclerotic lesion. 225
Poor coping skills are more prevalent among members of lower SES, and may be
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associated with decreased perception of life-control, increased cortisol levels,
greater incidence of clinical depression, hypertension, progression of
atherosclerotic disease, congestive heart failure, sudden death, and other forms of
CAD.225 Aggressive stress intervention and psychological counseling has shown
benefit in patients with CAD, and one major study has demonstrated that these
interventions have been successful in improving post-infarction survival in
patients with "type-A," or stress-prone, personalities.80,85 Exposure to stress
associated with urban living, limited control of life choices, and poor coping skills
are factors more common to the urban poor, and may contribute to the increased
CAD risk among the indigent.
Unemployment, Frustration, Fatalism, and Their effect on Cardiac Risk
factors
Loss of employment directly and rapidly effects individual stress levels. 10,126
Unemployed persons, or persons not in the labor force are two to five times more
likely to assess their health as poor than those currently employed. The
unemployed spend more time in the hospital, see a physician more frequently,
spend twice as many days in bed due to illness, and report almost twice as many
chronic illnesses.218
Life stress can precipitate cardiovascular disease and increase cardiovascular
mortality rates.10 In addition, social isolation, depression due to lack of social
support,122 deterioration of the family unit, poor stress coping styles, job stress (or
stress associated with unemployment), hostility, and unresolved anger are among
the psychosocial factors which may link low socioeconomic status to increased
coronary artery disease.4
Mattiasson and associates70 demonstrated that the threat of unemployment
precipitated sleep problems and increased both serum cholesterol concentration
and risk of cardiovascular disease in middle-aged men. Unemployed workers are
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one-and-one-half times as likely to suffer sudden cardiac death.4 This association
may be due to a perceived loss of control over one's life and is further supported
by the fact that blue collar workers who have less decision making capabilities and
control over their jobs have higher mortality rates than those in the professional
occupations with greater control over their destiny. High psychological pressure
and low decision latitude on the job have been associated with both increased
blood pressure and coronary risk in numerous studies,4, 10,279,328 and recent
research has shown that stress and low decision latitude are correlated with
increased 24-hour ambulatory blood pressure, even during sleep. Roe329 reported
that a fatalistic attitude (which is bred out of social failure) has been found in
under-employed and unemployed men and women, regardless of race. This study
further demonstrated that it is not ambition but rather non-achievement in a
competitive environment that may influence blood pressure levels.
A recent study conducted in the Seattle Washington metropolitan area indicated
that urban blacks were over three times more likely to be unemployed compared to
their urban white counterparts, however the same study also demonstrated that
over 2.1 times more black adults than whites had failed to complete high school,
and were without diplomas.302
Poor living conditions in early childhood and adolescence increase the risk of
both poor financial status and atherosclerotic heart disease in later life, [see Fig.
27]4 but the risk of CAD is not increased in those whose economic condition
improves in later life.297 In fact, Lynch, Kaplan and associates297 demonstrated
that individuals who experience poor socioeconomic conditions as both children
and adults are almost twice as likely to die as those who were poor as children, but
whose socioeconomic condition improved in adulthood. Those individuals who
have gone from low to high SES have mortality rates identical to these who have
always been in a high SES. The data presented by Lynch and colleagues297
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together with recently published work by Baker et al,298 implicates adult
socioeconomic status as the more likely predictor of death from CAD.
Figure 27: Standardized Mortality Ratios for CAD in Men 35 to 74 Years of
Age, From 1968 to 1978, Compared to Birthplace Infant Mortality in 192125.
_________________________________________________________________
Barker JD, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales.
Lancet 1986;1:1077-1081.
The stress of unemployment may potentiate certain CAD risk behaviors which
are frequently associated with unemployment and are more prevalent among
members of low SES. Farrow's764 data demonstrates that the unemployed smoke
and drink more, are more violent, make detrimental changes in their diets, and
show a 50% increase in morbidity and mortality from preexisting CAD. Since
members of low SES tend to experience unemployment for longer periods and
more frequently than the affluent, and because those who choose to remain in
welfare dependency have, in effect, extended their exposure to potential
"unemployment" stressors, they may be at increased risk for a cardiovascular
event.
Eating Habits and Family Gathering Traditions and Their Effect on CAD
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Risk
A number of epidemiologic studies suggest that poor living conditions in
childhood and adolescence contribute to increased risk of CAD.4,649 This
increased risk may reflect, among other factors, childhood differences in eating
habits and diet.
The French suffer 40% fewer heart attacks than do Americans although they
consume as much saturated fat, and use as much or more tobacco products.35,59,61
This difference in cardiovascular events among international populations [see Fig.
11] is due to differences in sociocultural (i.e. lifestyle) factors, and not due to a
genetic predisposition to disease among specific population subgroups. 35 At the
Boston University School of Medicine, the eating habits of fifty middle-class and
middle-aged people from Framingham Massachusetts were compared with those
of a similar group of fifty from Paris, France. The French tended to linger over
three course lunches lasting an hour and a half, consuming 57% of their daily
calories prior to 2 p.m. This largest meal was followed by several hours of
afternoon activities, with a light but leisurely dinner. The Americans consumed
only 38% of their calories prior to 2 p.m, spent much less time consuming their
meals, were more likely to skip breakfast, and tended to consume significantly
more "fast foods". Americans tended to snack more often, typically three hours
after lunch. Unlike the French, dinner was the largest American meal, typically
followed by sedentary activities like watching television. 59
According to a recent study conducted at the Memorial University of
Newfoundland, overnight fasting followed by skipping breakfast was associated
with enhanced blood platelet aggregation. This may contribute to increased
susceptibility to myocardial infarction among individuals who are prone to
skipping of breakfast.66 A three-year study of 2,034 men and women between the
ages of 50 and 89 years which examined the effect of increased meal frequency on
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plasma lipids was conducted by Edelstein and associates.71 Those study
participants who ate four meals daily experienced lower total cholesterol levels
(0.23 mmol/L lower; p=0.01) and lower LDL cholesterol levels (0.16 mmol/L
lower; p=0.06) than those eating only once or twice daily, even though the
frequent eaters consumed more calories, total fat, and cholesterol.
The French are more active and much less obese than Americans as a
population. An active body is less likely to store fat, has a lower heart rate,
synthesizes less LDL cholesterol, and significantly more HDL cholesterol. 59 It is
possible that eating habits, activities surrounding meal times, stress associated
with mealtime activities, and meal gathering traditions may alter cardiovascular
risk factors associated with a given diet. Members of higher SES are more likely
to live in stable families observing beneficial meal traditions, are less obese, and
may be more likely to adopt or incorporate the leisurely French or European style
of meal-gathering traditions.
Dietary Fat and Cholesterol Consumption and CAD
As early as 1948, Ancel Keys, one of the pioneers in cardiovascular disease
epidemiology and the father of modern cardiovascular preventive medicine,
advanced the idea that CAD and other degenerative diseases were not the
inevitable result of the aging process, but rather were related to nutritional factors
such as dietary fat consumption.275,276,463 Subsequent epidemiologic studies by
Kahn,36 Lopez-S, et al,376 and Slattery and Randall2 confirmed this hypothesis.
Consumption of a diet high in animal fat is clearly associated with adverse
effects on blood lipids, including LDL cholesterol. Dietary cholesterol and
saturated fatty acids with 12, 14, and 16-carbon atomic structures have been
shown to raise serum cholesterol.891
Dietary Fat Source Versus Fat Quantity and CAD.
Not all sources of fat appear to be equally deleterious with respect to CAD. The
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diets of the Greenlanders, French, and Cretan islanders contain as much (or more)
fat per calories consumed as the American diet, yet these populations suffer from
the occurrence of heart disease at rates which are a fraction of the incidence seen
in epidemiologic studies conducted in the United States. Olive oil is the primary
fat source of the French and the Cretan islanders, fish oil (EPA) is the primary
source among Greenland eskimos. Although fat from any source can contribute to
obesity, there appears to be a lesser CAD risk associated with certain fats
(monounsaturated, alpha-linolenic fatty acids (a precursor of EPA from vegetable
sources), and EPA).
Additionally, dietary fat consumption variably effects hemostatic factors
including both the aggregation of platelets, and coagulation factors: Saturated
fats may increase platelet aggregation, whereas omega-3 fats may decrease these
factors.856,857,858,859,860
The Cholesterol J-Curve Phenomenon
Serum cholesterol levels are directly proportional to CAD mortality, however,
they are not consistent in their direct proportionality to all-cause mortality. In
pooled population studies,5 total mortality from all causes was increased with
increasing cholesterol in men only. In women, cholesterol levels from 160mg/dL
to the highest levels reported (>240mg/dL) showed no significant differences in
all-cause mortality. In both men and women, cholesterol levels below 160mg/dL
were associated with increased mortality from all causes, including multiple-site
cancers, hemorrhagic stroke, COPD, chronic liver disease, and death by violence,
[see Fig. 28].5 In a study of a representative sample of the U.S. population, low
cholesterol levels were strongly associated with non-cardiovascular mortality in
people aged >70 years,5,911 and two studies have indicated that this relationship is
strongest among people of low SES, and among those who are sedentary, and
abuse alcohol or tobacco.911,912
Figure 28: Relative Risk of Total Mortality Plotted Against Total Cholesterol
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A Pooled Population Study
______________________________________________________________
From: LaRosa5
The increase in cancer and all-cause mortality seen in meta-analyses of primary
prevention trials is largely due to the negative results of the World Health
Organization trial of clofibrate,5,908 and to the mildly negative or neutral results of
other pharmaceutical trials, rather than due to any adverse effect associated with
dietary and lifestyle interventions.
Hypercholesterolemia is prevalent in urbanized, high-income countries, and less
common in Third World countries.279 People in developed countries tend to
consume significantly more dietary saturated animal fat than do people in third
world countries whose fat consumption is typically half of the amount consumed
in the United States.442 It has been demonstrated that in Third World urban areas
of increasing affluence, lower levels of HDL cholesterol and higher levels of
atherogenic LDL cholesterol are found. In third World countries which are
undergoing rapid development and urbanization, such as Malaysia, CAD mortality
is rapidly accelerating as tobacco use is increasing, and the average Malaysian
urban diet is incorporating increased amounts of fat.279
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Research by Wilder et al,852 which was conducted among 912 urban residents of
lower-income, inner-city Baltimore, showed that there was a significant trend
(p<0.05) toward decreasing intake of high fat food with increasing age, regardless
of race. The researchers found no significant differences by race or sex in high-fat
food intake, suggesting that age and SES, rather than race, may influence the fat
content of the diet, [see Table 9].
Table 9: Average Daily Frequency of High Fat Food Consumption
Age Group
Blacks
Whites
p value
18-35
4.6
4.4
0.68
36-55
4.0
3.7
0.32
56-69
>70
3.4
3.2
3.4
3.1
0.88
0.92
___________________________________________________________________________________________________
From: Wilder et al852
Evidence based on actual dietary intake from a compilation of 171 clinical and
epidemiologic studies suggests that consumption of total dietary fat has decreased
in the United States between 1950 and 1984,853 however, between 1960 and 1971,
blacks appeared to have increased their consumption of fat, which was
accompanied by a 322% increased mortality from prostate cancer in addition to
significant increases in cardiovascular mortality among blacks during this
period.854
Changes in Carbohydrate Consumption.
Antar and associates277 reviewed data for per capita food supplies in the United
States between 1889 and 1961, and concluded that two significant changes had
occurred in the American diet over the previous seventy years. There were slight
increases in the consumption of dietary fat, including saturated fat from both
animal sources and hydrogenated oils, and significant decreases in the
consumption of complex carbohydrates and starches such as cereal grains, apples,
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potatoes, and whole grain flours which were replaced by increased consumption of
heavily processed simple sugars and syrups. The authors noted an increase in
animal sources of protein in the last decade of their study (1951-1961), and a
decrease in vegetable sources of protein. They concluded that changes in
carbohydrate consumption may have been a contributing factor to the increase of
ischemic heart disease in America. Lopez-S, et al,376 similarly noted an increase in
consumption of simple carbohydrate with a concurrent decrease in the
consumption of complex carbohydrates in a study of European food consumption
between 1934 and 1959.
Subsequent research has shown that ingestion of large amounts of refined simple
sugar is associated with increases in all major fractions of serum lipids, while
intake of complex carbohydrates, grain products, and starches have the opposite
effect, possibly due to different fiber contents of the dietary regimens. 277,355,356,357
The indigent, and specifically the urban poor, consume significantly more refined
sugars and carbohydrates than do the affluent.
Trans-fats and Hydrogenated Oils.
Prior to 1990, there was a dearth of reports in the clinical literature on the
pathophysiologic effects of trans-fatty acids in the human diet. Trans-fatty acids
are created by the hydrogenation of vegetable oils. They are also formed naturally
in the rumen of cattle and comprise approximately 5% of dairy and beef fat.306,915
The seminal article by Mensink and Katan907 suggested deleterious effects upon
both HDL and LDL cholesterol subfractions in healthy subjects consuming diets
containing 10% of energy as trans-fat. Similarly, the research of Zock and
Katan,916 showed that a diet containing 7.7% of energy as trans-fat increased LDL
and decreased HDL cholesterol even when compared to a diet containing saturated
fat.916,306 Additionally, the consumption of hydrogenated oils and trans-fatty acids
has been associated with increased incidences of chronic degenerative diseases,
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including CAD306 and cancer.604
Hydrogenated oils are created by the bubbling of hydrogen gas through liquid
vegetable oil, adding hydrogen atoms to the double chemical bonds of these
unsaturated fats, and causing them to act like a saturated fat, solidifying at room
temperature. This process increases the shelf-life of the oil, and of the food
products made with the oil. Trans-fatty acids, mostly derived from the full or
partial hydrogenation of vegetable oils and supplied primarily in the form of
margarine, constituted about 6% of the dietary fat in the average American diet in
1985, and considerably more in the diets of individuals who consume large
quantities of fried foods, margarine, cookies, crackers, white breads and
pastries.307 Margarine is one of the primary sources of trans-fat in the human diet,
and recent U. S. Department of agriculture statistics show that margarine is now
the leading contributor of total fat in the American diet, and may currently
account for over 7% of all dietary fat consumed in the United States.560,603 The
trans-fatty acid content of typical margarines sold in the United States is high, and
ranges from 10 to 30% of total fat content, however levels as high as 60% have
been reported.306 The consumption of trans-fats increased progressively in the
United States in the first half of this century and paralleled the increases in CAD
observed during this period, however consumption has remained relatively stable
at around 6-7% of total dietary fat consumption in the past few decades. Increased
consumption of trans-fats, however, is associated with lower levels of education,
and with lower SES,306 which may contribute to the increased risk of CAD, and
acute cardiovascular events associated with the indigent.
Trans-fat consumption has been associated with increases in atherogenic low
density lipoprotein, decreases in protective high density lipoprotein, adverse
effects upon hemostatic factors including increases in platelet aggregation, and
decreases in the normal production of prostaglandins, which act as free radical
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scavengers, and regulate the blood clotting process.306,307,603,907,916 Theoretically,
trans-fats could precipitate acute coronary events by accelerating the
atherosclerotic process through adverse lipid effects, while simultaneously
increasing the potential for thrombosis through adverse effects on prostaglandins
and platelet aggregation. In fact, trans-fats have been associated with an increased
risk of acute coronary events in at least one major clinical study. In a recent study
of 521 people by Ascherio and co-workers,306 it was determined that 239 patients
who recently had suffered a myocardial infarction were significantly more likely
to have consumed greater amounts of trans-fatty acids (in the form of partially
hydrogenated vegetable oils or margarines) than the 282 healthy control subjects.
In addition to acute events, trans-fats have also been associated with chronic CHD.
A British case-control study by Thomas et al918 determined that persons dying of
CHD had a higher proportion of trans-fatty acids (in this population largely
derived from the partial hydrogenation of marine oils rather than vegetable oils) in
their adipose tissue than did persons who died from other causes. Willett,
Stampfer, and co-workers917 found an increased risk of CHD which was associated
with increased trans-fatty acid intake in a large prospective study of women.
Trans-fats have also been associated with other degenerative, free radicalmediated diseases. Australian researchers found that melanoma patients
consumed twice the amount of hydrogenated polyunsaturated fats as compared to
healthy controls.604
Exposure to dietary trans-fatty acids is "almost universal" in industrialized
countries.306 Because the indigent in the United States tend to consume more fried
foods, margarine, crackers, pastries, french fries, and other refined and highlyprocessed baked-goods (which frequently contain more that 10% of their total fat
as trans-fat306) than do the affluent, they have a higher per-capita consumption of
the artificially produced trans-fats. Because members of lower SES tend to
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consume more animal fat from beef and dairy sources, the American poor also
have a higher per-capita consumption of naturally occurring trans-fats. These
combined factors may increase the risk for acute and chronic coronary events
among the indigent.
Polyunsaturated Fats and Oils.
Although polyunsaturated fatty acids (PUFAs) have been associated with
decreases in blood cholesterol, research has demonstrated that the non-linolenic
acid members of this class of fatty acids can produce an increase in platelet
aggregation,859,970 PUFAs serve as a major source of lipid peroxides which may
accelerate the pathological oxidative modification of lipoproteins. 970
Obesity and Dietary Fat Consumption
Obesity is clearly and significantly related to dietary fat consumption, and is
caused by an imbalance between calories consumed and calories expended
through metabolic or physical activity.3, 115, 253, 294 Because foods which are high in
fat supply as much as 2.25 times as many calories per ounce,3 less of these foods
need to be consumed to reach an imbalance between caloric intake and
expenditure. Furthermore, 27% of the calories contained in carbohydrates are
used and lost in the metabolic process of digestion and assimilation, whereas only
3-6% of fat calories are similarly required for internal processing. Americans
consume as much as 40% of their dietary intake in the form of fats,602,855 and it is
not surprising that the incidence of obesity among adults in the United States is
high: Approximately 19% of men and 28% of women are considered
overweight.294
Obesity, Race, SES and Mortality
Some data suggests that obesity may predispose individuals to lower
socioeconomic status and increase the risk of developing hypertension and
diabetes-related CAD. Gortmaker and co-workers332 found that obese young
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women were less likely to marry, had lower incomes, and had less education than
non-obese women, and that obese young men were less likely to marry than nonobese men of the same age. In two studies of almost 70,000 women, Rimm and
associates demonstrated a strong association between low SES and obesity.264,265
The Charleston Heart Study266 examined the influence of obesity on mortality, and
found that it was predictive of all cause and CAD mortality in black men, but not
in white men.
Weight reduction had the greatest effect, and was more effective than dietary
sodium reduction or stress management in a study which examined lifestyle and
dietary modifications, and their effect on blood pressure. Sodium restriction and
stress management were of intermediate effect and were more effective than
calcium, magnesium, potassium or fish oil supplementation. 913
The First National Health and Nutrition Examination Survey demonstrated that
black women had age-adjusted weights which were 9 to 16 pounds higher than
those of white women, regardless of SES.4 That this racial predisposition to
obesity is probably environmental rather than genetic is validated by two studies
by Garn et al,267,268 which found that girls in low SES (predominantly black)
families are similar to, or slightly less obese than female children in high income
families, however low SES women are more likely to be obese after adolescence
than their high-income counterparts.
Obesity has not consistently been associated with increased risk of death from
CAD or all-cause mortality in several clinical studies. This has often confounded
the results, especially when these studies were structured to determine excess
mortality among the obese. Epidemiologists examining the data from the Harvard
Alumni Health Study181 have determined that cigarette smokers tended to be
thinner and less healthy than non-smokers. The death rate among smokers was
elevated in both the very thin and the very heavy. Among non-smokers, however,
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increased risk of death was directly associated with increased body weight. Low
SES blacks tend to be more obese than affluent blacks, and the indigent tend to be
more obese than the wealthy, regardless of race.
Diabetes, Fat Consumption and SES
Epidemiologic Studies and Diabetes
The incidence of adult onset, non insulin-dependent diabetes mellitus (NIDDM),
a significant independent risk factor for CAD, is greatest among members of
lower socioeconomic groups,42,383 who tend to be more obese.383 Similar to
observations concerning the association of CAD and SES, the association of
diabetes and low SES has not always remained constant. Interestingly, Grover407
noted in a 1948 public health report that mortality per 100,000 from diabetes
mellitus was from 55 to 120% higher among whites than among non-whites
between the years 1919 and 1941. This risk factor shift may reflect the greater
consumption of dietary fat, sedentary lifestyles, and greater tendency toward
obesity among whites versus blacks during this period. In support of this
hypothesis, Kesilman411 noted that obesity was a rarity among 2,230 American
black males examined between 1937 and 1941, and numerous researchers have
documented the infrequent occurrence of diabetes among rural African blacks who
consume little dietary fat, and are rarely sedentary or obese.812,813,814
Recently, Grossman et al302 found that the ten-year adjusted death rate from
diabetes was almost four times higher among urban blacks than among urban
whites, and Knapp et al42 reported in 1985 that low SES Mexican-Americans have
a greater prevalence of diabetes than whites. Kelley and co-workers383 reported in
1993 that diabetic patients from the socially and economically deprived inner city
were less likely to use insulin, had a shorter duration of diabetes, were older and
tended to live alone, and were more likely to smoke and to have cardiovascular
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disease than were patients from more prosperous areas.
Pathophysiology and Prevention of Diabetes.
Diabetes is one of the major risk factors for the development of CAD, and
significantly increases the risk of CAD morbidity and mortality. 14,17,21,32,34,80,81,82
Diabetes causes metabolic, hemostatic, coagulation and lipid abnormalities, and
has been associated with increased plasma fibrinogen.729 Adult onset (Type II)
diabetes is characterized by insulin resistance of the body's cells due to increased
body fat. Approximately 90% of U.S. adults with adult-onset diabetes are
obese,253,279 and between 50 and 80% of Type-II diabetes, and 30% of diabetes
deaths are estimated to be preventable by control of obesity.115
Diabetes and Diet.
Recent research has determined that the amount of fat a person consumes is
directly proportional to the risk of developing adult-onset diabetes. In a threeyear study of 123 non-diabetic patients with impaired glucose tolerance,271
researchers determined that study participants who subsequently developed
diabetes had the highest mean consumption of fat (43.4% of total calories). Those
individuals who remained glucose intolerant but did not develop diabetes
consumed an intermediate amount of fat, and those who converted to normal
glucose tolerance consumed the least fat. Because adult-onset diabetes is more
prevalent among obese individuals, dietary counseling is the foundation of
diabetes treatment.80,279 The presence of abdominal fat (expressed as high waistto-hip ratios) is predictive of the subsequent development of diabetes. 52,253 The
use of weight control, reduced saturated fat intake, increased consumption of
complex carbohydrates, increased consumption of fiber, and the even distribution
of daily caloric intake (through multiple small meals) are effective methods of risk
reduction in diabetics.
Dietary antioxidants may be beneficial in the treatment of Type I and Type II
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diabetes, because oxygen free radicals have been implicated in the pathogenesis of
the disease.486 Furthermore, tissue antioxidant status may be compromised under
conditions of dietary restriction for weight loss,486 (frequently recommended in the
treatment of diabetes), and dietary supplementation may address this deficit. It is
important to note that iron overload may promote diabetes by increasing
production of free radicals, and vitamin C may enhance iron absorption in patients
with high iron intakes (especially from animal sources), thereby potentially acting
as a pro-oxidant in diabetics with a positive blood iron balance.668
Pancreatic beta cells, which are responsible for the production of insulin, are
vulnerable to destruction by free radicals generated by the body's own immune
system in Type I diabetes. Antioxidants have proven effective in preventing
diabetes in animal models subjected to active oxygen species,485 however
controversy exists concerning the risk of vitamin E supplementation in
autoimmune disorders including Type I (Juvenile Onset) diabetes and lupus
because of the immune-enhancing properties of the vitamin.668
Pediatric Nutrition Education Efforts, Obesity, and Diabetes.
The best hope for prevention of obesity and its associated diseases is through
programs of nutritional education directed toward school children, teenagers and
mothers which emphasize dietary counseling for reduction of fat and total caloric
intake, good dietary sources of antioxidants and fiber (including fresh fruits and
vegetables), and a program of regular physical exercise.294 These programs are of
urgent necessity among the indigent who are at greater risk of pediatric and adult
obesity, and of adult-onset diabetes.
Dietary Fiber Consumption, Socioeconomic Status and CAD risk.
Fiber is provided exclusively by vegetable sources, and is well known to lower
serum cholesterol without changing serum triglycerides or HDL cholesterol. 891
Fiber is not found in fats, sugars, meat, fish, milk or dairy products, and in most
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beverages. The foods highest in fiber are complex carbohydrates, and include
unprocessed whole grains, wheat bran, brown rice, legumes, seeds and nuts, and
fruits and vegetables.247,294 Most edible plants contain large amounts of vitamins
and minerals, and are also are an excellent source of pectins, gums and soluble
fibers which have all been shown to lower serum cholesterol,226,294,875,877,891
prevent CAD,875,878 hypertension,875,879 certain forms of cancer,875,880,881
gastrointestinal disorders,875,882 diabetes,875,883 and aid in weight loss.668,875,880
Dietary fiber is the structural part of plant foods, and includes polysaccharides
(cellulose, hemicellulose, pectin, mucilage and gums from vegetables and fruits),
and lignin (from fruits with seeds, and grains) that are not able to be digested by
enzymes within the human gastrointestinal tract. Dietary fiber is divided into two
basic classifications (soluble and insoluble) based on hydrophilicity and solubility.
Soluble fiber, consisting of pectins, mucilages and gums, dissolves and thickens
in water forming a hydrophilic gel. These fibers are found in a variety of whole
grains, legumes, the pulp and rind of fruits, seeds, and in seaweed. Soluble
pectins, mucilages and gums chelate, or bind with, intestinal bile acids and steroid
materials. This chelating effect is responsible for the reduction of blood
cholesterol by preventing the intestinal absorption of bile acids and steroid
materials, the building blocks of cholesterol.278,294 Soluble fiber also keeps blood
glucose levels more constant, and may be especially beneficial in diabetes by
providing tight glycemic control, and reducing the post-prandial insulin demand.
By forming a gel in the gastrointestinal tract, soluble fiber slows and modulates
the absorption of nutrients into the bloodstream, avoiding hyperglycemic
elevations, and hypoglycemic troughs in blood glucose levels. 226
Insoluble fiber, often called roughage, consists of cellulose, hemicellulose and
lignin. It is supplied by the woody, structural parts of plants including fruit and
vegetable skins, seeds, husks, hulls, and bran--most of which are typically
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removed by the modern process of refining. The bulking effect that the insoluble
fibers have on the stool allows more water to be drawn in to dilute the toxic
contents of the stool, and speeds transit time through the gastrointestinal
tract.247,294 This increased motility may also decrease the absorption of fats
contained within the gastrointestinal contents, and may reduce the amount of bile
salt acids which are potentially reabsorbed in the small intestine, ultimately
reducing blood cholesterol levels. Additionally, speeding intestinal transit may
limit exposure of the intestinal wall to toxic or carcinogenic compounds in the
stool, reducing the risk of colon cancer, diverticular disease, and irritable bowel
syndrome.875 Both soluble and insoluble fiber may have value in weight control
by adding bulk to the meal and enhancing feelings of post-prandial satiety.226
Phytosterols, Tocotrienols and their Association with Fiber and Serum Cholesterol
Extraction and processing of fiber from plant products to create a concentrated
fiber supplement may not provide the same degree of hypocholesterolemic benefit
that may be received from the consumption of the whole food. Plants are
nutritionally dense complex carbohydrates which supply other substances in
addition to fiber which can also effect serum cholesterol levels. These substances
include phytosterols and tocotrienols. Phytosterols are plant sterols which have
the ability to limit absorption of both endogenous and exogenous cholesterol, and
subsequently lower serum cholesterol in moderate doses.891 Sources of
phytosterols include seeds, nuts, whole wheat, corn, soybeans, and many vegetable
oils. Soy protein is rich in nonsteroidal estrogens, or phytoestrogens of the
isoflavone class, which suppress tumor growth in vitro and may be partly
responsible for the low breast cancer incidence among Chinese and Japanese
women who have a high soy intake.900
Tocotrienols are chemically related to tocopherol, or vitamin E. These
substances have been shown to have 3-hydroxy-3-methylglutaryl coenzyme A
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(HMG co-A) reductase inhibition activity, and subsequently lower serum
cholesterol.891 Tocotrienols are found in cereal seeds and palm oil, however the
saturated C16 palmitic acid found in palm oil may antagonize the
hypocholesterolemic effects of the tocotrienols supplied by the oil.
Epidemiological and Clinical Studies.
As early as 1961, Antar and associates277 postulated that significant reductions
in the consumption of whole flour and grains, an important source of fiber,
between 1889 and 1961 may have been a factor in the CAD increases during this
same period. These researchers also theorized that the four-fold decrease of apple
consumption during this seventy-year period, and the concomitant increase in
citrus consumption may also have been partially responsible for CAD increases
during this period since dietary pectin is found in the flesh of the apple, but only in
the uneaten rind of citrus fruit. In 1962, Adelson and Keys355 found that men with
high levels of serum cholesterol had statistically significantly lower intakes of
grain products, than did men with lower levels of serum lipids, and in the early
1970s, Burkitt and Trowell876 linked low intake of dietary fiber with several
Western diseases.
People in developed countries tend to consume significantly less dietary fiber
(about 10-20 grams per day) than do people in third world countries who typically
consume 30 to 50 grams of fiber daily.247,442 The current recommended dietary
fiber intake for healthy American adults is 20 to 35 g/d,875 however average
consumption in the United States is about 11 grams per day. Among the American
poor, consumption is even less.
Epidemiologic studies by two groups of British clinicians in the early 1970s
demonstrated that rural Africans with high fiber intakes had lower incidences of
numerous chronic degenerative diseases including CAD, obesity, diabetes,
diverticulitis, irritable colon, hiatus hernia, hemorrhoids, colon cancer, gallstones,
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and dental caries.304,305 Similarly, epidemiologic studies of rural Africans in the
early decades of this century demonstrated that diabetes, gallstones, peptic ulcer
disease, kidney stones, endocrine disorders of the pituitary and thyroid, and
prostatic hypertrophy were a rarity among these population groups. 812,813,814,815
These degenerative diseases are endemic to urbanized societies which tend to
consume less fiber, and they are frequently associated with increasing affluence
[See Table 5]. It is difficult, however, to isolate the effect of fiber alone since
most people who consume less fiber may also consume more calories from fat;
exercise less; consume fewer dietary sources of antioxidant vitamins (including
beta carotene, vitamin E, and vitamin C); consume less protective vegetable
substances (including phytoestrogens, phytochemicals, flavonoids, isoflavones,
phytosterols, tocotrienols and arginine); and may be more likely to smoke, and be
of lower SES.306,900
Dietary fiber may confer additional benefits in the reduction of CAD risk.
Recent evidence suggests that vegetarians and individuals with high fiber intakes
are less likely to be hypertensive than those individuals who have low-fiber
intakes,303 possibly because high-fiber foods are an excellent source of potassium.
Short-term studies utilizing high-fiber diets have shown beneficial reductions in
post-prandial glucose, serum cholesterol, and insulin requirements in persons with
Type II (adult onset) diabetes.294 Extreme excesses in fiber consumption,
however, can lead to decreased absorption of minerals including calcium, zinc,
iron, copper, magnesium, and chromium.247,668
Prevalence of Smoking, Attitudes to Smoking, and the Access to Tobacco
Products by Adolescents.
Smoking is clearly related to heart disease, and cessation of smoking may have a
greater effect in reducing the long-term risk of CAD than changes in any other risk
factor,496 with the possible exception of diet.5,914 Smoking may increase exposure
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to psychological stress by increasing a smoker's tolerance of a stressor, 496,790 and
may interact synergistically with psychological stress to increase CAD
risk.496,786,787 Smoking has been described as a habit as addictive as the use of
heroin or cocaine,223, 295 is well recognized to have a marked negative impact on
life expectancy, may double the risk for CAD morbidity and mortality after
controlling for all other known risk factors,496 is the single greatest cause of death
in the United States,115 and is significantly more prevalent among blacks,497 the
young,497 the poor,497 individuals with limited control over their jobs or lives,709
and those reporting higher levels of stress.496,497 Because blacks tend to be
concentrated at the lower end of the socioeconomic spectrum and frequently report
experiencing more life stress than whites, they are significantly more likely to
report being a smoker than are whites. Stress differences, however, are more
potent than race in determining smoking status.497
Historical Background of Smoking.
The deleterious effects of smoking may take as long as 20 to 35 years after
smoking initiation to manifest as chronic degenerative disease.343,344,345 The use of
tobacco products in the United States remained relatively low for the first four
decades of this century, however at the onset the second World War, cigarette use
increased dramatically from about 2,000 per annum in 1940 to almost 3,500
cigarettes per adult smoker per year by 1945.296 This phenomena, which occurred
predominantly among men, was undoubtedly due to the inclusion of four packs of
cigarettes in each of the military field rations, or K-rations, which were distributed
to American GIs during World War II,337,475 and certainly was responsible in part
for the dramatic increases in CAD among American males following the war.
Cigarette use began to slowly decline from its highest point in 1963 around the
time of the publication of the first Surgeon General's report, and is currently at its
lowest level since World War II.222,341,342 In 1965, 60% of black males and 51% of
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white males were smokers. In 1985, those numbers fell to 41% and 32%
respectively.497 The recent focus of tobacco advertising has been women, children
and minorities,223,336,338 and consequently tobacco use has declined less rapidly
among these groups. Pierce and co-workers336 found that in girls younger than
18 years, smoking initiation increased abruptly around 1967, when women's
cigarette brands and their aggressive advertising campaigns were introduced. This
increase was highest in those females who had never attended college. Feigelman
and Gorman497 reported that 35% of adult white females were smoking in 1965,
with only 28% still continuing to smoke in 1985. For black women, the
consumption of cigarettes remained virtually unchanged over the same 20-year
period: 33% were smoking in 1965, and 32% were still smoking in 1985.
It is estimated that 58% of teenage smokers purchase cigarettes illegally, 339 and
these illegal sales occur more than twice as frequently in black as in white
neighborhoods.340 A 1994 population-based study by Grossman and coworkers302 indicated that over 67% more urban black mothers smoke than urban
white mothers, and other national studies have documented excessive rates of
smoking among black men.
Demographics and Epidemiology of Smoking.
In a recent review article on the human costs of tobacco use, MacKenzie and
associates223 noted that even the three life insurance firms which are owned by
tobacco companies charge smokers nearly double for term life insurance because
smokers are almost twice as likely as non-smokers to die at any given age.
Smoking causes disease and aggravates existing disease. The risk of developing
CAD is greatly increased among men and women with diabetes who smoke, and is
much higher in smokers than non-smokers with or without diabetes.220 According
to a report of the Surgeon General,221,222 smokers have as much as a four-fold
greater incidence of CAD, a 70% greater CAD death rate, and a four-fold greater
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risk of sudden death than non-smokers. In a review of articles published between
1977 and 1993, (which identified factors contributing to death in the United
States), CAD was identified as the most common cause, and the use of tobacco
products was identified as the greatest contributor to mortality. 115 Heart disease,
lung cancer, stroke, and hypertension are all smoking- related diseases which are
more prevalent among the poor and among black Americans [see Table10].
Table 10: Smoking Related Illnesses by Race and Sex
Disease
White Males
Black Males
White Females
Black Females
Lung Cancer
79.3
125.3
33.5
33.9
Oral Cancer 17.2
22.5
---
---
Heart Disease
257.8
308.2
126.7
191.5
Stroke
Hypertension
35.2
21.2
64.2
28.3
29.6
20.0
53.8
39.8
__________________________________________________________________________________________________________________
Adapted from: Feigelman W, and Gorman B.497 Heart disease and stroke figures were collected by the National Vital Statistics System on
age-adjusted death rates for selected causes of death per 100,000 population for 1983, National Center for Health Statistics (1986:Table 21).
Cancer statistics are age-adjusted cancer incidence rates per 100,000 population reported to the National Cancer institute, National Center for
Health Statistics (1986:Table 36); Hypertension statistics are age-adjusted rates per 100,000 adults aged 25 to 74 for 1976-1980, National Center
for Health Statistics (1985:Table 8, p.125).
An increased rate of death observed among the very thin in several clinical
studies has often confounded the results especially when these studies were
structured to determine excess mortality among the obese. Epidemiologists
examining the data from the Harvard Alumni Health Study,181 a study following
predominantly white, high SES men enrolled as Harvard undergraduates between
1916 and 1950, have determined that cigarette smokers were thinner than nonsmokers and that the mortality rate among smokers was 82% higher than among
non-smokers. Furthermore, among smokers (who comprised half the study
population), the death rate was elevated in both the very thin and the very heavy.
Among non-smokers, however, increased risk of death was directly associated
with increasing weight. The heaviest non-smoking men had a 67% higher
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adjusted mortality than subjects who weighed 20% below the United States norm.
These data suggest that obesity is a risk factor for CAD among non-smokers, that
obesity potentiates the deleterious effects of smoking (by increasing the rate of
death from CAD among obese smokers), and that smoking increases the risk of
death from cancer or other degenerative diseases (which often manifest themselves
as weight loss associated with smoking). These findings further demonstrate that
the risk of death from smoking is probably greater that the risk of death from
obesity alone.
Of the 2 million American adults who died in 1986, 76% of those reported to
have died at a relatively young age (45 to 64 years) had been smokers. 214 There is
a strong inverse relationship between the level of education and current smoking
status.4,219 Currently, higher rates of smoking are prevalent among blue-collar
workers, blacks, the unemployed, and among those of low income and lower
socioeconomic status, however data suggests that this trend has not been
consistent over time. In the United States, smoking was more prevalent in the
early decades of the twentieth century among the affluent who were able to more
easily afford the habit, than among the rural indigent whites and blacks. Between
1916 and 1950, the rate of smoking among high-SES Harvard undergraduztes was
over 50%,181 and in 1954, nearly twice as many medium income Europeans were
identified as heavy smokers as compared with low income Europeans. 444
Currently, this situation has been reversed among those of high-SES, both in
Europe and in the United States. This reversal took place within the decade of the
1960s, and undoubtedly contributed to the CAD risk factor reversal between the
socioeconomic classes in America.
The Pathophysiology of Smoking.
The adverse effects of smoking on the cardiovascular system involve numerous
mechanisms610 including a direct toxic and vasoconstrictive effect on the vessel
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wall,496,611 alterations in serum lipids,612 increases in low density lipoprotein
oxidation,837 increases in vascular hydraulic stress and myocardial oxygen
consumption (secondary to smoking-associated increases in heart rate),610
increases in blood pressure,496,788 circulating catecholamines,496,613,614,788 platelet
hyperactivity,615,616,625,872 thrombosis and thrombin generation,610,615,625,872
erythrocyte peroxidation,899 plasma fibrinogen,719,730,731,732,872 increased indices of
oxidative stress and lipid peroxidation,899 and decreased production of tissue
plasminogen activator (TPA), a beneficial endogenous thrombolytic.617,618 The
effect of smoking on serum catacholamines can further increase platelet
hyperactivity and adhesiveness, leading to potential thrombosis and cardiovascular
events.610,619 Kannel and co-workers732 attributed one-quarter to one-half of the
increased risk of atherothrombotic cardiovascular disease associated with smoking
to the effect of smoking on plasma fibrinogen concentrations, and subsequent
hemostatic abnormalities. Ascherio et al,823 in a 4-year follow-up study of the
dietary iron intake and the incidence of CAD among almost 45,000 men, noted
that increased intake of heme iron, (supplied in the diet predominantly by meat),
was associated with a significantly increased risk of myocardial infarction in
smokers. These authors postulated that excess heme iron potentiated the oxidation
of LDL, (especially in the absence of sufficient dietary antioxidants, and in the
presence of oxidative stresses such as smoking), and noted that smoking was
associated with increased heme iron and dietary fat intake, and reduced
consumption of fiber and antioxidant vitamins.
Tobacco smoke generates highly reactive phenoxy free radicals by itself, and
interacts within the body to create a cascade of other destructive free radicals 281,899
which have been implicated in the pathogenesis of myocardial ischemia and
infarction.479,480,481
Research indicates that smoking may interfere with vitamin C absorption, while
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increasing vitamin C requirements.469,640 Recent data published by Margetts and
Jackson282 at the University of Southhampton indicates that smokers, who have
the highest metabolic demand for antioxidant protection, are less likely to
consume adequate quantities of foods which are high in antioxidant nutrients, than
are non-smokers. This study examined the dietary habits of 618 smokers and
compared their diets to those of 1,224 non-smokers. The researchers concluded
that the smokers were at increased risk of developing chronic disease not only due
to the physiopathologic effects of smoking, but also due to the fact that their diets
were higher in fat and seriously inadequate in specific anti-oxidant nutrients.
Smokers ate significantly more white bread, sugar, cooked meat dishes, butter, and
whole milk, while consuming less whole meal bread, high fiber cereals, fruits, and
carrots. The frequent selection of white breads in lieu of whole grain varieties by
smokers is significant in light of the results of one major population study 851,891
which found that this choice was associated with a 37% increased risk of coronary
events (p=0.006). Margetts and Jackson further stated that smokers consumed
more fat, and had lower intakes of fiber, protein, vegetables, beta carotene, and
vitamin C. This nutritional deficit, according to the researchers, was likely to
further exacerbate the damage caused by smoking. These findings are similar to
those reported in other studies which examined the relationship between diet and
smoking.283,284,285,286,287,469,571,572,595,596,641
Pacht and colleagues498 found deficient levels of vitamin E in chronic cigarette
smokers. Similarly, Riemersma and associates469 found low vitamin E levels
among angina patients who were smokers, and Brown et al899 found that smokers
sustained an increased free radical load (characterized by increased indices of lipid
peroxidation) because of their exposure to large quantities of reactive free radicals
in the gas and tar phases of cigarette smoke. The researchers determined that this
increased lipid peroxidation was reduced in vitro following vitamin E
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supplementation. These findings are in accordance with other clinical research
which suggests that smoking reduces plasma vitamin E levels, and increases
oxidative stress.590,591
Numerous researchers have reported lower antioxidant levels of plasma carotene
among smokers.282,469,471,571,572,595,596,642 A recent report from the American Journal
of Clinical Nutrition demonstrated that non-smokers who regularly encounter
second-hand cigarette smoke (approximately 20 hours per week or more) had
significantly lower levels of vitamin C than non-smokers who were not exposed to
smoke, although their dietary intakes of the vitamin were comparable. Similarly,
Rimersma et al,469 in a recent clinical study evaluating the protective effect of
antioxidant vitamins against angina pectoris and CAD, noted that smokers were
found to have lower vitamin C levels than non-smokers. The National Health and
Nutrition Examination Survey,639 found plasma vitamin C levels to be lowest in
those who smoked the most cigarettes. The Health Professionals Follow-up Study
of over 50,000 male health professionals revealed that high serum levels of
vitamin C reduced the risk of non-fatal myocardial infarction or death in cigarette
smokers.471
Cigarette Smoking and Alcohol Consumption.
Cigarette smoking is linked with increased alcohol consumption. Excessive
alcohol consumption, (and especially concentrated forms of alcohol devoid of
antioxidant flavonoids like those found in red wine), can further increase the
oxidative stress on the body by increased production of free radicals during the
metabolism of ethanol.484 Examining data from the Physicians' Health Study,
Robbins and co-workers625 reported that over twice as many smokers among the
22,071 American male physicians studied reported daily drinking as compared
with never-smokers.
Smoking, Oxygen-Free Radical Damage, and Atherogenesis.
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Smokers have significantly higher serum concentrations of atherogenic low
density lipoprotein (LDL) cholesterol,288,612 and decreased levels of beneficial high
density lipoprotein cholesterol (HDL).625 The increased oxidative stress brought
on by smoking (and reduced levels of cardioprotective HDL secondary to
smoking), renders LDL more susceptible to atherogenic modification by
oxidation,471,589,590,591,609 and may simultaneously predispose the vasculature to
vasospasm.482 Additionally, serum LDL in smokers has a greater potential for
oxidation due to high ratios of phenoxy and other free radicals and reactive
oxygen species to antioxidant vitamins in smokers.281,282 These deficits are caused
by lower dietary intakes of antioxidants, and greater metabolic demand in
smokers.282 Oxidized LDL is more likely to be taken up by monocytes and
macrophages (a chemotactically activated monocyte) to form foam cells which
become the foundation of atherosclerotic plaque and atheroma, leading to CAD. 281,
289,333,471,573,574,578,891
Research shows that scavenger receptors located upon the
monocyte are responsible for stimulating and activating the monocyte to become a
macrophage. These scavenger receptors are sensitive to oxidized LDL (LDLOX),
but are insensitive to unaltered LDL particles.891 Furthermore, oxidized LDL may
contribute to atherogenesis by reducing macrophage motility in the arterial
intima,577 increasing monocyte accumulation,578 and increasing cytotoxicity.579 In
vitro studies have demonstrated that flavonoids, one of the many forms of dietary
antioxidants which most smokers consume in lesser quantities, 282,283,284,285,286,287,288
may prevent the cytotoxicity of oxidized LDL.566
The Nicotine Paradox.
Demographic data indicates that the indigent497,719 and those who are
experiencing significant life stress are more likely to smoke,496,497 while
concomitantly engaging in lifestyles and dietary practices which are more likely to
exacerbate the biochemically-adverse effects of smoking. Furthermore, data
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suggests that smoking may adversely effect an individual's ability to cope with
stressful life situations. Epstein and Perkins496 stated that smoking reduces anxiety
and sensitivity to unpleasant situations which may lead to "increased and extended
attempts to actively cope with ongoing stressful tasks to the point where coping
becomes physiologically maladaptive." Experiencing psychological stress
frequently leads to increased smoking for subjective stress reduction, 496,791
however smoking exacerbates stress-induced increases in autonomic nervous
system activity, and increases serum catecholamines.496,699,788 Gilbert789 called this
differential effect of smoking on specific psychological and subjective responses
the "nicotine paradox".
In the setting of cardiovascular disease, it has been hypothesized that the
increased dietary or supplemental consumption of antioxidant vitamins and
flavonoids by smokers might inhibit the oxidation of LDL cholesterol into its
atherogenic form333,537,565,570,587 while preserving normal endothelial function,334
however the benefits of smoking cessation probably exceed those conferred by
nutritional supplementation or improved diet in established smokers. 335
In summary, smoking is associated with significant increases in oxidative stress,
and with reductions in the intake of dietary antioxidant nutrients, thus causing an
imbalance between these destructive and protective processes in the human body.
Smoking is more prevalent among the lower socioeconomic class, 497 and its
detrimental effects are therefore most likely experienced by the indigent. Stress
counseling, and instruction in coping skills and techniques may be of benefit when
combined with smoking cessation counseling, especially among members of lower
socioeconomic status.
Alcohol Consumption, the French Paradox, and Socioeconomic Status.
The associations between alcohol consumption and cardiovascular disease are
complex. Studies indicate that regular moderate use of alcohol is associated with
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a lower risk of major coronary events.197,198,202,280,402,403,476,543,544,545 Beneficial
increases in high density lipoprotein (HDL) levels subsequent to moderate alcohol
consumption have been suggested as a possible mediating factor for this protective
effect.202 However, heavy alcohol consumption and problem drinking are
associated with an increased incidence of hypertension,
arrhythmias, alcoholic cardiomyopathies, and an increased mortality from all
causes, including cardiovascular disease, coronary heart disease, liver disease, and
cancer.190,191,197,198,199,201,202,203,476,543 Excessive alcohol consumption is frequently
associated with smoking,625 inadequate diet,901 malnutrition and nutritional
deficiencies,889,901 malabsorption,901 low plasma antioxidant status,889 increased
indices of oxidative stress (increased serum MDA),889 low socioeconomic
status,552 and high psychological stress.552 These factors have been suggested as
potential major confounders in the determination of associations between alcohol
consumption and CAD.552,625 In a review by McGinnis and associates115 of
articles published between 1977 and 1993 which identified factors contributing to
death in the United States, the abuse of alcohol was identified as the third most
prominent contributor to mortality, after use of tobacco and inadequate diet and
exercise. In a 1994 population-based study of 1.5 million northwestern whites,
blacks, urban American Indians, and Alaskan natives who were followed for ten
years, Grossman and co-workers302 demonstrated that age-adjusted alcohol-related
deaths per hundred thousand were 28% higher among urban blacks than among
urban whites.
According to the National Mortality Follow-back Survey, of the approximately
two million Americans who died in 1986, 84.5% of those who died at the youngest
age were reported to have consumed 12 or more alcoholic drinks per day. 214
Alcohol abuse is estimated to have been a major contributing factor in 60 to 90
percent of cirrhosis deaths,115 and black adults are 60% more likely to have died of
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cirrhosis of the liver than whites.214
Alcohol consumption is greatest among individuals of lower socioeconomic
status, among men, and among young adults. Respondents in clinical surveys who
are obese, who smoke, and who do not use seat-belts are more likely to be among
the 9% of all adults who identify themselves as chronic heavy alcohol
consumers.190, 200, 204 It is estimated that this small group of heavy drinkers may
consume 40-50% of all alcoholic beverages.200
Excessive alcohol consumption may have an adverse effect on serum antioxidant
levels which is independent of nutritional status. Excessive consumption of
alcohol has been associated with low serum vitamin E levels,499,889
malondialdehyde (MDA) markers of oxidative stress and free radical activity, 889
and with significant losses of serum magnesium. This "magnesium wasting" may
account for the vasopressor effect and arrhythmias which have been associated
with the excess consumption of alcohol. Numerous studies have shown that
alcoholics have lower serum beta carotene,901 alpha tocopherol,889 selenium,889 and
ascorbic acid889 concentrations than control subjects who drink moderately.
Excessive alcohol ingestion is one of the foremost factors which is known to
aggravate hypertension, and has been strongly associated with the development of
hypertensive disease in urbanized populations in the Third World.279
Alcohol is metabolized into the double free radical acetaldehyde, which can
attack and cause protein cross-linking damage to hepatic and cardiac tissues.281,484
This may account for alcohol-induced cardiomyopathies and fibrotic cirrhosis
which commonly occur in chronic heavy drinkers. These deleterious effects of
alcohol may be magnified in low SES populations, and among smokers 282 whose
diets tend to be deficient in many basic nutrients, including anti-oxidant vitamins,
selenium, and magnesium.
Epidemiology of Alcohol Consumption and the French Paradox.
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The French and Italians, who lead the world in per capita consumption of wine
(147 and 153 liters per person per year respectively)661 are among the lowest in the
incidence of, and mortality from CAD,61,392 although their fat intake, LDL, and
HDL cholesterol levels are similar to higher risk populations such as the United
States. Epidemiological studies suggest that consumption of alcohol at the level
of 20-30 grams per day, (similar to the level of intake in France), can reduce the
risk of CHD by at least 40%.873 The French consume 18 times as much wine per
capita as do Americans, and 30 times more than the Fins. Alcohol is commonly
believed to protect from CAD by preventing atherosclerosis through the action of
increasing HDL cholesterol. Theoretically, this effect would increase hepatic
uptake of LDL, and reduce the potential of LDL oxidation. Small clinical and in
vitro studies have suggested that alcohol may raise HDL in some individuals, but
large-scale epidemiological studies have shown that serum concentrations of this
factor are no higher in France than in other higher-risk countries,873 shedding some
doubt on the alcohol-HDL hypothesis. The antioxidant flavonoid compounds
present in red wine, however, may be partly responsible for the reduced risk of
CAD among wine drinkers, since the French consume more of these polyphenolic
flavonoids than do most other populations.467,570 Additionally, alcohol is may
protect from CHD by its effects on hemostatic mechanisms. Data from a study
conducted in Caerphilly, Wales, suggests that platelet aggregation, which is
directly related to CAD, is significantly inhibited by alcohol consumption at those
levels of intake which have traditionally been associated with reduced risk of
CAD. Research conducted by Folts et al at the University of Wisconsin, Madison
demonstrated that red wine possessed twice the anti-platelet activity of beer or
white wine. The researchers postulated that unlike white wine, the process of
creating red wine allows the crushed grape skins, stems and seeds to remain in
contact with the juice during fermentation. This solid material, which is later
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filtered and removed, contains antioxidant flavonoids which have been shown to
possess anti-platelet activity. Additionally, red grapes which are grown in a cool,
moist climate contain an antioxidant and antifungal agent called resveratrol, which
is also an inhibitor of platelet activity.
Inhibition of platelet reactivity and adhesiveness by wine may be one
explanation for the paradoxically low rates of coronary heart disease in France,
since pilot studies have confirmed that platelet reactivity is lower in France than in
Scotland.873
Because French per capita absolute alcohol consumption is 50% higher than the
Italians, twice that of Americans and four times that of the Fins, this may account
for the much higher morbidity and mortality from alcoholism among the French.661
Alcohol consumption versus CAD risk forms a "U-shaped" curve, with the
greatest benefits conferred upon moderate drinkers, and the least benefits
bestowed upon non-drinkers and excessive drinkers.280,543 Meade and
associates733 showed that non-drinkers had higher plasma fibrinogen levels than
drinkers, which additionally may be partly responsible for the slightly increased
risk of CAD among abstainers. It is feasible that members of upper SES may be
more likely to moderate their drinking, and may tend to choose wine as a beverage
of choice more frequently than the indigent, thereby reducing their CAD
risk.402,476,543,544,545,569,570
Destructive Personal Behaviors and Their Relationship to SES
There is evidence that socioeconomic status effects behavioral styles, as well as
coping styles.4 It is also conceivable that behavior and coping styles may effect
socioeconomic status. Stephen Covey108 defines habits which are present in
successful people, or those who have attained high socioeconomic status. They
include self-discipline, independence, teamwork, cooperation, empathy,
unselfishness, personal integrity, responsibility, prioritization, goal-setting,
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communication, and striving for excellence. Bennett, in his "Book of Virtues"
similarly defines principles of life-success including self-discipline, compassion,
personal responsibility, courage, work ethic, loyalty, faith, and honesty.
According to the Report of the National Commission on America's Urban
Families,224 the traditional family is the institution which has historically been
responsible for teaching these constructive personality traits which cannot be
enforced by laws but which are essential to both personal happiness and societal
success. Because single parent and dysfunctional families are more prevalent
among the impoverished, destructive personal behavior is associated with lower
SES; because the American social welfare system encourages and rewards single
motherhood, weakens the traditional family, and disproportionately impacts upon
the families of the poor, destructive personal behavior is associated with lower
SES; and because of increasing tendencies among many Americans to abdicate to
institutions other than the family the responsibility for instilling a belief system
and the establishment of moral guidelines for our children, these positive
personality traits may not be taught as thoroughly, or received as enthusiastically
as in previous generations of Americans.
Hope is a strong motivating factor, and the possession of a personal dream
allows men and women to press forward toward the attainment of that goal.
Dependency upon a social system or upon society for long-term support and
subsistence ultimately robs individuals of their independence and dignity,
quenches their ambition, and steals their dream of hope.
VIII. Dietary Electrolyte Mineral, Mineral, and Antioxidant
Vitamin and Flavonoid Consumption and CAD.
Dietary Antioxidants, Recommended Daily Allowance, and SES
Certain lifestyle modifications may be reducing cardiovascular risk factors
within certain upper socioeconomic population groups. These modifications
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include a reduction in tobacco use,102,103 increased intake of potassium, fiber, antioxidant vitamins, and flavonoids (due to increased fruit and vegetable
consumption),67,68,69,105,106,467 blood pressure control secondary to weight loss,183
reduction in dietary sodium intake,99,105,156,184,185,186,187,188,189 and improvements in
maternal health.107 These lifestyle modifications are less likely to be undertaken
by the indigent. Furthermore, the poor may require even higher levels of dietary
antioxidant nutrients due to exposure to significantly greater amounts of free
radicals generated daily by environmental pollutants including radiation,
insecticides, herbicides, cigarette smoke, automotive exhaust, water pollution, and
smog, which are all characteristic elements of the modern urban environment more
common to members of the lower socioeconomic class.487,491
The Recommended Daily Allowance, or RDA, is the arbitrary level of intake of
a given essential nutrient which has been set by the Food and Nutrition Board of
the National Research Council (NRC),487,489 and is defined by the NRC as "the
level of intake of an essential nutrient considered...to be adequate to meet the
known nutritional needs of practically all healthy persons." 665 Many nutrition
scientists believe that the RDA are too low,487,489,491,804 and represent nutrient
intakes sufficient to prevent deficiency disease or symptoms in healthy individuals
rather than to ensure optimal health or therapeutic effect.487,489 The first RDAs
were developed in 1943 to facilitate dietary planning and the procuring of food
supplies for the armed forces,487 however they are currently being used as
guidelines for public assistance food programs and may therefore exert more
considerable influence over the diets and vitamin intake of the poor, 491,664 than
over the diets of the affluent, who are more likely to take nutritional supplements.
According to Smith and Turner: "Through the past four decades, the RDA have
been increasingly used in statutory and regulatory food programs. They serve...as
the indirect basis for the definition of poverty."664
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The Ratio of Dietary Sodium to Magnesium and Potassium in Hypertension.
Sodium and potassium are essential electrolyte minerals which are involved in
the regulation of muscle contractile force and relaxation, bio-electrical functions
including nerve stimulation and generation of bio-electrical impulses, and the
regulation of cellular water balance and the intra-cellular distribution of fluids.
Magnesium, an essential mineral which helps promote the absorption and
storage of sodium and potassium, is involved in carbohydrate and amino acid
metabolism, and is essential for the conversion of blood sugar into energy. Proper
magnesium levels are critical for the normal functioning of nerves and muscles
(including the heart), and Magnesium is involved in the regulation of
neuromuscular contractions by countering the stimulating effect of calcium.
Magnesium may reduce blood cholesterol levels and possibly reduce the risk of
atherosclerosis. The dietary need for magnesium increases when blood
cholesterol levels are elevated, and when consumption of calcium and protein is
high.844,845
Sodium is supplied by seafood, poultry, red meat, and in many refined and
processes foods. Food sources of potassium include all vegetables, especially
green leafy vegetables, whole grains, fruits, potatoes, and seeds. Magnesium is
found chiefly in fresh green vegetables, raw unmilled wheat germ, soybeans,
whole grains, figs, corn, apples, oil-rich seeds and nuts, seafood, and milk.844,845,846
The typical American diet is deficient in magnesium and potassium,151 but high in
sodium.145 These mineral and electrolyte imbalances may be further exaggerated
in the diets of the poor. A low dietary sodium to magnesium and potassium ratio is
more important to the normalization of blood pressure than simple reduction of
sodium intake alone. Increased sodium intake secondary to the consumption of
refined and processed foods has been associated with the risk of hypertension. 279
Ohambo and co-workers330 emphasized that increased salt intake was a major
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factor in the increased incidence and prevalence of hypertension in urbanized
Africans, and particularly those within the middle-class. A decreased intake of
potassium associated with a decline in the intake of vegetables has been suggested
as playing an etiological role in the development of hypertension in peoples
moving from rural to urban areas,279,327 and an increased intake of calories,
coupled with decreased activity levels and resulting obesity has been linked to the
occurrence of hypertension in the Third World.279,331
Low magnesium concentrations have been linked to hypertension occurring
both at rest and during stress, and to vasospasms in the coronary
arteries.152,153,154,155 Conditions which have been associated with reduction of
blood magnesium levels include psychological stress, alcoholism, and diabetes,
and these are frequently associated with elevated blood pressure.145,247,844,845,846
Magnesium supplementation has been shown to decelerate hypertensive response
and abnormal cardiovascular reactions to stress.145 Potassium supplementation
and sodium restriction have been shown to be beneficial as a nutritional approach
to antihypertensive therapy.14,156,157,158,159,184,185,186,187,188,189,844,845,846 A potassium
depleted diet was associated with increased blood pressure in both
normotensive255 and hypertensive individuals.256
Dietary Calcium Intake, Hypertension, and CAD.
Calcium is an essential element which is involved in the blood-clotting process,
and in the regulation of heart rate and blood pressure through its bioelectrical
effects on nerve stimulation and through its cellular effects upon vascular smooth
muscle contraction.472,844,845,846 Milk and dairy products are the major sources of
calcium.247,844,845,846
Clinical and Epidemiologic Studies
The observation that regions with hard water high in calcium content
experienced lower cardiovascular mortality initiated the original epidemiologic
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interest in the relationship between calcium and cardiovascular disease. Studies of
populations which are at high risk of developing hypertension show that a low
dietary calcium intake correlates with increased prevalence of hypertension. 253,257
Serum ionized calcium has been reported to be lower in hypertensive persons than
normotensive persons,208, 209 and increasing dietary calcium intake has been shown
to reduce elevated blood pressure in several population groups. 190-192,209 Recent
clinical evidence suggests a beneficial hypotensive effect of calcium
supplementation in some hypertensive persons.210,211,258 Several dietary surveys
suggest that hypertensives as a group consume less calcium than normotensive
persons,200 and that individuals of low SES tend to consume less calcium than the
affluent. Watson and co-workers194 report that rural black hypertensive women
consume diets very low in calcium, and in studies assessing dietary intakes, it was
determined that hypertensives consumed less (and in one study, an average of 25%
less) calcium than normotensives.195,196 Knapp and co-workers,42 in a study of
low-SES Mexican-Americans in the San Antonio Heart Study, reported that
calcium intake was very low, and constituted only 55% to 67% of the RDA.
These researchers commented that calcium intake increased with increasing SES.
Dietary Iron Intake and CAD.
Iron is a mineral concentrate in the blood which is also present in every living
cell. All iron in the human body exists as a chelate, and is bound to protein. The
major function of iron is to combine with protein and copper to make hemoglobin,
the material which gives red blood cells their color and serves as a transport for
oxygen between the lungs and tissues.844 Iron is supplied in the American diet
primarily from animal sources including organ meats and red meats such as beef,
pork, or lamb.823,844,845,846 This form of iron, which exists in the form of
hemoglobin, is designated "heme iron", and is more completely absorbed than is
non-heme iron.823,841,844,855 Plant sources of iron supply the mineral in the form of
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non-heme iron, and include leafy green vegetables, whole grains, dried fruits,
legumes, and molasses. In men with replete iron stores, 26% of dietary heme iron
is absorbed, compared with only 2.5% of non-heme iron. In iron deficiency,
absorption of heme iron increases moderately, whereas the absorption of nonheme iron increases approximately nine-fold.841 These data suggest that although
both animal and plant sources of iron are equally capable of replenishing iron
stores in anemic deficiency, the consumption of heme iron as a primary dietary
source of iron is more likely to lead to an iron overload situation in individuals
with normal or positive iron balances.
Clinical and Epidemiologic Studies
Several clinical studies have indicated that high iron stores may increase the risk
of acute cardiovascular events. Most of these studies have suggested that high
iron intake (particularly from animal sources), is associated with an increased risk
of acute thrombotic events, but not with an increased risk of atherosclerosis.823 In
a recent prospective study among 1,932 Finnish men by Salonen and coworkers,827 dietary intake of iron and serum ferritin (predominantly supplied in the
Finnish diet by meat828) was strongly associated with acute myocardial infarction.
Similarly, in a 4-year follow-up study of almost 45,000 men with no previous
history of CAD, Ascherio et al823 found that dietary intake of heme iron,
(primarily supplied by red meat), but not non-heme iron, was associated with an
increased risk of acute cardiovascular events including AMI. These researchers
noted that intake of non-heme iron was directly associated with an increased
dietary intake of vitamins and fiber, and inversely associated with smoking and
risk of myocardial infarction.
Consistent with a positive association between heme iron intake and increased
coronary risk is the 20-year follow-up observation by Snowdon, Phillips and
Fraser,555 who reported a 60% increased risk of fatal coronary disease among both
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male and female Seventh Day Adventists consuming meat at least six times per
week as compared with those consuming meat less than once per week. In a
subsequent analysis of this same Adventist Health Study data base ten years later
by Fraser et al,851 beef consumption was related to definite fatal CHD in men
(p<0.001, relative risk 2.31, 95% CI, 1.11-4.78) but not in women (relative risk
0.76, 95% CI, 0.37-1.56) despite good statistical power to detect such an
association in females. It is possible that the relatively lower iron balance and
lower heme iron status commonly observed among women, or a protective effect
of estrogen in premenopausal women, may have been responsible for this
differential.
Campbell and Junshi,855 in their comprehensive ecologic survey of dietary,
lifestyle, and mortality characteristics of 65 counties in rural China, noted that
although the rural Chinese consumed relatively little red meat and animal protein,
iron intake in China was surprisingly high, averaging about 37g/d, especially when
compared to a U.S. intake of only 18g/d. Although serum iron levels were higher
among the Chinese, the prevalence of degenerative diseases, including CAD, was
significantly less than among Americans, or among other Westernized nations.
These researchers noted that 95% of the iron intake of the Chinese, however, was
in the non-heme form, and was supplied by plant sources. This suggests that iron
source, and not iron levels may be predictive of CAD morbidity and mortality.
These clinical and epidemiologic studies, however, found no evidence of
increased chronic coronary atherosclerotic risk associated with increased iron
intake. Interestingly, Miller and Hutchins842 found that histologic evidence of iron
overload was not associated with increased coronary atherosclerosis on postmortem coronary arteriography, and in fact noted that this was a rare pathologic
finding.
Free iron acts as a catalyst in the production of free radicals and has been
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implicated in lipid peroxidation,824 oxidation of LDL,823 and ischemic myocardial
damage.825,826 In vitro, heme iron has been shown to cause extensive oxidation of
low density lipoproteins.843
Although body iron is so tightly bound that there may not be free iron available
in vivo under physiological conditions, oxidative stress (in the form of smoking,
diabetes, and antioxidant vitamin deficiencies) can free iron from serum
ferritin,823,838,839 increasing the potential for free radical damage. Supporting the
hypothesis that heme iron acts as a pro-oxidant in vivo, and validating previous
clinical research, Ascherio et al823 found that a high intake of antioxidant vitamin
E may prevent the adverse cardiovascular effects of excess heme iron
consumption,830,831,832,833 and concluded that oxidative stress resulting from
smoking837 and hyperglycemia associated with diabetes834,835,836 may enhance it. A
lack of significant overall association between serum ferritin and myocardial
infarction in a case control study by Stampfer et al,840 which was nested within the
Physicians' Health Study, may have been due to a lower baseline risk of CAD, low
prevalence of smoking, diabetes, and hypercholesterolemia among the study
cohort, and possibly due to the fact that half of the physicians were taking high
doses of antioxidant beta carotene which may have modified the effect of
increased iron stores. Many of these physicians were also taking prophylactic
aspirin which can cause gastrointestinal bleeding, and subsequently reduce body
iron stores.
A preexisting condition of oxidative stress may be required for the manifestation
of the adverse effects linked to higher iron stores. American blacks are three times
more likely to have high body iron stores, (30% versus 10%),885 and iron may be
one of the greatest contributors to free radical injury in the body.885,886 A
condition of oxidative stress is more likely to exist in individuals of low SES.
Thus, blacks who have a high oxidative potential due to increased body iron
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stores, are at increased risk for CAD due to a greater prevalence of tobacco use,
diabetes or other hyperglycemic conditions, and environmental stress, and are less
likely to consume sufficient quantities of dietary anti-oxidants.
Dietary Selenium Intake and CAD.
Selenium, an essential nutritional trace element, is a structural component of,
and a cofactor for the antioxidant enzyme glutathione peroxidase, and has been
widely studied for its effects on cardiovascular disease. Selenium is a natural
antioxidant which preserves the elasticity of tissue by delaying oxidation of
polyunsaturated fatty acids, and is necessary for the production of prostaglandins,
a deficiency of which may result in increased platelet aggregation, and increased
cardiovascular risk.844 Dietary sources of selenium include whole grains, brazil
nuts, brewer's yeast, dairy products, fish, shellfish, poultry, egg yolk, cereals,
mushrooms and onions,668,844,845,846 however absolute selenium content of plants is
dependent upon local soil selenium levels. Sulfur compounds contained in widely
used fertilizers inhibit plant absorption of selenium. 844 Selenium content of foods
is easily reduced by heat, processing, and cooking. Refining of grains reduces
their selenium content by 50 to 75%; boiling by 45%.844 Inorganic forms of
selenium are toxic and carcinogenic at very high intakes in animals. 490 Chelated
selenium, which has been organically bound to yeast, is safer, however the
therapeutic window is rather narrow.
A growing number of nutrition scientists have been reluctantly persuaded that
higher intakes of selenium may have positive health benefits by reducing the risk
of degenerative disease such as cancer and CAD.488 ,490,672 On the basis of lower
blood selenium levels among U.S. cancer patients, and based upon animal studies
showing a reduction in experimental tumorigenesis, it has been postulated that
selenium might be a protective factor against cancer.488,490
Clinical and Epidemiologic Studies
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Although little difference was noted in early epidemiological analyses of the
incidence of cancer between population groups living in countries with high
versus low selenium intake,673 an epidemiologic study reported in 1976 in the
Archives of Environmental Health demonstrated a significant relationship between
cancer incidence in males and soil distribution of selenium in the United States,
and recently it has been demonstrated that selenium supplementation did reduce
the risk of cancer when given to selenium-deficient populations.269,668
Additionally, three prospective studies reported an inverse association between
serum selenium levels and the subsequent incidence of cancer.490,683
Selenium has been negatively associated with the incidence of CAD and risk of
cardiovascular death in a number of clinical and epidemiological studies. The
soils of Finland and New Zealand are selenium depleted.488,490 These populations
have about half the selenium intake of those in the United States, and have
significantly higher risk of coronary death.488 Finland is first, and New Zealand is
fourth among 30 nations in incidence of, and death from CAD.61
Endemic selenium deficiency in Keshan provence, China, is associated with
serious cardiomyopathies.490
The first study of selenium levels and CAD mortality was published by Salonen
in 1982 and demonstrated that the risk of cardiovascular death in individuals with
low serum selenium levels (<45μg/L) was more than twice as great as the CAD
death rate for those with higher selenium levels. Over the past decade, numerous
other studies have indicated that lower selenium levels may be associated with an
increased risk of CAD. A study published in 1985 by Salonen and associates585
demonstrated an association between low serum selenium levels and the increased
risk of death from coronary artery disease. Kok and co-workers,584 [see Fig. 29] in
a 9-year follow-up study in the Netherlands, measured toenail selenium levels,
(which tend to reflect selenium intake status over years), and found a significant
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reduction in selenium levels (p<0.05) in subjects suffering from myocardial
infarctions compared with controls.
The state of Ohio, which has one of the lowest national soil selenium levels, has
an 11.4 % higher death rate from ischemic heart disease as a percentage of total
deaths than the national average.217
Figure 29: Serum Selenium Levels in CAD Patients Versus Control Subjects.
_______________________________________________________________________________
Adapted From: Kok FJ, De Bruijn AM, et al. Serum selenium, vitamin antioxidants, and cardiovascilar mortality:
a 9-year follow-up study in the Netherlands. Am J Clin Nutr 1987;45:462-468
Experimental observations have suggested that selenium intake must be below a
critical threshold before cardiovascular risk is increased, and that the therapeutic
window is narrow. Excessive intake produces severe toxicity, promotes diarrhea,
hair and nail loss, and may be carcinogenic.668 Selenium is supplied by food
sources which may be less frequently consumed by the indigent. Because
excessively cooked, refined and over-processed foods, (which are more common
to the poor), have reduced selenium content, these factors may combine to
increase oxidative risk among members of lower SES.
Antioxidant Vitamins and Coronary Artery Disease: Epidemiology.
With-in population studies have shown an inverse relationship between vitamin
consumption and cardiovascular mortality.469 In the Unites States, industrial
vitamin C production (indicative of population consumption, following adjustment
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for exports) is inversely related to CAD mortality over the past 20 years. 645 In the
United Kingdom, regional mortality rates in the early 1970s were inversely related
to calculated vitamin C intake, and reflected long-established regional gradients in
lifestyle and social circumstance.650 In a retrospective epidemiological study
begun at UCLA in 1971, Enstrom et al646 examined the long term effects of
vitamin C intake on the health of 11,348 adults, and found a one-year increase in
life expectancy for women and a six-year increase for men consuming an average
of 500mg of vitamin C supplements per day.
Because of the free radical quenching protective effects of alpha-tocopherol,
beta carotene, and ascorbic acid, some nutrition scientists recommend prophylactic
supplementation for individuals at high risk for free radical attack due to
exogenous (environmental), or endogenous (due to disease or stress) free
radicals.491 This recommendation is particularly relevant to the indigent, who are
more likely to be exposed to increased environmental stresses in the modern urban
environment of the inner city.
Laboratory and Clinical Studies of Vitamins E:
Vitamin E, (or alpha tocopherol, which is the predominant form of the vitamin in
animal tissues), is a fat-soluble vitamin which is widely accepted to be the primary
physiological antioxidant in man.472,488,844,845,846 Vitamin E reduces cardiac oxygen
demand, promotes vasodilation, reduces blood pressure (through diuresis and
vasodilation), and acts as a highly effective antithrombin by inhibiting coagulation
of blood and reducing platelet aggregability.844,845,846 Chronic deficiency of
vitamin E causes atherosclerotic lesions in primates and laboratory animals. 67
Vitamin E is synergistic with selenium and improves its absorption, but is an iron
antagonist and may reduce iron absorption if taken concomitantly with inorganic
iron supplements. Tocopherols occur in highest concentrations in cold pressed
vegetable oils, soybeans, and whole raw seeds and nuts.844,845,846
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Vitamin E prevents the oxidative destruction of saturated fatty acids and vitamin
A. Polyunsaturated fatty acids (PUFA) are readily absorbed by the tissues and are
heavily incorporated into external cellular membranes which are susceptible to
free radical attack.281,970 Diets high in PUFA have been reported to predispose to
chemically induced carcinogenesis, and several studies on the role of dietary fat in
heart disease have suggested that the reduction in serum cholesterol associated
with increased PUFA intake has been accompanied by an increase in the incidence
of cancer.490,677 Dietary PUFA (except linolenic acid, a precursor of EPA) have
been associated with increased platelet aggregation.859,970 It is important that
increases in dietary PUFA, which is a common recommendation for cardiovascular
patients, be accompanied by an increase in vitamin E intake, since diets rich in
PUFA increase the rate of oxidation and subsequent depletion of vitamin E, and
because vitamin E can reduce platelet aggregation. Animals fed diets rich in
PUFA show increased urinary excretion of Malondialdehyde (MDA), indicating
increased free radical activity.680 The primary source of PUFA, vegetable oils, are
a rich source of vitamin E (if they have not been heated or highly processed),
however laboratory studies demonstrate that high levels of vitamin E (300 IU-- an
amount which could only be achieved by dietary supplementation), were required
to effectively neutralize free radical activity associated with increased feeding of
PUFA. Amounts supplied by dietary sources (30 IU) were significantly less
effective.490,680 Validating this finding, an inverse relationship between serum
vitamin E levels and cancer has been found in seven epidemiologic
studies,580,669,670,679,685,686,687 and vitamin E supplementation has been shown to
suppress indexes of lipid peroxidation in the blood of both smokers and nonsmokers, without effecting plasma lipoprotein concentrations. 899 Because low
density lipoprotein is one of the main transports for vitamin E and cholesterol in
the blood stream, pharmacologic and certain dietary interventions resulting in
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reductions in LDL and serum cholesterol may reduce serum vitamin E in
individuals whose diets are not supplemented.488,490 Hypolipidemic drug therapy
may act as a vitamin E antagonist and reduce serum vitamin E.844
Free radical science suggests that more is not always better concerning
antioxidants. There are optimal tissue concentrations of vitamin E, and excessive
doses may not only confer no additional protection, but may result in a prooxidant situation. Extremely elevated intakes of tocopherol in laboratory animals
have actually increased free radical tissue damage in in vitro studies. However,
nature has built in a regulatory system to prevent abnormally high tissue levels of
vitamin E, since tocopherol is a poorly absorbed lipid with 50% or more passing
through the gastrointestinal system in the excreta. A ten-fold increase in intake is
required to double tissue concentrations in man.488
Clinical and Epidemiologic Studies
In two large clinical studies conducted by Stampfer et al470 and Rimm et al,471
vitamin E supplements were associated with a reduced risk of congestive heart
failure. In an analysis of almost 45,000 men in the Health Professional Follow-up
Study database by Ascherio and associates,823 the use of vitamin E, or multivitamin supplements, was associated with a significantly decreased risk of
myocardial infarction. These results suggest that higher supplemental doses of
vitamin E may be beneficial in patients with CAD, especially those on diets high
in polyunsaturated fatty acids.
The Nurses' Health Study, [see Fig. 30], a study of 121,700 women between the
ages of 34 and 59 which was conducted by Manson and co-workers,69,805 used
food frequency questionnaires to demonstrate a relationship between dietary
intakes of foods rich in vitamin E and beta carotene, and the reduction in the risk
of cardiovascular disease.
Figure 30: Dietary Vitamin E Consumption and CAD in Men and Women
Page 159
___________________________________________________________________________________________________________
From: Rimm et al,471 and Stampfer et al.470
A recent analysis of the same data by Stampfer et al470 revealed that the protective
effect of vitamin E was attributable to supplemental vitamin E at pharmacological
levels exceeding 100 IU per day. Since dietary intakes of alpha tocopherol in the
United States typically range from 4 to 16 IU per day, the former level of intake
would be extremely difficult to achieve from diet alone.804 Those women who took
100 mg. vitamin E supplements (in addition to 15mg of beta carotene daily)
experienced a 36% reduction in myocardial infarction, and women with the
highest dietary vitamin E intake, and who consumed vitamin E supplements daily
for two years, had a 41% reduction in risk (multivariant risk 0.59).
The Health Professionals Follow-up Study,471 involving 51,529 male health
professionals, demonstrated similar cardiovascular benefits of a diet rich in
antioxidants. As in the Nurses' Health Study, these male participants' antioxidant
vitamin intake was assessed by a dietary questionnaire, and coronary heart disease
was assessed by medical record review. After controlling for age and coronary
risk factors, higher dietary vitamin E intake levels were associated with a
significantly lower risk for CAD. For men consuming more than 60 IU (an
amount usually requiring vitamin supplementation), the risk of myocardial
infarction or cardiac death was 36% less (multivariant risk 0.64) than in those men
consuming 7.5 I.U. per day. CAD risk was lowest for the men with the highest
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dietary vitamin E intake who additionally took at least 100 IU of vitamin E
supplements daily for two years.
Low serum Vitamin E may be a greater risk factor for myocardial infarction than
either high blood pressure or elevated serum cholesterol alone, according to
research sponsored by the World Health Organization, and reported by Gey et al67
in the Multinational Monitoring Project of Trends and Determinants of
Cardiovascular Disease (MONICA) study, [See Fig. 31]. In the MONICA study,
Gey and co-workers67 compared plasma antioxidant levels among 16 different
groups of 100 men each from regions with a six-fold difference in CAD mortality
and reported a strong inverse correlation (p=0.002) between plasma vitamin E and
mortality from ischemic heart disease which was independent of lipid levels.
Figure 31: Inverse Correlation Between Plasma Vitamin E and Mortality
From CAD in Cross-Cultural Epidemiology: The MONICA Study.
______________________________________________________________________________________________________
From: Gey et al,67
This inverse relationship for CAD mortality was strongest for vitamin E. Low
serum vitamin E alone was an accurate predictor for fatal myocardial infarction in
60% of cases studied. Death from Acute Myocardial Infarction was accurately
predicted in 80% of patients with both low serum vitamin E and elevated serum
cholesterol; and fatal outcomes were accurately predicted in 90% of patients with
low serum levels of both vitamin E and A in conjunction with high serum
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cholesterol, and elevated blood pressure. These findings were consistent with
earlier scholarship published by Gey.580
Cavarocchi and associates681 found that pretreatment of coronary bypass
patients with 2,000 IU of vitamin E significantly inhibited the generation of
destructive oxygen free radicals during surgery, and DeMaio and co-workers583
found that vitamin E supplementation reduced the incidence of restenosis in
patients undergoing percutaneous transluminal coronary angioplasty (PTCA).
Rimersma and co-workers469 found an inverse relationship between the risk of
angina pectoris and vitamin E levels. Individuals with serum vitamin E levels in
the lowest quintile (<18.9 μM/L) had almost a threefold greater risk of angina than
did individuals in the highest quintile (>28.2 μM/L), [See Fig. 32].
Figure 32: Risk of Angina Pectoris and Plasma Concentrations of Vitamin E
___________________________________________________________________________________________________________
From: Riemersma et al.469
Similarly, Byers870 reported that an increased dietary intake of vitamin E reduced
death from myocardial infarction.
A prospective study of antioxidant vitamins and the incidence of CAD in
women, which was conducted by Manson et al,805 used food frequency
questionnaires to estimate dietary intake of vitamin E, and found that the
incidence of CAD was lowest among women with the highest intake of alpha
tocopherol.
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Laboratory and Clinical Studies of Vitamin C:
Vitamin C, or ascorbic acid, is an essential water-soluble antioxidant vitamin
and reducing agent which neutralizes various oxygen free radicals, detoxifies
carcinogenic organic radicals, converts nitroso compounds into less carcinogenic
products, and prevents nitrosamine formation in the intestinal tract. 490 Vitamin C
is the least stable of vitamins, and rapidly looses potency through exposure to
light, heat, and air, which stimulate the activity of oxidative enzymes. Stress
increases the body's need for Vitamin C, which is used up more rapidly under the
increased oxidative conditions of stress. Vitamin C enhances the intestinal
absorption of iron by reducing ferric iron to the more easily absorbed ferrous form,
enhances the absorption of magnesium and calcium, and prevents the oxidation of
vitamin E.844,845,846 Good sources of this vitamin include most fresh fruits and
vegetables.844,845,846
The current RDA for vitamin C, 60mg for adults, is an amount easily met by
most American diets, however numerous researchers recommend significant
increases in the RDA.489,491,673,674,804 At very high intakes, vitamin C has been
reported to reduce spontaneous tumors in mice, increase anti-inflammatory and
antimicrobial activity, enhance immunity, and prolong the survival of cancer
patients relative to historical controls.490,673,675,676 High concentrations in vitro of
ascorbate can inhibit LDL oxidation, and reduce uptake of oxidized LDL by
macrophages. Furthermore, ascorbate has been shown to be as potent an
antioxidant as probucol, while also protecting endogenous LDL antioxidants alpha
tocopherol and beta carotene by serving as a sacrificial antioxidant. 804 The in vivo
effects of ascorbate in the prevention of LDL oxidation have not been fully
delineated.
Calculated ascorbic acid intake from fresh green vegetables was inversely
correlated with standardized mortality from CAD and cerebrovascular
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accident,105,650,667 and low plasma levels of vitamin C have been associated with
high incidence of cancer, as well as deaths due to non-malignant causes.669,670,671
Earlier concern by some scientists over proposed adverse effects of large doses of
vitamin C, (dependency, renal calculi, and destruction of vitamin B 12 ), have been
allayed by subsequent research.490 Free radical scientists have known that
although ascorbic acid typically acts as an antioxidant in model systems, under
some conditions it can act as a pro-oxidant.488 Vitamin C can increase absorption
of dietary iron (particularly iron supplied by red meat and in the more reactive
form of heme iron) which acts as a catalyst in free radical formation. Extremely
high doses of vitamin C in patients with high positive heme iron balances may
further increase tissue iron stores, and increase the potential for free radical tissue
damage.488,668
Clinical and Epidemiologic Studies
Vitamin C did not demonstrate a significant protective effect against the risk of
developing CAD in women in the Nurses' Health Study,69,470 and was found to be
less protective than vitamin E or beta carotene, however other epidemiologic
evidence does suggest protective cardiovascular benefits for vitamin C. 580,581,804
The Health Professionals Follow-up Study471 revealed a cardiovascular protective
role for vitamin C in male smokers, however the benefit of vitamin C
supplementation among non-smoking men was not statistically significant.
Ramirez and Flowers659 found that men with angiographically-evident coronary
atherosclerosis and regional wall kinetic abnormalities had lower serum vitamin C
levels (leucocyte ascorbic acid levels) than those with normal angiograms,
irrespective of smoking status. Rimersma and associates469 evaluated the
protective effect of vitamin C in the reduction of the risk of angina pectoris.
Although not as strong as the protective relationship for vitamin E, vitamin C did
demonstrate benefit. In this study, the quintile with the highest vitamin C levels
Page 164
(>57.4 μM/L) had an 80% lower risk for angina when compared to subjects with
the lowest dietary vitamin C intakes (<13.1 μM/L), [See Fig. 33].
Figure 33: Risk Of Angina Pectoris and Plasma Concentrations of Vitamin C
___________________________________________________________________________________________________________
From: Rimersma et al,469
Smokers were found to have lower vitamin C levels than non-smokers, but the
inverse relationship between vitamin C levels and angina pectoris persisted even
after controlling for smoking and other risk factors.
The Basel Study489,580,663 used two investigatory techniques, including a crosscultural investigation of blood plasma vitamin C levels in subjects from areas of
high, medium, and low CAD, and a prospective study of disease incidence in a
cohort of men living in Basel, Switzerland whose blood plasma ascorbate levels
had been established upon previous examination. The results showed a close
negative correlation between plasma vitamin C levels and the incidence of CAD;
very high levels of ascorbic acid were recorded in areas of low mortality, whereas
the levels were consistently lower in areas of medium and high disease
incidence.489
Additional epidemiological studies have also suggested that low plasma vitamin
C levels are associated with increased CAD risk. In a study conducted among
elderly Chinese-Americans, Choi and associates806 showed that plasma ascorbic
acid levels were positively associated with high density lipoprotein cholesterol
levels, and inversely related to both blood pressure and the prevalence of
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hypertension. Three years later, Morgan and co-workers807 were able to replicate
these results in a different population study. In a cross-cultural epidemiological
study conducted in Europe, Gey et al67 observed an inverse correlation between
plasma vitamin C and heart disease mortality.
Data collected during the San Antonio Heart Study42 demonstrated that intake of
vitamin C was most effected by SES, with the poor consuming significantly less of
the vitamin than those of higher SES.
Laboratory and Clinical Studies of Beta Carotene:
Beta carotene is a retinoid plant pigment and anti oxidant vitamin which is a
precursor to retinol or vitamin A, but is essentially innocuous because of its
limited absorption and conversion to vitamin A (which has greater toxicity and
potential for hypervitaminosis than beta carotene). Vegetables and fruits with
dark green, yellow, or orange pigments are excellent sources of beta carotene, and
these include the dark-green leafy vegetables, kale, turnip greens, spinach, swiss
chard, collard greens, mustard greens, beet greens, broccoli, brussels sprouts, red
pepper, okra, endive, carrots, cantaloupe, pumpkins, squash, and sweet potatoes.
Beta carotene constitutes only 25% of total blood carotenoids. Alpha carotene,
lycopene, cryptoxanthin, zeaxanthin, and leutin, which constitute the remaining
75%, may also have important anti-oxidant properties [see Fig. 35].468,488 Most of
these non-beta carotenoids are found in many of the same foods as beta carotene,
however alpha carotene is found primarily in orange vegetables, and leutin and
zeaxanthin are found predominantly in green vegetables. Lycopene rarely occurs
in the same foods as beta carotene, and is supplied by tomatoes, pink grapefruit,
and watermelon. The few clinical studies showing lack of benefit from beta
carotene supplementation in chronic degenerative disease may be due to the
inadvertent exclusion of these other important carotenoids when single-entity
carotene supplements were used versus whole foods. Subsequently, dietary
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sources supplying the full spectrum of carotenoids may be preferable to single
carotenoid supplementation.
Normal individuals vary markedly in the plasma response to a standard oral dose
of pure beta carotene, or to its dietary equivalent in cooked carrots, with some
subjects showing little increase, and others a marked response. 682 Extremely high
doses of beta carotene can turn the skin yellow because man, unlike most
laboratory species, is one of the least selective animals and absorbs all dietary
carotenoids.488 There is some evidence that high doses may potentiate liver
damage from excessive alcohol consumption.668
Beta carotene is able to quench singlet oxygen, and is associated with
purportedly protective foods.490 Beta carotene prevents lipid peroxidation in vivo
in an animal model,488 however it has been characterized as an "unusual"
antioxidant because it functions as a free radical scavenger only at low oxygen
pressure, and at atmospheric pressure, it may act as a pro-oxidant.684
Clinical and Epidemiologic Studies.
There is epidemiologic evidence for a linkage between reduced CAD and cancer
incidence and consumption of foods rich in beta carotene.490,678 Menkes and coworkers670 found a significant inverse association between serum retinol levels
and the subsequent incidence of lung cancer.
In the Nurses' Health Study, Manson et al69 and Stampfer et al470 showed that
women who consumed more than 15 milligrams of dietary beta carotene daily
reduced their risk of stroke by 40% and their risk of heart attack by 22%.
In an earlier analysis of the Nurses Health Study database, Manson et al805
found that the incidence of heart disease was lowest among women with the
highest dietary beta carotene intake.
The Health Professionals' Follow-up Study, conducted by Rimm et al,471
evaluated the effects of daily beta carotene intake on age-adjusted relative risk of
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CAD in men. Patients with the highest beta carotene intake (>19,034 IU/day) had
a 29% lower risk of coronary artery disease (multivariate relative risk of 0.71, p
value for trend=0.02) than patients with the lowest intake (<3,969 IU/day), [See
Fig. 34].
Figure 34: Beta Carotene Consumption and the Risk of CAD in Men
___________________________________________________________________________________________________________
From: Rimm et al,471
Other epidemiological studies have suggested an inverse relationship between
beta carotene intake and risk of CAD, and acute myocardial infarction. In a
preliminary analysis of the extensive US Physicians' Health Study, Gaziano et
al588 showed that beta carotene supplementation was associated with a statistically
significant 44% reduction in major cardiovascular events, (including myocardial
infarction, stroke, and death from cardiovascular disease), among a subgroup of
physicians with chronic stable angina who had been taking 50mg of beta carotene
(83,300 IU, or the equivalent of consuming ten carrots) on alternate days.
A subsequent study by Gaziano and co-workers,808,894 of 1,299 elderly
Massachusetts residents, demonstrated that those individuals who were in the
highest quartile for dietary beta carotene intake had the lowest risk of myocardial
infarction and fatal cardiovascular disease. The age and sex adjusted relative risk
for fatal cardiovascular disease during five years of follow-up was 0.54 (95% CI;
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0.34-0.87), and relative risk of fatal myocardial infarction was 0.25 (95% CI; 0.090.67). Adjustment for smoking and alcohol consumption did not significantly
change these results.
Antioxidants and Effect upon Serum Lipids
Although vitamin E has been shown to prevent the oxidative modification of
LDL in vitro, in three clinical studies of vitamin supplementation471,597,598,599 no
significant alteration of serum lipid ratios in vivo was detected. Rimersma and coworkers469 found that vitamin E did not alter LDL or HDL levels, possibly
indicating that vitamin E's cardiovascular benefit is related to its antioxidant and
anti-platelet effects. Increased serum levels of vitamin C, however, have been
associated with beneficial blood lipid effects including increased HDL and
decreased LDL subfractions.68,651
Free Radical Theory
In the late 1950s, Denham Harman first formulated the free radical theory of
disease and tissue damage, and recommended the use of antioxidant vitamins to
reduce this damage. Subsequently, free radicals have been implicated in over one
hundred human degenerative diseases.871
All cells in the body use oxygen to break down nutrients and to generate energy
within the mitochondria of the cells. During the process of breathing, oxygen is
inhaled into the lungs and is bound to carrier molecules of hemoglobin and
transported by the blood to all other body tissues. Stable oxygen atoms contain a
nucleus and eight pairs of electrons which orbit about that nucleus. Oxygen
usually arrives at the tissue sites in this stable form, but occasionally it looses an
electron in transit and arrives in the form of an unstable oxygen free radical. All
free radicals exist for an infinitesimally brief moment in the form of atoms or
molecules possessing one or more unpaired electrons. Typically an electron (or
multiple electrons) is missing from one or more of the outermost (and most
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vulnerable) atomic orbits of a free radical. The resulting electrical imbalance
causes a free radical to be highly reactive and unstable, as it immediately seeks to
abduct nearby electrons to resolve its own internal imbalance.281,869 This process is
accomplished within nanoseconds, and the theft of an electron from a neighboring
fat or protein molecule often results in a chain reaction in which one molecule
after another in a cell steals an electron from its neighbor. In the process, proteins
are denatured, and fats are peroxidized, permanently damaging them and changing
their character and structure. Because of their highly vulnerable outer electron
orbitals, cellular proteins and lipids are the primary free radical targets.
Phospholipids comprise the outer cellular membrane, and the semi-rigid fibrils of
the cytoskeleton and nuclear matrix are composed primarily of proteins. These
proteins and lipids can be irreparably damaged by oxidative free radical attack,
leading to degenerative disease of body organ systems. Living cells attempt to
repair damaged components, but cumulative damage occurs over decades, and this
cumulative damage is thought to be responsible for the process of aging. The
"cumulative damage theory" was tested in 1993 when researchers from Southern
Methodist University in Dallas demonstrated that fruit flies which were genetically
engineered to resist free radical damage lived 30% longer. This is the first direct
evidence that free radical damage does cause aging. Indirect evidence, however,
has been available for decades.
The superoxide free radical is an unstable form of oxygen with a powerful
electron hunger. Living cells produce a protective enzyme, superoxide dismutase
(SOD), in response to the presence of the superoxide free radical. SOD is capable
of quenching and neutralizing superoxide. Research has shown that the longevity
of an organism is directly proportional to the amount of SOD that it contains.
Studies have also shown that lifespan is inversely proportional to metabolic rate.
Animals with the highest lifespan have the highest levels of SOD when expressed
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as a function of their metabolic rate. This may explain why fruit flies, which
produce very little SOD in relation to their size and metabolic rate, have a life span
which is measured in days, and why long-term caloric restriction, which reduces
the metabolic rate, has been shown to extend lifespan in certain species. The
bacterium radiodurans contains the highest level of SOD, and the greatest
concentration of the antioxidant enzymes peroxidase and catalase of all living
creatures, enabling it to resist the damaging effects of radiation, and to thrive
within nuclear reactors.
The hydroxy radical, a "fearsomely reactive radical,"869 attacks whatever atoms
or molecules are nearby, leaving behind a legacy in the form of self-propagating
free-radical chain reactions which result in the damage and destruction of living
tissues. If hydroxy radicals are generated in close proximity to membranes or
lipoproteins, lipid peroxidation occurs, which is implicated in the development of
atherosclerosis. If these radicals are generated in proximity to DNA, they can
attack the purine and pyrimidine bases and cause potentially carcinogenic
mutations.869 A significantly less reactive radical is the oxygen free radical,
superoxide, which is created by the addition of one electron to the oxygen
molecule during molecular accidents during which molecules within living tissue
react directly with free oxygen. An example of this is the oxidation of
catecholamines which occurs subsequent to stress reactions. Consequently,
superoxide can react with free iron and copper ions to form the more damaging
hydroxy radical.869 Free iron and copper ions are both contained in heme iron
(supplied primarily by red meat) and are more readily available, and therefore
potentially more reactive than is elemental iron contained in non-heme iron
derived from plant sources. Stress, therefore, may generate catecholamines which
react with oxygen to form the superoxide radical which, in the presence of high
iron stores from animal sources, can react to form the most atherogenic form of
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free radicals, the hydroxy radical. This series of events may explain the increased
atherogenic risk associated with stress, and the interaction of stress and diet,
especially among individuals consuming the substantial quantities of red meat and
the more limited quantities of antioxidant nutrients typically found in the
traditional Western diet.
All free radicals are produced by metabolic processes occurring within the body
or through interaction with the environment, [See Table 11].281,486
Table 11: The Sources of Free Radicals Within the Body
1.
2.
Natural cellular energy processes.
The immune system (monocytes, including neutrophils and macrophages generate
free radicals to destroy invading bacteria and viruses), and inflammatory response.
3. Environmental pollution, and various toxins.
4. Alcohol, (the double free radical acetaldehyde is a metabolic end-product).
5. Tobacco smoke.
6. All forms of electromagnetic radiation (including sunlight, radon, cosmic
radiation).
7. Stress.
8. Catecholamines (react with oxygen to form the superoxide free radical).
9. Side effects of certain drugs, (i.e. adriamycin).
10. The process of respiration (1 to 3% of the oxygen we breathe is used to make the
free radical superoxide.
_____________________________________________________________________________________
Adapted from: Sharma281 and Halliwell869
Free Radicals and the "Western Diseases"
Subsequent research has confirmed the role of free radicals in the etiology of
both CAD and cancer, which are the principal Western nation killer
diseases.67,486,489,491,580,662,663 The diseases associated with free radicals are
degenerative in nature and include cancer, CAD, senile cataracts, atherosclerosis,
adult-onset diabetes, rheumatoid arthritis, ulcerative colitis, Crohn's disease,
ischemic stroke, Reynaud's disease, Behcet's disease, ulcers, and
emphysema.281,486,491 By one estimate, more than 85% of all chronic and
degenerative diseases are the result of oxidative damage.666
During ischemic re-perfusion, oxygen free radicals are produced which may lead
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to further tissue damage and re-perfusion injury,652,655,656,657 the development of
arrhythmias,653 and the depression of myocardial contractility.654 Grech and coworkers656 postulated that activated neutrophils may be the source of re-perfusion
associated free radical generation during the progressive neutrophil leucocyte
infiltration of damaged myocardium.
It is necessary that free radicals be contained to prevent wide-spread tissue
damage. Containment clearly depends upon sophisticated systems that involve
vitamins E and C, and trace elements selenium, manganese, copper and zinc, and
probably involves both beta carotene and vitamin A.489
Antioxidants and Prevention of Oxidative Modification of LDL
Antioxidant molecules are stable electron donors which are able to neutralize
reactive and unstable free radicals by fulfilling the free radical's electron hunger,
yet without becoming a reactive free radical themselves. Antioxidant molecules
are complex, and possess such large numbers of electron orbitals that the loss of a
single electron, while temporarily resulting in the formation of a free radical, does
not result in a reactive molecule. When vitamin E, (found within membranes and
lipoproteins), blocks the chain reaction of lipid peroxidation by scavenging the
intermediate peroxy radical, the resulting tocopherol radical is predominantly nonreactive, and is easily converted back into alpha tocopherol by vitamin C. 869
Vitamins E, C, and A, beta carotene, and the flavonoid compounds are all potent
antioxidants,281,471,562,563,564,571,572,830,831,832,833,869 and are supplied in the human diet
primarily by plant sources. Dietary antioxidants are easily destroyed during
cooking, food processing and storage,487,658 and individuals who consume
significant quantities of heavily refined and processed foods may have
significantly lower intakes of antioxidants. Recent clinical studies provide
persuasive evidence that poor plasma status of these antioxidant nutrients does
occur in Westernized nations, and that this deficiency is associated with an
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increased risk of CAD and cancer.67,489,580,663 Numerous epidemiological casecontrol studies have shown a strong inverse correlation between CAD and stroke
mortality and the consumption of fresh green vegetables, (from which antioxidant
vitamin intake could retrospectively be calculated).105,489,554,650,667 The incidence
of, and mortality from cancer has also been found to be negatively associated with
plasma antioxidants, including vitamins A and C, and beta carotene in studies
conducted in Hawaii,669 Washington,670 and Boston.671
Antioxidant levels may effect longevity in the human. Epidemiologic evidence
suggests that vitamin C may increase human life-span,646 and animal studies have
shown that vitamin E intake is proportional to longevity in mammals. 647
Antioxidants inhibit the oxidative modification of LDL, and may significantly
reduce the risk of CAD according to several epidemiological and clinical
studies.67,69,469,470,471,580,581,582,588 The susceptibility of LDL to oxidation has been
correlated with the severity of atherosclerosis,621 and this susceptibility is
dependent on tissue and serum antioxidant status.830 The resistance of LDL to
oxidation is directly proportional to the level of antioxidants such as beta carotene
and lipid soluble vitamin E contained within the LDL
particle,281,468,470,488,571,572,573,574,810,830,831,832,833,869 and vitamin C has been shown to
stabilize and protect these endogenous antioxidants contained within the LDL
particle, [See Fig. 35].592,869
Figure 35: Antioxidant Levels within Serum LDL
and the Onset and Degree of Lipid Peroxidation
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___________________________________________________________________________________________________________
From: Esterbauer et al,468
Vitamin E may possess greater inhibitory effect on LDL oxidation than either
beta carotene or vitamin C.595,624 Oxidized LDL is chemotactic for circulating
monocytes,281,578,891 and may be selectively taken up by the monocytes or
macrophages, processed by the scavenger receptor mechanism, and incorporated
into the cholesterol esters that become fatty streaks and plaque in the arterial wall,
(forming pathologically-modified, relatively immobile monocytes, or "foam cells")
initiating the atherosclerotic process.281,471,573,574,809,891 Oxidized LDL may also
contribute to atherogenicity by the reduction of macrophage motility in the arterial
intima,577 increasing sub-intimal monocyte accumulation,578 and by increasing
cytotoxicity in vascular smooth muscle and endothelial cells. 579 Oxidized LDL
may exacerbate existing coronary lesions by increasing vasoconstriction in the
arteries.620 Interestingly, the scavenger receptors on activated monocytes are
insensitive to unaltered LDL, suggesting that only the oxidatively modified
LDLOX and not LDL itself is inherently atherogenic.891 Apparently, increased
HDL levels may reduce atherogenic risk by reducing the potential for LDL
oxidation, or by removal and disposal of the oxidized portions of the LDL
particles prior to their incorporation in the arterial wall as atheromatous streaks. 891
Dietary Fats and LDLOX
Certain dietary fats are more resistant to oxidative modification. Oleic Acid, an
omega-9 C18:1 monounsaturated fatty acid supplied primarily by olive oil, is one of
the most resistant fatty acids, and is more resistant to oxidation than is linoleic
acid.891 Because dietary fat intake determines the type of fat which is incorporated
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into the phospholipids and triglycerides contained in the LDL particle, dietary fat
consumption can directly effect the potential for LDL oxidation. This may explain
the protective effect associated with the olive oil-rich Mediterranean diet.
Vitamins and LDLOX
Sufficient quantities of water-soluble antioxidants (such as vitamin C) are
required in the hydrophilic environment of intracellular spaces, 593 and sufficient
lipid-soluble antioxidants (such as vitamin E, or carotene) are required in the
blood, within the LDL particle,832,833 and in the sub-endothelial space, (a
hydrophobic environment in which much of the oxidation of LDL particles occurs,
and which favors the protective effect of the fat-soluble antioxidant vitamins over
water-soluble vitamins) to neutralize free radical oxidative attack on arterial
intima and on LDL subfractions which results in atherogenesis. 537,594 Indeed,
intracellular antioxidant levels may be more important than serum levels in the
inhibition of cell-mediated oxidation of LDL.471,586 Lipid soluble antioxidants are
transported within the LDL molecules in the serum, preventing or reducing the
process of toxic lipid peroxidation of these molecules by free radicals, 483,832
reducing the formation of vessel wall irritants which can damage arterial intima,
and preventing the suppression of the synthesis of prostacyclin (PGI 2), a natural
antioxidant hormonal compound which helps to prevent the formation of abnormal
blood clots.392 In addition, data suggests that the flavonoid antioxidants and other
plant phenolic compounds can inhibit lipid peroxidation in vitro, 869 and inhibit
cyclo-oxygenases, which may reduce the risk of acute myocardial infarction by
reducing the potential for thrombosis.568
Laboratory and Clinical Studies of Folate and the B Vitamins.
Folic acid (Folate, or Folacin) is part of the water-soluble vitamin B-complex and
functions as a coenzyme, together with vitamins B12 and C, in the metabolism of
proteins. One of the primary roles of folic acid is the formation of heme, the iron-
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containing protein found in hemoglobin which is necessary for the formation of
red blood cells. Folic acid is produced primarily by plants, and is supplied in the
diet by whole grain cereals and breads, fresh green leafy vegetables, fruits,
oranges, cantaloupe, beans, broccoli, spinach, cabbage, cauliflower, peas, sweet
potatoes, beets, greens, sprouts, and yeast.844,845 Processing and refining destroy
folate. Folate levels are 50% higher respectively in whole grain breads than in
white bread.253 Folic acid is also destroyed by exposure to heat, light, air, and
during storage.844,845 There is some evidence which suggests that folic acid may
be beneficial in the treatment of atherosclerosis,472,844 and reduced levels of folate
have been associated with an increased risk for early-onset CAD.925 Excessive
alcohol consumption increases the need for folic acid either through malabsorption
of the vitamin, or by inadequate diet (which is common among alcoholics).
Vitamin B6
Vitamin B6 is an essential, water-soluble vitamin which plays a crucial role in
both cardiovascular and immune function. It assists in the normal function of
linoleic acid, in the release of glycogen for energy, and helps maintain the balance
between sodium and potassium.844,845 Leafy green vegetables, whole grain cereals,
potatoes, legumes, fruits, spinach, lentils, and soybeans are some of the primary
sources of vitamin B6 in the human diet.844,845,846 Processing, refining, and light
destroy vitamin B6. Vitamin B6 levels are 400% higher in whole grain breads than
in white bread.253
In numerous clinical studies, Vitamin B6 status has been shown to be negatively
correlated with aging in humans,921 and a deficiency status has been shown to
increase plasma levels of homocysteine,622,925 a marker for increased risk of CAD,
stroke, and vascular disease.622,923,924,925,926,927,928 Clinical research suggests that
the bioavailability of piroxidine supplementation does not change with age, and
that the risks associated with vitamin B6 deficiency may be reduced by
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supplementation with pyridoxine.622,920,921 Because of dietary inadequacies,
vitamin B6 deficiency is more prevalent among members of lower Socioeconomic
status.
Vitamin B12
Vitamin B12 (or cobalamin) is a water soluble essential vitamin which is unique
in that it is the only naturally occurring organic compound containing cobalt as
part of its structure, and is the most structurally complex of the vitamins. Vitamin
B12 cannot be synthesized by the human body, and animal protein is essentially the
only substantial natural source of the vitamin in the diet.844 Because vitamin B12 is
supplied by animal sources including eggs, dairy products, poultry, and fish, 253,472
supplementation may be required by vegetarians, and by older individuals who
may tend to consume less animal protein. Conditions of increased oxidative
stress, fatigue, or recovery from illness may also warrant increases in vitamin B 12
intake,472 and supplementation among the elderly may also be prudent. Numerous
investigators have reported serum cobalamin deficiency among the elderly, and a
recent examination of the extensive Framingham database by Lindenbaum and coworkers919 showed that deficient serum cobalamin levels were found among over
40% of 548 elderly surviving members of the original Framingham cohort.
Deficient levels were found in only 18% of younger control subjects. Vitamin B 12
deficiency is associated with increased levels of homocysteine. The risks
associated with vitamin B12 deficiency may be reduced by supplementation with
cobalamin, especially among the elderly.919
Clinical and Epidemiologic Studies
A prospective study by Stampfer et al, 622 the Physicians' Health Study
investigation which was published in 1992, demonstrated an increased risk of
myocardial infarction among American physicians with elevated levels of plasma
homocysteine. Physicians with the highest levels of homocysteine were three
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times more likely to suffer a myocardial infarction than those with the lowest
levels. Folate and vitamin B6 were shown to reduce otherwise elevated levels of
homocysteine in a subgroup, and reduce the risk of acute myocardial infarction.
This research confirms previous scholarship published in 1991 in the New
England Journal of Medicine923 by researchers in Ireland and Great Britain, who
found that 28 to 42% of patients with CAD, cerebral vascular disease, or
peripheral vascular disease had elevated levels of homocysteine. Similarly, Boers
et al,926 Malinow et al,927 and Genest et al928 showed that elevated levels of
homocysteine predicted premature onset of CAD, PVD, and stroke in both men
and women. In December 1993, an association between B-vitamin intake and
homocysteine levels was confirmed by an analysis of the extensive Framingham
database of 1,160 elderly men and women age 67 to 96, and published in the
Journal of the American Medical Association. This report clearly demonstrated an
association between plasma homocysteine levels and B6, B12, and folate
consumption. Nearly 30% of the 1,100 Framingham patients examined had
elevated levels of homocysteine, and two-thirds of those with elevated levels also
had sub-therapeutic plasma levels of B6, B12, and folate.
Similarly, Clarke and co-workers923 demonstrated that patients with high serum
levels of homocysteine were nearly 28 times more likely to develop premature
vascular disease than those with normal levels. A case-control study examining
early onset CAD among 101 white male patients, and 108 white male controls
conducted by Pancharuniti et al925 demonstrated an inverse correlation between
plasma levels of homocysteine and those of both vitamin B12 and folate, and found
that elevated plasma homocysteine was an independent risk factor for early-onset
CAD.
Although the American poor typically consume adequate amounts of animal
protein, and therefore are not likely to be deficient in vitamin B12, the indigent
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consume less foods which are high in the other B vitamins and folate than do the
affluent, rendering the poor more susceptible to deficiencies of these vitamins,
potential increases in homocysteine levels, and increased risk of CAD.
Laboratory and Clinical Studies of Flavonoids.
Flavonoids (or bioflavonoids) are a large group of polyphenolic antioxidants
which occur as natural compounds found in fruits, vegetables, nuts, seeds, leaves,
flowers, bark (tea), and wine.281,467,561,562 Flavonoids represent an important class
of antioxidants which may have a stronger scavenging effect upon oxygen free
radicals than the antioxidant vitamins.623 The most important flavonoids in human
nutrition are anthrocyanins, flavonols, flavones, catechins, and flavanones. 467 In
food plants, they impart color to flowers, stems, the skin of fruits, and leaves.
Many of the medicinally active substances in herbs are bioflavonoid compounds.
Bioflavonoids were first isolated as an "impurity" in a preparation of vitamin C
by Hungarian researcher Albert Szent-Gyorgi who named the substance "vitamin
P." Szent-Gyorgi, who subsequently won the Nobel Prize in medicine for the
discovery of vitamin C, determined that the flavonoid compounds had biological
activity which was distinct from that of vitamin C, and were beneficial in
protecting the capillaries.472 Subsequent research has demonstrated that they
possess powerful antioxidant activity, and may reduce atherogenesis and inhibit
the formation of blood clots.467,472,473,474,542 Flavonols are scavengers of free
radicals such as superoxide anions,563 singlet oxygen,564 and lipid peroxy
radicals,575 and have the ability to protectively sequester metal ions through
liganding.576 This process of free radical scavenging interrupts radical chain
reactions, stabilizes cellular processes, preserves cellular integrity, and reduces
intracellular oxidative damage, and the oxidation of serum LDL. Oxidized LDL is
atherogenic and may be important in the pathogenesis of atherosclerotic
disease.467,567 Research has demonstrated that Quercitin, a major flavonol,
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inhibits the oxidation and cytotoxicity of LDL in vitro.565,566 Additionally,
Flavonoids inhibit lipid peroxidation and cyclo-oxygenases,568,869 resulting in
reduced platelet aggregation. This may reduce the potential for thrombosis, and
coronary artery disease.568,869
Although not classified as vitamins, both animal and clinical studies have
demonstrated that flavonoids possess vitamin activity, and some researchers
consider them to be essential for humans.472 They are synergistic with other
antioxidant compounds such as vitamin C, and exert a beneficial effect on
capillary stability and permeability.294 High serum iron status, and particularly
iron from animal sources, may compromise the potentially protective effects of the
phenolic flavonoid compounds. Similar to ascorbate and to many of the other
antioxidant vitamins and nutrients, phenolic compounds have shown pro-oxidant
effects when mixed with high concentrations of iron ions in vitro. 568 This suggests
that the less tightly bound and more reactive elemental iron contained in heme iron
(supplied by red meat) may, in the situation of a positive heme iron balance, cause
dietary phenolic compounds to paradoxically react as pro-oxidants. High heme
iron status is a condition which is more common to members of the lower
socioeconomic class in America who tend to have high animal protein intakes, and
equivalent iron intakes to those of higher SES.42 Because the indigent are less
likely to obtain iron (in its non-heme form) from plant sources, this may place the
American poor at greater risk for acute thrombotic events.
Clinical and Epidemiologic Studies
A recent epidemiologic study from the Netherlands, the Zutphen Elderly
Study,467 an extension of the Dutch cohort of the pioneering seven-country study
by Keys,522,526,527,546,600 assessed patients' intake of certain flavonoids found in
fruits, vegetables, tea, and wine. Researchers measured the concentration of
flavonoids in various foods, and used dietary surveys to estimate the quantity of
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flavonoids consumed by 805 men (aged 65 to 84 years) between 1985 and 1990.
The primary sources of flavonoids for these men were black tea (which accounted
for 61% of their intake), onions (13%), and apples (10%). During the five-year
period there were 43 deaths. Even after adjusting for other factors known to be
protective against heart disease, the risk of dying was three times higher in the
men with the lowest flavonoid intake.
There is a significant body of additional research verifying the beneficial effects
of the flavonoid compounds. Frankel and associates542 reported that antioxidant
phenolic substances in red wine (which contains 10 to 20 mg/L of combined
flavonoids569) inhibited the oxidation of human LDL in vitro. Cold pressed olive
oil also contains antioxidant phenolic substances which have shown the ability to
completely stop the in vitro oxidation of LDL. The flavonoid compounds present
in red wine may be partly responsible for the reduced risk of CAD among wine
drinkers (the "French Paradox").467,570
Because members of lower SES tend to consume significantly fewer vegetables
and fruits than the affluent, they may consume less than the 20 to 30 milligrams of
bioflavonoids that the average American consumes on a daily basis, and may be at
greater risk of developing CAD or death. Additionally, research indicates that low
dietary intake of flavonoids is associated with increased lifetime cigarette
smoking, which further potentiates the risk of CAD in this population. 467
IX. Summary, Conclusions and Recommendations
The Legacy of the Welfare State.
Since 1960, the population of the United States increased by 41%, and the
Gross Domestic Product has nearly tripled. During this period, however, total
social spending by all levels of government (measured in constant 1990 dollars)
has risen from $143.73 billion to $787.0 billion--more than a five-fold increase.405
The legacy of this social welfare spending is enormous. Following World War II
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and prior to 1960, the gross federal debt remained stable, at around $250 billion.
Since the institution of the federal welfare programs in the mid 1960s, and their
proliferation in the 1970s, the gross federal deficit has grown exponentially [see
Fig. 36].
Figure 36: Gross Federal Debt, 1945 to 1992
_________________________________________________________________________________
Source: The Cato Institute
Inflation-adjusted spending has increased by 630% on welfare and by 225% on
education, yet during this same thirty-year period, there has been almost a 600%
increase in violent crime; more than a 400% increase in illegitimate births; a 300%
increase in the rate of divorce; a tripling of the number of American children
living in single-parent homes; more than a tripling of the teenage suicide rate; and
a precipitous drop of almost 80 points on the Scholastic Aptitude Test (SAT)
scores. 405 States spending the most tax dollars per pupil on public education
frequently have the worst students in academic performance. Although the
District of Columbia's per pupil expenditures are among the highest in the nation,
its public schools are last in the nation in academic testing scores.
Crime is increasing exponentially in American cities despite a hemorrhaging of
federal and state tax dollars into prevention and rehabilitation programs. Despite
police and prison spending which is four times the national average, and despite
one of the strictest gun laws in the nation, Washington, D.C. remains the murder
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capitol of the United States.
When the great Society social welfare spending programs were first established
in the early 1960s, approximately 12.3% of the American people were living at or
below the poverty level. After thirty years and an expenditure of over $2.3 trillion
on welfare programs, the percentage of Americans living at or below the poverty
level is currently unchanged or worsened; and is now estimated to be between
12.3% and 15%, depending on the type of measurement used to determine the
level of poverty.109,160 According to the most recent census data, the number of
American poor increased in 1992 by 3.4% to 36.8 million persons. This represents
an increase of three times the rate of population growth, and the highest level
achieved since 1962, which was prior to the creation of most federally funded
social welfare programs.160 Black and Hispanic Americans were three times more
likely to be poor than whites, and 1992 census data indicated that one third of all
blacks lived in poverty and 29.3% of all Hispanics were poor,160 although these
population groups receive a disproportionately higher per capita share of federal
social welfare dollars.
The food stamp program has experienced exponential growth within the last
decade, increasing in cost to the American taxpayers by 55% to $22 billion
between 1990 and 1993 alone. During this same period, there was a 35% increase
in the number of food stamp recipients to 27 million Americans.
Although the percentage of Americans below the poverty level appears to be
slightly increasing despite the exponential increase in welfare spending, and
although this expansion in American poverty has paralleled the explosion of crime
in America, poverty has almost nothing to do with crime. In a recent review of the
social science literature on violence and delinquency, Heritage Foundation scholar
Patrick Fagan demonstrates that it is changing family structure and dynamics, and
not poverty which effects crime in the United States. If the poverty-causes-crime
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hypothesis were correct, one would expect to see crime rates fall as incomes rise,
and vice versa. History clearly negates this view. Crime in America rose
gradually from 1905 to 1933, a period of economic growth and rising personal
incomes, however when the Great Depression hit, the crime rate fell dramatically
as families were pulled together for their survival.
Conversely, data from all 50 states show a direct correlation between the rise of
single-parent families and the increase in juvenile crime. In fact, a 10-point
increase in the percentage of children living in single-parent homes accompanies a
17 percent increase in juvenile crime. Even in high-crime, inner-city
neighborhoods, well over 90 percent of children from intact, stable families never
commit crimes, while only 30 percent of children from broken homes in these
same neighborhoods avoid criminal behavior.
The statistical data seems to implicate dysfunctional single parent families and
not single parent families arising from the death of a spouse. As important as two
parents are, it is not the number of parents who raise a child that effects his
inclination towards criminality and aggression; it is also the quality of his
relationship with his family. Single-parent families of illegitimate children led by
never-married welfare-dependent women are radically different from families led
by widows raising legitimate children. In the latter family, the memory of the
father is present, even if he is not, lending the mother a measure of necessary
moral authority. Children of such families demonstrate none of the pathology
associated with children of never-married parents. Families dependent upon
welfare are significantly more likely to be headed by never-married mothers, and
are therefore vastly more susceptible to these pathological behaviors.
The expansion of the social welfare state has negatively impacted upon both the
non-working recipients of welfare and upon working Americans. Due in large
part to decades of escalating social welfare spending, the current American tax
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structure is confiscatory by comparison with four decades ago, and frequently
forces wives and mothers of young children into the work place to maintain a
standard of living.809 Since 1950, prior to the establishment of all federally funded
social welfare programs, the income tax burden on an average American family of
four has increased over 6-fold from 4% of income in 1950 to 24% of income in
1980.405 In the 1990s, the tax burden of an average family with children has
increased by a factor of over nine times the rate imposed in 1950, and currently
this average family pays 37.6% of their gross earnings for federal, state and local
taxes, Social Security, and Medicare.809 The current average family tax burden
totals over 45% if the "employer contribution" to Social Security tax, which
actually represents a hidden portion of employee compensation, is taken into
account. The amount of this tax burden exceeds the current annual cost of the
average home mortgage.809
In Sweden, Norway, and Eastern Europe, the tragic
legacies of their social welfare programs have literally devastated national
economies and crippled their middle class,109 yet these programs have not
significantly alleviated poverty in those countries.
Among Americans of lower socioeconomic status, the social welfare program
and federal taxation policies have been responsible for a number of detrimental
effects including:
1) Causing the loss of independence and personal initiative by the creation of
multi-generational wards of the state. Family fragmentation generates a
particularly debilitating form of poverty: welfare dependency. This is especially
true for unmarried adolescent mothers, nearly 80% of whom receive welfare
within 5 years of becoming a parent. More than 40% of long-term and lifetime
welfare recipients had their first child at age 17 or younger.224 Because the underclass of non-productive citizens is experiencing slow growth across the United
States, and rapid acceleration in major urban areas, this poses a significant
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economic threat to certain communities whose pool of productive tax-paying
citizens remains stable, and constitutes a crisis to communities whose productive
working population is shrinking.
2) Causing or facilitating the breakup of the family, by selectively rewarding
single parenthood, while removing benefits for traditional two-parent households.
According to the Report of the National Commission on America's Urban
Families, "The current welfare system, through it's misguided incentives, keeps
families apart. For example, for a woman on [Aid to Families with Dependent
Children (AFDC)], it is better for her to collect AFDC than to marry the father of
her children if the father is not holding a high wage job." 224 For those families not
receiving federal assistance, current federal tax policies will increase the tax
burden on 52% of married couples. A "marriage penalty" is written into the new
IRS tax code requiring husbands and wives to pay $1,244 more in federal tax than
they would if they were divorced or living together out of wedlock. 810
3) Placing incentives on illegitimate birth by providing increasing monthly
stipends for the birth of each successive child, or otherwise helping to facilitate
illegitimate births. In fact, although the poor constitute between 12.3 to 15 percent
of the American population,160 one third of all U.S. births in 1993 were to mothers
on Medicaid,312 a government program providing hospitalization and medical care
to the poor or to persons of limited income, ninety percent of which is financed
through federal tax dollars, and ten percent of which is financed through state and
local funds. In 1993, two hundred and sixty Medicaid patients in twelve States,
58% of whom were additionally receiving assistance through Aid to Families with
Dependent Children (AFDC) which covers primarily single mothers, received
fertility drugs which were paid for by Medicaid.312 Sixty three percent of these
women already had children and two women already had eight children each, all
of whom were currently on public assistance. The state of New Jersey alone spent
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almost a quarter of a million dollars on fertility assistance to Medicaid recipients
in 1993 alone, even in light of the fact that most private health insurance plans do
not cover infertility services.
4) Causing or facilitating the abdication of personal, family, and community
responsibilities by the appearance that the state will fulfill those responsibilities
for the individual, and by placing economic dis-incentives upon the fulfillment of
those responsibilities. In 1961, John Kennedy challenged and inspired the
American people with, "Ask not what your country can do for you--ask what you
can do for your country." Richard Nixon wrote that by the end of the decade of
the 1960s, however, "many people were asking why the federal government had
not done all the things it had promised and undertaken to do for them." 888
5) The establishment of an "entitlement mentality" by convincing members of
lower SES that society is responsible for their support and sustenance. By
defining social welfare programs as "entitlement programs," the American
government has delivered a dangerous and misleading message to the economic
under-class it should rather seek to motivate and "lift by its bootstraps." Certain
members of the American under-class perceive these programs as payment of a
debt owed, rather than as governmentally-sponsored charity. Senator Robert
Byrd406 recently criticized the Supplemental Security Income (SSI) federal
disability program for making disability cash payments to individuals solely on the
basis of their claim to be drug addicts or alcoholics. He further stated concern that
this well-intentioned entitlement program was being misused by parents who were
coaching children to fail tests or misbehave in school in order to be classified with
a behavioral disorder and qualify for monthly SSI disability payments of up to
$446.00. Byrd stated that he was concerned about "the damage that is being done
to our children, in teaching them that their future lies not in hard work, but in
ripping off the federal government."406
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6) Increasing Hopelessness and Despair among the working poor by placing
negative incentives on the American work ethic, and among welfare recipients by
the bureaucratic stripping of their dignity and by the establishment of an almost
inescapable cycle of dependency. Concerning the social welfare programs
established in the early 1960s under Lyndon Johnson's "Great Society", Richard
Nixon wrote: "The problems were real and the intention worthy, but the method
was foredoomed. By the end of the decade its costs had become almost
prohibitively high in terms of the way it had undermined fundamental
relationships within our federal system, created confusion about our national
values, and corroded American belief in ourselves as a people and as a nation."
The former President further stated, "From 1960 to 1969, the cost of welfare
benefits for families with dependent children nearly tripled. More than a quarter
of a trillion federal dollars was spent between 1964 and 1969 in an attempt to
eradicate poverty and inequality. But instead of solving problems, these programs
themselves became part of the problem, by raising hopes they proved unable to
fulfill...Perhaps most demoralizing of all, the working poor watched while the
non-working poor made as much money--and in some cases even more money--by
collecting welfare payments and other unemployment benefits. This began a bitter
cycle of frustration, anger, and hostility."888
7) Ethnic polarization, by convincing the poor that society is responsible for their
problems, and by demoralizing the productive working poor by granting economic
perks to the non-working poor equal to or greater than those capable of being
earned by the working poor. Congress is currently considering legislation which
will further establish the dependence of the indigent upon the social welfare
system, and further polarize the working poor and middle class by granting
welfare recipients a short-cut to the lifestyle of the self-reliant upper middle class.
Housing and Urban Development (HUD) assistant secretary for fair housing
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Roberta Achtenberg has called the current administration's $60 billion Housing
Choice and Community Reinvestment Act "the largest investment in civil rights
that the federal government [has] made in the past fifteen years." An additional
$149 million is being sought by HUD for the "Moving to Independence" program,
which will provide rental vouchers to indigent people in inner-city public housing
projects to move into surrounding middle class and affluent suburbs. HUD is
using the Section 8 program, passed by congress in 1974, to provide $7 billion this
year, and $14 billion per year by 1996 in direct rent subsidies to approximately
two million low-income families. These rent subsidy vouchers will entitle welfare
recipients and their families to live in apartments with rents as high as $1,657 per
month, ($19,884 per year), for a four bedroom apartment in some well-to-do areas,
a higher rent than the vast majority of American upper middle-class renters are
currently paying.887
In addition to these programs which increase resentment among the working
poor, there is an increasing national tendency to shift blame on American society
for both the socioeconomic status and criminal behavior of the poor. This attitude
grants "psychological absolution" to criminal activity if the perpetrator is poor,
and may encourage criminal behavior among the indigent.
The Probable Cause of the Paradoxical Shift of SES associated Risk.
The paradoxical shift in SES-associated cardiovascular disease risk may be
explained by differential changes which occurred between high and low
socioeconomic classes in the decade of the sixties. These changes involved
modifications in lifestyle and diet, and either placed individuals at greater or at
lesser risk of oxidative modification of LDL cholesterol [see Table 12 and 13], or
degenerative tissue injury. Changes which were instituted by higher SES
Americans were predominantly influenced by the recommendations of both the
American Heart Association and the Surgeon General of the United States in early
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1964. Changes which were instituted by lower SES Americans were primarily
influenced by popular advertising, peer influence, and the American social welfare
system, and began within the same decade. While the affluent lived in stable
neighborhoods, had greater access to health education, eschewed saturated fat,
cholesterol, and tobacco, and began to embrace an active lifestyle, the American
poor migrated to the unstable and stressful environment of the inner city. Here the
under-class increased consumption of highly processed foods rich in saturated fat
and cholesterol, and were increasingly exposed to radio, print media, and
television advertising which encouraged the use of tobacco and alcohol. The poor
abandoned their "indigent" diet of vegetables, fruits and cereal grains in favor of a
highly processed, high-fat, "urbanized" diet high in sugar and salt. Availability of
federal welfare dollars allowed greater affordability of high fat foods, or presented
opportunities for diversion of money to purchase tobacco products, and the nonproductivity and demoralization of a dependent welfare existence encouraged an
increasingly sedentary lifestyle.
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TABLE 12: Factors Effecting the Oxidation of LDL Cholesterol and Their
Prevalence among Individuals of Low or High SES in the United States, 1900
to 1964.
Page 192
TABLE 13: Factors Effecting the Oxidation of LDL Cholesterol and Their
Prevalence among Individuals of Low or High SES in the United States since 1964.
Page 193
Working Hypothesis
1. Factors causing the rise in CAD mortality which was documented primarily
among the upper socioeconomic class between 1900 and 1940:
During the white majority migration from the farms to the cities, urbanization
resulted in the fragmentation of the nuclear and the extended family, decreased
social support, and increased stress. Technological advances, which were more
accessible in urban areas, resulted in more sedentary lifestyles, and increasing
affluence was associated with the adoption of popular, although deleterious,
dietary and lifestyle changes. These included the abandonment of the traditional
"rural diet" of vegetables, fruits and grains; the adoption of an "urban diet" rich in
saturated animal fat and highly processed and refined foods; and the increased
affordability and availability of tobacco products among the upper socioeconomic
class. These factors contributed to the rise in CAD incidence, acute coronary
events, and coronary death rates observed among the affluent during this period.
2. Factors causing greater CAD mortality among members of low SES after 1960:
The establishment of the social welfare "Great Society" programs of the early
1960s accelerated the migration of the rural poor to the cities, subjecting the
indigent to significantly greater stress than was experienced in the rural areas.
The decade of the 1960s saw a marked trend toward the disintegration of the
traditional supportive nuclear family which accelerated in the vacuum created by
an American moral decline, and the abandonment of the Judeo-Christian basis for
a "national ethic." A federal tax structure placing increasing burdens upon the
American working family, driving mothers of young children into the work-force,
and a national social welfare policy preferentially rewarding fatherless families
further contributed to the disintegration of the supportive nuclear family unit, and
the increase of despair, dependency, and hopelessness among the American
indigent. The family has historically been the bastion of this support, and its
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weakening in the moral vacuum of the 1960s left in its wake dysfunctional
members who were more vulnerable to the ravages of psychological stress, and
who were at increased risk of acute, catecholamine-mediated coronary events.
Into these dysfunctional households were born increasing numbers of children
whose unwed mothers were destined to remain single due to destructive incentives
built into the American social welfare system, further establishing the
abandonment of responsibility and cycle of despair. The feeling of powerlessness
among those entrapped within the social welfare system increased the life stress of
those consigned to the system, and drove others to regain that lost power and selfdetermination through violent criminal activity which primarily impacted the
urban poor, and further increased the stress and the cycle of hopelessness of their
seemingly inescapable condition.
Additionally, the urban indigent experienced a shift from an active rural lifestyle
and a healthy agrarian diet (high in fiber, indoles, flavonoids, cruciferous
vegetables, phytochemicals, and natural dietary sources of antioxidant vitamins
and minerals) to a subsidized and more expensive urban diet which was higher in
fat, lower in fiber, and consisted largely of highly refined and vitamin-depleted
foodstuffs. Prior to 1960, the poor had a lower risk for sudden coronary death and
CAD mortality than did the rich because the poor could not afford the luxurious
indulgences of the affluent of that era, including a leisurely lifestyle, and a diet
rich in saturated fat. The poor were less able to afford tobacco products than were
the wealthy. In the first half of this century, blacks, and the rural poor consumed
diets out of economic necessity. These healthy foods cost less than the more
"prestigious" highly processed or prepared foods. The rural poor led significantly
more active lifestyles associated with the demands of a farming economy, and
frequently were members of stable family groups characterized by the presence of
both parents, and of the extended family members. Following 1960, an abrupt
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change occurred. Changes in lifestyle, environment, dietary habits, or other
factors known to contribute to CAD could not individually account for increases
in CAD mortality observed among the poor, but collective changes in many or all
of these risk factors could acount for the magnitude of the observed increases.
Increases in refined sugar intake, tobacco consumption, alcohol abuse, sedentary
lifestyle, and decreases in the consumption of high-fiber complex carbohydrates
all served to increase the risk of CAD among the indigent. These dietary and
lifestyle changes are consistent with populations experiencing increasing affluence
while not having access to, or choosing to ignore a model of preventive dietary
and lifestyle changes [see Fig. 37].
Figure 37: Income among Rural Bantu, Urban Blacks, and White Europeans
and Corresponding Animal Fat and Vegetable Fat Intake, and Serum
Cholesterol
with Superimposed Rates of Electrocardiographically Evident AMI
______________________________________________________________________________________________
Adapted from: Brock and Bronte-Stewart444
A documented nine-year decline in physical activity occurred primarily among
members of lower SES in the late 1960s, and continued into the decade of the
1970s. Transition from the higher daily exercise and intense activity levels
associated with a rural self-sufficient lifestyle, to a more sedentary lifestyle
associated with non-productive social welfare dependency, resulted in an
increased risk of CAD among the poor.
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The poor abandoned a rural lifestyle rarely associated with the use of tobacco
products due to monetary, social, and religious restrictions. In the cities, the use
of tobacco products increased considerably due to greater affordability, relaxation
of social and moral restrictions, and increased access and advertising exposure to
tobacco products.
The urban poor, and specifically the blacks, benefited less from, or had less
access to patient and consumer preventive education concerning the advisability of
reducing of animal fat and cholesterol intake, and smoking cessation. Both the
Surgeon General's and the American Heart Association's 1964 recommendations
on smoking and dietary changes were largely unheard or unheeded by the lower
socioeconomic class.
3. Factors causing an early decline in CAD death rates primarily among members
of higher SES, first seen in California in the early 1960s, and seen nationally by
the end of the decade:
California led the nation in the quest for a healthier lifestyle, including smoking
cessation and dietary improvements. A significant reduction in the percentage of
smokers occurred primarily among those of upper SES in the mid to late 1960s,
and the acceptance of the importance of reduced fat and cholesterol diets
contributed directly to this national trend of reduced CAD mortality which
occurred primarily among the affluent. Data from several long- term population
studies suggests that reductions in mean serum cholesterol were more significant,
and were achieved more rapidly by the highly educated.35
Additional research suggests that reduction in milk and butterfat intake, and
increased consumption or substitution of monounsaturated fats and vegetables
(which are dietary practices more common among members of higher SES), may
have been responsible for significant reductions in CAD risk. 476,891 In the Seven
Countries Study, Keys et al546 demonstrated that the CAD death rate was
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negatively correlated with the percentage of dietary calories from
monounsaturated fats such as olive oil. Consumption of monounsaturated fat is
highest among the affluent in the United States.
In addition to changes in diet and smoking habits which were adopted by
Americans in the decade of the sixties and subsequently, data indicates that
millions of Americans have become more active in their leisure time, and that
members of higher SES tend to be more active than the indigent or less educated.35
Californians have also led the nation in the adoption of more active lifestyles.
This may also have contributed to early CAD reductions there.xxx
4. Factors causing greater CAD incidence among younger members of lower SES;
the increases in acute CAD among both the indigent young and among women;
and the narrowing of the CAD margin between women and men:
The environment common to the urban poor is conducive to stress-associated
disorders. There is a high prevalence of hypertension and an increased potential
for psychosocial effects on blood pressure and hemostatic factors among blacks
and the indigent. Living in an unstable urban environment increases cortisol
levels. This, in conjunction with drug and alcohol abuse, tobacco use, a sedentary
lifestyle, and dietary insufficiencies associated with poverty, increases the risk of
acute thrombotic events. The young urban poor have greater exposure to these
risks.
Tobacco advertisers target (or have targeted) blacks, the young, and women.
Alcohol and high-fat food advertisers frequently target urban blacks. These
advertising campaigns have been responsible for increases in smoking initiation
and fat consumption among younger blacks, and for increases in smoking
initiation among women (and particularly younger women of lower SES). They
have contributed to the narrowing margin of CAD incidence between blacks and
whites, and have reduced the margin between men and women.
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Differences in rates of acute CAD between men and women parallel changes in
smoking behavior over time, with the margin of men's use of tobacco versus
women increasing from 1931 through 1950, and narrowing since 1960.
Concomitant increases in female smokers following aggressive advertising
campaigns directed at women in the late 1960s and early 1970s were probably
responsible for the narrowing of the gap between female and male CAD deaths in
the last two decades.
Increased caffeine, tobacco and salt consumption is more prevalent among those
of lower SES, and among the urban young. Drug abuse is more prevalent among
the urban poor, and is most prevalent among the youthful poor. These behaviors
increase serum catecholamines, heighten the effects of stress, and may precipitate
acute coronary events among the younger urban poor.
Mortality data by race and sex for 1960 through 1975 indicated that
improvements in CAD mortality occurred for white males but not black males,
which is consistent with differences in smoking behavior between the two races
during this period, and presently. Currently, younger members of lower SES are
significantly more likely to engage in CAD risk behavior, have poorer coping
skills, and demonstrate significantly more aggressive behavior.
Social support appears to have a protective effect against CAD. This may
explain why women, who tend to have stronger social relationships and intimate
ties than men, experience lower CAD rates, however the greater trend toward nontraditional or dysfunctional families among the indigent may be reversing this
protective trend more exclusively among poor women. Social isolation,
depression due to lack of social support, deterioration of the family unit, poor
stress coping styles, job stress or the stresses associated with joblessness, and
unresolved anger and hostility are among the psychosocial factors which may link
low SES to increased CAD. Frustration and perceived loss of control over one's
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life due to repeated non-achievement and social failure, conditions more common
to young members of lower SES, may result in a fatalistic attitude which increases
psychological pressure and coronary risk.4,10,279,328,328
5. Factors causing reduced incidence of CAD among older blacks and older
members of lower SES:
This phenomenon may be due to an unmasking of a true genetic resistance to
CAD among blacks who predominate the lower SES. This resistance is suggested
by the reduced rates of CAD consistently seen in clinical studies of blacks in the
first half of this century, and is validated by recent angiographic studies showing a
decreased prevalence of coronary atherosclerotic plaques in blacks, by
epidemiologic studies showing lower incidence of CAD among upper SES blacks
than among whites of lower or higher SES, and by census data showing
consistently lower mortality from CVD among older blacks versus whites.
According to U.S. Census data,217 major cardiovascular diseases accounted for
37.7% of deaths reported due to all causes in 1989 among blacks and for 44.3% of
those deaths reported among whites. From birth through age 69, black mortality
from major CVD (16.1% of all deaths) consistently exceeds that of whites
(10.65% of all deaths) as a percentage of total deaths, however by age seventy
(and consistently thereafter), whites succumb to CVD at a significantly higher
rate.217
The reduction of certain at-risk behaviors (drug abuse, stressful lifestyle related
to urban violence, hostile behavior, smoking, alcohol abuse, and dietary abuses)
which are more common to youthful members of lower socioeconomic status may
occur less frequently among elderly blacks, resulting in a statistical shifting of
increased CAD risk, (and especially an increased risk of acute events), to younger
members of low SES, [see Fig. 38].
Figure 38: Relative Risk of Cardiac Arrest in Blacks as Compared to Whites
According to Age
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Bars are 95% Confidence Intervals.
A relative risk of 1 would represent an equal risk for both blacks and whites.
____________________________________________________________________________________________
From: Becker et al.178
Many of the at-risk behaviors described above could explain the significant
increases in acute (thrombotic or arrhythmic) deaths among younger blacks which
account for most of the increased risk prior to age 70. At age 70 and beyond,
increases in CAD deaths among older whites are primarily due to chronic
(atherosclerotic) disease. Research has shown that of the known risk factors for
CAD, stress has the greatest potential for rapidly increasing the incidence of acute
CAD in a younger population. Because acute CAD was relatively uncommon
among blacks and among the indigent prior to the decade of the 1960s, and
because significant increases have occurred among blacks and among the indigent
since the establishment of the Great Society social welfare programs, the welfare
system itself may be responsible for these deleterious effects by adversely
effecting life stress, lifestyle or diet among those who have subjected themselves
to, and have become dependent upon the system. If the welfare system were
examined as though it constituted a risk factor for CAD, exposure to this "risk
factor" would be greatest among younger members of low SES. Exposure to this
"risk factor" results in significantly increased risk of CAD versus similarly aged
individuals of higher SES who were not exposed.
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Since blacks who have lived to a older age have survived the higher risk of acute
CAD which strikes younger blacks at a greater frequency, a possible resistance to
chronic CAD (which becomes evident at advanced age among blacks) may benefit
blacks more greatly than similarly aged whites.
Other research701 has demonstrated that older employed subjects are more
likely to be in jobs with greater decision latitude--in part due to advancements and
promotions--and therefore may be subjected to lower levels of occupational stress
that their younger counterparts.
Older members of lower SES may benefit from the formation of more stable
social relationships which may be lacking in many younger indigent nontraditional families. In one study, the major difference between the minority high
and low CAD risk groups was the degree of social support.237 The group with the
higher rate of CAD maintained fewer close family and social ties. The low risk
group had strong nuclear families, and maintained close social ties with other
members of the ethnic group. Social networks, religion and a stable marriage
reduces stress and associated CAD risk, and the young urban poor are more poorly
represented in these areas than their older counterparts. The elderly have a greater
commitment to religion, more stable social connections, and are more likely to be
in a stable marriage.
6. Factors causing reduced CAD risks among high SES blacks:
High SES blacks are more likely to be older, and less likely to be currently
exposed to the social welfare system than are their younger counterparts. They are
more likely to have greater autonomy over, and less stress associated with their
daily lives. Reduced CAD risk in these individuals may be due to migration from
stressful inner city environments to the more secure suburban areas, which
together with improved diet, increased exercise, smoking cessation, and other
beneficial lifestyle variables (more consistently and more rapidly adopted by the
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affluent, the more mature, and the more educated) certainly play a large role in this
differential.
Blacks with the lowest incidence of CAD are rural African blacks who consume
very little or no meat and dairy products,442,444,448,460 and who observe a low-fat
diet similar to the Mediterranean dietary regimen described by de Lorgeril, [see
Fig. 39], consisting largely of vegetables and unrefined cereals high in thiamine,
antioxidant vitamins, and fiber.451,461 Highly educated blacks are more likely to
institute such a diet, or to remain compliant on an austere saturated animal-fat
limiting diet, than those who are less educated.
Figure 39: The Mediterranean Food Pyramid and the USDA Food Pyramid
__________________________________________________________________________________________________________________
__
Source: DeLorgeril,270,850 The U.S. Department of Agriculture; Harvard School of Public Health
7. Factors causing increased CAD among older members of upper SES:
This phenomenon may possibly be due either to an age-related unmasking of
increased genetic resistance to CAD among blacks who predominate the lower
SES, or to concomitant increases in risk behaviors among members of higher SES
to a greater extent than their lower SES counterparts. Because this CAD risk factor
shift typically occurs after age 65, this may reflect the stress of retirement which
may weigh more heavily upon members of upper SES whose lifestyles may
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change more radically, and who may have their personal identities more closely
tied to their occupations. Frustration and perceived loss of control over one's life
due to abdication of personal responsibility for day-to-day decisions is prevalent
in nursing facilities631 which are more affordable to older members of upper SES.
Additionally, life changes which disrupt relationships (such as retirement
involving residential moves) have the greatest effect on CAD risk,225,236 and
members of upper SES are more likely to experience, or are more able to afford
these types of sweeping changes at retirement.
Recommendations to Reduce CAD Risk Associated with Lower SES.
1. Redesign the welfare system.
a. Change public policy to counter dependency social factors by stopping taxsubsidization of behaviors which virtually guarantee high rates of illegitimacy.
b. Encourage responsible behavior by requiring all able recipients of welfare to
work in exchange for their benefits, and by requiring AFDC mothers with older
children to contribute community service in exchange for benefits received.
c. Reverse the destructive incentives for single parenthood built into the welfare
system by reduction of economic penalties on marriage for single mothers.
d. Limit both the monetary value and duration of social welfare benefits to the
non-working poor to prevent demoralizing the productive working poor.
e. Encourage the church, community, and extended family to reassume many of
the responsibilities of caring for the poor currently shouldered by the federal
government.
2. Change federal tax codes which place additional economic penalties on married
working couples, families, and the working poor .
a. This could be accomplished by the adoption of the 17% flat tax reform
proposed in U.S. Representative Richard Armey's Freedom and Fairness
Restoration Act. This act provides substantial marriage and per-child deductions
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which would essentially remove the working poor and the lower middle class from
the tax roles.
3. Reform the judicial system to establish significant penalties to deter criminal
activity while expediting and limiting the appeals process.
a. Special emphasis should be given to the establishment of swift and strong
penalties for criminal activity most likely to impact the urban poor, with minimal
or limited opportunities for appelate delay.
4. Remove the economic barriers that keep the under-class in poverty, and weaken
the family.
a. Provide tax incentives for businesses to locate in urban enterprise zones,
incentives for tenant ownership, and responsible investment in low-income
housing.
b. Remove both economic and healthcare incentives for poor women to raise
children without fathers, and strengthen social taboos discouraging elective single
parenthood.
c. Improve efforts to collect child-support payments by requiring parents to
report child-support obligations to the IRS which is empowered to deduct
delinquent payments from tax refunds.
d. Require fathers to take responsibility for their children and obtain gainful
employment through the elimination, limitation, or rapid reduction of social
welfare benefits for non-working, absent, or non-supportive fathers with children,
and the requirement of special courses in responsible fatherhood as a condition for
any interim welfare benefits.
e. Provide job placement assistance and effective employment counseling, and
after a minimum period, require recipients of welfare to obtain gainful
employment, or to constructively contribute or serve the state in some capacity.
5. Reform public education to include instruction on an ethical system of values,
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encouragement of individual responsibility, parental involvement, and instruction
on CAD risk factors, exercise, beneficial lifestyle modifications, and nutrition.
a. Reestablish the fundamental purpose of education, providing for both
intellectual and moral education of the young.
b. Establish inner-city community-based or church-based public education
programs on lifestyle modifications, nutritional and dietary interventions, exercise,
hypertension, weight and obesity counseling.
c. Establish programs of psychosocial intervention, including stress and coping
skills, counseling, and support groups for anger resolution.
d. Establish instruction on general health guidelines to include risk factors for
CAD, and patient information concerning heart attack symptoms, smoking
cessation, alcohol abuse counseling, medication compliance, regular medical
follow-up, dietary interventions, exercise, lifestyle modification counseling,
reduction in fat and sodium, maternal health counseling, treatment and control of
hypertension, and bood glucose and diabetes control.
6. Establish national guidelines to improve access and quality of health care for
the poor.
a. Require health care cost sharing at a fixed level for both those on welfare and
the working poor.
7. Establish smoking cessation support and counseling programs, especially within
the inner city.
8. Establish effective and accessible community-based screening for known and
suspected CAD risk factors within the inner city to include drug use, obesity,
stress, inadequate diet, hypertension, hyperlipidemia, adult-onset diabetes, chronic
welfare dependency, and other risk factors.
9. Establish and facilitate programs of psychological counseling, stress coping
skills, and depression counseling within major urban areas:
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a. Review assertive, healthy ways to express anger, along with relaxation
techniques to foster tranquility, and to reduce hostilities.
b. Instruction on active, healthy coping styles.
c. Strengthen the role of churches, synagogues, and religious organizations.
10. Establish national policies, or grass roots community efforts to rebuild and
preserve the traditional two-parent family, and support and preserve the role of the
extended family.
a. Legislatively reverse the destructive incentives for single parenthood built
into the welfare system, and reduce the CAD risk factor of social isolation through
community and church efforts.
b. Modify tax law to encourage the proliferation and preservation of traditional
two-parent families.
c. Establish methods to successfully integrate married couples, (who currently
are under-represented), in federally-subsidized housing projects. Much of the
crime problem confronting residents in public housing stems from the absence of
stable married couples, and married adult males who can function as good role
models for adolescents.
d. Rescind no-fault divorce laws for parents with children.
e. Remove major obstacles to adoption.
f. Encourage and support the establishment of extended family groups.
11. Improve opportunities for productive employment, and require healthy
recipients of social welfare to contribute by working for their benefits.
a. This program can be patterned after the Houston, Texas model which
was
challenged by the ACLU and ruled an unfair requirement due to the fact that it
existed in no other state.
12. Facilitate indigent patient programs for antihypertensive or cardiovascular
disease therapy through coordination with pharmaceutical concerns.
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a. Improved tax incentives could be offered to pharmaceutical concerns for the
institution of such programs, however this should be managed by private
enterprise, or by the local community to remain effective.
13. Help to establish or encourage proper youth role models who advocate
acceptance of individual responsibility, and eschew blame-shifting.
a. This program should be managed by private enterprise, or by the local
community to ensure its effectiveness.
b. Identify risk taking behavior more common among those of lower SES, and
determine ways to discourage it or channel it in a positive direction.
14. Return to religious and moral codes of ethical standards.
a. Remove federal and legislative prohibitions against the free establishment of
religion-based moral or ethical programs within the public sector.
15. Establish programs to improve environmental factors, especially urban
conditions more common to members of the lower socioeconomic class:
a. Address urban environmental hazards and pollutants.
16. Design a widely acceptable, easily-adopted diet based on the Mediterranean,
European, or Pacific Rim Model [see Fig 39].
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APPENDIX A
List of Figures
Figure
Title
Page
1.
Death Rate Due to CAD 1900 through 1988
2.
Decline in Age-Adjusted Mortality From All Causes Since 1972
5
3
Prevalence of CAD 1960-62 by Race and Social Class
6
4.
All-Cause Mortality by Education and Race
11
5.
All-Cause Adult Mortality by Income
12
6.
All-Cause Adult Mortality by Employment Status
14
7.
A Graph of the Paradoxical 1964 Risk Factor Shift
17
8.
Incidence of CAD by age and SES, 1960-62 and 1967-69
19
9.
State Economic Areas With Late CAD Mortality Decline
24
10.
Males Dying From Acute and Chronic CAD 1931-1980
26
11.
Death Rates From CAD by Country in Adult Males
30
12.
Mortality in Secondary Prevention Trials
34
13.
Mortality in Primary Prevention Trials
35
14.
Poverty Rates of Families With Children by Race
15.
Incidence of CAD versus Sugar Consumption in 30 Countries
83
16.
Fat Consumption Versus CAD Mortality in 20 Countries in 1973
84
17.
Fat and Milk Product intake versus CAD Deaths in 40 Countries
85
18.
Household Composition, 1960-1990
106
19.
Married Couple Families with Working Wives 1960-1990
APPENDIX A (Continued)
107
Figure
4
51
Title
Page
20.
Percentage of Children Wishing More Time With Their Mothers
109
21.
Single Mother Families and Poverty
110
22.
Percentage of Unmarried Teenage Mothers, 1970 and 1990
111
Page 209
23.
Poverty Rates of Families With Children By Race: 1959-1990
114
24.
Premarital Births By Race: 1960-1964 and 1985-1989
115
25.
Incidence of Hypertension by Level of Tension in Men aged 45-59
125
26.
The Control Hypothesis in Hypertension, CAD and Sudden Death
134
27.
CAD Mortality In Men (1968-78) Versus Infant Mortality
141
28.
Relative Risk of Mortality Plotted Against Cholesterol Level 146
29.
Serum Selenium Levels in CAD Patients Versus Controls
194
30.
Dietary Vitamin E Consumption and CAD in Men and Women
199
31.
Inverse Correlation Between Vitamin E and CAD
32.
Plasma Vitamin E and Risk of Angina Pectoris
202
33.
Plasma Vitamin C and Risk of Angina
206
34.
Beta Carotene and Risk of CAD in Men
210
35.
Antioxidant Levels Within Serum LDL
218
36.
Gross Federal Debt, 1945-1992
37.
Income vs. Fat Intake among Rural Bantu, Urban Blacks, Whites
246
38.
Relative Risk of Cardiac Arrest in Blacks versus Whites by Age
252
39.
The Mediterranean Food Pyramid versus the USDA Food Pyramid
255
201
229
APPENDIX B
List of Tables
Table
Title
Page
1.
Risk Factors For Atherosclerosis......................................................
3
2.
Death rate per 100,000 from CAD, 1940 and 1945..........................
39
3.
4.
Reported Exercise by Americans, 1977.............................................
Mortality and Cardiovascular Events on Mediterranean
57
Versus American Heart Association Diet..........................................
72
5.
Diseases of Wealth and Poverty........................................................
75
6.
Composition of Three Low CAD Risk Diets vs American Diet........
79
7.
Characteristics of Strong Families......................................................
105
8.
The Process of Atherosclerosis.........................................................
137
Page 210
9.
Average Daily Frequency of High Fat Food Consumption...............
147
10.
Smoking Related Illnesses by Race and Sex.......................................
167
11.
12.
Sources of Free Radicals Within the Body........................................
Factors Effecting the Oxidation of LDL and Their Prevalence
Among Low or High SES in the United States, 1900 to 1964...........
215
13.
Factors Effecting the Oxidation of LDL and Their Prevalence
Among Low or High SES in the United States, since 1964...............
Page 211
241
242
References
1. Berleston DM et al. Epidemiology of the killer chronic diseases, in Nutrition and the Killer Diseases,ed. M.
Winick, (New York: John Wiley and Sons, 1981), p 17-55.
2. Slattery ML et al, "Trends in coronary heart disease mortality and food consumption in the US between 1909 and
1980", Am J. Clin Nutrition, 47:1060-1067, 1988
3. Brown JE, Identifying diet-disease relationships, in The Science of Human Nutrition, Harcourt Brace Jovanovich,
1990, p 7-10.
4. Kaplan GA, Keil JE. Socioeconomic factors and cardiovascular disease: A review of the literature. Circulation
1993; 88(4, pt 1):1973-98.
5. LaRosa JC. "Cholesterol Lowering, Low Cholesterol, and Mortality", Am J Cardiol 1993; 72:776-786.
6. Blackburn H et al, "Heart disease" in Health and Preventive Medicine, 12th ed., ed. J. Last (Norwalk,
Conn:Apple-Century-Croft, 1985), p 1159-1193.
7. Roemer MI. "The value of medical care for health promotion", American Journal of Public Health 1984; 74:243248.
8. Vital Statistics of the United States, 1985; vol. II. Mortality Part A. National Center for Health Statistics, PHS#
88-1101, Washington DC: U.S. Government Printing Office, 1988.
9. Charting the Nation's Health Trends since 1960, DHHS publication no. (PHS) 85-125 (Washington D.C.:National
Center For Health Statistics, 1985).
10. Eliot RS. Is it Worth Dying For? How to Make Stress Work For You Not Against You, Bantam, 1989.
11. Vital Statistics of the United States, 1985(1988); vol I, National Center for Health Statistics, PHS 88-1101,
Washington D.C.: U.S. Government Printing Office.
12. Juvenile Justice Digest, Vol 1; Aug 4, 1993.
13. Hespel P. "Changes in plasma lipids and apoproteins associated with physical training in middle-aged sedentary
men," Am Heart J 1988; 115:786-792.
14. Houston, MC. "New Insights and New Approaches for the Treatment of Essential Hypertension", Am Heart J
1989; 117:911-951.
15. Kaplan, NM. Clinical Hypertension. 4th ed. Baltimore: The Williams and Wilkins Co, 1986:1-56.
16. The 1988 Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood
Pressure. Arch Intern Med 1988;148:1023-38.
17. Castelli WP. Epidemiology of Coronary Artery Disease: The Framingham Study. Am J Med 1984;76:4-12.
18. Hypertension Detection and Follow-up Program Cooperative Group. Five-year findings of the Hypertension
Detection and Follow-up Program. JAMA 1979;242:2562-71.
19. Rowland M, Roberts J. Blood Pressure Levels in Persons 6-74 years: United States 1976-1980, Advance data.
National Center for Health Statistics, Vital and Health Statistics. No. 84. Washington D.C.: United States
Department of Health and Human Services, United States Public Health Service, October 8, 1982.
20. Neaton JD, Kuller LH, Wentworth D, Borhani NO. Total and cardiovascular mortality in relation to cigarette
smoking, serum cholesterol concentration, and diastolic blood pressure among black and white males followed up for
Page 212
five years. Am heart J 1984;108:759-69.
21. Castelli W, Leaf A. Identification and assessment of cardiac risk--an overview. Cardiology Clin 1985;3:171-8.
22. Veterans Administration Cooperative Study Group on Antihypertensive Agents. Effects of treatment on
morbidity in hypertension. II. JAMA 1970;213:1143-52.
23. Smith WM. Treatment of mild hypertension: Results of a ten-year intervention trial. Circ Res 1977;40(Suppl
I)I98-I105.
24. Perry HM Jr. Treatment of mild hypertension: Preliminary results of a two-year feasibility trial. Circ Res
1977;40(Suppl I)I180-I187.
25. Helgeland A. Treatment of mild hypertension: a five year controlled drug trial. The Oslo study. Am J Med
1980;69:725-32.
26. Report by the Management Committee. The Australian Therapeutic Trial in Mild Hypertension. Lancet
1980;1:1261-1267.
27. Greenberg G, Brennan PJ, Miall WE. Effects of diuretic and beta-blocker therapy in the Medical Research
Council Trial. Am J Med 1984;76:45-51.
28. Multiple Risk Factor Intervention Trial Research Group. Multiple Risk Factor Intervention Trial. Risk factor
changes and mortality results. JAMA 1982;248:1465-1477.
29. Amery A, Birkenhager W, Brixko P, et al. Mortality and morbidity results from the European Working Party in
High Blood Pressure in the Elderly trial. Lancet 1985;1:1349-54.
30. Mittinen TA, Huttunen JK, Naukkarlnen V et al. Multifactorial primary prevention of cardiovascular diseases in
middle-aged men. Risk factor changes, incidence, and mortality. JAMA 1985;254:2097-2102.
31. Wilhelmsin L, Tibblin G, Werko, L. A primary preventive study in Gothenberg, Sweden. Prev Med 1972;1:15360.
32. Kannel WB, Sorlie P. Hypertension in Framingham. In: Paul O, ed. Epidemiology and control of hypertension.
New York: Stratton Intercontinental Medical Books, 1975:553.
33. Goldberg RJ, Gore JM et al. Recent changes in the attack and survival rates of acute myocardial infarction (1975
through 1981). The Worcester Heart Attack Study. JAMA 1986;255:2774-9
34. Kannel WB, Eaker ED. Psychosocial and other features of coronary heart disease: Insights from the Framingham
study. Am Heart J 1986;112:1066-73
35. Stamler J. Research related to risk factors. Circulation 1979;60(7):1575-87.
36. Kahn HA. Change in serum cholesterol associated with changes in the United States civilian diet, 1909-1965.
Am J Clin Nutr 1970;23(7):879-882.
37. Wright JT Jr. Profile of systemic hypertension in black patients. Am J Cardiol 1988;61:41H-45H.
38. Weir MR, Saunders E. Pharmacologic management of systemic hypertension in blacks. Am J Cardiol
1988;61:46H-52H.
39. Kannel WB. Role of blood pressure in cardiovascular morbidity and mortality. Prog Cardiovasc Dis 1974;17:524
40. Messerli FH. Management of essential hypertension in the black patient: Profiling as the initial approach to
treatment. JAMA 1989;81(1):17-23
Page 213
41. Rostand SG, Kirk KA et al. Racial differences in the incidence of treatment for end stage renal disease. N Engl J
Med 1982;306:1276-1289.
42. Knapp JA, Haffner SM et al. Dietary intakes of essential nutrients among Mexican-Americans and AngloAmericans: The San Antonio Heart Study. Am J Clin Nutr 1985;42:307-316.
43. Gillum RF, Liu KC. Coronary heart disease mortality in United States Blacks, 1940-1978: Trends and
unanswered questions. Am Heart J 1984;108:728-732
44. Phillips JH, Bruce GE. A review of cardiovascular diseases in the white and negro races. Medicine 1960;39:241289.
45. Watkins LO. Epidemiology of coronary artery disease in black populations: Methodologic proposals. Am Heart J
1984;108:635-640.
46. Levy RI, Feinleib M. Risk factors for coronary artery disease and their management. In: Braunwald E, ed. Heart
Disease. A textbook of cardiovascular medicine. Philadelphia. WB Saunders, 1980:1246.
47. Kottke TE, Young DT, McCall MM. Effect of social class on recovery from myocardial infarction. Minn Med
1980;63:590-597.
48. Hagstorm RM, Federsteil CF, Ho WY. Incidence of myocardial infarction and sudden death from coronary artery
disease in Nashville, Tennessee. Circulation 1971;44:884-890.
49. Cassel J, Heyden S, Bartel AG, et al. Incidence of coronary heart disease by ethnic group, social class and sex.
Arch Intern Med 1971;128:901-906.
50. Tyroler HA, Knowles MG,et al. Ischemic heart disease risk factors and 20-year mortality in middle-age Evans
County Black Males. Am Heart J 1984;108:738-746.
51. Cardiovascular and cerebrovascular disease. vol IV. Report of the Secretary's Task Force on Black and Minority
Health, HHS, 1986.
52. Hiser E. "Obesity: Stress and the big gutted man." Nutrition Letter. Eating Well 1994;IV(4):93
53. Multiple Risk Factor Intervention Trial Research Group, JAMA 1982;248(12):1465-1477
54. McLanahan S., and Booth K. "Mother-only families: Problems, prospects and politics." Journal of Marriage and
the Family 1989;51:557-580.
55. Davidson N. "Life without father." Policy Review, Winter 1990:40.
56. Hess T, "Recruiting fathers to heal a nation." Citizen 1993; 7(10):1-4. 57. Readership poll, Newsweek, August
30, 1993.
57. Friedman M and Rosenman RH. Type A Behavior and Your Heart. New York: Knopf, 1974
58. Selye H. Stress Without Distress. Philadelphia: Lippincott, 1974.
59. Biggs M. "The long lunch theory." Nutrition Letter. Eating Well 1994;IV(4):94
60. Clarkson TB, Weingand KW, et al. Mechanisms of atherogenesis. Circulation 1987;76(Suppl 1):20-28.
61. Armstrong BK, Mann JI et al. Commodity consumption and ischemic heart disease mortality, with special
references to dietary practices. J Chron Dis 1975;28:455-469.
62. Harper AE. Coronary heart disease-an epidemic related to diet? Am J Clin Nutr 1983;37:669-681.
Page 214
63. Stallones RA. The rise and fall of ischemic heart disease. Sci Am 1980;243:53-9.
64. Kiplinger Washington Editors. The Kiplinger Washington Letter 1994;71(6):2
65.Ravnskov U. Cholesterol lowering trials in coronary heart disease: frequency of citation and outcome. British
Med J 1992;305:15-19
66. Cifkova, R. Science News 139,16:246
67. Gey KF, Puska P, Jordan P, Moser UK. Inverse correlation between plasma vitamin E and mortality from
ischemic heart disease in cross-cultural epidemiology. Am J Clin Nutr 1991;53:326S-334S
68 Vitamin C and high density lipoprotein. Medical World News (32,8:11)
69.Manson JE, Stampfer MJ, et al. Antioxidant vitamins and secondary prevention of cardiovascular disease in high
risk women. Circulation 1993; 88,4(Pt 2):I70
70.Mattiasson I, Lindgarde F, Nilsson JA, Theorell T. Threat of unemployment and cardiovascular risk factors:
longitudinal study of quality of sleep and serum cholesterol concentrations in men with threatened redundancy.
British Med J 1990; 301:461-6.
71.Edelstein SL, Barrett-Connor E, Wingard D, Cohn B. Increased meal frequency associated with decreased
cholesterol concentrations: Rancho Bernardo, CA 1984-1987. Am J Clin Nutr 1992;55:664-9.
72. Maynard C., Weaver W. et al. Hospital mortality in acute myocardial infarction in the era of reperfusion therapy
(the myocardial infarction triage and intervention project. Am J Cardiol 1993;72:877-882.
73. Gillum RF. Acute myocardial infarction in the United States, 1970-1983. Am Heart J. 1987;113:804-811.
74. Neaton JD, Blackburn H et al. Serum cholesterol level and mortality findings for men screened in the Multiple
Risk Factor Intervention Trial. Arch Int Med 1992;152:1490-1500
75. Jacobs D, Blackburn H. et al. Report on the conference on low blood cholesterol: mortality associations.
Circulation 1992;86:1046-1060.
76. Hulley SB, Walsh JMD, Newton TB. Health policy on blood cholesterol: Time to change directions. Circulation
1992;86:1026-1029.
77. Muldoon MF, Manuck SB, Matthews KA. Lowering cholesterol concentrations and mortality: a quantitative
review of primary prevention trials. Br Med J 1990;301:309-314.
78. Warram JH,Lori MB, et al. Excess mortality associated with diuretic therapy in diabetes mellitus. Arch Intern
Med 1991;151:1350-1356
79. Aberg A, Bergstrand R, Johansson S. et al. Cessation of smoking after myocardial infarction. Effects on mortality
after 10 years. Br Heart J 1983;49:416-422.
80. Davenport J. Whittaker K. Secondary prevention in elderly survivors of heart attacks. AFP 1988;38(1):216-224
81. Schlant RC, Forman S et al. The natural history of coronary heart disease: prognostic factors after recovery from
myocardial infarction in 2789 men. The 5-year findings of the coronary drug project. Circulation 1982;66:401-14.
82. The prognostic importance of plasma glucose levels and of the use of oral hypoglycemic drugs after myocardial
infarction im men. Diabetes 1977;26:453-65.
83. Haft JI. Role of blood platelets in coronary artery disease. Am J Cardiol 1979;43(6):1197-206.
Page 215
84. Eliot RS. Coronary artery disease:Biobehavioral factors. Circulation 1987;76(Suppl I):I110-11.
85. Blumenthal JA, Levenson RM. Behavioral approaches to secondary prevention of coronary heart disease.
Circulation 1987;76(1Pt2):I130-7.
86. Shaw LW. Effects of a prescribed supervised exercise program on mortality and cardiovascular morbidity in
patients after a myocardial infarction. The National Exercise and Heart Disease Project. Am J Cardiol
1981;48(1):39-46.
87. Leon AS, Connett J et al. Leisure-time physical activity levels and risk of coronary heart disease and death. The
Multiple Risk Factor Intervention trial. JAMA 1987;258:2388-95.
88. Saltin B. Lindgarde F. et al. Physical training and glucose tolerance in middle-aged men with chemical diabetes.
Diabetes 1979;28(Suppl 1):30-2.
89. Freknay GA, Leslie DK. Effects of an exercise program on selected flexibility measurements of senior citizens.
Gerontologist 1975;15:182-3.
90. Seals DR, Allen WK et al. Elevated high density lipoprotein cholesterol levels in older endurance athletes. Am J
Cardiol 1984;54(3):390-3.
91. Blackburn H, Taylor HL et al. Premature ventricular complexes induced by stress testing. Their frequency and
response to physical conditioning. Am J Cardiol 1973;31(4):441-9.
92. Trial of clofibrate in the treatmment of ischaemic heart disease. Five-year study by a group of physicians of the
Newcastle upon Tyne region. Br Med J 1971;790(4):767-75.
93. Clofibrate and niacin in coronary heart disease. JAMA 1975;231:360-81.
94. Ischaemic heart disease:a secondary prevention tria using clofibrate. Report by a research committee of the
Scottish Society of Physicians. Br Med J 1971;790(4):775-84.
95. Wilhelmsson C, Vedin JA et al. Smoking and myocardial infarction. Lancet 1975;1(7904):415-20.
96. Koenig K. Recommendations of the scientific councils of the International Society and Federation of Cardiology
on risk reduction after myocardial infarction. Adv Cardiol 1986;33:28-39.
97. Sparrow D, Dawber TR. The influence of cigarette smoking on prognosis after a first myocardial infarction. A
report from the Framingham study. J Chron Dis 1978;31(6-7):425-32.
98. Intact group investigators. Retardation of angiographic progression of coronary artery disease by nifedipine.
Lancet 1990;335:1109-13.
99. Houston MC. New insights and approaches to reduce end-organ damage in the treatment of hypertension:
Subsets of hypertension approach. Am Heart J 1992;123:1337-67.
100. Stamler J, Stamler R. Intervention for the prevention and control of hypertension and atherosclerotic diseases:
United States and international experience. Am J Med 1984;76:13-36.
101. Moser M. Clinical trials, diuretics, and the management of hypertension. Arch Intern Med 1984;144:789-93.
102. Abbott RD, Yin Y et al. Risk of stroke in male cigarette smokers. New Engl J Med 1986;315:717-20.
103. Colditz GA, Bonita R, et al. Cigarette smoking and risk of stroke in middle-aged women. New Engl J Med
1988;318:937-41.
104. Miller GD, Kuller LH. Trends in mortality from stroke in Baltimore, Maryland: 1940-1941 through 1968-1969.
Am J Epidemiol 1973;98:233-42.
Page 216
105. Acheson RM, Williams DRR. Does consumption of fruits and vegetables protect against stroke? Lancet 1983;
1:1191-3.
106. Khaw KT,Barrett-Conner E. Dietary potassium and stroke-associated mortality:a 12-year prospective
population study. New Engl J Med 1987;316:235-40.
107.Barber DJP, Osmond C. Death rates from stroke in England and wales predicted from past maternal mortality.
Br Med J 1987;295:83-6.
108. Covey, S.R. The Seven Habits of Highly Effective People. Fireside: Simon and Schuster. New York, 1990
109. Robertson P. The Turning Tide: The Fall of Liberalism and the Rise of Common Sense. Dallas: Word, 1993.
110. Gillman MW, Kannel WB, Belanger A, D'Agostino RB. Influence of heart rate on mortality among persons
with hypertension: The Framingham Study. Am Heart J 1993;125:1148-1154.
111. Hespel P. et al. Changes in plasma lipids and apoproteins associated with physical training in middle aged
sedentary men. Am Heart J 1988;115:786-92.
112. Pappas G, Queen S, Hadden W, Fisher G. The increasing disparity in mortality between socioeconomic groups
in the United States, 1960 and 1986.
N Engl J Med 1993;329:103-9.
113. Keil JE, Sutherland S, Knapp R, Lackland D, Gazes P, Tyroler H. Mortality rates and risk factors for coronary
disease in black as compared to white men and women. N Engl J Med 1993;329:73-8.
114. Guralnik J, Land K, Blazer D, Fillenbaum G, Branch L. Educational status and life expectancy among older
blacks and whites. N Engl J Med 1993; 329:110-6.
115. McGinnis J, Foege W. Actual causes of death in the United States. JAMA 1993;270:2207-2212.
116. Brenner MH. Economic change, alcohol consumption and heart disease mortality in nine industrialized
countries. Soc Sci Med 1987;25:119-32.
117. Starrin B, Larsson G, Brenner SO. Regional variations in cardiovascular mortality in Sweden--structural
vulnerability in the local community. Soc Sci Med 1988;27:911-7.
118. Moser KA, Goldblatt PO, Fox AJ, Jones DR. Unemployment and mortality:comparisons of the 1971 and 1981
longitudinal study census sample. Br Med J 1987;294:86-90.
119. Beale N, Nethercott S. Job loss and health--the influence of age and previous morbidity. J R Coll Gen Pract
1986;36:261-4.
120. Kammerling R, O'Connor S. Unemployment rate as predictor of rate of psychiatric admission. Br Med J
1993;307:1536-9.
121. Faris REL, Dunham HW. Mental disorders in urban areas. Chicago:Hafner, 1939.
122. Bolton W, Oatley K. A longitudinal study of social support and depression in unemployed men. Psychol Med
1987;17:453-60.
123. Melville D, Hope D, Bennison D, Barraclough B. Depression among men made involuntarily redundant.
Psychol med 1985;15:789-93.
124. Eales MJ. Depression and anxiety in unemployed men. Psychol Med 1988;18:935-45.
125. Campbell DA,Radford JMC, Burton P. Unemployment rates; an alternative to the Jarman index? Brit Med J
Page 217
1991;303:750-5.
126. Holmes TH, Rahe RH. The social readjustment rating scale. J Psychosom Res 1967;11:213-218.
127. Kessler RC, Turner JB, Hoare JS. Unemployment and emotional functioning in a community sample. Am
Sociol Rev 1989;24:648-57.
128. Newton J. Preventing mental illness. Routledge:London, 1988.
129. Kaplan GA, Keil JE. "Socioeconomic Factors and Cardiovascular Disease: A review of the Literature",
American Heart News, Nov. 10, 1993.
130. Haan M, Kaplan GA, Camacho T. Poverty and health: prospective evidence from the Alameda County Study.
Am J Epidemiol 1987;125:989-998.
131. Wilson TW, Kaplan GA, Kauhanen J, Cohen RD, Wu M, Salonen R, Salonen JT. The association between
plasma fibrinogen concentration and five socioeconomic indices in the Kuopio Ischemic Heart Disease Risk Factor
Study. Am J Epidemiol 1993;137:292-300.
132. Marmot MG,Kogevinas M,Elston MA. Social/economic status and disease. Ann Rev Public Health 1987;
8:111-135.
133. Goldberg KC, Hartz AJ, Jacobsen SJ, Krakauer H, Rimm AA. Racial and community factors influencing
coronary artery bypass graft surgery rates for all 1986 Medicare patients. JAMA 1992; 267:1473-1477.
134. Ford E, Cooper R, Castaner A, Simmons B, Mar M. Coronary arteriography and coronary bypass surgery
among white and other racial groups relative to hospital-based incidence rates for coronary artery disease: findings
from the NHDS. Am J Public Health 1989; 79:437-440.
135. Oberman A,Cutter G. Issues in the natural history and treatment of coronary heart disease in black populations:
surgical treatment. Am Heart J. 1984;108(Pt 2):688-694.
136. Maynard C, Fisher LD, Passamani ER, Pullum T. Blacks in the Coronary Artery Surgery Study (CASS): race
and clinical decision making. Am J Public Health 1986;76:1446-1448.
137. Holme I, Helgeland A, Hjermann I, Leren P. Socioeconomic status as a coronary risk factor: The Oslo study.
Acta Med Scand Suppl 1982; 660:147-151.
138. Doornbos G, Kromhout D. Educational level and mortality in a 32-year follow-up study of 18-year old men in
the Netherlands. Int J Epidemiol 1990;19:374-379.
139. Fox AJ, Goldblatt PO. Longitudinal study 1971-1975: England and Wales. Office of Population Censuses and
Surveys. London: Her Majesty's Stationery Office; 1982.
140. Salonen JT. Socioeconomic status and risk of cancer, cerebral stroke, and death due to coronary heart disease
and any disease: a longitudinal study in eastern Finland. J Epidemiol Community Health 1982;36:294-297.
141. Hirdes JP,Forbes WF. The importance of social relationships, socioeconomic status and health practices with
respect to mortality among healthy Ontario males. J Clin Epidemiol 1992;45:175-182.
142. Keil JE, Loadholt CB, Weinrich MC, Sandifer SH, Boyle E Jr. Incidence of coronary heart disease in blacks in
Charleston, South Carolina. Am Heart J 1984; 108(Pt 2):779-786.
143. Rogot E, Sorlie PD, Johnson NJ, Schmitt. A mortality study of 1.3 million persons by demographic, social and
economic factors: 1979-1985 Follow-up. National Institutes of Health. 1992. NIH Publication No. 92-3297:1-5.
144. Kitagawa EM, Hauser PM. Differential Mortality in the United States: A Study in Socioeconomic
Epidemiology. Cambridge, Mass: Harvard University Press; 1973.
Page 218
145. Schmieder RE, Ruddel H, von Eiff AW. Cardiovascular Therapy and Stress. In Messerli FH (ed):
Cardiovascular Drug Therapy Philadelphia: WB Saunders, 1990:219-228.
146. Selye H: Forty years of stress research. The principal remaining problems and misconceptions. Can Med Assoc
J 115:53, 1976.
147. Selye H: The stress concept. In Wheatley D (ed). Stress and the Heart. New York: Raven Press,1977:1-11.
148. Eliot RS, Buell JC, Dembroski TM. Biobehavioral perspectives on coronary artery disease, hypertension and
sudden cardiac death. Acta Med Scand 1982; (Suppl)660:203.
149. Eliot RS, Buell JL. The role of CNS in cardiovascular disorders. Hosp Pract 1983; 18:189
150. Keys A, Simonsen E. Mortality and coronary heart disease among men studied for 23 years. Arch Intern Med
1971;128:201.
151. Morgan KJ, Stampley GL, Zambik ME et al. Magnesium and calcium dietary intakes of the US population. J
Am Coll Nutr 1985;4:195.
152. Ruddel H, Gogolin E, Neus H. Magnesium and kardiovaskulare Reaktivitat wahrend
Belastungsuntersuchungen. Magnesium Bull 1982;4:98
153. Altura BM, Altura BT. Role of magnesium ions in contractility of blood vessels and skeletal muscles.
Magnesium Bull 1981;3:102.
154. Altura BM, Altura BT, Gebrewold A, et al. Magnesium deficiency and hypertension: Correlation between
magnesium-deficient rats and microcirculatory changes in situ. Science 1984;223:1315.
155. Schmieder R, Ruddel H, Neus H et al. Magnesium homeostasis in hypertensives: Impact on hemodynamic
pattern at rest and during challenge (abstract). J Am Coll Nutr 1985;4:378.
156. MacGregor G, Markandu N, Smith S et al. Moderate potassium supplementation in essential hypertension.
Lancet 1982;2:567-570.
157. Khaw K, Thom S. Randomized double blind cross-over trial of potassium on blood pressure in normal subjects.
Lancet 1982;2:1127-1129.
158. Khaw K, Barrett-Conner E. Dietary potassium and blood pressure in a population. Am J Clin Nutr
1984;39:963-968.
159. Ophir O, Peer G, Gilad J, et al. Low blood pressure in vegetarians: The possible role of potassium. Am J Clin
Nutr 1983;37:755-762.
160. Facts from the Current Population Survey, March Supplement. Bureau of the Census: The Changing Situation
of Americans and their Families. U.S. Department of Commerce Economics and Statistics Administration; CPS-676
(11/93)
161. Facts Sheet for the Current Population Survey. Bureau of the Census: U.S. Department of Commerce
Economics and Statistics Administration; US GPO 1992-0-330-846; BC-1433(06/92)
162. Narins RG. Mild hypertension: a therapeutic dilemma. Kidney Int 1984;26:881-94.
163. Stern MP, Brown BW, Haskel WL et al. Cardiovascular risk and the use of oestrogens or estrogen-progestagen
combinations. JAMA 1976;235:811.
164. Falkner B, Onesti G, Angelakos ET. Hemodynamic response to mental stress in normal adolescents with
varying degree of genetic risk for essential hypertension. In Yamori Y, Lovenberg W, Freis E (eds): Prophylatic
Page 219
Approach to Hypertensive Diseases. New York: Raven Press, 1979:pp 149-156.
165. Neus H, Ruddel H, Schulte W. The long term effect of noise on blood pressure. J Hypertension 1985;3:31.
166. von Eiff AW. The role of the autonomic nervous system in the etiology and pathogenesis of essential
hypertension. Jpn Circ J 1970;34:147.
167. von Eiff AW, Schulte W, Hensch G. Classification of homogeneous blood pressure groups and the specific
hemodynamic pattern of borderline hypertension. In Yamori Y, Lovenberg W, Freis E (eds): Perspectives in
Cardiovascular Research. Prophylatic Approach to Hypertensive Diseases. New York: Raven Press, 1979:pp 315319.
168. Brod J, Fencl V, Hejl Z. Circulatory changes underlying blood pressure elevation during acute emotional stress
(mental arythmetic) in normotensive and hypertensive subjects. Clin Sci 1959;18:269.
169. von Eiff AW, Gogolin E, Jacobs U et al. Heart rate reactivity under mental stress as a predictor of blood
pressure development in children. J Hypertension 1985;3(Suppl 4):89.
170. von Eiff AW, DFG-Forschungsbericht Bonn-Bad Godesberg. Fluglarmwirkungen. Eine interdisziplinare
Untersuchung uber die Auswirkungen des Fluglarms auf den Menschen. Der medizinische Untersuchungsteil. Bd. I.
Bolt, Boppard, 1974, pp 349-424.
171. Cobb S, Rose RM. Hypertension, peptic ulcer and diabetes in air traffic controllers. JAMA 1973;244:489.
172. Schmeider RE, Messerli FH, Ruddel H. Risk for arterial hypertension. Cardiol Clin 1986;4:57.
173. Bright MB: A follow-up study of the commission on chronic illness morbidity survey in Baltimore: I. Tracing a
large population sample over time.
J Chronic Dis 1967;20:707-716.
174. Carpenter A. Facts About the Cities. New York, NY: HW Wilson Co; 1992.
175. Lombardi G, Gallagher EJ, Gennis P. Outcome of Out-of-Hospital Cardiac Arrest in New York City: The PreHospital Arrest Survival Evaluation (PHASE) Study. JAMA 1994;271:678-683.
176. Becker LB, Ostrander MP, Barrett J, Kondos GT. Outcome of cardiopulmonary resuscitation in a large
metropolitan area: where are the survivors? Ann Emerg Med 1991;20-355-361.
177. Blendon RJ, Aiken LH, Freeman HE, Corey CR. Access to medical care for black and white Americans: a
matter of continuing concern. JAMA 1989;261:278-281.
178. Becker LB, Han BH, Meyer PM et al. Racial differences in the incidence of cardiac arrest and subsequent
survival. N Engl J Med 1993;329:600-606.
179. Cowie MR, Fahrenbruch CE, Cobb LA, Hallstrom AP. Out of hospital cardiac arrest: racial differences in
outcome in Seattle. Am J Public Health 1993;83:955-959.
180. Hecker MM. Report of the Secretary's Task Force on Black and White Minority Health: Volume 1, Executive
Summary. Washington, DC:US Government Printing Office; 1985.
181. Lee I-M, Manson J, et al. Body weight and mortality: a 27-year follow-up of middle-aged men. JAMA
1993;270:2823-2828.
182. Whitehead M. The Black Report and The Health Divide. In: Townsend P, Davidson N eds. Inequalities in
Health. London, England: Penquin; 1992.
183. Fagerberg B, Anderson O, Isaksson B, et al. Blood pressure control during weight reduction in obese
hypertensive men: Separate effects of sodium and energy restriction. Br Med J 1984;288:11-14.
Page 220
184. Meneely G, Battarbee H. High sodium-low potassium environment and hypertension. Am J Cardiol
1976;3:318-326.
185. Prineas R, Blackburn H. Clinical and epidemiological relationships between electrolytes and hypertension. In:
Horan M, Blaustein M, Dunbar J et al., eds. NIH Workshop on Nutrition and Hypertension. New York: Biomedical
Information Corp. 1985.
186. Porter G. Chronology of the sodium hypothesis in hypertension. Ann Intern Med 1983;98(5, pt 2):720-724.
187. Dahl L. Salt intake in hypertension. In: Genset J, ed. Hypertension. New York: McGraw-Hill Book Co.,548558. 1977.
188. Glieberman L. Blood pressure and dietary salt in human populations. Ecol Food Nutr 1973;2:143-146.
189. Morgan T, Adam W, Gilles A, et al. Hypertension treated by salt restriction. Lancet 1978;1:227-230.
190. Gruchow H, Sobcinski K, Baboriak J. Alcohol, nutrient intake, and hypertension in U.S. adults. JAMA
1985;253(11):1567-1570.
191. Harlan W, Hull A, Schmouder R et al. Blood pressure and nutrition in adults. Am J Epidemiol 1985;120:17-28.
192. McCarron D, Morris C, Henry H. Blood pressure and nutrient intake in the United States. Science
1984;224:1392-1398.
193. Malarkey W. Perception of social support and blood pressure. Ohio State University General Clinical Research
Center. Personal communication, Feb 24, 1994.
194. Watson R, Langford H, Abernathy J et al. Urinary electrolytes, body weight, and blood pressure: Pooled crosssectional results among four groups of adolescent females. Hypertension 1980;2(suppl I):93-98.
195. McCarron D, Morris C, Cole C. Dietary calcium in human hypertension. Science 1982;217:267-269.
196. Barret-Conner E, Suarez L. Dairy products, calcium and blood pressure. Am J Clin Nutr 1983;38:457-461.
197. Kagan A, Yano K, Rhoads G, McGee D. Alcohol and cardiovascular disease: The Hawaiian experience.
Circulation 1981;64(2):27-31, monograph 81.
198.Klatsky A, Friedman G. Alcohol and Hypertension. In: Horan M, Blaustein M, Dunbar J et al., eds. NIH
Workshop on Nutrition and Hypertension. New York: Biomedical Information Corp. 1985.
199. Dyer A, Stamler J, Pauo O, et al. Alcohol, cardiovascular risk factors, and mortality: The Chicago experience.
Circulation 1981;64(2):20-30, monograph 81.
200. Elmer P. Dietary methods in cardiovascular disease critique. in: Vital and Health Statistics, Dietary
Methodology Workshop for the Third National Health and Nutrition Examination Survey, National center for Health
Statistics, U.S. Department of Health and Human Services.Series 4; No. 27:35. 1992.
201. Wallace R, Lynch C, Promrehn M et al. Alcohol and hypertension: Epidemiologic and experimental
considerations. The Lipid Research Clinics Program. Circulation 1981;64(2):41-47, monograph 81.
202. Gordon T, Ernst N, Fisher M, Rifkind B. Alcohol and high density lipoprotein cholesterol. Circulation
1981;64(2)63-66, monograph 81.
203. Calahan D. Quantifying alcohol consumption: Patterns and problems. Circulation 1981;64(2):7-13, monograph
81.
204. Gentry E, Kalsbeek W, Hogelin G, et al. The risk factor surveys. II. Design, methods, and estimates from
Page 221
combined state data. Am J Prev Med 1985;1(6):9-14.
205. Shekelle RB, Shryock AM, Paul O, et al. Diet, serum cholesterol, and death from coronary heart disease: The
Western Electric Company Study. N Engl J Med 1981;304:65-70.
206. Shekelle RB, Stamler J, Paul O et al. Dietary lipids and serum cholesterol level: Change in diet confounds the
cross-sectional association. The Western Electric Study. Am J Epidemiol 1982;115:506-514.
207. Prineas R, Jacobs D, Crow R, et al. Coffee, tea and VPB. J Chron Dis 1980;33:67-72.
208. McCarron D, Morris C. Calcium and Hypertension. In: Horan M, Blaustein M, Dunbar J et al., eds. NIH
Workshop on Nutrition and Hypertension. New York: Biomedical Information Corporation. 1985.
209. Henry H, Morris C, Parrott-Garcia M. Increasing calcium intake lowers blood pressure: The literature reviewed.
J Am Dietet Assoc 1985;85:182-5.
210. Johnson NE, Smith E, Freudenheim J. Effects on blood pressure of calcium supplementation of women. Am J
Clin Nutr 1985;42:12-17.
211. McCarron M, Morris C, Cole C. Blood pressure response to oral calcium in persons with mild to moderate
hypertension. Ann Intern Med 1985;103:825-831.
212. Tillotson JL, Kato MA, Nichaman MZ, et al. Epidemiology of coronary heart disease and stroke in Japanese
men living in Japan, Hawaii, and California: Methodology for comparison of diet. Am J Clin Nutr 1973;26:177-184.
213. Kato MA, Tillotson JL, Nichaman MZ et al. Epidemiological studies of coronary heart disease and stroke in
Japanese men living in Japan, Hawaii, and California. Am J Epidemiol 1973;97:372-385.
214. Seeman I. National Mortality Followback Survey: 1986 Summary, United States. National Center for Health
Statistics. Vital Health Stat 20(19);1992
215. U. S. Bureau of the Census. Current Population Reports, P23-181, Households, Families, and Children: A 30Year Perspective. U.S. Government Printing Office, Washington, D.C., 1992.
216. Vital Statistics of the United States, 1988; vol. II. Mortality Part A. National Center for Health Statistics, PHS#
91-1101, Washington DC: U.S. Government Printing Office, 1991.
217. Vital Statistics of the United States, 1989; vol. II. Mortality Part B. National Center for Health Statistics, PHS#
92-1102, Washington DC: U.S. Government Printing Office, 1992.
218. Ries P. Educational differences in health status and health care. National Center for Health Statistics. Vital
Health Stat 10(179). 1991.
219. Pierce JP, Fiore MC, Novotny TE, Hatziandreu EJ, Davis RM. Trends in cigarette smoking in the United
States: Projections to the year 2000. JAMA 1989;261:61-65.
220. Suarez L, Barrett-Connor E. Interaction between cigarette smoking and diabetes mellitus in the prediction of
death attributed to cardiovascular disease. Am J Epidemiol 1984;120(5):670-675
221. U.S. Department of Health and Human Services: The Health Consequences of Smoking: Cardiovascular
Disease. A report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service,
Office on Smoking and Health. 1983.
222. U.S. Department of Health and Human Services: Reducing the Health Consequences of Smoking--25 years of
progress. A report of the Surgeon General. U.S. Department of Health and Human Services, Public Health Service,
Office on Smoking and Health.1989.
223. MacKenzie TD, Bartecchi CE Schrier RW. The human costs of tobacco use. N Engl J Med 1994;330:975-980.
Page 222
224. Ashcroft J, chairman. Famlies First. Report of the National Comission on America's Urban Families. U.S.
Government Printing Office, Washington D.C. 1993.
225. Eliot RS, Morales-Ballejo HM. The Heart, Emotional Stress, and Psychiatric Disorders. In: Schlant RC,
Alexander RW, ed. Hurst's the Heart: Arteries and Veins. 8th ed., McGraw Hill, Inc. New York. 1994.
226. Eliot RS. From Stress to Strength: How toLightenYour Load and SaveYour Life. Bantam. New York. 1994.
227. Dimsdale JE, Herd JA. Variability of plasma lipids in response to emotional arousal. Psychosom Med
1982;44:413-430.
228. van Doornen LJP, Orlebeke KF. Stress, personality and serum cholesterol level. J Human Stress 1982;8:24-29.
229. Freeman LJ Nixon PGF et al. Psychological Stress and silent myocardial ischemia. Am Heart J 1987;114:477482.
230. Lown B, DeSilva RA, et al. Psychophysiologic factors in sudden cardiac death. Am J Psychiatry
1980;137:1325-1335.
231. Verrier Rl, Lown B. Behavioral stress and cardiac arrythmias. Ann Rev Physiol 1984;46:155-176.
232. Baroldi G, Fazi G, Mariani F. Sudden coronary death: A postmortem study in 208 selected cases compared to
97 "control" subjects. Am Heart J 1979;98:20-31.
233. Tazalaar HD, Karch SB et al. Cocaine and the heart. Hum Pathol 1987;18:195-199.
234. Harburg E, Schull WJ, et al. A family set method for determining heredity and stress: I. A pilot survey of blood
pressure among Negroes in high and low stress areas, Detroit, 1966-1967. J Chronic Dis 1970;23:83-92.
235. Faulkner B, Kushner H et al. Sodium sensitivity, growth, and family history of hypertension in young blacks. J
Hypertens 1986;4 (suppl 5):
S381-S383.
236. Syme SL. Socioenvironmental factors in heart disease. In: Beamish RE, Singal PK, Dhalla ND, (eds): Stress
and Heart Disease. Boston. Martinus Nijhoff Publishing. 1985:60-70.
237. Marmot MG, Syme SL. Acculturation and coronary heart disease in Japanese Americans. Am J Epidemiol
1976;104:225-247.
238. Berkman LF, Syme SL. Social Networks, host resistance, and mortality: A nine-year follow-up study of
Alameda county residents. Am J Epidemiol 1979;109:186-204.
239. Clarkson TB, Kaplan JR et al. Psychosocial influences on the pathogenesis of atherosclerosis among nonhuman primates. Circulation 1987;76(Suppl 1):29-40.
240. Nerem RM, Levesque MJ, Cornhill JF. Social environment as a factor in diet-induced aortic atherosclerosis in
rabbits. Science 1980;208:1475-1476.
241. Williams RB Jr, Barefoot JC, Shekelle RB. The health consequences of hostility. In: Chesney MA, Rosenman
RH. (eds): Anger and Hostility in Cardiovascular and Behavioral Disorders. Washington, D.C. Hemisphere
Publishing. 1985:173-185.
242. Rosenman RH, Brand RJ et al. Coronary Heart Disease in the Western Collaborative Group Study: Final
follow-up experience of 81/2 years. JAMA 1975;233:872-877.
243. Julius M, Harburg E, et al. Anger-coping types, blood pressure, and all cause mortality: A follow-up in
Techumseh, Michigan (1971-1983). Am J Epidemiol 1986;124:220-233.
Page 223
244. Jefferson JW. Biologic treatment of depression in cardiac patients. Psychosomatics 1987;26(suppl 11):31-36.
245. Chodzko-Zajko WJ, O'Connon PJ. Plasma Cortisol, the dexamethasone supression test and depression in
normal adult males. J Psychosom Res 1986;30:313-320.
246. Sims A. Neurosis and mortality: Investigating an association. J Psychosom Res 1984;28:353-362.
247. Baker S, Henry R. Parent's Guide to Nutrition. D. Estridge, ed. Addison-Wesley. Reading, Massachusetts.
1992.
248. Dossey L. Healing Words: The Power of Prayer and the Practice of Medicine. Harper: San Fransisco. 1993.
249. Byrd RC. Positive therapeutic effects of intercessory prayer in a coronary care unit population. Southern
Medical Journal 1988;81(7):826-829.
250. Markovitz, JH, Matthews KA, et al. Psychological predictors of hypertension in the Framingham study: Is there
tension in hypertension? Journal of the American Medical Association 1993;270:2439-2443.
251. Rosengren A, Orth-Gomer K, et al. Stressful life events, social support, and mortality in men born in 1933.
British Medical Journal 1993;307:1102-1105.
252. Marceau M, Kouame N, et al. Effects of different training intensities on 24-hour blood pressure in hypertensive
subjects. Circulation 1993; 88:2803-2811
253. Whitney EN, Rolfes SR. Diet and Health. in: Understanding Nutrition, 6th edition. West. Minneapolis. 1993.
254. Ullrich IH, Reid CM, Yeater RA. Increased HDL cholesterol levels with a weight lifting program. Southern
Medical Journal 1987;80:328-331.
255. Krishna GG, Miller E, Kapoor S. Increased blood pressure during potassium depletion in normotensive men.
New England Journal of Medecine 1989;320:1177-1182.
256. Krishna GG, Kapoor SC. Potassium depletion exacerbates essential hypertension. Annals of Internal Medicine
1991;115:77-82.
257. McCarron et al. Dietary calcium and blood pressure: Modifying factors in specific populations. Am J Clin Nutr
(suppl) 1991;54:215-219.
258. Clark K. Calcium and Hypertension: Does a relationship exist? Nutrition Today July/Aug 1989, pp. 21-26.
259. Keleman MH and coauthors. Exercise training combined with antihypertensive drug therapy: Effects on blood
lipids,blood pressure, and left ventricular mass. JAMA 1990;263:2766-2771.
260. Massie BM. To combat hypertension, increase activity. The Physician and Sportsmedicine 1992;20:89-111.
261. Caspersen CJ, Christenson GM, Pollard RA. Status of the 1990 physical fitness and exercise objectives:
evidence from NHIS 1985. Public Health Rep. 1986;101:587-592.
262. Millar WJ, Wigle DT. Socioeconomic disparities in risk factors for cardiovascular disease. Can Med Assoc J.
1986;134:127-132.
263. Helmert U, Herman B, et al. Social class and risk factors for coronary heart disease in the Federal Republic of
Germany: results of the baseline survey of the German Cardiovascular Prevention Study (GCP). J Epidemiol
Community Health 1989;43:37-42.
264. Rimm IJ, Rimm AA. Association between socioeconomic status and obesity in 59,566 women. Prev Med.
1974;3:543-572.
Page 224
265. Oken B, Hartz A, Giefer E, Rimm AA. Relationship between socioeconomic status and obesity changes in 9046
women. Prev Med. 1977;6:447-453.
266. Stevens J, Keil JE et al. Body mass index and body girths as predictors of mortality in black and white men. Am
J Epidemiol 1992;135:1137-1146.
267. Garn SM, Ryan AS. Replicating the income-related reversal of fatness. Ecology of Food and Nutrition.
1981;10:237-239.
268. Garn SM, Hopkins PJ, Ryan AS. Differential fatness gain of low income boys and girls. Am J Clin Nutr.
1981;34:1465-1468.
269. Junshi C, Campell TC, Junyao L, Peto R. Diet, Lifestyle, and Mortality in China: A study of the
Characteristics of 65 Chinese Counties. Oxford, England: Oxford University Press; Ithaca, NY:Cornell University
Press; China:Peoples Medical Publishing House. volumes I, and II; 1990. (ISDN: 0-19-261843-1).
270. de Lorgeril M, Marmelle N, et al. A Mediterranean-type Diet in the Secondary Prevention of Coronary Heart
Disease. Circulation 1993;88(4 part 2, supplement);abs# 3415:I-635.
271. Beasley RP, Bulger RJ et al, eds. Does a High-Fat Diet Promote Development of Diabetes? The University of
Texas Houston Health Science Center Lifetime Health Letter. March 1994, 6(3):6
272. Popkin BM, Kenou G, Zhai F et al. The nutrition transition in China: a cross-sectional analysis. Eur J Clin Nutr
1993 May;47(5):333-346.
273. Kafatos A, Kouroumalis I, et al. Coronary heart disease risk-factor status of the Cretan urban population in the
1980s. Am J Clin Nutr 1991;54:591-598.
274. Kuller LH. Epidemiology of cardiovascular diseases: current perspectives. Am J Epidemiol 1976;104:425-496.
275. Keys A. Nutrition in relation to etiology and course of degenerative diseases. J Am Dietet Assn 1948;24:281295.
276. Keys A, Anderson JT. The relationship ot the diet to the development of atherosclerosis in man. In: Symposium
on Atherosclerosis. Nat Acad Sci 1954;338;181
277. Antar MA, Ohlson MA, Hodges RE. Changes in retail market food supplies in the United States in the last
seventy years in relation to the incidence of coronary heart disease, with special reference to dietary carbohydrates
and essential fatty acids. Am J Clin Nutr 1964;14:169-178.
278. Wells AF, Ershoff BH. Beneficial effects of pectin in prevention of hypercholesterolemia and increase in liver
cholesterol in cholesterol-fed rats.
J. Nutrition 1961;74:87.
279. Roe, DA. Geriatric Nutrition, Third ed. Englewood Cliffs, N.J.: Prentice Hall. 1992.
280. Klatsky AL, Armstrong MA. Alcohol and 22 Year Coronary Disease Mortality. Circulation 1993 Oct;88(4 part
2);abstract 364:I-70.
281. Sharma, H. How Free Radicals Are Created. Freedom from Disease. Veda. Toronto. 1994:41-72.
282. Margetts BM, Jackson AA. Interactions between people's diet and their smoking habits: the dietary and
nutritional survey of British adults. British Medical Journal 1993;307:1381-1384.
283. Thompson RL, Margetts BM et al. Cigarette smoking and food and nutrient intakes in relation to coronary heart
disease. Nutrition Research Reviews 1992;5:131-152.
Page 225
284. Cade J, Margetts BM. The relationship between diet and smoking: is the diet of smokers different? J Epidemiol
Community Health 1991:45:270-272.
285. Wichelow MJ, Erzinclioglu SW, Cox BD. A comparison of the diets of non-smokers and smokers. Br J Addict
1991;86:71-81.
286. Bolton-Smith C, Woodward M, Brown CA, et al. Nutrient intake by duration of ex-smoking in the Scottish
Heart Study. Br J Nutr 1993;69:315-332.
287. Strickland D, Graves K, Lando H. Smoking status and dietary fats. Prev Med 1992;21:228-236.
288. Gregory J, Foster K et al. The dietary and nutritional survey of British adults. London Her Majesty's Stationery
Office, 1990.
289. Steinberg D, Parthasarthy S, et al. Beyond cholesterol: modifications of low density lipoproteins that increase
its atherogenicity. N Engl J Med 1989;320:915-924.
290. Manson JE, Tosteson H, et al. The primary prevention of myocardial infarction. N Engl J Med 1992;326:14061416.
291. Paffenbarger RS, Hyde RT, Wing AL. Physical activity and physical fitness as determinants of health and
longevity. In: Brouchard C, Shepard RJ, et al, eds. Exercise, Fitness, and Health. Champaign Ill: Human Kinetics
Books; 1990.
292. Powell HE, Caspersen CJ, et al. Physical activity and chronic diseases. Am J Clin Nutr. 1989;49:999-1006.
293. Powell HE, Thompson PD et al. Physical activity and the incidence of coronary heart disease. Ann Rev Public
Health 1987;8:253-287.
294. Robinson CH, Lawler MR, et al. Normal and Therapeutic Nutrition. 17th edition. New York: Macmillan; 1986.
295. The health consequences of smoking: nicotine addiction: a report of the Surgeon General. Rockville, MD.:
Department of Health and Human Services, 1988:15. (DHHS publication no. (CDC) 88-8406.)
296. Strategies to control tobacco use in the United States: a blueprint for public health action in the 1990s. Smoking
and tobacco control monographs no. 1. Rockville MD.: Department of Health and Human Services, 1991. (NIH
publication no. 92-3316).
297. Lynch JW, Kaplan GA, et al. Childhood and adult socioeconomic status as predictors of mortality in Finland.
Lancet 1994;343:524-527
298. Baker D, Illsley R, Vagero D. Today or in the past? The origins of ischemic heart disease. J Public Health Med
1993;15:243-248.
299. Rose G. Cardiovascular Disease. In: Holland WH, Detels R, Knox G, eds. Oxford textbook of public health,
vol. 3. Oxford: Oxford Medical Publications, 1991:175-187.
300. Illsley R, Baker D. Contextual variations in the meaning of health inequality. Soc Sci Med 1991;32:359-365.
301. Marmot MG, Adelstein AM et al. Changing social class distribution of ischemic heart disease. British Medical
Journal 1978;2:1109-1112.
302. Grossman DC, Krieger JW, et al. Health Status of Urban American Indians and Alaskan Natives. JAMA
1994;271:845-850.
303. Anderson JW. Plant fiber and blood pressure. Ann Intern Med. 1983;98:842-846.
304. Burkitt DP et al. Dietary Fiber and Disease. JAMA. 1974;229:1068-1074.
Page 226
305. Trowell H. Ischemic heart disease and dietary fiber. Am J Clin Nutr. 1972;25:926-932.
306. Ascherio A, Hennekens CH, et al. Trans-Fatty Acids Intake and Risk of Myocardial Infarction. Circulation
1994;89:94-101
307. Senti FR, ed. Health Aspects of Dietary trans Fatty Acids: August 1985. Bethesda Md: Federation of American
Societies for Experimental Biology; 1988.
308. Seedat YK. The prevalence, etiology, and complications of hypertension in the South African black population.
in: Prophylactic Approach to Hypertensive Diseases, eds. Yamori Y, Lovenberg W, Freis ED. New York: Raven
Press, 1979,p.7.
309. Seedat YK, Seedat MA. An interracial study of the prevalence of hypertension in an urban South African
population. Trans Roy Soc Trop Med Hyg, 1982;76:62.
310. Seedat YK, Seedat MA, Hackland DBT. Biosocial factors and hypertension in urban and rural Zulu. S Afr Med
J,1982;61:999.
311. Cassel JC. Studies of hypertension in migrants. in: Epidemiology and Control of Hypertension, Papers and
Discussion from the Second International Symposium on the Epidemiology of Hypertension, 1974. Stratton
Intercontinental Medical Book Co.,1975, pp. 41-61.
312. Beck M, Rosenberb D et al. The Infertility Trap. Newsweek. April 4,1994; Vol 123(14):30-31.
313. Prevention Profile, Health, United States, 1991, National Center for Health Statistics, Washington DC: U.S.
Government Printing Office, 1991.
314. Adams PF, Benson V. Current estimates from the National Health Interview Survey. 1991. National Center for
Health Statistics, Vital Health Stat 10(184).
315. Moriyama IM, Grover M. Statistical studies of heart diseases I. Heart diseases and allied causes of death in
relation to age changes in the population. Public Health Rep 1948;63:537-545.
316. Woolsey TD, Moriyama IM. Statistical studies of heart diseases II. Important factors in heart disease mortality
trends. Public Health Rep 1948;63:1247-1273.
317. Grover M, Pennell MY. Statistical studies of heart diseases VII. Mortality from eight specific forms of heart
disease among white persons. Public Health Rep 1950;65:819-839.
318. Epstein FH. The epidemiology of coronary heart disease--a review. J Chronic Dis 1965;18:735-774.
319. Borhani ND, Hechter HH. Recent changes in CVR disease mortality in California. Am J Public Health
1964;79:140-160.
320. Kleinman JC, Feldman JJ, Monk MA. The effects of changes in smoking habits on coronary heart disease
mortality. Am J Public Health 1979;69:795-802.
321. Stern MP. The recent decline in ischemic heart disease mortality. Ann Intern Med 1979;91:630-640.
322. Kannel WB, Thom TJ. Implications of the recent decline in cardiovascular mortality. Cardiovascular Med
1979;4:983-997.
323. Stamler J. Lifestyles, major risk factors, proof and public policy. Circulation 1978;58:3-19.
324. Cooper R, Tsong Y, et al. Is the recent decline in coronary heart disease mortality in the United States
attributable to lower rates of influenza and pneumonia? Prev Med 1980;9:559-568.
Page 227
325. Slater CH, Smith DP, et al. Ischemic heart disease: footprints through the data. Am J Clin Nutr 1985;42:329341.
326. Goldman L, Cook F et al. Evidence that hospital care for acute myocardial infarction has not contributed to the
decline in coronary mortality between 1973-1974 and 1978-1979. Circulation 1982;65:936-942.
327. Marmot MG. Geography of blood pressure and hypertension. Brit Med Bull, 1984;40:380-386.
328. Cottington EM, Brock BM, et al. Psychological factors and blood pressure in the Michigan statewide blood
pressure survey. Am J Epidemiol, 1985;121:515-529.
329. Roe DA. Health and Nutritional Status of Working and Non-working Mothers in Poverty Groups. USDL
Contract 51-36-71-02, Final Report. Ithaca, N.Y.: Cornell University Press, 1971.
330. Ohambo HP, Okanga J, Karkar AHT. The pattern of heart disease. in: Health and Disease in Kenya. eds:Vogel
LC, Muller RS, et al. Nairobi: Kenya Literature Bureau, 1974, pp. 473-478.
331. Pobee JM, Larbi EB, et al. Blood pressure distribution in rural Ghanian population. Trans Roy Soc Trop Med
Hyg. 1977;71:66
332. Gortmaker SL, Must A et al. Social and economic consequences of overweight in adolescence and young
adulthood. N Engl J Med 1993;329:1008-1012.
333. Steinberg D, Parthasarathy S, et al. Beyond cholesterol: modifications of low-density lipoprotein that increase
its atherogenicity. N Engl J Med 1989;320:915-924.
334. Kearney JF Jr, Gaziano JM et al. Dietary antioxidants preserve endothelium-dependent vessel relaxation in
cholesterol-fed rabbits. Proc Natl Acad Sci USA 1993;90:11880-4.
335. The Alpha Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and Beta
Carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-1035.
336. Pierce JP, Lee L, Gilpin E. Smoking initiation by adolescent girls, 1944 through 1988: an association with
targeted advertising. JAMA 1994;271(8):608-611.
337. Kennet L. The American Soldier in World War II. New York, New York: Charles Scribner's Sons; 1987:94.
338. Pierce JP, Gilpin E, Burns DM, et al. Does tobacco advertising target young people to start smoking: evidence
from California. JAMA 1991;266:3154-3158.
339. Accessibility of cigarettes to youths aged 12-17. MMWR Morb Mortal Wkly Rep. 1992;41:485-488.
340. Klonoff EA, Landrine H, et al. The problem and sociocultural context of single cigarette sales. JAMA
1994;271:618-620.
341. Miller R. U.S. cigarette consumption, 1900 to date. In: Harr W, ed. Tobacco yearbook. Bowling Green, Ky:
Cockrel Corporation; 1981.
342. U.S. Department of Agriculture. Tobacco situation and outlook report. Washington, DC: US Department of
Agriculture, Commodity Economics Division, Economic Research Service, TS 224; Sept 1993.
343. Fielding JE. Preventing colon cancer: yet another reason not to smoke.
J Natl Cancer Inst 1994; 86:183-191.
344. Giovannucci E, Rimm E, et al. A prospective study of cigarette smoking and risk of colorectal adenoma and
colorectal cancer in U.S. men. J Natl Cancer Inst 1994; 86:183-191.
345. Giovannucci E, Colditz GA, et al. A prospective study of cigarette smoking and risk of colorectal adenoma and
Page 228
colorectal cancer in U.S. women. J Natl Cancer Inst 1994; 86:192-199.
346. House JS, Kessler RC, et al. Social stratification, age, and health. In: Schaie KW, Blazer D, et al., eds. Aging,
health behaviors, and health outcomes. Hillsdale, N.J.:Lawrence-Earlbaum Associates. 1992:1-32.
347. Davis DL, Dinse GE, Hoel DG. Decreasing cardiovascular disease and increasing cancer among whites in the
United States from 1973 through 1987. JAMA 1994;271:431-437
348. McCormick J, Skrabanek P. Coronary heart disease is not preventable by population interventions. Lancet
1988;ii:839-841.
349. Miller AB. How do we interpret the "bad news" about cancer? JAMA 1994;271(6):468.
350. Alexander F. Emotional factors in essential hypertension. Psychosom Med 1939;1:175-179.
351. Niaura R, Goldstein MG. Psychological factors affecting physical condition. Cardiovascular disease literature
review, Part II: Coronary artery disease and sudden death and hypertension. Psychosom Med 1992;2:146-155.
352. Eliot, RS. Director, Institute of Stress Medicine, International. Personal communication, April 22, 1994.
353. Sommers-Flanagan J, Greenburg RP. Psychosocial variables and hypertension: A new look at an old
controversy. Journ Nerv Ment Dis 1989;1:15-24.
354. Dzau VJ. Atherosclerosis and hypertension: Mechanisms and interrelationships. J Cardiovasc Pharmacol
1990;15(suppl5):S59-S64.
355. Adelson SF, Keys A. Diet and some health characteristics of 123 business and professional men. Agricultural
Research Service, ARS 62-11, Washington D.C., 1962. U.S. Department of Agriculture.
356. Antar MA, Ohlson MA. Effects of simple and complex carbohydrates on thrombus formation, stypven time, and
serum lipids in young men and women. (Abstract) Fed Proc 1963;22(Part 1):327.
357. Hodges RE, Ohlson MA. Total serum lipids, cholesterol and triglycerides following ingestion of diets with two
sources of carbohydrate. (Abstract) Fed Proc 1963;22(Part 1):209.
358. Wenneker MB, Epstein AM. Racial inequalities in the use of procedeures for patients with ischemic heart
disease in Massachusetts. JAMA 1989;261:253-257.
359. Ford E, Cooper R. et al. Coronary arteriography and coronary bypass survey among whites and other racial
groups relative to hospital-based incidence rates for coronary artery disease: findings from NHDS. Am J Public
Health 1989;79:437-446.
360. Hannan EL, Kilburn H et al. Interracial access to selected cardiac procedeures for patients hospitalized with
coronary artery disease in New York State. Med Care 1991;29:430-441.
361. Wenneker MB, Weisman JS, Epstein AM. The association of payer with utilization of cardiac procedeures in
Massachusetts. JAMA 1990;264:1255-1260.
362. Peniston RL, Adams-Campbell L, et al. Coronary Arteriographic findings in black patients and risk markers for
coronary artery disease. Am Heart J 1994;127:552-559.
363. Pearson TA. Risk factors for arteriographically defined CAD [dissertation]. Baltimore: Johns Hopkins
University, 1983:274.
364. Sue-King L, Watkins LO. Coronary arteriographic findings in black veterans [abstract]. Circulation
1984;70(Suppl II):410.
365. Maynard C, Fisher LD, et al. Blacks in the Coronary Artery Surgery Study:risk factors and coronary artery
Page 229
disease. Circulation 1986;74:64-71.
366. Carryon P, Matthews MM. Clinical and coronary arteriographic profile of 100 black Americans:focus on
subgroup with undiagnosed suspicious chest discomfort. J Natl Med Assoc 1987;79:265-272.
367. Simmons BE, Castaner A, et al. Coronary artery disease in blacks of lower socioeconomic status: angiographic
findings from the Cook County Hospital Heart Disease Registry. Am Heart J 1988;116:90-97.
368. Freedman DS, Gruchow HW, et al. Black/white differences in risk factors for arteriographically documented
coronary artery disease in men. Am J Cardiol 1988;62:214-219.
369. Peniston RL, Randall OS. Coronary artery disease in black Americans 1920-1960: the shaping of medical
opinion. J Natl Med assoc 1989;81:591-600.
370. Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Heralth Service,
U.S. Department of Health, Education, and Welfare, 1964.
371. Walker WJ. Changing United States life-style and decreasing vascular mortality: cause or coincidence? N Engl
J Med 1977;297:163-165
372. Mortality trends for the leading cause of death in the United States, 1950-1969. Series 20, No. 16 (DHEW
Publication No. [HRA]74-1853). Rockville Maryland, National Center for Health Statistics, 1974. p.10.
373. Strom A, Jensen RA. Mortality from circulatory diseases in Norway 1940-1945. Lancet 1951;1:126-129.
374. Malmros H. The relation of nutrition to health: a statistical study of the effect of war-time on atherosclerosis,
cardiosclerosis, tuberculosis, and diabetes. Acta Med Scan 1950;246[Suppl]:137-153.
375. United States Department of Agriculture: Agricultural Statistics 1976. Washington, D.C., Government Printing
Office, 1976, pp 106,142,384,414,561.
376. Lopez-S A, Krehl W, et al. Relationship between food consumption and mortality from atherosclerotic heart
disease in Europe. Am J Clin Nutr 1966;19:361-369
377. Susser M, Watson W, Hopper K. Sociology in Medicine. 3rd ed. New York, N.Y.: Oxford University
Press;1985.
378. Antonovsky A. Social class and the major cardiovascular diseases. J Chronic Dis 1968;21:65-106.
379. Morgenstern H. The changing association between social status and coronary heart disease in a rural
population. Soc Sci Med 1980;14A:191-201.
380. Kritz-Silverstein D, Wingard DL, Barrett-Conner E. Employment status and heart disease risk in middle-aged
women: the Rancho Bernardo Study. Am J Public Health 1992;82:215-219.
381. Black D, Morris JN, Smith C. Report of the working group on inequalities in health. London: Department of
Health and Social Security, 1980.
382. Townsend P, Phillmore P, Beattie A. Health and deprivation--inequality and the North. London:Routledge,
1988.
383. Kelley WF, Mahmood R, et al. Influence of social deprivation on illness in diabetic patients. Br Med J
1993;307:1115-1116.
384. Matthews KA, Kelsey SF, et al. Educational attainment and behavior and biologic risk factors for coronary
heart disease in middle-aged women. Am J Epidemiol 1989;129:1132-1144.
385. Holme I, Helgeland A, et al. Physical activity at work and at leisure in relation to coronary risk factors and
Page 230
social class: a 4-year mortality follow-up. The Oslo Study. Acta Med Scand 1981;209:277-283.
386. Salonen JT, Slater JS, et al. Leisure time and occupational physical activity: risk of death from ischemic heart
disease. Am J Epidemiol 1988;127:87-94.
387. Kaplan GA, Lazarus NB, et al. Psychosocial factors in the natural history of physical activity. Am J Prev Med
1991;7:12-17.
388. Moriyama I, Woolsey T, Stamler J. Observations on possible factors responsible for the sex and race trends in
cardiovascular-renal mortality in the U.S. J. Chronic Diseases 1958;7:401-412.
389. Acheson RM. The etiology of coronary heart disease. Yale J Biol Med 1962;35:143.
390. Stamler J. Cardiovascular disease in the U.S. Am J Cardiol 1962;10:319.
391. Keys A. Diet and the development of coronary heart disease. J Chronic Diseases 1956;4:364.
392. Bierman EL, Chait A. Nutrition and diet in relation to hyperlipidemia and atherosclerosis. in: Shils ME, Young
VR, eds. Modern Nutrition in Health and Disease. Philadelphia, Lea and Febiger; 1988(VII edition):1283-1297.
393. Yeracaris CA, Kim JH. Socioeconomic differentials in selected causes of death. Am J Public Health
1978;68:342-351.
394. Pamuck ER. Social class inequality in mortality from 1921 to 1972 in England and Wales. Population Studies
1985;39:17-31.
395. Marmot MG, McDowall ME. Mortality decline and widening social inequalities. Lancet 1986;2:274-276.
396. Fox AJ, Goldblatt PO, Jones DR. Social class mortality differentials: artefact, selection, or life-circumstances? J
Epidemiol Community Health 1985;39:1-8.
397. Lerner M, Stutz RN. Mortality by socioeconomic status, 1959-1961 and 1969-1971. Md State Med J
1978;27:35-42.
398. Wing S, Barnett E, et al. Geographic and Socioeconomic variation in the onset of decline of coronary heart
disease mortality in white women. Am J Public Health 1992;82:204-209.
399. Wing S, Casper M, et al. Socioenvironmental characteristics associated with the onset of decline of ischemic
heart disease mortality in the United States. Am J Public Health 1988;78:923-926.
400. Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial Results. I.
Reduction in incidence of coronary heart disease. JAMA 1984;251:351-364.
401. Lipid Research Clinics Program: The Lipid Research Clinics Coronary Primary Prevention Trial Results. II.
The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA 1984;251:365374.
402. St Leger AS, et al. Factors associated with cardiac mortality in developed countries with particular reference to
the consumption of wine. Lancet 1979;1:1017-1019.
403. Castelli, WP, et al. Alcohol and blood lipids. Lancet 1977;2:153-155.
404. Alexander GR et al. Am J Public Health 1993;83:1721-1725.
405. Bennett WJ. The Index of Leading Cultural Indicators. The Heritage Foundation 1993;1:1-23.
406. Senator Robert Byrd, D-W.Va, chairman of the Senate Appropriations Committee, Associated Press Wire
Release, Washington, D.C., May 14, 1994.
Page 231
407. Negro Mortality. III. Course of Mortality from Specific Causes, 1920-1944. Public Health Reports
1948;63:201-213.
408. Negro Mortality. VIII. Mortality from Heart Disease among Negroes as Compared with White Persons. Public
Health Reports 1951;66:57-80.
409. Heart Disease and Tuberculosis. Public Health Reports 1946;61:1425.
410. Charlewood GP, Frylinck R. Discrepancies in disease incidence between the European and South African
Negro (Bantu). South African M.J. 1951;25:551-556.
411. Kesilman M. The incidence of essential hypertension in white and negro males. Medical Record 1941;154:1619.
412. Hartnett WG, Ratcliffe HE. Study of hypertension on southern negroes. Southern Med J 1948;41:847-848.
413. Saunders GM, Bancroft H. Blood pressure studies on negro and white men and women living in the Virgin
Islands of the United States. Am Heart J 1942;23:410-423.
414. Crile G. The Surgical Treatment of Hypertension. W.B. Saunders Co. Philadelphia, 1938: pp.29,37.
415. Donnison CP. Blood pressure in African natives, bearing upon etiology of hypertension and atherosclerosis.
Lancet 1929;1:6.
416. Brink AJ. The coronary vessels in the Bantu. Clin Proc 1949;8:137-149.
417. Becker BJP. Cardiovascular diseases in the Bantu and coloured races of South Africa. S Af J Med Sci
1946;11:1,97.
418. White PD. Heart Disease. 2nd ed. New York: MacMillan Co. 1937.
419. Burch GE, Voorhies NW. A study of the incidence of coronary occlusion and angina pectoris in the white and
negro races. Am J Med Sci 1939;198:685-690.
420. Peery TM, Langsam SM. Study of cardiovascular disease in Charlestown, S.C. based upon necropsy statistics.
Am Heart J 1940;19:424.
421. Schwab EH, Schultze VE. Heart disease in the American negro.
Am HeartJ 1932;7:710.
422. Davison HM, Thoroughman J. A study of heart disease in the negro races. South Med J 1928;21:464.
423. Hunter WS. Coronary occlusion in negroes. J Amer Med Assoc 1946;131:12.
424. Allen FP. Cardiovascular impairment among 1,000 negro factory workers. J Indust Hyg 1931;13:164-168.
425 Schwab EH, Shulze VE. Incidence of heart disease and of etiological types in southern dispensary. Am Heart J
1931;7:223-224.
426. Weiss MM, Prusmack JJ. Essential hypertension in negro. Am J Med Sci 1938;195:510-516.
427. Blache JO, Handler FP. Coronary artery disease. A comparison of the rates and patterns of development of
coronary atherosclerosis in the negro and white races with its relation to clinical coronary artery disease. Archives of
Pathology 1950;50:189-198.
428. Gager LT, Dunn WL. Heart disease in Washington, D.C.; study of etiologic types and factors of race, age, and
sex in 1,200 cases. Med Ann Dist Columbia 1933;2:112-117.
Page 232
429. Hedley OF. Study of 450 fatal cases of heart disease occuring in Washington (D.C.) hospitals during 1932 with
special reference to etiology, race, and sex. U.S. Public Health Reports 1935;50:1127-1153.
430. Johnston C. Racial differences in incidence of coronary schlerosis. Am Heart J 1936;12:162-167.
431. Lisa JR, Ring A. Myocardial infarction or gross fibrosis; analysis of 100 necropsies. Arch Int Med
1932;50:131-141.
432. Laws CL. Etiology of heart disease in whites and negroes in Tennessee. Am Heart J 1933;8:608-615.
433. Holoubek AB. Heart disease in the south; statistical study of 1,045 cardiac deaths. Am Heart J 1945;29:168177.
434. Stone CT, Vanzant FR. Heart disease as seen in southern clinic; clinical and pathological survey. JAMA
1927;89:1473-1477.
435. Bruenn HG, Turner KB, Levy RL. Notes on cardiac pain and coronary disease; correlations of observations
made during life with structural changes found at autopsy in 476 cases. Am Heart J 1936;11:34-40.
436. Levy RL, Bruen HG. Acute fatal coronary insufficiency. JAMA 1936;106:1080-1085.
437. Ashman R. Electrocardiographic study of caucasians and negroes. Tri State M J 1941;13:2686.
438. Yater WM, Traum AH, et al. Coronary artery disease in men 18-39 years of age, report of 866 cases, 450 with
necropsy examinations. Am Heart J 1948;36:334-372, 481-526, 683-722.[Three citations].
439. Thomas J. Analysis of 317 cases of heart disease in negroes. JAMA 1946;38:202-205.
440. Federal Security Agency, United States Public Health Service, Office of Vital Statistics: Vital Statistics, in
Special Report. 1948;27:295.
441. Keil PG, McVay LV. A comparative study of myocardial infarction in the white and negro races. Circulation
1956;13:712-718.
442. Walker ARP, Arvidsson UA. Fat intake, serum cholesterol concentration, and atherosclerosis in the South
African Bantu. Part I. Low fat intake and the age trend of serum cholesterol concentration in the South African
Bantu. J Clin Invest 1954;33:1358-1365.
443. Higginson J, Pepler WJ. Heart disease in the Bantu and white race. J Clin Invest 1954;33:1366.[
444. Brock JF, Bronte-Stewart B. Arteriosclerosis in African populations. Minnesota Med 1955;38:852-863.
445. Elliot GA. Coronary arteries and their diseases in the Bantu. The Leech 1953;23:25.
446. Elliot GA. Coronary diseases among Bantu negroes. Minerva Med 1953;1:465-470.
447. Garb S. Current status of anticoagulants in the treatment of myocardial infarction. Am J Med Sci 1955;229:534548. (see p. 539)
448. Batson E. Different diets of Europeans, Cape Blacks, and the Bantu race.
J Social Rec (Pretoria)1953;4:113.
449. Registrar-General, Decennial Supplement England and Wales, 1951, Occupational Mortality. London: H.M.
Stationery Office, Part 1; page 13.
450. Holoubek JE, Holoubek AB. Heart disease in the South. Am Heart J 1947;34:715-721.
451. Higginson J, Pepler WJ. Fat intake, serum cholesterol concentration, and atherosclerosis in the South African
Page 233
Bantu. Part II. Atherosclerosis and coronary artery disease. J Clin Invest 1954;33:1366-1371.
452. Brull L, et al. Les etas de carence en Belgique pendant l'occupation allemande, 1940-1944. p. 286, Editions
Soledi Liege, 1945.
453. Simonart E. La denutrition de guerre: Etude clinique, anatomo-pathologique et therapeutique. Acta medica
belgica. p. 262, Bruxelles, 1947.
454. Gsell O. Klinik und Pathogenise von Hungerkrankheit und Hungerodem in Hottinger A, Gsell O, et al.
Hungerkrankheit, Hungerodem, Hungertuberkulose, Basel, Benno Schwalbe. 1948, p. 121.
455. Schettler, G. Zum Einfluss der Ernahrung auf den Cholesteringehalt des Blutes. Klin Wchnschr 1950;28:565.
456. Peery TM, Langsam SM. Study of cardiovascular disease in Charlestown, S.C. with particular reference to
hypertension. Arch Int Med 1939;64:971-987.
457. Florey C du V, Melia RJW, Darby SC. British Medical Journal 1978;1:635.
458. Crile, George. Diseases peculiar to civilized man. Archives of Surgery 1940;41:236.
459. Syme SL, Hyman MM, Enterline PE. Journal of Chronic Diseases 1964;17:277.
460. Gillanders AD. Nutritional heart disease. Brit Heart J 1951;13:177-196.
461. Goldberg L, Thorp JM, Sussman S. A survey of vitamins in African foodstuffs. S Afr J Med Sci 1946;11:121134.
462. Levine SA, Brown CL. Medicine 1929;8:245.
463. Keys A, Mickelsen O, et al. The relationship in man between cholesterol levels in the diet and in the blood.
Science 1950;112:79.
464. Keys A. The cholesterol problem. Voeding 1952;13:539.
465. Groen J, Tjiong BK, et al. The influence of nutrition, individuality and some other factors, including various
forms of stress, on the serum cholesterol; an experiment of nine months duration in 60 normal human volunteers.
Voeding 1952;13:556.
466.Mittleman MA, Maclure M, et al. Triggering of acute myocardial infarction by heavy physical exertion;
protection against triggering by regular exertion.
N Engl J Med 1993;329:1677-1683.
467. Hertog MGL, Feskens EJM, et al. Dietary antioxidant flavonoids and risk of coronary heart disease: the
Zutphen Elderly Study. Lancet 1993;342:1107-1111.
468. Esterbauer et al. Free Rad Res Commun 1989;6:67.
469. Riemersma RA, Wood DA, et al. Risk of angina pectoris and plasma concentrations of vitamins A, C, and E
and carotene. Lancet 1991;337:1-5.
470. Stampfer MJ, Hennekens CH, et al. Vitamin E consumption and the risk of coronary artery disease in women.
N Engl J Med 1993;328:1444-1449.
471. Rimm EB, Stampfer MJ, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J
Med 1993;328:1450-1456.
472. Hendler SS. The Doctors' Vitamin and Mineral Encyclopedia. Simon and Schuster: New York, N.Y.; 1990.
Page 234
473. Afanasev IB et al. Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin
in lipid peroxidation. Biochemical Pharmacology 1989;38:1763-1769.
474. Havsteen B. Flavonoids, a class of natural products of high pharmaceutical potency. Biochemical
Pharmacology 1983;32:1141-1148.
475. U.S. Army Center of Military History, May 14, 1993 [personal communication].
476. Artaud-Wild S, Connor S. Differences in coronary mortality can be explained by differences in cholesterol and
saturated fat intakes in 40 countries but not France and Finland: a paradox. Circulation 1993;88:2771-2779.
477. Cerutti PA. Prooxidant states and tumor promotion. Science 1985;277:375-381.
478. Bierenbaum ML, Reichstein RP, et al. Effects of canola oil on serum lipids in humans. J Am Coll Nutr
1991;10:228-233.
479. Kloner RA. Introduction to the role of oxygen radicals in myocardial ischemia and infarction. Free Rad Biol
Med 1988;4:5-7
480. McCord J. Free radicals and myocardial ischemia: overview and outlook. Free Rad Biol Med 1988;4:9-14.
481. Burton K. Evidence of direct toxic effects of free radicals on the myocardium. Free Rad Biol Med 1988;4:1524.
482. Rubanyi G. Vascular effects of oxygen-derived free radicals. Free Rad Biol Med 1988;4:107-120.
483. Gower JD. A role for dietary lipids and antioxidants in the activation of carcinogens. Free Rad Biol Med
1988;5:95-111.
484. Rice-Evans C, ed. Free radicals, cell damage and disease. London: The Richelieu Press. 1988.
485. Oberley L. Free radicals and diabetes. Free Rad Biol Med 1988;5:113-124.
486. Godin D, Wohaieb S. Nutritional deficiency, starvation, and tissue antioxidant status. Free Rad Biol Med
1988;5:165-176.
487. Pryor W. Views on the wisdom of using antioxidant vitamin supplements. Free Rad Biol Med 1987;3:189-191.
488. Bieri JG. Are the recommended allowances for dietary antioxidants adequate? Free Rad Biol Med 1987;3:193197.
489. Diplock A. Dietary supplementation with antioxidants. Is there a case for exceeding the recommended daily
allowance? Free Rad Biol Med 1987;3:199-201.
490. Draper H. Micronutrients and cancer prevention: Are the RDAs adequate? Free Rad Biol Med 1987;3:203-207.
491. Jacobson HN. Dietary standards and future developments. Free Rad Biol Med 1987;3:209-213.
492. Williams. Endocrine responses to stress and psychological stimuli. in: Endocrinology, 7th ed. 1985:662-915
493. Goldstein MG, Niaura R . Psychological factors affecting physical condition. Cardiovascular disease literature
review, Part I: Coronary artery disease and sudden death. Psychosom Med 1992;2:134-145.
494. Williams RB. The role of the brain in physical disease. Folklore, normal science, or paradigm shift? JAMA
1990;263(14):1971-1972.
495. Grignani G, Soffiantino F, et al. Platelet activation by emotional stress in patients with coronary artery disease.
Circulation 1991;83[suppl II]:II-128-II-136.
Page 235
496. Epstein L, Perkins K. Smoking, stress, and coronary heart disease. J Consulting and Clin Psychol
1988;56(3):342-349.
497. Feigelman W, Gorman B. Toward explaining the higher incidence of cigarette smoking among black
Americans. J Psychoactive Drugs 1989;21(3):299-305.
498. Pacht ER, et al. Deficiency of vitamin E in the alveolar fluid of cigarette smokers. Journal of Clinical
Investigation 1986;77:789-796.
499. Bjorneboe GA, et al. Decreased serum concentration of vitamin E in alcoholics. Annals of Nutrition and
Metabolism 1988;32:56-61.
500. Bordia AK. The effect of vitamin C on blood lipids, fibrinolytic activity, and platelet adhesiveness in patients
with coronary artery disease. Atherosclerosis 1980;35:181-187.
501. Cordova C, et al. Influence of ascorbic acid on platelet aggregation in vitro and in vivo. Atherosclerosis
1982;41:15-19.
502. Sarji E, et al. Decreased platelet vitamin C in diabetes mellitus: Possible role in hyperaggregation. Thrombosis
Research 1979;15:639.
503. Jandak J, Steiner M, Richardson PD. Alpha tocopherol, an effective inhibitor of platelet adhesion. Blood
1989;73:141
504. Kanofsky JD, Kanofsky PD. Prevention of thromboembolic disease by vitamin E. N Engl J Med 1981;305:173.
505. Henry JP. Coronary heart disease and the arousal of the adrenal cortical axis. In: Dembrowski TM, Schmidt
TH, Blumchen G (eds): Biobehavioral Basis of Coronary Heart Disease. Basel, Karger. 1983:365-381.
506. Woody WS. Incidence of heart disease in negro race. Virginia M Monthly 1924;50:784-787.
507. Wetherbee H, Tyroler H. The relation of migration to coronary heart disease risk factors. Arch Int Med
1971;128:976-981.
508. Bright MB: A follow-up study of the commission on chronic illness morbidity survey in Baltimore: II. Race and
sex differences in mortality.
J Chronic Dis 1967;20:717-729.
509. Bright MB: A follow-up study of the commission on chronic illness morbidity survey in Baltimore: III.
Residential mobility and prospective studies.
J Chronic Dis 1969;21:749-759.
510. Kaplan BH, Cassel JC, et al. Occupational mobility and heart disease. Arch Int Med 1971;128:938-942.
511. Lakka TA, Nenailanen JM, et al. Relation of leisure-time physical activity and cardiorespiratory fitness to the
risk of acute myocardial infarction in men. N Engl J Med 1994;330:1549-54.
512. Powell KE, Thompson PD, et al. Physical activity and the incidence of coronary heart disease. Annu Rev Public
Health 1987;8:253-287.
513. Paffenbarger RS Jr, Wing AL, Hyde RT. Physical activity as an index of heart attack risk in college alumni. Am
J Epidemiol 1987;108:161-175.
514. Paffenbarger RS Jr, Hyde RT, Wing AL, et al. Physical activity, all-cause mortality, and longevity of college
alumni. N Engl J Med 1986;314:605-613.
515. Paffenbarger RS Jr, Hyde RT, Wing AL, et al. The association of changes in physical-activity level and other
Page 236
lifestyle characteristics with mortality among men. N Engl J Med 1993;328:538-545.
516. Morris JN, Everett MG, et al. Vigorous exercise in leisure time: Protection against coronary heart disease.
Lancet 1980;2:1207-1210.
517. Garcia-Palmieri MR, Costas R Jr, et al. Increased physical activity: a protective factor against heart attacks in
Puerto Rico. Am J Cardiol 1982;50:749-755.
518. Yudkin J. Diet and coronary thrombosis, hypothesis and fact. Lancet 1957;2:155-162.
519. Yudkin J. Dietary fat and dietary sugar in relation to ischaemic heart disease and diabetes. Lancet 1964;2:4-5.
520. McGandy RB, Hegsted DM, Stare FJ. Dietary fats, carbohydrates, and atherosclerotic vascular disease. New
Engl J Med 1967;277:417-419; 469-471.
521. Masironi R. Dietary factors and coronary heart disease. Bull World Hlth Org 1970;42:103-114.
522. Keys A, Aravanis C, et al.. Epidemiological studies in relation to coronary heart disease: characteristics of men
aged 40-59 in seven countries. Acta Med Scand 1966[suppl]:460
523. Keys A. Sucrose in the diet and coronary heart disease. Atherosclerosis 1971; 14:193-200.
524. Keys A. Letter to the editor. Atherosclerosis 1973;18:352.
525. Shekelle RB, Shyrock AM et al. Diet, serum cholesterol and death from coronary heart disease. N Engl J Med
1981;304:65-70.
526. Keys A, with 15 collaborators. Seven Countries-A Multivariate Analysis of Death and Coronary Heart
Disease. A Commonwealth Fund Book. Cambridge, Mass: Harvard University Press; 1980:1-381.
527. Keys A. (ed): Coronary heart disease in Seven Countries. Circulation 1970;41(suppl I).
528. Connor SL, Gustafson JR et al. The cholesterol/saturated fat index: an indication of the hypercholesterolaemic
and atherogenic potential of food. Lancet 1986;1:1229-1232.
529. The Surgeon General's Report on Nutrition and Health. Washington, DC: US Department of Health and
Human Services; DHHS Publication No. (PHS)88-50210, 1988.
530. National Research Counsel. Diet and Health, Implications for Reducing Chronic Disease Risk. Washington,
DC: National Academy Press, 1989.
531. National Cholesterol Education Program. Report of the Expert Panel on Population Strategies for Blood
Cholesterol Reduction. US Department of Health and Human Services, NIH publication No. 90-3046, 1990.
532. Turpeinen O. Effect of cholesterol-lowering diet on mortality from coronary heart disease and other causes.
Circulation 1979;59:1-8.
533. Renaud S, de Lorgeril M. Dietary lipids and their relation to ischaemic heart disease: from epidemiology to
prevention. J Intern Med 1989;225:1-8.
534. de Lorgeril M. Atlanta, GA. Personal communication, Nov 11, 1993.
535. Joossens JV, Brems-Heyns E, et al. The pattern of food and mortality in Belgium. Lancet 1977;1:1069-1072.
536. Statistiques des causes medicales de deces. INSERM. Tome II. Regulats par region. 1972;187:327.
537. Esterbauer H, Dieber-Rotheneder M, et al. Role of vitamin E in preventing the oxidation of low density
lipoprotein. Am J Clin Nutr 1991;53:314S-321S.
Page 237
538. Connor WE, Cerqueira MT, et al. The plasma lipids, lipoproteins, and diet of the Tarahumara Indians of
Mexico. Am J Clin Nutr 1978;31:1131-1142.
539. Shaper AG, Jones KW. Serum cholesterol, diet and coronary heart disease in Africans and Asians in Uganda.
Lancet 1959;2:534.
540. Kagan A, Harris BR, Winkelstein W Jr. Epidemiologic studies of coronary heart disease and stroke in Japanese
men living in Japan, Hawaii, and California: demographic, physical, dietary, and biochemical characteristics. J
Chron Dis 1974;27:345-364.
541. Worth RM, Kato H, et al. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in
Japan, Hawaii, and California: mortality. Am J Epidemiol 1975;102:481-490.
542. Frankel EN, Kanner J, et al. Inhibition of oxidation of human low-density lipoprotein by phenolic substances in
red wine. Lancet 1993;341:454-457.
543. Marmot M, Brunner E. Alcohol and cardiovascular disease: the status of the U shaped curve. Brit Med J
1991;303:565-568.
544. Moore RD, Pearson TA. Moderate alcohol consumption and coronary artery disease: a review. Medicine
1986;65:242-267.
545. Hegsted DM, Ausman LM. Diet, alcohol and coronary heart disease in men. J Nutr 1988;118:1184-1189.
546. Keys A, Menotti A, et al. The diet and 15-year death rate in the Seven Countries study. Am J Epidemiol
1986;124:903-915.
547. Becker N, Illingworth DR, et al. Effects of saturated, monounsaturated, and n-6 polyunsaturated fatty acids on
plasma lipids, lipoproteins, and apoproteins in humans. Am J Clin Nutr 1983;37:355-360.
548. Mattson FH, Grundy SM. Comparison of effects of dietary saturated, monounsaturated, and polyunsaturated
fatty acids on plasma lipids and lipoproteins in man. J Lipid Res 1985;26:194-202.
549. Grundy SM. Comparison of monounsaturated fatty acids and carbohydrates for lowering plasma cholesterol. N
Engl J Med 1986;314:745-748.
550. Mensink RP, Katan MB. Effect of monounsaturated fatty acids versus complex carbohydrates on high density
lipoproteins in healthy men and women. Lancet 1987;1:122-125.
551. Kazawa Y, Niskizawa M, et al. Eicosapentaenoic acid of serum lipids of Japanese islanders with low incidence
of cardiovascular disease. J Nutr Sci Vitaminol 1982;28:441-453.
552. Briefel RB, Sempos CT, eds. Dietary methodology workshop for the third National Health and Nutrition
Examination Survey. National Center for Health Statistics. Vital Health Stat 4(27). 1992.
553. Kato H, Tillotson J, et al. Epidemiologic studies of coronary heart disease and stroke in Japanese men living in
Japan, Hawaii, and California. Am J Epidemiol 1973;27:345-364.
554. Kushi LH, Lew RA, et al. Diet and 20-year mortality from coronary heart disease: The Ireland-Boston Diet
Heart Study. N Engl J Med 1985;312:811-818.
555. Snowdon DA, Phillips RL, Fraser GE. Meat consumption and fatal ischemic heart disease. Prev Med
1984;13:490-500.
556. Kromhout D, Bosschieter EB, Coulander CD. The inverse relationship between fish consumption and 20-year
mortality from coronary heart disease. N Engl J Med 1985;312:1205-1209.
Page 238
557. The Medicaid Access Study Group. Access of Medicaid recipients to outpatient care. N Engl J Med
1994;330:1426-1430.
558. Snapper I. Chinese Lessons to Western Medicine. New York: Interscience Publishers, 1941:160. .
559. Voerhoef AW. Het cholesterol gehalte in het bloed bij versckillende rassen. Diss. Amsterdam. 1920.
560. Hrabak D. Media madness over trans fatty acids triggers confusion. Environmental Nutrition 1994;17(7):3.
561. Kuhnau J. The flavonoids: a class of semi-essential food components: their role in human nutrition. World Rev
Nutr Diet 1976;24:117-20.
562. Hertog MGL, Hollman PCH, et al. Estimation of daily intake of potentially anticarcinogenic flavonoids and
their determinants in adults in the Netherlands. Nutr Cancer 1993;20:21-29.
563. Robak J, Gryglewski RJ. Flavonoids are scavengers of superoxide anion. Biochem Pharmacol 1988;37:83-88.
564. Husain SR, Cillard J, Cillard P. Hydroxy radical scavenging activity of flavonoids. Phytochemistry
1987;26:2489-2492.
565. De Whalley CV, Rankin SM et al. Flavonoids inhibit the oxidative modification of low density lipoproteins.
Biochem Pharmacol 1990;39:1743-1749.
566. Negre-Salvagyre A, Salvagyre R. Quercetin prevents the cytotoxicity of oxidized low-density lipoproteins by
macrophages. Free Radic Biol Med 1992;12:101-106.
567. Steinberg D, Pathasarathy S, et al. Modifications of low density lipoprotein that increase its atherogenicity. N
Engl J Med 1989;320:915-924.
568. Laughton MJ, Evans PJ, et al. Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and
phenolic dietary additives: relationship to antioxidant activity and to iron-reducing ability. Biochem Pharm
1991;42:1673-1681.
569. Hertog MGL, Hollman PCH, van de Putte B. Content of potentially anticarcinogenic flavonoids of tea
infusions, wines, and fruit juices. J Agric Food Chem 1993;41:1242-1246.
570. Frankel EN, Kanner J, et al. Inhibition of oxidation of human low density lipoprotein by phenolic substances in
red wine. Lancet 1993;341:454-457.
571. Ascherio A, Stampfer MJ, et al. Correlations of vitamin A and E intakes with the plasma concentrations of
carotenoids and tochopherols among American men and women. J Nutr 1992;122:1792-1801.
572. Stryker WS, Kaplan LA, et al. The relation of diet, cigarette smoking, and alcohol consumption to plasma beta
carotene and alpha tocopherol levels. Am J Epidemiol 1988;127:283-296.
573. Steinberg D, Witztum JL. Lipoproteins and atherogenesis: current concepts. JAMA 1990;264:3047-3052.
574. Diplock AT. Antioxidant nutrients and disease prevention: an overview. Am J Clin Nutr 1991;53:Suppl:189S193S.
575. Sorata Y, Takahama U, Kimura M. Protective effect of quercetin and rutin on photosensitized lysys of human
erythrocytes in the presence of hematoporphyrin. Biochem Biophys Acta 1982;799:313-317.
576. Takahama U. Inhibition of lipoxygenase-dependent lipid peroxidation by quercitin: mechanism of antioxidant
function. Phytochemistry 1985;24:1443-1446.
577. Quinn MT, Parthasarathy S, Steinberg D. Endothelial cell derived chemotactic activity for mouse peritoneal
macrophages and the effects of modified forms of low density lipoprotein. Proc Natl Acad Sci USA 1985;82:5949-
Page 239
5953.
578. Quinn MT, Parthasarathy S, et al. Oxidatively modified low density lipoproteins: a potential role in recruitment
and retention of monocyte/macrophages during atherogenesis. Proc Natl Acad Sci USA 1987;84:2995-2998.
579. Hessler JR, Robinson AL Jr, Chisolm GM III. LDL-induced cytotoxicity and its inhibition by HDL in human
vascular smooth muscle and endothelial cells in culture. Atherosclerosis 1979;32:213-229.
580 Gey KF, Brubacher GB, Stahelin HB. Plasma levels of antioxidant vitamins in relation to ischemic heart disease
and cancer. Am J Clin Nutr 1987;45:Suppl:1368-1377.
581 Enstrom JE, Kanim Le, Klein MA. Vitamin C intake and mortality among a sample of the United States
population. Epidemiology 1992;3:194-202.
582 Gaziano JM, Manson JE, et al. A prospective study of beta carotene in fruits and vegetables and decreased
cardiovascular mortality in the elderly. Am J Epidemiol 1992;136:985. abstract.
583. DeMaio SJ, King SB III, et al. Vitamin E supplementation, plasma lipids, and incidence of restenosis after
percutaneous transluminal coronary angioplasty (PTCA). J Am Coll Nutr 1992;11:68-73.
584. Kok FJ, de Bruiijn AM, et al. Serum selenium, vitamin antioxidants, and cardiovascular mortality: a 9-year
follow-up study in the Netherlands. Am J Clin Nutr 1987;45:462-468.
585. Salonen JT, Salonen R, et al. Serum fatty acids, apolipoproteins, selenium and vitamin antioxidants and the risk
of death from coronary artery disease. Am J Cardiol 1985;56:226-231.
586. Parthasarathy S. Evidence for an additional intracellular site of action of probucol in the prevention of oxidative
modification of low density lipoprotein: use of a new water-soluble probucol deravitive. J Clin Invest 1992;89:618621.
587. Esterbauer H, Dieber-Rotheneder M, et al. Role of vitamin E in preventing the oxidation of low density
lipoprotein. Am J Clin Nutr 1991;53:Suppl:314S-321S.
588. Gaziano JM, Manson JE, et al. Beta carotene therapy for chronic stable angina. Circulation
1990;82:SupplIII:III-201. abstract.
589. Harats D, Ben-Naim M, et al. Cigarette smoking renders LDL susceptible to peroxidative modification and
enhanced metabolism by macrophages. Atherosclerosis 1989;79:245-252.
590. Duthie GG, Arthur JR, James WPT. Effects of smoking and vitamin E on blood antioxidant status. Am J Clin
Nutr 1991;53:Suppl:1061S-1063S.
591. Hoshino E, Shariff R, et al. Vitamin E supresses increased lipid peroxidation in cigarette smokers. J Parenter
Enteral Nutr 1990;14:300-305.
592. Jialal I, Grundy SM. Preservation of the endogenous antioxidants in low density lipoprotein by ascorbate but
not probucol during oxidative modification. J Clin Invest 1991;87:597-601.
593. Stocker R, Frei B. Endogenous antioxidant defenses in human blood plasma. In: Sies H, ed. Oxidative stress:
oxidants and antioxidants. Orlando Fla.: Academic Press, 1991:213-243.
594. Niki E, Yamamoto Y, et al. Membrane damage due to lipid oxidation. Am J Clin Nutr 1991;53:Suppl:201S205S.
595. Princen HMG, van Poppel G, et al. Supplementation with vitamin E but not beta carotene in vivo protects low
density lipoprotein from lipid peroxidation in vitro: effect of cigarette smoking. Arterioscler Thromb 1992;12:554562.
Page 240
596. Nierenberg DW, Stukel TA, et al. Determinants of plasma levels of beta carotene and retinol: Skin Cancer
Prevention Study Group. Am J Epidemiol 1989;130:511-521.
597. Rimm EB, Giovannucci EL, Stampfer MJ, et al. Reproducibility and validity of an expanded self-administered
semi-quantitative food frequency questionnaire among male health professionals. Am J Epidemiol 1992;135:11141126.
598. Stampfer MJ, Willett WC, et al. The effect of vitamin E on lipids. Am J Clin Pathol 1983;79:714-716.
599. Kalbfleisch JH, Barboriak JJ, et al. Alpha tocopherol supplements and high density lipoprotein levels. Br J Nutr
1986;55:71-77.
600. Keys A, Aravanis C, Blackburn H. Epidemiological studies related to coronary heart disease: characteristics of
men aged 40-59 in seven countries. Acta Med Scand 1967;suppl:1-392.
601. Blot WJ, Li J-Y, et al. Nutrition intervention trials in Linxian, China: supplementation with specific
vitamin/mineral combinations, cancer incidence, and disease-specific mortality in the general population. J Natl
Cancer Inst 1993;85:1483-1492.
602. Greenberg ER, Baron JA, et al. The Polyp Prevention Study Group. A clinical trial of antioxidant vitamins to
prevent colorectal adenoma. N Engl J Med 1994;331:141-147.
603. Williams DG. Alternatives 1994;5(13):97-99.
604. Polyunsaturated fat consumption and the incidence of melanoma. N.Z. Med J 1991;104(916):322.
605. Giovannucci E, Rimm EB, et al. A prospective study of dietary fat and risk of prostate cancer. J Natl Cancer
Institute 1993;85:1571-1579.
606. Gann P, Hennekens C, Sacks F et al. Prospective study of plasma fatty acids and risk of prostate cancer. J Natl
Cancer Institute 1994;86:281-286.
607. Adlercreutz H, Markkanen H, Watanabe S. Plasma concentrations of phyto-oestrogens in Japanese men. Lancet
1993;342:1209-1210.
608. Dyberg J, Bang HO. Effects on hemostasis by feeding eicosapentaenoic acid. In: Nutritional Factors:
Modulating Effects on Metabolic Processes. Beers RS, Bassett EG, eds. New York: Raven Press, 1981.
609. Church DF, Pryor WA. Free radical chemistry of cigarette smoke and its toxological implications. Environ
Health Prospect 1985;64:111-126.
610. Kimura S, Nishinaga M, et al. Thrombin generation as an acute effect of cigarette smoking. Am H J
1994;128:7-11.
611. Pittilo BM. Cigarette smoking and endothelial injury: a review. In: Diana JN, ed. Tobacco smoking and
atherosclerosis. New York: Plenum Press, 1990:61-78.
612. Murchison LE, Fyfe T, et al. Effects of cigarette smoking on serum lipids, blood glucose, and platelet
adhesiveness. Lancet 1966;2:182-184.
613. Cryer PE, Haymond MW, et al. Norepinephrine and epinephrine release and adrenergic mediation of smokingassociated hemodynamic and metabolic effects. N Engl J Med 1976;295:573-577.
614. Myers MJ, Benowitz NL, et al. Cardiovascular effects of smoking in patients with ischemic heart disease.
Chest 1988;93:14-19.
615. Hawkins RI. Smoking, platelets, and thrombosis. Nature 1972;236:450-452.
Page 241
616. Nowak J, Murray JJ, et al. Biochemical evidence of a chronic abnormality in platelet and vascular function in
healthy individuals who smoke cigarettes. Circulation 1987;76:6-14.
617. Allen RA, Kuft C, et al. Effect of chronic smoking on fibrinolysis. Arteriosclerosis 1985;5:443-450.
618. Haire WD, Goldsmith JC, et al. Abnormal fibrinolysis in healthy male cigarette smokers: Role of plasminogen
activator inhibitors. Am J Hematol 1989;31:36-40.
619. O'Brien. Some effects of adrenaline and anti-adrenaline compounds on platelet in vitro and in vivo. Nature
1963;200:763-764.
620. Jern C, Eriksson E, et al. Changes of plasma coagulation and fibrinolysis in response to mental stress. Thromb
Haemostas 1989;62:767-771.
620. Kugiyama K, Kerns SA, et al. Impairment of endothelium-dependent arterial relaxation by lysolecithin in
modified low-density lipoproteins. Nature 1990;344:160-162.
621. Regnstrom J, Nilsson J, et al. Susceptibility to low-density lipoprotein oxidation and coronary atherosclerosis in
man. Lancet 1992;339:1183-1186.
622. Stampfer MJ, Malinow Mr, et al. A prospective study of plasma homocyst(e)ine and risk of infarction in U.S.
physicians. JAMA 1992;268:877-881.
623. Zhao BL, et al. Scavenging effect of extracts of green tea and natural antioxidants on active oxygen radicals.
Cell Biophysics 1989;14(2):175-185.
624. Jialal I, Grundy SM. Effect on combined supplementation with alpha tocopherol, ascorbate, and beta carotene
on low-density lipoprotein oxidation. Circulation 1993;88:2780-2786.
625. Robbins AS, Manson JE, et al. Cigarette smoking in a cohort of U.S. male physicians. Ann Intern Med
1994;120:458-462.
626. Kannel WR, Belanger A, et al. Physical activity and physical demand on the job and risk of cardiovascular
disease and death: The Framingham Study. Am Heart J 1986;112:820-825.
627. Ginzberg E. Improving health care for the poor. lessons from the 1980s. JAMA 1994;271(6):464-467.
628. Fielding JE, Cumberland WG, Pettitt L. Immunization status of children of employees in a large corporation.
JAMA 1994;271:525-530.
629. Carstairs V, Morris R. Deprivation: explaining differences in mortality between Scotland, England, and Wales.
Br Med J 1989;299:886-889.
630. Wood DA, Riemersma RA, et al. Linoleic and Eicosapentaenoic Acids in adipose tissue and platelets and risk
of coronary heart disease. Lancet 1987;i:177-180.
631. Post CA, The importance of being in control. Cardisense
1994;4(3):1-3.
632. House JS, Landis KR, Umberson D. Social relationships and health. Science 1988;241:540-545.
633. Orth-Gomer R, Johnson J. Social network interaction and mortality. A six-year follow-up study of a random
sample of the Swedish population. J Chronic Dis 1987;40:949-957
634. House JS, Robbins C, Metzner HL. The association of social relationships and activities with mortality:
prospective evidence from the Techumseh community health study. Am J Epidemiol 1982;116:123-140.
Page 242
635. Welin L, Tibblin G, et al. Prospective study of social influences on mortality. The study of men born in 1913
and 1923. Lancet 1985;i:915-918.
636. Helsing K, Szklo M. Mortality after bereavement. Am J Epidemiol 1981;114:41-52.
637. Cassel J. The contribution of the social environment to host resistance. Am J Epidemiol 1976;104:107-123.
638. Cobb S. Social support as a moderator of life stress. Psychosom Med 1976;38:300-314.
639. Schectman G, Byrd JC, Gruchow HW. The influence of smoking on vitamin C status in adults. Am J Publ
Health 1989;79:158-162.
640. Kallner AB, Hartman D, Hornig DH. On the requirements of ascorbic acid in man: steady state turnover and
body pool in smokers. Am J Clin Nutr 1981;34:1347-1355.
641. Fulton M, Thomson M, et al. Cigarette smoking, social class, and nutrient intake: relevance to coronary heart
disease. Eur J Clin Nutr 1988;42:797-803.
642. Stryker WS, Kaplan LA, et al. The relation of diet, cigarette smoking, and alcohol consumption to plasma beta
carotene and alpha tocopherol levels. Am J Epidemiol 1988;127:283-296.
643. Riemersma RA, Oliver M, et al. Plasma antioxidants and coronary heart disease: vitamins C and E, and
selenium. Eur J Clin Nutr 1990;44:143-150.
644. Thomson M, Fulton M, et al. A comparison of the nutrient intake of some Scottish men with dietary
recommendations. Human Nutr Appl Nutr 1985;39a:443-455.
645. Ginter E. Decline of coronary mortality in the United States and vitamin C. Am J Clin Nutr 1979;32:511-512.
646. Enstrom JE, Kanim LE, Klein MA. Vitamin C intake and mortality among a sample of the United States
Population. Epidemiol 1992;3:194-202.
647. Concoby R. Vitamin C and life extension. in: Nicol D, ed. A report from the American Commission on AntiAging. New York: Hanford Press,1993.
648. Smith WCS, Turnstall-Pedoe H, et al. Concomitants of excess coronary deaths--major risk factor and lifestyle
findings from 10,359 men and women in the Scottish heart Health Study. Scot Med J 1989;34:550-555.
649. Barker JD, Osmond C. Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales.
Lancet 1986;1:1077-1081.
650. Knox EG. Ischaemic heart disease mortality and dietary intake of calcium. Lancet 1973;i:1465-1467.
651. Werbach M. Nutritional Influences on Illness. Connecticut:Keats Publishing, 1987.
652. Guarnieri C, Ferrari R, et al. Effect of tocopherol on hypoxic perfused and re-oxygenated heart muscle. J Mol
Cell Cardiol 1978;10:893-906.
653. Bernier M, Hearse DJ, Manning AS. Reperfusion-induced arrythmias and oxygen-derived free radicals. Circ
Res 1986;58:331-340.
654. Bell D, Jackson M, et al. Inflammatory response, neutrophil activation, and free radical production after acute
myocardial infarction: effect of thrombolytic treatment. Br Heart J 1990;63:82-87.
655. Lapenna D, de Gioia S, et al. Heightened free radical activity in angina pectoris. Am J Cardiol 1993;72:830831.
656. Grech ED, Dodd NJF, et al. Free radical generation during angioplasty reperfusion for acute myocardial
Page 243
infarction. Lancet 1993;341:990-991.
657. Grech ED, Jack CI, et al. Differential free radical activity after successful and unsuccessful thrombolytic
reperfusion in acute myocardial infarction. Coronary Art Dis 1993;4:769-774.
658. Esterbauer H, Jurgens G, et al. Autooxidation of human low density lipoprotein: loss of polyunsaturated acids
and vitamin E and generation of aldehydes. J Lipid Res 1987;28:495-509.
659. Ramirez J, Flowers NC. Leucocyte ascorbic acid and its relationship to coronary heart disease in man. Am J
Clin Nutr 1980;33:2079-2087.
660. W.P.G. Livestock and Poultry Farming. In: Encylcopaedia Britannica; vol.10; Chicago: William Benton,
1979:1279.
661. M.Ke. Alcohol Consumption. In: Encylcopaedia Britannica; vol.1; Chicago: William Benton, 1979:444.
662. Pryor WA. The free-radical theory of aging revisited: a critique and suggested disease-specific theory. In:
Butler RN, Spritt RL, et al, eds. Modern Biological Theories of Aging. New York: Raven Press;1987:89-112.
663. Gey KF. On the antioxidant hypothesis with regard to atherosclerosis. Biblthea Nutr Dieta 1986;37:53-91.
664. Smith J, Turner J. A perspective on the history and use of the Recommended Daily Allowances. Currents,
Journal of Food, Nutrition and Health 1986;2:4.
665. Committee on Dietary Allowances, Food and Nutrition Board. Recommended Daily Allowances. 9th ed.
Washington, D.C.: U. S. A. National Academy of Sciences, National Research Council, 1980.
666. Niwa Y, Hanssen M. Protection for life: How to Boost your Body's Defenses Against Free Radicals and the
Aging Effects of Pollution and Modern Lifestyles. Wellingborough:Thorsons Publishers Ltd, 1989:9.
667. Palgi A. Association between dietary changes and mortality rates: Israel 1949-1970; a trend-free regression
model. Amer J Clin Nutr 1981;34:1569-1583.
668. Herbert V, Kasdan T. Misleading nutrition claims and their gurus. Nutrition Today 1994;29(3):28-35.
669. Nomura A, Stemmermann G, et al. Serum vitamin levels and the risk of cancer specific sites in men of Japanese
ancestry in Hawaii. Cancer Res 1985;45:2369-2372.
670. Menkes M, Comstock G, et al. Serum beta carotene, vitamins A and E, selenium and the risk of lung cancer. N
Engl J Med 1986;315:1250-1254.
671. Willett W, Polk B, et al. Relation of serum vitamins A and E and carotenoids to the risk of cancer. N Engl J
Med 1985;310:430-434.
672. Committee on Diet, Nutrition, and Cancer. Diet, nutrition and cancer. Washington, D.C.:National Academy of
Sciences;1982.
673. Pauling L. How to live longer and feel better. New York: W.H. Freeman, 1987.
674. Pauling L. Vitamin C and the common cold. New York: W.H. Freeman, 1970.
675. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer. Prolongation of survival
times in terminal human cancer. Proc Natl Acad Sci U.S.A. 1976;73:3685-3689.
676. Anderson R. The immunostimulatory, anti-inflammatory, and anti-allergic properties of ascorbate. Adv Nutr
Res 1984;6:19-45.
677. Williams R, Sorlie P, et al. Cancer incidence by levels of cholesterol. J Am Med Assoc 1981;245:247-252.
Page 244
678. Mettlin C. Epidemiologic studies on vitamin A and cancer. Adv Nutr Res 1984;6:47-65.
679. Wald N, Boreham J, et al. Plasma retinol, beta carotene and vitamin E levels in relation to the future risk of
breast cancer. Br J Cancer 1984;49:321-324.
680. Dhanakoti S, Draper H. Response of urinary malondialdehyde to factors which stimulate lipid peroxidation in
vivo. Unpublished results, in: Reference 22: Draper HH, Bird RP. Micronutrients and cancer prevention: are the
RDAs adequate? Free Rad Biol Med 1987;3:203-207.
681. Cavarocchi N, England M, et al. Superoxide generation during cardiopulmonary bypass: is there a role for
vitamin E? J Surgical Res 1986;40:519-527.
682. Brown E, Bieri J, et al. Plasma response in normal men to various carotenoid sources. Fed Proc 1987;46:1189.
683. Willet W. Vitamin A and selenium intake in relation to human cancer risk. In: Hayashi Y, Nagao M, et al., eds.,
Proc 16th International Symposium on Diet, Nutrition, and Cancer, Japanese Sci Soc Press, The Netherlands:
Utrecht;1986:237-245.
684. Burton G, Ingold K. Beta Carotene: an unusual type of lipid antioxidant. Science 1984;224:569-573.
685. Horwitt M. The promotion of vitamin E. J Nutr 1986;116:1371-1377.
686. Salonen J, Salonen R, et al. Risk of cancer in relation to serum concentrations of selenium and vitamins A and
E: matched case-control analysis of prospective data. Br Med J 1985;290:417-420.
687. Stahelin H, Rosel F, et al. Cancer, vitamins, and plasma lipids: prospective Basel study. J natl Cancer Inst
1984;73(6):1463-1468.
688. Russek H, Zohman B. Reactive significance of heredity, diet and occupational stress in coronary heart disease
of young adults. Am J Clin Sci 1958;235:266-277.
689. Pearson H, Joseph J. Stress and occlusive coronary artery disease. Lancet 1963;1:415-418.
690. Wolf S. Psychosocial forces in myocardial infarction and sudden death. Circulation 1969;40(suppl IV):IV-74IV-83.
691. Haft J, Fani K. Stress and the induction of intravascular platelet aggregation in the heart. Circulation
1973;48:164-169.
692. Rozanski A, Bairey C, et al. Mental stress and the induction of silent myocardial ischemia in patients with
coronary artery disease. N Engl J Med 1988;318:1005-1012.
693. LaVeau P, Rozanski A, et al. Transient left ventricular dysfunction during provocative mental stress in patients
with coronary artery disease. Am Heart J 1989;118:1-8.
694. Haft J, Arkel Y. Effect of emotional stress on platelet aggregation in humans. Chest 1976;70:501-505.
695. Levine S, Towell B, et al. Platelet activation and secretion associated with emotional stress. Circulation
1985;71:1129-1134.
696. Jern C, Hadenvik H, et al. Haematological changes during acute mental stress. Br J Haematol 1989;71:153-156.
697. Larsson P, Hjemdahl P, et al. Altered platelet function during mental stress and adrenaline infusion in humans:
evidence for an increased aggregability in vivo as measured by filtragometry. Clin Sci 1989;76:369-376.
698. Matthews K, Haynes S. Type A behavior pattern and coronary disease risk: update and critical evaluation. Am J
Epidemiol 1986;123:923-960.
Page 245
699. Dimsdale J, Ziegler M. What do plasma and urinary measures of catecholamines tell us about human stressors?
Circulation 1991;83[suppl II]:II-36-II-42.
700. Coumel P, Leenhardt A. Mental activity, adrenergic modulation, and cardiac arrythmias in patients with heart
disease. Circulation 1991;83[suppl II]:II-58-II-70.
701. Schnall P, Pieper C, et al. The relationship between "job strain," workplace diastolic pressure, and left
ventricular mass index. Results of a case control study. JAMA 1990;263:1929-1935.
702. Pickering T, Harshfield G, et al. Comparison of blood pressure during normal daily activities, sleep, and
exercise in normal and hypertensive subjects. JAMA 1982;247:992-996.
703. Devereux R, Pickering T, et al. Left ventricular hypertrophy in patients with hypertension: importance of blood
pressure response to regularly recurring stress. Circulation 1983;68:470-476.
704. Karasek R. Job demands, job decision latitude, and mental strain: implications for job redesign. Admin Sci Q
1979;24:285-307.
705. Karasek R, Baker D, et al. Job decision latitude, job demands and cardiovascular disease: a prospective study of
Swedish men. Am J Publ Health 1981;71:694-705.
706. Karasek R, Theorell T, et al. Job characteristics in relation to the prevalence of myocardial infarction in the
U.S. Health Examination Survey (HES) and Health and Nutrition Examination Survey (HANES). Am J Public
Health 1988;78:910-919.
707. Alfredson L, Karasek R, Theorell T. Myocardial infarction risk and psychosocial environment: an analysis of
the male Swedish working force. Soc Sci Med 1982;3:463-467.
708. Schwartz J, Pieper C, Karasek R. A procedeure for linking psychosocial job characteristics data to health
surveys. Am J Public Health 1988;78:904-909.
709. Pieper C, LaCroix AZ, Karasek RA. The relationship of psychosocial dementions of work with coronary heart
disease risk factors: a meta-analysis of five United States data bases. Am J Epidemiol 1989;129:484-494.
710. Mathews K, Cottington EM, et al. Stressful work conditions and diastolic blood pressure among blue collar
factory workers. Am J Epidemiol 1987;126:280-291.
711. Gelernt M, Hochman J. Acute myocardial infarction triggered by emotional stress. Am J Cardiol 1992;69:15121513.
712. Muller J, Toffler G, et al. Circadian variations and triggers of onset of acute cardiovascular disease. Circulation
1989;79:733-743.
713. Muller J, Toffler G, et al. Probable triggers of onset of acute myocardial infarction. Clin Cardiol 1989;12:473475.
714. Rozanski A, Krantz D, Bairey C. Ventricular responses to mental stress testing in patients with coronary artery
disease: pathophysiological implications. Circulation 1991;83(suppl II):II-137-II-144.
715. Myers A, Dewar H. Circumstances attending 100 sudden deaths from coronary artery disease with coroner's
necropsies. Br Heart J 1975;37:1133-1143.
716. Guibbini R, Galli M, et al. Effects of mental stress on myocardial perfusion in patients with ischemic heart
disease. Circulation 1991;83[suppl II]II-100-II-107.
717. Young DZ, Dimsdale JE, et al. Left ventricular performance during psychological stress. Eur J Nucl Med
1989;15:118.
Page 246
718. Deanfield JE, Shea M, et al. Silent myocardial ischemia due to mental stress. Lancet 1984;2:1001.
719. Rosengren A, Wilhelmsen L, et al. Social influences and cardiovascular risk factors as determinants of plasma
fibrinogen concentration in a general population sample of middle aged men. Br Med J 1990;300:634-638.
720. Wilhelmsen L, Svardsudd K, et al. Fibrinogen as a risk factor for stroke and myocardial infarction. N Engl J
Med 1984;311:501-505.
721. Meade TW, Mellows S, et al. Haemostatic function and ischaemic heart disease: principal results of the
Northwick Park heart study. Lancet 1986;ii:533-537.
722. Stone MC, Thorp JM. Plasma fibrinogen--a major coronary risk factor. J R Coll Gen Pract 1985;35:565-569.
723. Kannel WB, Wolf PA, et al. Fibrinogen and risk of cardiovascular disease. The Framingham study. JAMA
1987;258:1183-1186.
724. Markowe HLJ, Marmot MG, et al. Fibrinogen: a possible link between social class and coronary heart disease.
Br Med J 1985;291:1312-1314.
725. Rosengren A, Wedel H, et al. Coronary heart disease and mortality among men from different occupational
classes in Sweden. Br Med J 1988;297:1497-1500.
726. Marmot MG, Shipley MJ, Rose G. Inequalities in death--specific explanations of a general pattern? Lancet
1984;i:1003-1006.
727. Holme I, Helgeland A, et al. Four-year mortality by some socioeconomic indicators: the Oslo Study. J
Edidemiol Community Health 1980;34:48-52.
728. Reed D, McGee D, et al. Social networks and coronary heart disease among Japanese men in Hawaii. Am J
Epidemiol 1983;117:384-396.
729. Fuller JH, Keen H, et al. Haemostatic variables associated with diabetes and its complications. Br Med J
1979;ii:964-966.
730. Korsan-Bengtsen K, Wilhelmsen L, et al. Blood coagulation and fibrinolysis in a random sample of 788 men 54
years old. II. Relations of the variables to "risk factors" for myocardial infarction. Thrombosis et Diathesis
Haemorrhagica 1972;28:99-108.
731. Meade TW, Imeson J, Stirling Y. Effects of changes in smoking and other characteristics on clotting factors and
the risk of ischaemic heart disease. Lancet 1987;ii:986-988.
732. Kannel WB; D'Agostino RB, Belanger AJ. Fibrinogen, cigarette smoking and risk of cardiovascular disease:
insights from the Framingham study. Am Heart J 1987;113:1006-1010.
733. Meade TW,Chakrabarti R, et al. Characteristics involving fibrinolytic activity and plasma fibrinogen
concentrations. Br Med J 1979;i:153-156.
734.Astrand N-E, Hanson BS, Isacsson S-O. Job Demands, job decision latitude, job support, and social network
factors as predictors of mortality in a Swedish pulp and paper company. Brit J Industrial Med 1988;1:334-340.
735. Specchia G, Falcone C, et al. Mental stress as a provocative test in patients with various clinical syndromes of
coronary heart disease. Circulation 1991;83[supplII]:II-108-II-114.
736. Allman BJC, Zimbler A. Determination of the relationships between psychological stress levels and blood
pressure,pulse and respiratory rates, weight and cigarette consumption. S Afr Med J 1988;73:113-116.
Page 247
737. L'Abbate A, Simonetti I, et al. Coronary dynamics and mental arithmetic stress in humans. Circulation
1991;83[suppl II];II-94-II-99.
738. Weiner H. Stressful experience and cardiorespiratory disorders. Circulation 1991;83[supplI]:II-2-II-8.
739. Siegrist J, Matschinger H, et al. Atherogenic risk in men suffering from occupational stress. Atherosclerosis
1988;69:211-218.
740. Krantz D, Raisen S. Environmental stress, reactivity and ischaemic heart disease. Br J Med Psychol 1988;61:316.
741. Verrier R, Dickerson L. Autonomic nervous system and coronary blood flow changes related to emotional
activation and sleep. Circulation 1991;83[supplI]:II-81-II89.
742. Brown V, Eisenberg S, Ginsburg H. [in:] Diet, Lifestyle, and Coronary Risk. Lipids and Atherogenesis. New
York:Cahners Publishing Co., 1991:11-12.
743. Friedman M, Rosenman RH, Carroll V. Changes in the serum cholesterol and blood clotting time in men
subjected to cyclic variations of occupational stress. Circulation 1958;17:852.
744. Thomas CB, Murphy EA. Further studies on cholesterol levels in the Johns Hopkins medical students: The
effect of stress at examination. J Chron Dis 1958;8:661.
745. Wolf S, McCabe W, et al. Change in serum lipids in relation to emotional stress during rigid control of diet and
exercise. Circulation 1962;26:379.
746. Kasl SV, Cobb S, Brooks GW. Changes in serum urine acids and cholesterol levels in men undergoing job loss.
JAMA 1968;206:1500.
747. Jenkins CD, Hames CG, Zyzanski SJ. Psychological traits and serum lipids. Psychosom Med 1969;31:116.
748. Rahe RH, Rubin RT, et al. Psychological correlates of serum cholesterol in men: a longitudinal study.
Psychosom Med 1971;33:399.
749. Taggart P, Carruthers M. Endogenous hyperlipidemia induced by emotional stress of racing drivers. Lancet
1971;i:363.
750. Goldstein JL, Kitta T, Brown MS. Defective lipoprotein receptors and atherosclerosis. N Engl J Med
1983;309:288.
751. Johnson JV. The impact of workplace and social support, job demands and work control upon cardiovascular
disease in Sweden. (Report No.1), Stockholm:Department of Psychology, University of Stockholm, Division of
Environmental and Organisational Psychology, 1986.
752. Alfreddson L, Karasek R, Theorell T. Myocardial infarction risk and psychosocial work environment: an
analysis of the male Swedish working force. Soc Sci med 1982;16:463-467.
753. Theorell T, Floderus-Myrhed B. "Workload" and risk of myocardial infarction--a prospective psychosocial
analysis. Int J Epidemiol 1977;6:17-21.
754. Alfredsson L, Spetz C-L, Theorell T. Type of occupation and near-future hospitilization for myocardial
infarction and some other diagnoses. Int J Epidemiol 1985;14:378-388.
755. Mausner B, Platt ES. Smoking: A behavioral analysis. New York:Pergamon Press, 1971.
756. McArthur C, Waldron E, Dickenson J. The psychology of smoking. J Abnorm Psychol 1958;56:267-275.
757. Devereux RB, Pickering TG, et al. Left ventricular hypertrophy in patients with hypertension: importance of
Page 248
blood pressure response to regularly recurring stress. Circulation 1983;68:470-476.
758. Theorell T, Knox S, et al. Blood pressure variations during a working day at age 28: effects of different types of
work and blood pressure level at age 18. J Human Stress 1985;11:36-41.
759. Frankenhaeuser M. Coping with stress at work. Int J Health Serv 1981;11:491-510.
760. Suarez EC, Williams RB. Situational determinants of cardiovascular and emotional reactivity in high and low
hostile men. Psychosom Med 1989;51:404-418.
761. Hamburg DA. Frontiers of research in neurobiology. Science 1983;222:969.
762. French-Belgian Cooperative Group: Ischemic heart disease and psychological patterns: prevalence and
incidence studies in Belgium and France. Adv Cardiol 1982;29:25-31.
763. Haynes SG, Feinleib M. Women, work, and coronary heart disease: prospective findings from the Framingham
heart study. Am J Public Health 1980;70:133-141.
764. Farrow SC. Unemployment and health: A review of methodology, in: Cullen J, Siegrist J (eds): Breakdown in
Human Adaption to Stress. Boston: Martinus Nijhoff; vol 1, 1984:149-158.
765. Ruberman W, Weinblatt E, et al. Psychosocial influences on mortality after myocardial infarction. N Engl J
Med 1984;311:552-559.
766. Orth-Gomer K, Unden AL. Type A behavior, social support and coronary risk. Interaction and significance for
mortality in cardiac patients. Psychosom Med 1990;52:59-72.
767. Johnson JV, Hall EM. Job strain, work place social support, and cardiovascular disease: a cross-sectional study
of a random sample of the Swedish working population. Am J Public health 1988;78:1336-1342.
768. Medalie J, Goldbourt V. Angina pectoris among 10,000 men:II. Psychosocial and other risk factors as
evidenced by a multivariate analysis of a five-year incidence study. Am J Med 1976;60:910-921.
769. Blumenthal JA, Burg MM, et al. Social support, type-A behavior, and coronary artery disease. Psychosom Med
1987;49:331-340.
770. Deanfield JE, Kensett N, et al. Silent myocardial ischemia due to mental stress. Lancet 1984;2:1001-1004.
771. Selwyn AP, Ganz P. Myocardial ischemia in coronary disease. N Engl J Med 1988;318:1058-1060.
772. Rozanski A, Bairey CN, et al. Mental stress and the induction of silent myocardial ischemia in patients with
coronary artery disease. N Engl J Med 1988;318:1005-1012.
773. Krantz DS, Helmers KF, et al. Cardiovascular reactivity and mental stress-induced myocardial ischemia in
patients with coronary artery disease. Psychosom Med 1991;53:1-12.
774. Va Veau PJ, Rozanski A, et al. Transient left ventricular dysfunction during provocative mental stress in
patients with coronary artery disease. Am Heart J 1989;118:1-8.
775. Reich P, DeSilva RA, et al. Acute psychological disturbance preceeding life-threatening ventricular arrythmias.
JAMA 1981;246:233-235.
776. Tavazzi L, Zotti AM, Rondanelli R. The role of psychological stress in the genesis of lethal arrythmias in
patients with coronary artery disease. Eur Heart J 1986; (suppl A):99-106.
777. Schwartz PJ. Stress and sudden cardiac death: the role of the autonomic nervous system. Journal of Clinical
Psychiatry Monograph Series 1984;2:7-13.
Page 249
778. Follick MJ, Gorkin L, et al. Psychological stress as a predictor of ventricular arrythmias in a post-myocardial
infarct population. Am Heart J 1988;116:32-36.
779. Lown B, DeSilva RA. Roles of psychological stress and autonomic nervous system changes in provocation of
ventricular premature complexes. Am J Cardiol 1978;41:979-985.
780. Kamarck T, Jennings JR. Biobehavioral factors in sudden cardiac death. Psychol Bull 1991;109:42-75.
781. Shapiro AP. Psychological factors in hypertension: an overview. Am Heart J 1988;116:632-637.
782. Light KC. Psychosocial precursors of hypetension:experimental evidence. Circulation 1987;76(suppl I);I-67-I76.
783. Houston BK. Psychological variables and cardiovascular and neuroendocrine reactivity.In: Handbook of Stress,
Reactivity, and Cardiovascular Disease. Matthews KA, Weiss SM, et al, (Eds.), New York: John Wiley; 1986:207229.
784. Dimsdale, JE. Research links between psychiatry and cardiology: hypertension, type A behavior, sudden death,
and the psychology of emotional arousal. Gen Hosp Psychiatry 1988;10:328-338.
785. James SA. Psychosocial precursors of hypertension: a review of the epidemiologic evidence. Circulation
1987;76(suppl I):I-60-I-66.
786. Epstein LH, Jennings JR. Smoking, stress, cardiovascular reactivity and coronary heart disease. In: Handbook
of Stress, Reactivity, and Cardiovascular Disease; Matthews KA, Weiss SM, et al. (Eds.), New York:John Wiley;
1988:291-310.
787. Dembroski TM, MacDougall JM, et al. Selective cardiovascular effects of stress and cigarette smoking in
young women. Health Psychology 1985;4:153-167.
788. Cryer PE, Haymond MW, et al. Norepinephrine and epinephrine release and adrenergic mediation of smokingassociated hemodynamic and metabolic events. N Engl J Med 1976;295:573-577.
789. Gilbert DG. Paradoxical tranquilizing and emotion-reducing effects of nicotine. Psych Bull 1979;86:643-661.
790. Krantz DS, Contrada RJ, et al. Environmental stress and biobehavioral antecedents of coronary heart disease. J
Consulting and Clin Psychol 1988;56:331-341.
791. Conway TL, Vickers RR, et al. Occupational stress and variation in cigarette, coffee, and alcohol consumption.
J Health and Soc Behavior 1981;22:155-165.
792. Maisel A, Wright M, et al. Norepinephrine kinetics in hypertrophic cardiomyopathy. In: Hypertrophic
Cardiomyopathy. Marion B, Toshimo H, eds. Tokyo:University of Tokyo Press, 1989:129-139.
793. Thomas J, Marks B. Plasma norepinephrine in congestive heart failure. Am J Cardiol 1978;41:233-243.
794. Creager M, Faxon D, et al. Determinants of clinical responses and survival in patients with congestive heart
failure treated with captopril. Am Heart J 1982;104:1147-1154.
795. Nadeau R, DeChamplain J. Plasma Catecholamines in acute myocardial infarction. Am Heart J 1979;98:548554.
796. Karlsberg R, Cryer P, Roberts R. Serum plasma catecholamine response early in the course of acute myocardial
infarction: relationship to infarct extent and mortality. Am Heart J 1981;102:24-29.
797. Ziegler M, Lake C, Kopin I. The sympathetic nervous system defect in primary orthostatic hypotension. N Engl
J med 1977;296:293-297.
Page 250
798. Goldstein D. Plasma catecholamines in essential hypertension: an analytic review. Hypertension 1983;5:86-99.
799. Cleland J, Dargie H. Arrythmias, catecholamines, and electrolytes. Am J Cardiol 1988;62:55A-59A.
800. Frankenhaeuser M. The sympathetic-adrenal and pituitary-adrenal response to challenge: comparison between
the sexes. In: Dembroski T, Schmidt T, Blumchen G, (eds.), Biobehavioral Bases of Coronary heart Disease.
Basel:Karger; 1983.
801. Collins A, Frankenhaeuser M. Stress responses in male and female engineering students. J Human Stress
1978;4:43-48.
802. James G, Jenner D, et al. Differences in catecholamine excretion rates, blood pressure, and lifestyle among
young Western Samoan men. Hum Biol 1985;57:635-647.
803. Davidson L, Baum A. Chronic stress and posttraumatic stress disorders. J Consult Clin Psychol 1986;54:303308.
804. Machlin LJ, Sauberlich HE. New Views on the function and health effects of vitamins. Nutrition Today
1994;29(1):25-29.
805. Manson JE, Stampfer MJ, et al. A prospective study of antioxidant vitamins and incidence of coronary heart
disease in women. Circulation 1991;84(Suppl II):2168.
806. Choi ESK, McGandy RB, et al. The prevalence of cardiovascular risk factors among elderly Chinese
Americans. Arch Intern Med 1990;150:413-418.
807. Moran JP, Cohen L, et al. Plasma ascorbic acid concentrations relate inversely to blood pressure in human
subjects. Am J Clin Nutr 1993;57:213-217.
808. Gaziano JM, Manson JE, et al. Dietary beta carotene and decreased cardiovascular mortality in an elderly
cohort. J Am Coll cardiol 1992;19(3 Suppl A):377A.
809. Rector R. Reducing the crushing tax burden on American families. The Heritage Foundation Backgrounder;
March 7, 1994.
810. Herman T. Tax Report, The Wall Street Journal; May 11, 1994: p.A-1.
811. Nye L. Blood pressure in the aboriginal with a consideration of possible aetiological factors in hyperpiesia and
its relation to civilization. Med J Austrtailia 1937(Dec 4);2:1000.
812. Gilbert C, Gillman J. Diet and disease in the Bantu. Science 1944;99:398-399.
813. Beyers CF. Journ Med Assn South Africa 1927;1:606.
814. Gillman J. Am Journ Phys Anthropology 1936;21:313.
815. Eagle PC, Gillman J. South Afr Journ Med Sci 1938;3:1
816. Schulze VE, Schwab EH. Nervous factors in the development of hypertension. Am Heart J 1936;11:66.
817. Thomas J. Low incidence of coronary heart disease among 317 cases of heart disease at an all-negro hospital.
JAMA 1946;38:202.
818. Federal Security Agency. Death rates per one hundred thousand from disease of the coronary arteries among
white and negro populations. United States Public Health Service, Office of Vital Statistics: Vital Statistics, in
Special Report, 1948;27:295.
819. Hjermann I, Velve Byre K, et al. Effect of diet and smoking on the incidence of coronary heart disease: report
Page 251
from the Oslo Study Group of a randomized trial in healthy men. Lancet 1981;2:1303-1310.
820. Beaglehole R, La Rosa JC, et al. Serum cholesterol, diet, and the decline in coronary heart disease mortality.
Prev Med 1979;8:538-547.
821. Iacono JM. Dietary intervention studies to reduce risk factors related to cardiovascular diseases and cancer.
Prev Med 1987;16:516-524.
822. Stamler J. Primary prevention of coronary heart disease: the last 20 years. Am J Cardiol 1981;47:722-735.
823. Ascherio A, Willett WC, Rimm EB, Giovannucci EL, Stampfer MJ. Dietary iron intake and risk of coronary
disease among men. Circulation 1994;89:969-974.
824. Halliwell B. Current status review: free radicals, reactive oxygen species, and human disease: a critical
evaluation with special reference to atherosclerosis. Br J Exp Pathol 1989;70:737-757.
825. McCord JM. Is iron sufficiency a risk factor in ischemic heart disease? Circulation 1991;83:1112-1114.
826. Sullivan JL. The iron paradigm of ischemic heart disease. Am Heart J 1989;117:1177-1188.
827. Salonen JT, Nyyssonen K, et al. High stored iron levels are associated with excess risk of myocardial infarction
in Eastern Finnish men. Circulation 1992;86:803-811.
828. Ihanainen M, Salonen R, et al. Nutritional data collection in the Kuopio ischaemic heart disease risk factor
study: nutrient intake of middle-aged Eastern Finnish men. Nut Res 1989;9:597-604.
829. Snowdon DA, Phillips RL, Fraser GA. Meat consumption and fatal ischemic heart disease. Prev Med
1984;13:490-500.
830. Princen HMG, Poppek GV, et al. Supplementation with vitamin E but not beta carotene in vivo protects low
density lipoprotein from lipid peroxidation in vitro: effect of cigarette smoking. Arterioscler Thromb 1992;12:554562.
831. Jialal I, Grundy SM. Effect of dietary supplementation with alpha-tocopherol on the oxidative modification of
low density lipoprotein. J Lipid Res 1992;33:899-906.
832. Dieber-Rothender M, Puhl M, et al. Effect of oral supplementation with d-alpha-tocopherol on the vitamin E
content of human LDL and resistance to oxidation. J Lipid Res 1991;32:1325-1332.
833. Esterbauer H, Dieber-Rotheneder M, et al. Role of vitamin E in preventing the oxidation of low density
lipoproteins. Am J Clin Nutr 1991;53:314S-321S.
834. Chisolm GM, Kimberly CI, Penn MS. Lipoprotein oxidation and lipoprotein-induced cell injury in diabetes.
Diabetes 1992;(suppl 2):61-66.
835. Hunt JV, Dean RT, Wolf SP. Hydroxyl radical production and autooxidative glycosilation. Biochem J
1988;256:205-212.
836. Sakurai T, Sugioka K, Nakano M. O2-generation and lipid peroxidation during the oxidation of a glycated
polypeptide, glycated polylisine, in the presence of iron-ADP. Biochem Biophys Acta 1990;1043:27-33.
837. Frei B, Forte TM, et al. Gas phase oxidants of cigarette smoke induce lipid peroxidation and changes in
lipoprotein properties in human blood plasma. Biochem J 1991;277:133-138.
838. Biemond P, Swaak AG, et al. Superoxide-dependent and -independent mechanisms of iron mobilization from
ferritin xanthine oxidase. Biochem J 1986;239:169-173.
839. Koster JF, Slee RG. Ferritin, a physiological donor for microsomal lipid peroxidation. FEBS Lett. 1986;199-
Page 252
85-88.
840. Stampfer MJ, Grodstein F, et al. A prospective study of plasma ferritin and risk of myocardial infarction in U.S.
physicians. Circulation 1993;87:10 [Abstract].
841. Cook JD. Adaption in iron metabolism. Am J Clin Nutr 1990;51:301-308.
842. Miller M, Hutchins GM. Is iron overload a risk factor for coronary artery disease? Circulation 1993;88(No 4,
Part II):I-636 [abstract 3422].
843. Balla G, Jacob HS, et al. Hemin: a possible physiological mediator of low density lipoprotein oxidation and
endothelial injury. Arterioscler Thromb 1991;11:1700-1711.
844. Dunne LJ. Nutrition Almanac. New York: McGraw-Hill Publishing; 1990.
845. Garrison RH, Somer E. The Nutrition Desk Reference. New Canaan, Connecticut: Keats Publishing;1990.
846. Balch JF, Balch PA. Prescription for Nutritional Healing. Garden City Park, N.Y.: Avery Publishing Group;
1990.
847. Haenszel W, Kurihara M. Studies of Japanese migrants. I. Mortality from cancer and other diseases among
Japanese in the United States. J Natl Cancer Inst 1968;40:43-68.
848. Staszewski W, Haenszel W. Cancer mortality among the Polish-born in the United States. J Natl Cancer Inst
1965;35:291-297.
849. Roberts TL, Wood DA, et al. Adipose linoleic acid and risk of coronary heart disease in women. Circulation
1993;88(No.4, Pt. 2):I-221 [Abstract 1179].
850. de Lorgeril M, Renaud S, et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of
coronary heart disease. Lancet 1994;343:1454-1459.
851. Fraser GE, Sabate J, et al. A possible protective effect of nut consumption on risk of coronary heart disease.
The Adventist Health Study. Arch Intern Med 1992;152(7):1416-1424.
852. Wilder LB, Miller KW, et al. Intake of high fat foods among urban blacks and whites. Circulation
1993;88(No.4, Pt. 2):I-517 [Abstract 2785].
853. Stephen AM, Wald NJ. Trends in individual consumption of dietary fat in the Unites States, 1920-1984. Am J
Clin nutr 1990;52:457-469.
854. Hargreaves MK, Banquet C, Gamshadzahi A. Diet, nutritional status, and cancer risk in American blacks. Nutr
Cancer 1989;12:1-28.
855. Campbell TC, Junshi C. Diet and chronic degenerative diseases: perspectives from China. Am J Clin Nutr
1994;59(suppl):1153S-1161S.
856. Levine PH, Fisher M, et al. Dietary supplementation with omega-3 fatty acids prolongs platelet survival in
hyperlipidemic patients with atherosclerosis. Arch Intern Med 1989;149:1113-1116.
857. Mustard JF, Murphy EA. Effect of different dietary fats on blood coagulation, platelet economy, and blood
lipids. Br Med J 1962;1:1651-1655.
858. Renaud S. Dietary fats and thrombosis. Bibl Nutr Dieta 1977;25:92-101.
859. Renaud S, Godsey F, et al. Influence of long term diet modification on platelet function and composition in
Moselle farmers. Am J Clin Nutr 1986;43:136-150.
Page 253
860. Miller GJ, Martin JC, et al. Association between dietary fat intake and plasma factor VII coagulant activity: a
predictor of cardiovascular mortality. Atherosclerosis 1986;60:269-277.
861. Gordon T, Kagan A, et al. Diet and its relation to coronary heart disease in three populations. Circulation
1981;63:500-515.
862. Morris JN, Marr JW, Clayton DG. Diet and heart: a postscript. Br Med J 1977;2:1307-1314.
863. Shekelle RB, Missell L, et al. Fish consumption and mortality from coronary heart disease. N Engl J Med
1985;313:820.
864. Vollset SE, Heuch I, Bjelke E. Fish consumption and mortality from coronary heart disease. N Engl J Med
1985;313:821.
865. Curb JD, Reed DM. Fish consumption and mortality from coronary heart disease. N Engl J Med 1985;313:821822.
866. Norell SE, Ahlbom A, et al. Fish consumption and mortality from coronary heart disease. Br Med J
1986;293:426.
867. Lapidus L, Andersson H, et al. Dietary habits in relation to incidence of cardiovascular disease and death in
women: a 12-year follow-up of participants in the population study of women in Gothenburg, Sweden. Am J Clin
Nutr 1986;44:444-448.
868. Hunter DJ, Kazda I, et al. Fish consumption and cardiovascular mortality in Canada: an inter-regional
comparison. Am J Prev Med 1988;4:5-10.
869. Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence? Lancet
1994;344:721-724.
870. Byers T. Vitamin E supplements and coronary heart disease. Nutr Rev 1993;51:333-345.
871. Gutteridge JMC. Free radicals in disease processes: a compilation of cause and consequence. Free Radic Res
Commun 1993;19:141-158.
872. de Lorgeril M, Renaud S. Anomalies de l'hemostase et risque coronaire. Revue de Praticien 1992;42(17):21362140.
873. Renaud S, de Lorgeril M. Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet
1992;339(8808):1523-1526.
874. Young V, Pellett P. Plant proteins in relation to human protein and amino acid nutrition. Am J Clin Nutr
1994;59(suppl):1203S-1212S.
875. Anderson JW, Smith BM, Gustafson NJ. Health benefits and practical aspects of high-fiber diets. Am J Clin
Nutr 1994;59(suppl):1242S-1247S.
876. Burkitt TP, Trowell HC. Refined carbohydrate foods and disease. Some implications of dietary fibre. London:
Academic Press, 1975.
877. Anderson JW, Gustafson NJ. Hypercholesterolemic effects of oat and bean products. Am J Clin Nutr
1988;48:749-753.
878. Anderson JW, Deakins DA, et al. Dietary fiber and coronary heart disease. Crit Rev Food Sci Nutr 1990;29:95147.
879. Anderson JW. Plant fiber and blood pressure. Ann Intern Med 1983;98:843-846.
Page 254
880. Anderson JW, Bryant CA. Dietary fiber: diabetes and obesity. Am J Gastroenterol 1986;81:898-906.
881. Kromhout D, Bosschieter EB, de Lezenne Coulander C. Dietary fiber and 10-year mortality from coronary
heart disease, cancer, and all causes: the Zutphen study. Lancet 1982;2:512-522.
882. Madar Z, Odes HS. Dietary fiber research. Basel, Switzerland: Karger, 1990.
883. Anderson JW, Akanji AO. Dietary fiber--an overview. Diabetes Care 1991;14:1126-1131.
884. Robertson WBL. Atherosclerosis and ischaemic heart disease. Observations in Jamaica. Lancet 1959;1:444.
885. Herbert V. The antioxidant supplement myth. Am J Clin Nutr 1994;60:157-158.
886. Herbert V, Shaw S, et al. Most free radical injury is iron-related: it is promoted by iron, hemin, holoferritin, and
vitamin C, and inhibited by Desferoxamine and apoferritin. Stem Cells 1994;12:289-303.
887. Bovard J. Suburban Guerrilla. The American Spectator 1994;27(9):26-32.
888. Richard M Nixon. The Memoirs of Richard M. Nixon. New York: Simon and Schuster;1990:353-353.
889. Lecomte E, Herbeth B, et al. Effect of alcohol consumption on blood antioxidant nutrients and oxidative stress
indicators. Am J Clin Nutr 1994;60:255-261.
890. Johnston PK. Prefact to the Symposium on Vegetarian Nutrition. Am J Clin Nutr 1994;59(suppl):vii
891. Fraser G. Diet and coronary heart disease: beyond dietary fats and low-density-lipoprotein cholesterol. Am J
Clin Nutr 1994;59(suppl):1117S-1123S.
892. Anderson JT, Jacobs DR, Foster N, Keys A, et al. Scoring system for evaluating dietary pattern effect on serum
cholesterol. Prev Med 1979;8:525-537.
893. Hegsted DM, McGandy RB, et al. Quantitative effects of dietary fat on serum cholesterol in men. Am J Clin
Nutr 1965;17:281-295.
894. Hennekens CH, Gaziano JM. Antioxidants and heart disease: epidemiologic and clinical evidence. Clin Cardiol
1993;16(suppl):I10-I15.
895. Barradas MA, Christofides JA, et al. The effect of olive oil supplementation on human platelet function, serum
cholesterol-related variables and plasma fibrinogen concentrations: a pilot study. Nutr Res 1990;10:403-411.
896. Flavahan NA. Atherosclerosis or lipoprotein-induced endothelial dysfunction. Circulation 1992;85:1927-1938.
897. Beswick AD, Fehily AM, et al. Long-term diet modification and platelet activity. J Intern Med 1991;229:511515.
898. Palmer RMJ, Ashton DS, Moncada S. Vascular endothelial cells synthesize nitric oxide from arginine. Nature
1988;333:664-666.
899. Brown KA, Morrice PC, Duthie GG. Vitamin E supplementation suppresses indexes of lipid peroxidation and
platelet counts in blood of smokers and nonsmokers but plasma lipoprotein concentrations remain unchanged. Am J
Clin Nutr 1994;60:383-387.
900. Cassidy A, Bingham S, Setchell K. Biological effects of a diet of soy protein rich in isoflavones on the
menstrual cycle of premenopausal women. Am J Clin Nutr 1994;60:333-340.
901. Ahmed S, Leo MA, Lieber CS. Interactions between alcohol and beta carotene in patients with alcoholic liver
disease. Am J Clin Nutr 1994;60:430-436.
Page 255
902. Smith GD, Song S, Sheldon TA. Cholesterol lowering and mortality: the importance of considering the initial
level of risk. Br Med J 1993;306:1367-1373.
903. Hulley SB, Newman TB, et al. Should we be measuring blood cholesterol levels in young adults? JAMA
1993;269:1416-1419.
904. Schwartz DF, Grisso JA, et al. A longitudinal study of injury morbidity in an African-American population.
JAMA 1994;271:755-760.
905. Bassler TJ. "Regression" of atheroma. West J Med 1980;132:474-475.
906. Bassler TJ, Bassler TJ Jr. Long term mortality after primary prevention for cardiovascular disease. JAMA
1992;267:2183.
907. Mensink RP, Katan MB. Effect of dietary trans fatty acids on high density and low density lipoprotein
cholesterol levels in healthy subjects. N Engl J Med 1990;323:439-445.
908. Report from the committee of principal investigators. A coororative trial in the primary prevention of ischemic
heart disease using clofibrate. Br Heart J 1978;40:1069-1118.
909. Ornish D, Brown SE, et al. Can lifestyle changes reverse coronary heart disease? The Lifestyle Heart Trial.
Lancet 1990;336:129-133.
910. Mantzioris E, James M, et al. Dietary substitution with alpha-linolenic acid-rich vegetable oil increases
eicosapentaenoic acid concentrations in tissues. Am J Clin Nutr 1994;59:1304-1309.
911. Harris T, Feldman JJ, et al. The low cholesterol-mortality association in a national cohort. J Clin Epidemiol
1992;45:595-601.
912. Smith GD, Shipley MJ, et al. Plasma cholesterol concentration and mortality: The Whitehall Study. JAMA
1992;267:70-76.
913. Anonymous. The effects of non-pharmacologic interventions on blood pressure of persons with high normal
levels. Results of the trials of Hypertension Prevention, Phase I. JAMA 1992;267:1213-1220.
914. Goto Y, Moriguchi EH. Diet and ischemic heart disease in Japan. Atherosclerosis Rev 1990;21:21-33.
915. Parodi PW. Distribution of isomeric octadecenoic fatty acids in milk fat. J Dairy Sci 1976;50:1870-1873.
916. Zock PL, Katan MB. Hydrogenation alternatives: effects of trans fatty acids and stearic acid versus linoleic acid
on serum lipids and lipoproteins in humans. J Lipid Res 1992;33:399-410.
917. Willett WC, Stampfer MJ, et al. trans-Fatty acid intake in relation to the risk of coronary heart disease among
women. Lancet 1993;341:581-585.
918. van Oye E, Charles P. Contribution a l'etude de la fonction hepatique chez le noir Africain. vi. La
cholesterolemie. Ann soc belge de med trop 1952;32:297.
919. Lindenbaum J, Rosenberg IH, et al. Prevalence of cobalamin deficiency in the Framingham elderly population.
Am J Clin Nutr 1994;60:2-11.
920. Brattstrom LE, Israelsson B, et al. Folic acid--an innocuous means to reduce plasma homocysteine. Scand J
Clin Lab Invest 1988;48:215-221.
921. Ferroli CE, Trumbo PR. Bioavailability of vitamin B-6 in young and older men. Am J Clin Nutr 1994;60:68-71.
922. Mori TA, Vandongen R, et al. Effects of varying dietary fat, fish, and fish oils on blood lipids in a randomized
controlled trial in men at risk of heart disease. Am J Clin Nutr 1994;59:1060-1068.
Page 256
923. Clarke R, Daly L, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med
1991;324:1149-1155.
924. Coull BM, Malinow MR, et al. Elevated plasma homocyst(e)ine concentration as a possible independent risk
factor for stroke. Stroke 1990;21:572-576.
925. Pancharuniti N, Lewis CA, et al. Plasma homocyst(e)ine, folate, and vitamin B-12 concentrations and risk for
early-onset coronary artery disease. Am J Clin Nutr 1994;59:940-948.
926. Boers GHJ, Smals AGH, et al. Heterozygosity for homocysteinuria in premature peripheral and cerebral
occlusive arterial disease. N Engl J Med 1985;313:709-715.
927. Malinow MR, Kang SS, et al. Prevalence of hyperhomocyst(e)inemia in patients with peripheral arterial
occlusive disease. Circulation 1989;79:1180-1188.
928. Genest JJ, McNamara DN, et al. Plasma homocyst(e)ine levels in men with premature coronary artery disease. J
Am Coll Cardiol 1990;16:1114-1119.
929. Parkinson AJ, Cruz AL, et al. Elevated concentrations of omega-3 polyunsaturated fatty acids among Alaskan
Eskimos. Am J Clin Nutr 1994;59:384-388.
930. Davidson M, Bulkow LR, Gellin BG. Cardiac mortality in Alaska's indigenous and non-native residents. Int J
Epidemiol 1993;22:62-67.
931. Melby CL, Toohey ML, Cebrick J. Blood pressure and blood lipids among vegetarian, semivegitarian, and nonvegetarian African-Americans. Am J Clin Nutr 1994;59:103-109.
932. Clark LT, Karve MM, et al. Obesity, distribution of body fat and coronary artery disease in black women. Am J
Cardiol 1994;73:895-896.
933. Kumanyita S. Obesity in black women. Epidemiol Rev 1987;9:31-50.
934. Dawson D. Ethnic differences in female overweight: data from the 1985 National Health Interview Survey. Am
J Public Health 1988;78:1326-1329.
935. Gillum R. Overweight and obesity in black women: a review of published data from the National Center for
Health Statistics. J Natl Med Assn 1987;79:865-871.
936. Gillum RF. The association of body fat distribution with hypertension, hypertensive heart disease, coronary
heart disease, diabetes, and cardiovascular risk factors in men and women aged 18-79 years. J Chron Dis
1987;40:421-428.
937. Folsom AR, Burke GL, et al. Implications of obesity for cardiovascular disease in blacks: the CAD-DIA and
ARIC studies. Am J Clin Nutr 1991;53:1604S-1611S.
938. Adams-Campbell LL, Nwankwo M, et al. Body fat distribution patterns and blood pressure in black and white
women. J Natl Med Assn 1990;82:573-576.
939. Svec F, Rivera M, Huth M. Correlation of waist to hips ratio to the prevalence of diabetes and hypertension in
black females. J Natl Med Assn 1990;82:257-261.
940. Reading R, Raybould S, Jarvis S. Deprivation, low birth weight, and childrens' height: a comparison between
rural and urban areas. Br Med J 1993;307:1458-1462.
941. Dahl LK. Salt intake and salt need. N Engl J Med 1958;258:1152.
942. American Heart Association. Cardiovascular disease and stroke in African- Americans and other racial
Page 257
minorities in the United States: a statement for health professionals. Circulation 1991;83:1462-1480.
943. Bengtsson C, Bjorkelund C, et al. Associations of serum lipid concentrations and obesity with mortality in
women: 20 year follow up of participants in prospective population study in Gothenburg, Sweden. Br Med J
1993;307:1385-1388.
944. Lapidus L, Bengtsson C, et al. Distribution of adipose tissue and risk of cardiovascular disease and death: a 12
year follow up of participants in the population study of women in Gothenburg, Sweden. Br Med J 1984;289:12571261.
945. Hartz A, Grubb B, et al. The association of waist hip ratio and angiographically determined coronary artery
disease. Int J Obes 1990;14:657-665.
946. Thompson CJ, Ryu JE, et al. Central adipose distribution is related to coronary atherosclerosis. Arterioscler
Thromb 1991;11:327-333.
947. Cassel J, Heyden S, et al. Occupation and physical activity and coronary heart disease. Arch Int Med
1971;128:920-928.
948. Simpson ME. Social mobility, normlessness, and powerlessness in two cultural contexts. Amer Sociol Rev
1970;35:1002-1013.
949. Stuckert RP. Occupational mobility and family relationships. Social Forces 1963;41:301-307.
950. Seeman M. On the meaning of alienation. Amer Sociol Rev 1959;24:783-791.
951. Warner W, Abegglen JC. Big Business Leaders in America. New York: Harper Brothers, 1955.
952. Meier D, Bell W. Anomia and differential access to the achievement of life goals. Amer Sociol Rev
1959;24:189-207.
953. McDonough JR, Hames CG, et al. Coronary heart disease among negroes and whites in Evans County, Georgia.
J Chronic Dis 1968;18:443-468.
954. Miall WE, Del Campo E, et al. A longitudinal study of heart disease in a Jaimacan rural population. Bull World
Health Organization, 1971.
955. Pepler WJ, Meyer BJ. Interarterial coronary anastomoses and coronary arterial pattern: A comparison of South
African Bantu and European hearts. Circulation 1960;22:14-24.
956. Walker ARP, Walker BF. The bearing of race, sex, age, and nutritional state on the precordial
electrocardiograms of young South African Bantu and Caucasian subjects. Am Heart J 1969;77:441-459.
957. Kuller L. Sudden death in arteriosclerotic heart disease. Am J Cardiol 1969;24:617-628.
958. Chapman JM, Coulson AH, Clark V. Negro-white differences in risk factors and disease incidence in an
epidemiologic study of ischemic heart disease. Circulation 1970;42(suppl III):143.
959. Lilienfield AM. Variation in mortality from heart disease:Race, sex, and socioeconomic status. Publ Health Rep
1956;71:545-552.
960. McVay LF, Keil PG. Myocardial infarction with special reference to the Negro. Arch Intern Med 1955;96:762767.
961. Thomas WA, Blanche JO, Lee KI. Race and the incidence of acute myocardial infarction. Arch Intern Med
1957;100:423-429.
962. Roberts DW, Meck PG, Grueger DE. Prevalence of heart disease in a population of Baltimore. Circulation
Page 258
1956;14:988-989.
963. Moriyama IM, Woolsey TD. Statistical studies of heart disease: IX. Race and diabetes. Publ Health Rep
1951;66:355-368.
964. Pennel MY, Lehman JL. Statistical studies of heart disease: VIII. Mortality from heart disease among Negroes
as compared to white persons. Publ Health Rep 1951;66:57-80.
965. Bartel A, Heyden S, et al. Electrocardiographic predictors of coronary heart disease. Arch Intern Med
1971;128:929-937.
966. Hagstrom RM, Federspiel CF, Ho YC. Incidence of myocardial infarction and sudden death in Nashville,
Tennessee. Circulation 1971;44:884-890.
967. Oalmann MC, McGill HC Jr, Strong JP. Cardiovascular mortality in a community: results of a survey in new
orleans. Am J Epidemiol 1971;94:546-555.
968. Keil JE, Saunders DE Jr, et al. Acute myocardial infarction: period prevalence, case fatality, and comparison of
black and white cases in urban and rural areas of South Carolina. Am Heart J 1985;109:776-784.
969. Bowering J, Lowenberg RL, Morrison MA. Nutritional studies of pregnant women in East harlem. Am J Clin
Nutr 1980;33:1987-1996.
970. Salen P, de Lorgeril M, et al. Effects of a French Mediterranean diet on heart transplant recipients with
hypercholesterolemia. Am J Cardiol 1994;73:825-827.
971. Kids Count Data Book, a publication using best available data to measure the educational, social, economic and
physical well-being of children. The Annie E. Casey Foundation, Baltimore, MD 21202
Page 259