Cardiovascular Epidemiology and
Prevention
Nathan D. Wong, PhD, FACC, FAHA
Professor and Director, Heart Disease
Prevention Program, Division of Cardiology,
University of California, Irvine
Adjunct Prof. Epidemiology (UCLA and UCI)
Immediate Past President, American Society of
Preventive Cardiology
Textbooks
Cardiovascular Epidemiology:
Definitions, Concepts,
Historical Perspectives and
Statistics
Definitions
• CORONARY ARTERY DISEASE (CAD) or
CORONARY HEART DISEASE (CHD)
(often broadly referred to as ISCHEMIC
HEART DISEASE (IHD): primarily
myocardial infarction and sudden
coronary death, broader definition may
include angina pectoris, atherosclerosis,
positive angiogram, and revascularization
(perceutaneous coronary interventions, or
PCI such as angioplasty and stents)
• CARDIOVASCULAR DISEASE or CVD
includes CHD, cerebrovascular disease,
peripheral vascular disease, and other
cardiac conditions (congenital,
arrhythmias, and congestive heart failure)
Definitions (cont.)
• SURROGATE MEASURES include: carotid
intimal medial thickness (IMT), coronary
calcium, angiographic stenosis, brachial
ultrasound flow mediated dilatation (FMD)
• Hard endpoints include myocardial
infarction, CHD death, and stroke
Trends in cardiovascular procedures, United States: 1979–2009
1400
Procedures in Thousands
1200
1000
800
600
400
200
0
1979
1980
1985
1990
1995
2000
2005
2009
Years
Catheterizations
Bypass
PCI
Carotid Endarterectomy
Pacemakers
Note: Inpatient procedures only. Source: National Hospital Discharge Survey, NCHS, and NHLBI.
©2011 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2011
Direct and indirect costs (in billions of dollars)
of major cardiovascular diseases and stroke (United States: 2008)
200
190.3
180
160
Billions of Dollars
140
120
100
80
60
50.6
40
34.3
22.5
20
0
Heart disease
Hypertension
Stroke
Other CVD
Source: National Heart, Lung, and Blood Institute.
©2011 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2011
Projected Total Costs of CVD, 2015–2030 (in Billions 2008$) in the United States
1200
1117.6
Total Dollars (in Billions)
1000
800
886.2
704.7
564.9
600
408.5
400
245.2
194.1
121.1
250.5
186.7
153.2
200
320.0
223.8
143.0
97.0
156.9
132.4
111.2
87.1
74.1
44.6
57.0
197.8
69.1
0
All CVD
Hypertension
CHD
2015
2020
HF
2025
Stroke
Other CVDs
2030
Unpublished data tabulated by AHA using methods described in Circulation. 2011;123:933–944.
©2011 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2011
So how long have we known that
women are just not small men???
Prevalence of stroke by age and sex (NHANES: 2005–2008).
18
16
14.5
14.8
Percent of Population
14
12
10
8.2
8
7.2
6
4
2.4
1.6
2
0.3
0.5
0
20-39
40-59
Men
Age
60-79
80+
Women
Source: NCHS and NHLBI.
©2010 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2010
Development of Atherosclerotic
Plaques
Fatty streak
Normal
Lipid-rich plaque
Foam cells
Fibrous cap
Thrombus
Ross R. Nature. 1993;362:801-809.
Lipid core
PDAY: Percentage of Right Coronary Artery
Intimal Surface Affected With Early Atherosclerosis
30
Intimal
surface
(%)
Men
Raised lesions 30
Fatty streaks
20
20
10
10
0
30
0
15-19 20-24 25-29 30-34
White
30
20
20
10
10
0
0
15-19 20-24 25-29 30-34
Black
Age (y)
PDAY= Pathobiological Determinants of Atherosclerosis in Youth.
Strong JP, et al. JAMA. 1999;281:727-735.
Women
15-19 20-24 25-29 30-34
White
15-1920-2425-2930-34
Black
Most Myocardial Infarctions Are Caused
by Low-Grade Stenoses
Pooled data from 4 studies: Ambrose et al, 1988; Little et al, 1988; Nobuyoshi et al, 1991; and Giroud et al,
1992.
(Adapted from Falk et al.)
Falk E et al, Circulation, 1995.
Coronary Remodeling
Progression
Compensatory expansion
maintains constant lumen
Normal
vessel
(Adapted from Glagov et al.)
Glagov et al, N Engl J Med, 1987.
Minimal
CAD
Moderate
CAD
Expansion
overcome:
lumen narrows
Severe
CAD
Atherosclerotic Plaque Rupture and
Thrombus Formation
Intraluminal thrombus
Growth of thrombus
Blood Flow
Intraplaque thrombus
Adapted from Weissberg PL. Eur Heart J Supplements
1999:1:T13–18
Lipid pool
Features of a Ruptured
Atherosclerotic Plaque
• Eccentric, lipid-rich
• Fragile fibrous cap
• Prior luminal
obstruction < 50%
• Visible rupture
and thrombus
Constantinides P. Am J Cardiol. 1990;66:37G-40G.
Vulnerable Versus Stable
Atherosclerotic Plaques
Vulnerable Plaque
Lumen
Fibrous Cap
Lipid
Core
• Thin fibrous cap
• Inflammatory cell infiltrates:
proteolytic activity
• Lipid-rich plaque
Stable Plaque
Lumen
Lipid
Core
Fibrous Cap
Libby P. Circulation. 1995;91:2844-2850.
• Thick fibrous cap
• Smooth muscle cells:
more extracellular matrix
• Lipid-poor plaque
Correlation of CT angiography of the
coronary arteries with intravascular
ultrasound illustrates the ability of MDCT
to demonstrate calcified and non-calcified
coronary plaques (Becker et al., Eur J
Radiol 2000)
Non-calcified, soft, lipid-rich plaque in
left anterior descending artery (arrow)
(Somatom Sensation 4, 120 ml Imeron
400). The plaque was confirmed by
intravascular ultrasound (Kopp et al.,
Radiology 2004)
Pyramid of Risk
(Werner et al. Canadian Journal of
Cardiology 1998; 14(Suppl) B:3B-10B)
Approaches to Primary and
Secondary Prevention of
CVD
• Primary prevention involves prevention
of onset of disease in persons without
symptoms.
• Primordial prevention involves the
prevention of risk factors causative o
the disease, thereby reducing the
likelihood of development of the
disease.
• Secondary prevention refers to the
prevention of death or recurrence of
disease in those who are already
symptomatic
Risk Factor Concepts in
Primary Prevention
• Nonmodifiable risk factors include age,
sexc, race, and family history of CVD,
which can identify high-risk populations
• Behavioral risk factors include sedentary
lifestyle, unhealthful diet, heavy alcohol
or cigarette consumption.
• Physiological risk factors include
hypertension, obesity, lipid problems,
and diabetes, which may be a
consequence of behavioral risk factors.
Population vs. High-Risk
Approach
• Risk factors, such as cholesterol or blood
pressure, have a wide bell-shaped distribution,
often with a “tail” of high values.
• The “high-risk approach” involves
identification and intensive treatment of those
at the high end of the “tail”, often at greatest
risk of CVD, reducing levels to “normal”.
• But most cases of CVD do not occur among the
highest levels of a given risk factor, and in fact,
occur among those in the “average” risk group.
• Significant reduction in the population burden
of CVD can occur only from a “population
approach” shifting the entire population
distribution to lower levels.
Expected Shifts in Cholesterol Distribution
from High-Risk, Population, and
Combined Approaches
Population and CommunityWide CVD Risk Reduction
Approaches
• Populations with high rates of CVD are those with
Western lifestyles of high-fat diets, physical
inactivity, and tobacco use.
• Targets of a population-wide approach must be
these behaviors causative of the physiologic risk
factors or directly causative of CVD.
• Requires public health services such as
surveillance (e.g.,BFRSS), education (AHA,
NCEP), organizational partnerships (Singapore
Declaration), and legislation/policy (Anti-Tobacco
policies)
• Activities in a variety of community settings:
schools, worksites, churches, healthcare
facilities, entire communities
A conceptual framework for public
health practice in CVD prevention.
(From Pearson et al., J Public Health. 2001; 29:69 –78)
Communitywide CVD
Prevention Programs
• Stanford 3-Community Study (1972-75)
showed mass media vs. no intervention in
high-risk residents to result in 23% reduction
in CHD risk score
• North Karelia (1972-) showed public education
campaign to reduce smoking, fat
consumption, blood pressure, and cholesterol
• Stanford 5-City Project (1980-86) showed
reductions in smoking, cholesterol, BP, and
CHD risk
• Minnesota Heart Health Program (1980-88)
showed some increases in physical activity
and in women reductions in smoking
Materials Developed for US
Community Intervention
Trials
•
•
•
•
•
•
•
•
•
Mass media, brochures and direct mail
Events and contests
Screenings
Group and direct education
School programs and worksite
interventions
Physician and medical setting programs
Grocery store and restaurant projects
Church interventions
Policies
Foundations of CVD
Epidemiology
• Lack of reliable data on CVD noted
as early as 1880’s and in 1934 the
Society of Geographic Pathology
noted the frequency of
atherosclerotic lesions by country,
social class and occupation.
• In 1946 the first prospective study
of CVD was launched by Ansel
Keys in Minnesota businessmen.
Cholesterol intake and CHD Death Rate: The
Seven Countries Study
(n=12763 men aged 40-59)
Cholesterol and Mortality:
WHO Monica
(n=15 million men and women aged 25-64)
Migrant Studies
• Ni-Hon-San Study showed
Japanese living in Japan to have
the lowest cholesterol levels and
lowest rates of CHD, those living in
Hawaii to have intermediate rates
for both, and those living in San
Francisco to have the highest
cholesterol levels and CHD
incidence
Framingham Heart
Study
• Longest running study of cardiovascular disease in
the world
• Began in 1948 with original cohort of 5,209 subjects
aged 30-62 at baseline
• Biennial examinations, still ongoing, most of original
cohort deceased
• Offspring cohort of 5,124 of children of original cohort
enrolled in 1971, and more recently and still being
enrolled to better understand genetic components of
CVD risk are up to 3,500 grandchildren of the original
cohort.
• Routine surveillance of cardiovascular disease events
adjudicated by panel of physicians
Concept of cardiovascular
“risk factors”
Age, sex, hypertension, hyperlipidemia,
smoking, diabetes, (family history), (obesity)
Kannel et al, Ann Intern Med 1961
Framingham Most Significant
Milestones
• 1960 Cigarette smoking found to increase the risk of
heart disease
• 1961 Cholesterol level, blood pressure, and
electrocardiogram abnormalities found to increase the
risk of heart disease
• 1967 Physical activity found to reduce the risk of heart
disease and obesity to increase the risk of heart disease
• 1970 High blood pressure found to increase the risk of
stroke
• 1976 Menopause found to increase the risk of heart
disease
• 1978 Psychosocial factors found to affect heart disease
• 1988 High levels of HDL cholesterol found to reduce risk
of death
• 1994 Enlarged left ventricle (one of two lower chambers
of the heart) shown to increase the risk of stroke
9
Doubts about
cholesterol as
late as 1989
Total Cholesterol Distribution:
CHD vs Non-CHD Population
Framingham Heart Study—26-Year Follow-up
No CHD
35% of CHD
Occurs in
People with
TC<200
mg/dL
CHD
150
200
250
300
Total Cholesterol (mg/dL)
Castelli WP. Atherosclerosis. 1996;124(suppl):S1-S9.
1996 Reprinted with permission from Elsevier
Science.
Low HDL-C Levels Increase CHD Risk Even When
Total-C Is Normal
14-y incidence
rates (%) for
CHD
14
12
10
8
6
4
2
0
< 40 40–4950–59  60
HDL-C (mg/dL)
 260
230–259
200–229
< 200
Risk of CHD by HDL-C and Total-C levels; aged 48–83 y
Castelli WP et al. JAMA 1986;256:2835–2838
Messerli, F. H. N Engl J Med 199561
________________________________________________________
CK Friedberg on Hypertension:
Diseases of the Heart 1996
___________________________________________________________
“There is a lack of correlation in
most cases between the severity
and duration of hypertension and
development of cardiac
complications.”
_______________________________________________________________
Relation of Non-Hypertensive Blood
Pressure to Cardiovascular Disease
Vasan R, et al. N Engl J Med 2001; 345:1291-1297
10-year Age- Adjusted Cumulative Incidence
12%
Hazard Ratio*
<120/80 mm Hg
120-129/80-84 mm Hg
130-139/85-89 mm Hg
10%
SBP
10.1
8%
7.6
6%
2%
4.4
2.8
1.9
0%
Women
1.0
1.5
2.5
1.0
1.3
1.6
H.R. adjusted for age,
BMI, Cholesterol, Diabetes
and smoking *P<.001
5.8
4%
<120/80
120-129
130-139
Women Men
Men
Framingham Study: Subjects Ages 35-90 yrs.
Percent of Population With
Hypertension
90
80
70
60
50
40
30
20
10
0
78.8 79.0
82.3
67.6
74.7
69.1 70.1
52.1
46.5
45.4 46.1
35.2
Awareness
Total Population
NH Whites
Treatment
NH Blacks
Controlled
Mexican Americans
Extent of awareness, treatment and control of high blood pressure
by race/ethnicity (NHANES : 2005-2006).
Source: NCHS and NHLBI.
____________________________________________________________
Smoking Statement Issued in 1956 by
American Heart Association
___________________________________________________________
“It is the belief of the committee that much
greater knowledge is needed before any
conclusions can be drawn concerning
relationships between smoking and
death rates from coronary heart
disease. The acquisition of such
knowledge may well require the use of
techniques and research methods that
have not hitherto been applied to this
___________________________________________________________
problem.”
CHD Risk by Cigarette Smoking. Filter
Vs. Non-filter. Framingham Study. Men
<55 Yrs.
14-yr. Rate/1000
250
Non-Smoker
Reg. Cig. Smoker
Filter Cig. Smoker
200
206
210
150
100
210
119
112
50
59
0
Total CHD
Myocardial
Infarction
Prevalence of students in grades 9 to 12 reporting current cigarette use
by sex and race/ethnicity (YRBSS, 2009)
25
22.3
22.8
19.4
Percent of the Population
20
16.7
15
10.7
10
8.4
5
0
NH White
NH Black
Males
Hispanic
Females
Source: MMWR Surveill Summ. 2010;59:1–142.NH indicates non-Hispanic.
©2011 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2011
Prevalence of current smoking for adults > 18 years of age
by race/ethnicity and sex (NHIS: 2007-2009)
30
26.8
25
Percent of Population
22.9
23.6
19.9
20
18.9
17.9
17.0
15.4
15
9.3
10
5.4
5
0
Men
NH White
NH Black
Women
Hispanic
Asian*
American Indian/Alaska Native*
All percentages are age-adjusted. NH indicates non-Hispanic. *Includes both Hispanics and non-Hispanics. Data derived from Centers for Disease Control
and Prevention/National Center for Health Statistics, Health Data Interactive.
©2011 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2011
Diseases of The Heart
Charles K Friedberg MD, WB
________________________________________________________________
Saunders Co. Philadelphia, 1949
“The proper control of diabetes is
obviously desirable even though
there is uncertainty as to whether
coronary atherosclerosis is more
frequent or severe in the
uncontrolled diabetic”
______________________________________________________________
Risk of Cardiovascular Events in Diabetics
Framingham Study
_________________________________________________________________
Cardiovascular Event
Coronary Disease
Stroke
Peripheral Artery Dis.
Cardiac Failure
All CVD Events
Age-adjusted
Biennial Rate Age-adjusted
Per 1000
Risk Ratio
Men Women Men Women
39 21
1.5** 2.2***
15
6
2.9*** 2.6***
18 18
3.4*** 6.4***
23 21
4.4*** 7.8***
76 65
2.2*** 3.7***
_________________________________________________________________
Subjects 35-64 36-year Follow-up **P<.001,***P<.0001
Skepticism About Importance of Obesity
Keys A, Aravanis C, Blackburn H, et al. Ann Intern Med 1972;
77:15-27.
Concluded that all the excess risk of coronary heart
disease in the obese derives from its atherogenic
accompaniments, illogically leaving the impression that obesity
is therefore unimportant.
Mann GV. N Engl J Med 1974; 291:226-232.
“The contribution of obesity to CHD is either small or
non-existent. It cannot be expected that treating obesity is
either logical or a promising approach to the management of
CHD”.
Barrett-Connor EL. Ann Intern Med 1985; 103:1010-1019
NIH consensus panel is equivocal about the role of
obesity as a cause of CHD.
Relation of Weight Change to Changes in
Atherogenic Traits: The Framingham Study
Frantz Ashley, Jr. and William B Kannel
J Chronic Dis 1974
“Weight gain is accompanied by atherogenic alterations in
blood lipids, blood pressure, uric acid and carbohydrate
tolerance.”
“It seems reasonable to expect that correction of overweight
will improve the coronary risk problem.”
“Avoidance of overweight would seem a desirable goal in the
general population if the appalling annual toll from disease
is to be substantially reduced.”
Trends in the prevalence of obesity among US children and adolescents by age and survey year
(National Health and Nutrition Examination Survey: 1971-1974, 1976-1980, 1988-1994, 19992002 and 2005–2008)
20
16.0
15.9
16
Percent of Population
17.9
17.4
18
14
12
11.3
10.5
10
8
6.5
6.1
6
5.0
4.0
4
2
0
6-11
1971-1974
12-19
Age (Years)
1976-1980
1988-1994
1999-2002
2005-2008
Data derived from Health, United States, 2010: With Special Feature on Death and Dying. NCHS, 2011.
©2011 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2011
Age-adjusted prevalence of obesity in adults 20–74 years of age, by sex and survey year
(NHES: 1960–62; NHANES: 1971–74, 1976–80, 1988–94, 1999-2002 and 2005-08)
40
36.2
35
34.0
33.3
30
28.1
Percent of Population
26.0
25
20.6
20
16.8
17.1
15.7
15
12.2
12.8
10.7
10
5
0
Men
1960-62
1971-74
Women
1976-80
1988-94
1999-2002
2005-08
Data derived from Health, United States, 2010: With Special Feature on Death and Dying. NCHS, 2011.
©2011 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2011
Framingham Heart Study: Kannel et al., 1961
Why Use Risk Scores?
1) As early as 1976, former Framingham director Dr. William
Kannel had noted risk functions provide an “economic
and efficient method of identifying persons at high
cardiovascular risk who need preventive treatment and
persons at low risk who need not be alarmed about one
moderately elevated risk characteristic” (AJC 1976)
2) The ACC Bethesda Conference noted the intensity of
treatment should match a person’s risk (Califf RM, JACC
1996).
3) Studies show a physician’s estimate is only accurate 24%
of the time (Pignone et al, BMC health Serv Res 2003).
4) Routine use of global risk scores leads to greater use of
guideline-based therapy and modest improvements in
intermediate outcomes with no harm identified (Sheridan
et al. BMC Health Serv Res 2008).
Key Risk Scores Used in CHD and CVD Prediction
Risk Score (year)
Endpoint
Definition
Framingham, 1991 (Anderson)
10-year all CHD
CHD death, MI, unstable
angina, angina
Framingham, 1998 (Wilson)
10-year all CHD and CHD death, MI, unstable
hard CHD
angina, angina
ATP III, 2001 (Framingham)
10-year hard CHD
CHD death, nonfatal MI
PROCAM 2002 (Germany)
10-year hard CHD
CHD death, non-fatal MI
European SCORE 2003 and after 10-year CVD death
CVD death only (country
and region specific)
QRISK 2007 (England and
Wales)
10-year global CVD
CVD death, MI, stroke,
revascularization
Reynolds women (2007) and men 10-year global CVD
(2008) (Boston, USA)
CHD death, MI, stroke,
revascularization
Framingham Global CVD 2008
10-year global CVD
CVD death, all CHD, stroke,
heart failure, claudication
Pooled Cohort Equations 2013
(USA)
10-year and lifetime
ASCVD
Nonfatal/fatal MI & stroke
ATP III Framingham Risk Scoring
Assessing CHD Risk in Women
Step 4: Systolic Blood Pressure
Step 1: Age
Years
Points
20-34
-7
35-39
-3
40-44
0
45-49
3
50-54
6
55-59
8
60-64
10
65-69
12
70-74
14
75-79
16
Step 2: Total Cholesterol
TC
Points at
at Points at
(mg/dL)
Age 20-39
70-79
<160
0
160-199
4
200-239
8
240-279
11
13
Step 280
3: HDL-Cholesterol
HDL-C
(mg/dL)
60
Points
-1
50-59
0
40-49
1
Systolic BP
(mm Hg)
<120
120-129
130-139
140-159
160
Step 6: Adding Up the Points
Points
Points
if Untreated if Treated
0
0
1
3
2
4
3
5
4
6
Age
Total cholesterol
HDL-cholesterol
Systolic blood pressure
Smoking status
Point total
Step 7: CHD Risk
Points at
Points at
Points
Age 40-49 Age 50-59 Age 60-69 Age
0
0
3
2
6
4
8
5
10
7
Step 5: Smoking Status
Nonsmoker
Smoker
Points at
Age 20-39
0
9
0
1
2
3
4
0
1
1
2
2
Points at
Age 40-49
0
7
Point Total 10-Year Risk Point Total 10-Year
Risk
<9
<1%
20
11%
9
1%
21
14%
10
1%
22
17%
11
1%
23
22%
12
1%
24
27%
13
2%
25
30%
14
2%
15
3%
16
4%
17
5%
18
6%
19
8%
Points at Points at Points
at
Age 50-59 Age 60-69 Age 70-79
0
0
0
4
2
1
<40
2
Note: Risk estimates
were derived from the experience of the Framingham Heart Study,
a predominantly Caucasian population in Massachusetts, USA.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in
Adults.
JAMA. 2001;285:2486-2497.
© 2001, Professional Postgraduate Service
www.lipidhealth.org
ATP III Update ( 2004 )
LDL-C Treatment Targets
Risk Category
Initiate
TLC
LDL-C Goal
Consider
Drug Therapy
High risk:
CHD or CHD risk
equivalents
(10-year risk >20%)
<100 mg/dL
(optional goal: 100 mg/dL
<70 mg/dL)
100 mg/dL
(<100 mg/dL:
consider drug Rx)
Moderately high risk:
2+ risk factors
(10-year risk 10% to
20%)
<130 mg/dL
(optimal <100
mg/dL)
130 mg/dL
130 mg/dL
(100-129 mg/dL:
consider Rx )
Moderate risk:
2+ risk factors (risk
<10%)
<130 mg/dL
130 mg/dL
160 mg/dL
Lower risk:
0-1 risk factor
<160 mg/dL
160 mg/dL
190 mg/dL
Adapted from Grundy SM, et al. Circulation. 2004;110:227-239.
10-Year Framingham Total Cardiovascular
Disease Risk Score (D’Agostino et al, 2008)
Global Risk Scoring: Class 1a
ACCF/AHA Guideline for Assessment of Cardiovascular Risk
in Asymptomatic Adults, Circulation 2010
Recommendation to begin with a global risk
assessment using the Pooled Cohort Equations to
estimate 10-year ASCVD Risk
Pooled Cohort Equations 10-year
ASCVD Risk Calculator (Framingham,
ARIC, CARDIA, and CHS)
Lifetime Risks of Cardiovascular Disease Death by
Number of Risk Factors and Attained Age
(Berry et al. , 2012)
Men
Women
Optimal risk factors: total cholesterol <180 mg/dl, blood pressure <120/80, nonsmoking, non-diabetic.
Major risk factors: current smoker, diabetes, treated cholesterol or untreated
cholesterol >=240 mg/dl, treated hypertension or untreated systolic BP >=160 mmHg or
diastolic BP>=100 mmHg.
_______________________________________________________________________________
Lifetime Risk of CHD Increases with
Serum Cholesterol
___________________________________________________________________________
60
Cholesterol
57
50
<200 mg
200-239 mg
>240 mg
Percent
40
44
30
34
29
20
33
19
10
0
Men
Women
Framingham Study: Subjects age 40 years
DM Lloyd-Jones et al Arch Intern Med 2003; 1966-1972
Relation of Non-Hypertensive Blood
Pressure to Cardiovascular Disease
Vasan R, et al. N Engl J Med 2001; 345:1291-1297
10-year Age- Adjusted Cumulative Incidence
12%
Hazard Ratio*
<120/80 mm Hg
120-129/80-84 mm Hg
130-139/85-89 mm Hg
10%
SBP
10.1
8%
7.6
6%
2%
4.4
2.8
1.9
0%
Women
1.0
1.5
2.5
1.0
1.3
1.6
H.R. adjusted for age,
BMI, Cholesterol, Diabetes
and smoking *P<.001
5.8
4%
<120/80
120-129
130-139
Women Men
Men
Framingham Study: Subjects Ages 35-90 yrs.
Risk of Cardiovascular Events in
Diabetics
Framingham Study
_________________________________________________________________
Cardiovascular Event
Coronary Disease
Stroke
Peripheral Artery Dis.
Cardiac Failure
All CVD Events
Age-adjusted
Biennial Rate Age-adjusted
Per 1000
Risk Ratio
Men Women Men Women
39 21
1.5** 2.2***
15
6
2.9*** 2.6***
18 18
3.4*** 6.4***
23 21
4.4*** 7.8***
76 65
2.2*** 3.7***
_________________________________________________________________
Subjects 35-64 36-year Follow-up **P<.001,***P<.0001
Risk Factors for Future Cardiovascular Events: WHS
Lipoprotein(a)
Homocysteine
IL-6
TC
LDLC
sICAM-1
SAA
Apo B
TC: HDLC
hs-CRP
hs-CRP + TC: HDLC
0
1.0
2.0
4.0
6.0
Relative Risk of Future Cardiovascular Events
Ridker et al, N Engl J Med. 2000;342:836-43
Cardiovascular Health
Study
• 5,201 Medicare eligible individuals aged 65-102 at baseline
enrolled beginning 1992 at six field centers.
• Assessment of newer and older risk factors.
• Ongoing follow-up of cardiovascular events and mortality
• Subclinical disease measures included:
– carotid B-mode ultrasound for carotid IMT at Year 2,
Year 7, and Year 11
– m-mode echocardiographic measures of left ventricular
mass and dimensions, left atrial dimension done at
baseline (Year 2) (at UC Irvine) and follow-up (Year 7)
examinations.
– Ankle brachial index (ABI) for measurement of PAD
– Pulmonary function (FVC and FEV1)
Cardiovascular Health Study:
Combined intimal-medial thickness
predicts total MI and stroke
Cardiovascular Health Study (CHS) (aged 65+): MI or stroke rate 25% over 7
years in those at highest quintile of combined IMT (O’Leary et al. 1999)
Multiethnic Study of
Atherosclerosis
• 6,814 adults aged 45-80 enrolled at 6 field
centers, including Caucasians, AfricanAmericans, Hispanics, and Chinese beginning
2000.
• Extensive assessment of standard and novel
risk factors, unique blood cohort among 1000
subjects.
• Multiple evaluations of carotid IMT, ABI, and
coronary calcium. Ancillary studies of LV size
and extracoronary measures of calcification
(Harbor-UCLA) and abdominal aortic calcium
(UC San Diego) in full or partial cohorts.
MESA Study Design Features
Four examinations approximately two years apart,
exam 5 just completed
Major risk factors measured at each exam
Coronary calcium measured in entire cohort at
Exam 1, ½ cohort at Exam 2, ½ cohort at Exam
3, and in about 1000 pts in Exam 4.
Carotid IMT measured at Exam 1 and 2-3.
Cardiac MRI measured at Exam 1 and 2-3
Ankle Brachial Index
Pulse wave analysis
Endothelial function measures
Follow-up for CVD events and incident DM,
mortality
Cumulative Incidence of Any
Coronary Event by Coronary
Calcium Score: MESA Study
(Detrano et al., NEJM 2008)
Intermediate Risk
MESA Subjects
(n=1330)
C-statistics:
FRS alone 0.623
FRS+CAC 0.784 (p<0.001)
FRS+CIMT 0.652 (p=0.01)
FRS+FMD 0.639 (p=0.06)
FRS+CRP 0.640 (p=0.03)
FRS+FamHx 0.675
(p=0.001)
FRS+ABI 0.650 (p=0.01)
Yeboah J et al, JAMA 2012
Coronary Artery Risk Development in
Young Adults (CARDIA) – 5,115 adults
(half African-American) aged 18-30 at
baseline in 1985 enrolled at 4 field
centers.
– Ongoing evaluation (Year 20 exam recently
completed).
– Echocardiographic M-mode and 2D
measures available at Year 5 and Year 10
exams (UC Irvine Echo Reading Center)
– CT Coronary Calcium at Years 15 (HarborUCLA) and 20 (Wake Forest University)
NHANES Cross-Sectional and
Mortality Follow-up Studies
• NHES 1960, NHANES II 1976,
NHANES III 1988-1994, and
NHANES IV 2000-2012 crosssectional health survey and clinic
exam data
• NHES, NHANES 2,3 Mortality
Follow-up
Events/100 Patients*
Risk for CHD Increases with the
Number of Risk Factors: NHANES/NHEFS
--40--35 --30 --25 --20 --15 --10 --5 ----
0
35.0
N = 12,932
Risk Factors (RFs)
• SBP >140 mm Hg or
DBP >80 mm Hg
29.7
• TC >240 mg/dL
22.3
• BMI >27.3 kg/m2 (women)
>27.8 kg/m2 (men)
15.3
• Current smoker
• Diabetes
6.3
0
1
2
3
4-5
# of RFs (any combination)
Yusuf HR, et al. Prev Med. 1998;27:1-
*Cumulative 21 yr. incidence *1971-1992.
9.
Distribution of HTN Subtypes in the untreated
Hypertensive Population in NHANES III by Age
ISH (SBP 140 mm Hg and DBP <90 mm Hg)
SDH (SBP 140 mm Hg and DBP 90 mm
Hg)
IDH (SBP <140 mm
Hg and16%
DBP 90
mm Hg)
17%
16%
20%
100
20%
11%
70-79
80+
80
Frequency of
hypertension 60
subtypes in
all untreated 40
hypertensives
(%)
20
0
<40
40-49
50-59 60-69
Age (y)
Numbers at top of bars represent the overall percentage distribution of untreated
hypertension by age.
Franklin et al. Hypertension 2001;37: 869-874.
Does DM Carry a CVD or Mortality Risk Equivalent?
US Men and Women Ages 30-74
(age, gender, and risk-factor adjusted Cox regression) NHANES II FollowUp (n=6255)
(Malik and Wong, et al., Circulation 2004; 110: 1245-1250)
7
***
Relative Risk
6
***
5
***
4
***
***
***
3
***
***
***
2
*
**
1
0
CHD Mortality CVD Mortality Total Mortality
* p<.05, ** p<.01, **** p<.0001 compared to none
None
MetS
Diabetes
CVD
CVD+Diabetes
Mylifecheck.heart.org
Age-standardized prevalence estimates for poor, intermediate and
ideal cardiovascular health for each of the seven metrics of
cardiovascular health in the AHA 2020 goals, among US adults >20
years of age, NHANES 2005-2006 (baseline available data as of
January 1, 2010).
100.0
22.9
33.2
80.0
45.2
46.6
41.7
Percentage
61.4
60.0
72.2
32.9
23.2
40.0
76.8
38.4
41.2
3.2
20.0
30.4
33.8
24.5
31.7
15.0
17.1
Total
Cholesterol
Blood
Pressure
8.2
0.0
Current
Smoking
Body Mass
Index
Physical
Activity
Poor
Healthy Diet
Score
Intermediate
Fasting
Plasma
Glucose
Ideal
Fewer than 1% of US adults are at ideal levels for
all 7 measures of cardiovascular health!
©2010 American Heart Association, Inc. All rights reserved.
Roger VL et al. Published online in Circulation Dec. 15, 2010
Ideal Cardiovascular Health and
CVD Incidence: ARIC Study
(Folsom et al, JACC 2011)
Risk Factor Consortia
• The Emerging Risk Factors Collaboration incorporating
over 1.3 million person years at risk demonstrate
– the independent predictive value of C-reactive
protein with CHD and stroke among 54 prospective
studies (Lancet 2010)
– the clinical utility of C-reactive protein and
fibrinogen (NEJM 2012)
– the limited role of adding the novel lipid markers
apolipoprotein B, apolipoprotein A1, lipoprotein (a)
and lipoprotein-associated phospholipase A2 to
traditional lipid measures (JAMA 2012).
• The group also showed in 97 prospective studies the
strong relation of diabetes with deaths from vascular
disease and other causes (NEJM 2011).
Multinational Registries of
CAD Patients
• Euroaspire I, II, III, IV (just
completed 2013) – compares
adherence to recommended
lifestyle and therapies in secondary
prevention across European
countries.
• Prospective Urban Rural
Epidemiology (PURE) – 139,506
subjects enrolled among 600
communities in 17 low, middle and
high income countries.
Big Gap in use of
Evidence Based Drugs for Secondary Prevention in China
PURE study
55.4%
52.7%
Antiplatelets
Percentage(%)
50
40
Percentage(%)
60
32.8%
30
15.5%
14.9%
11.6%
20
10
3.4%
50
45
40
35
30
25
20
15
10
5
0
46.8%
40.2%
ACE-1/ARB
26.2%
6.4%
7.8%
12.8%
Yusuf S et al. Lancet. 2011;378(9798):1231-43
6.8%
Percentage(%)
Percentage(%)
0
50
45
40
35
30
25
20
15
10
5
0
45.4%
60
56.7%
44.9%
37.0%
Beta-blockers
S.Asia
China
11.9%
Malaysia
12.5%
Africa
6.8%
1.9%
Statins
37.3%
30
19.0%
20
10
0
S.America
Middle East
50
40
N.Amerrica/Europe
15.9%
4.8% 2.0%
1.4%
Interaction Between Therapies to Treat Atherosclerosis
28.9
Placebo Only
18.6
Statin Only
11.2
Statin+ASA
8.6
70% Reduction
Statin+ASA+BB
0
5
10
15
20
25
30
35
Coronary Event Rate (%)
Treatment in 4S 4444 Patients with CAD Only statin vs placebo randomized 5.4 years F/U
113
Placebo
24% Statin 24% Statin+ASA 8% Statin+ASA+Beta Blocker 18%
What are the Cost Savings from
Prevention Strategies in the US?
• Community-based programs to increase physical
activity, improve nutrition, prevent smoking
would provide a $5.60 return on investment for
every $1 spent within 5 years
• Comprehensive worksite wellness and school
based programs would reduce medical costs by
$3.27 and absenteeism costs by $2.73 for every $1
spent
• Building bike and pedestrian trials would save
$3 in medical cost savings for every $1 spent
Weintraub et al. Circulation 2011
What are the Cost Savings from
Prevention Strategies in the US?
• Reducing the population sodium intake to 1500 mg/day
would save $26.2 billion in healthcare savings annually
• A 40% cigarette price increase from taxes would reduce
smoking to 15.2% by 2025 with large gains in quality
adjusted life years (QALYs) (13 milllion) saving $682
billion
• Eliminating exposure to second hand smoke would save
$10 billion annually in healthcare costs
• Comprehensive coverage on smoking cessation
programs results in a $3 return per $1 spent
• Adherence to ATP III lipid primary prevention
guidelines would cost of $42,000 and BP therapy
$37,100 per life year saved