Collaborative Prospective
Studies of Cardiovascular
Disease
Nathan D. Wong, PhD
Professor and Director
Heart Disease Prevention Program, Division of Cardiology
Objectives
• Understand the design and structure of the
major ongoing NIH and CDC-supported
prospective epidemiologic studies of
cardiovascular disease
• Understand opportunities for research
projects and collaboration for residents,
cardiology fellows, and faculty.
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
Measurements
• Standard risk factors since inception of study,
except HDL-C began around 1970.
• Serial ECGs (first to document high rate of
unrecognized MIs)
• M-mode echocardiograms in 1980’s, first large
study to show prognostic importance of
increased LV mass
• Newer measures done in subsets include:
Carotid ultrasound, bone denistometry, coronary artery
calcium, and other novel risk factors and biomarkers
(e.g. natriuretic peptides)
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
• 1996 Progression from hypertension to heart failure described
____________________________________________________________
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
9
Doubts about
cholesterol as
late as 1989
Relative Risk of CHD by HDL and LDLCholesterol Men 50-70 Years of Age
Framingham Study
4-Year Follow-up, The Framingham Study
Morbidity Ratio:
3.5
25 mg/dl
3
55 mg/dl
2.5
85 mg/dl
1.9
2
1.5
1.2
1
1
0.5
2.9
0.6
0.4
0.1
0.2
0.3
100 mg/dl
160 mg/dl
220 mg/dl
0
LDL-Cholesterol
WB Kannel Am Heart J. 1985;110:1100-1107.
Risk factors for long-term coronary prognosis after
initial myocardial infarction: the Framingham Study.
Wong ND, Cupples LA, Ostfeld AM, Levy D, Kannel WB.
Am J Epidemiol. 1989 Sep;130(3):469-80. Links
• Age-adjusted analyses showed the risk of reinfarction to
be positively associated with blood pressure and serum
cholesterol. Risk of coronary death was strongly
associated with blood sugar level, systolic blood
pressure, serum cholesterol, heart rate, diabetes, and
interim reinfarction. In multivariable analyses, systolic
pressure, serum cholesterol, and diabetes were
predictive of reinfarction; relative weight was inversely
associated with reinfarction. Systolic pressure, serum
cholesterol, and the prevalence of diabetes persisted as
independent predictors of coronary death. When
adjustments were made for the effects of these
variables, women were at only half the risk of coronary
death compared with men.
_______________________________________________________________________________
Lifetime Risk of CHD Increases with
Serum Cholesterol
___________________________________________________________________________
60
50
Cholesterol
<200 mg
200-239 mg
57
>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
________________________________________________________
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.
Risk of Myocardial Infarction with
Isolated Systolic Hypertension
Annual Incidence Per 10,000
Framingham Study 24 Yr. Follow-Up
WB Kannel Prev Cardiol 1998; 1:32-39
Men ages
45-54 yrs.
Joint Influences of SBP and Pulse
Pressure on CHD Risk
Franklin SS….Wong ND et al, Circulation 1999
Franklin SS et al. Circulation. 1999;100:354-360.
Franklin SS, Lopez VA, Wong ND, et al. Single Versus
Combined Blood Pressure Components and Risk for
Cardiovascular Disease. The Framingham Heart Study.
Circulation Jan 2009
•
•
BACKGROUND: -The utility of single versus combined blood pressure (BP)
components in predicting cardiovascular disease (CVD) events is not established.
We compared systolic BP (SBP) and diastolic BP (DBP) versus pulse pressure (PP)
and mean arterial pressure (MAP) combined and each of these 4 BP components
alone in predicting CVD events.
Methods and Results-In participants in the original (n=4760) and offspring (n=4897)
Framingham Heart Study who were free of CVD events and BP-lowering therapy,
1439 CVD events occurred over serial 4-year intervals from 1952 to 2001. In pooled
logistic regression with the use of BP categories, combining SBP with DBP and PP
with MAP improved model fit compared with individual BP components (P<0.05 to
P<0.0001). Significant interactions were noted between SBP and DBP (P=0.02) and
between PP and MAP (P=0.01) in their respective multivariable models. Models with
continuous variables for SBP+DBP and PP+MAP proved identical in predicting CVD
events (Akaike Information Criteria=10 625 for both). Addition of a quadratic DBP(2)
term to DBP and SBP further improved fit (P=0.0016).
• Conclusions-Combining PP with MAP and SBP with DBP produced models
that were superior to single BP components for predicting CVD, and the extent
of CVD risk varied with the level of each BP component. The combination of
PP+MAP (unlike SBP+DBP) has a monotonic relation with risk and may provide
greater insight into hemodynamics of altered arterial stiffness versus impaired
peripheral resistance but is not superior to SBP+DBP in predicting CVD events.
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
_________________________________________________________________
Age-adjusted
Cardiovascular Event
Coronary Disease
Stroke
Peripheral Artery Dis.
Cardiac Failure
All CVD Events
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 of Coronary Heart Disease by Diabetic
Status According to Level of Risk Factors
Framingham Study
60
Wilson PWF, Kannel WB. Nutr. In Clin Care 1998
57.7
Women age 50 yrs.
50
Nondiabetic
Diabetic
44.9
40
%
29.7
30
20
16.5
12.9
10
10
5.9
1.8
3.5
5.2
6.8
3
0
Risk Factors
HBP (160)
Chol (240)
Cig Smoker
HDL-C (34)
ECG-LVH
No (120)
No (165)
No
No (58)
No
Yes
No
No
No
No
Yes
Yes
No
No
No
Yes
Yes
Yes
No
No
Yes
Yes
Yes
Yes
No
Yes
Yes
Yes
Yes
Yes
_______________________________________________________________
CVD Risk Imposed by ECG-LVH
Framingham Study 36-yr. Follow_______________________________________________________________
up
Age-adjusted
Risk
Excess
Risk
Rate per 1000
Ratio
per 1000
Age Men Women
Men Women
Men Women
35-64 164
135
4.7*** 7.4***
129
117
_____________________________________________________________
65-94 234
235
2.8*** 4.1***
151
178
Biennial Rate per 1000. CVD=CHD, stroke, peripheral
vascular disease, heart failure ***P<0.001
_____________________________________________________________
CVD Risk by Plasma Natriuretic
_______________________________________________________________
Peptides
Multivariate Hazard Ratio per SD Increment
Outcome
BNP
N-ANP
Death
1.27 (1.06-1.52)**
1.41 (1.14-1.74)***
Major CVD 1.28 (1.03-1.59)*
1.30 (1.02-1.67)*
Heart Failure 1.77 (1.31-2.41)*** 1.94 (1.37-2.75)***
AF
1.66 (1.30-2.11)*** 1.72 (1.302.28)***
Stroke/TIA 1.53 (1.16-2.02) ** 1.37 (0.99-1.89)
CHD
1.10 (0.89-1.37)
1.12 (0.88-1.42)
Framingham Offspring Study
Obesity-promoted natriuretic peptides are secreted from cardiomyocytes:
They play a
fundamental role in CV remodeling, volume homeostasis, and response to
ischemia.
TJ Wang et al. N Engl J Med 2004; 350:655-663.
____________________________________________________________
Lifetime Risk of Coronary Heart
Disease
in
the
Framingham
Study
______________________________________________________________
Men
At age 40 years: 48.6%
At age 70 years: 34.9%
Women
31.7%
24.2%
_________________________________________________________________
Lloyd-Jones et al. Lancet 1999; 353:89-92
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)
Procedure
BAS
E
Call
B
YR
3
Call
3
YR
4
Call
4
Tracking Update
X
X
X
X
X
X
Stressful Life Events
X
X
X
X
X
X
Depression Scale
X
X
X
Quality of Life
X
X
X
Social Support and
Network
X
X
X
Medications - Prescription
X
X
X
Physical Function:
ADL/IADL
X
X
Cognitive Function MMSE
X
OTC
3MSE
Digit Symbol
Substitution
X
X
X
X
X
X
X
X
X
Benton Visual Retention
Phlebotomy
X
Anthropometry - Weight
X
Standing Height
X
Waist Circumference
X
Hip Circumference
X
Arm Span
X
Procedure
BAS
E
Call
B
YR
3
Call
3
YR
4
Bioelectric Impedance
X
Seated Blood Pressure
X
Performance Measures:
15-ft Walk
X
X
Chair Stands
X
X
Grip Strength
X
X
X
Finger Tapping
X
X
Nutrition
X
Resting 12-Lead ECG
X
Physical Activity
X
Supine Ankle-Arm Blood
Pressure
X
Orthostatic Blood
Pressure
X
Vascular Ultrasound Carotid
X
X
X
Aortic
Pulmonary Function
X
Peak Flow
Six-Minute Walk/Oximetry
Holter Monitor
X
Cerebral MRI
Echocardiography
Spot Urine Collection
X
X
Call
4
Procedure
YR
5
Call
5
YR
6
Call
6
YR
7
Call
7
Tracking Update
X
X
X
X
X
X
Stressful Life Events
X
X
X
X
Depression Scale
X
X
X
X
Quality of Life
X
X
X
X
Social Support and
Network
X
X
Medications Prescription
X
X
X
X
X
X
X
OTC
Physical Function:
ADL/IADL
X
X
X
X
YR
8
X
X
X
X
X
Cognitive Function MMSE
3MSE
Digit Symbol
Substitution
X
X
X
X
X
X
X
X
X
X
X
ch
ol
ch
ol
opt
Benton Visual
Retention
Phlebotomy
X
Procedure
YR
5
Call
5
YR
6
Call
6
YR
7
Call
7
YR 8
Seated Blood Pressure
X
X
X
casu
al
Performance Measures: 15ft Walk
X
X
X
X
Chair Stands
X
X
Grip Strength
X
X
X
X
Finger Tapping
X
X
X
X
X
Nutrition
X
Resting 12-Lead ECG
X
Physical Activity
X
Supine Ankle-Arm Blood
Pressure
X
Orthostatic Blood Pressure
X
Vascular Ultrasound Carotid
X
Aortic
X
X
X
Pulmonary Function
X
Peak Flow
X
Six-Minute Walk/Oximetry
Holter Monitor
Cerebral MRI
X
(X
X)
Echocardiography
X
Bone Density/Body
Composition
X
X
Summary of Events
• Combined Cohort at Baseline (N=5888)
• Mean Age = 72 years
58% Women
16% African American
31% had Cardiovascular Disease at entry
Number of Events through June 30, 2002
• Angina 1064
• MI 696
• Heart Failure 1262
• Claudication 789
• Stroke 789
• TIA 212
• Death 2658
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)
Ankle Brachial Index as a Predictor of
Cardiovascular Mortality in the CHS Study
Newman A et al ATVB 1999
CHS Representative Recent
Publications
• Association of carotid artery intima-media thickness,
plaques, and C-reactive protein with future
cardiovascular disease and all-cause mortality: the
Cardiovascular Health Study. Circulation. 1;116 (3238). 7-3-2007
• Brachial Flow-Mediated Dilation Predicts Incident
Cardiovascular Events in Older Adults. The
Cardiovascular Health Study. Circulation. 4-23-2007
• Relationship between brachial flow-mediated dilation
and carotid intima-media thickness in an elderly
cohort: The Cardiovascular Health Study.
Atherosclerosis. 9-3-2007
CHS publications continued
• The association of alcohol consumption and incident
heart failure: the Cardiovascular Health Study. J Am
Coll.Cardiol. 2;48 (305-311). 7-18-2006
• Usefulness of aortic root dimension in persons > or = 65
years of age in predicting heart failure, stroke,
cardiovascular mortality, all-cause mortality and acute
myocardial infarction (from the Cardiovascular Health
Study). Am J Cardiol. 2;97 (270-275). 1-15-2006
• Left atrial volume, geometry, and function in systolic and
diastolic heart failure of persons >/=65 years of age (the
cardiovascular health study). Am.J.Cardiol. 1;97 (83-89).
1-1-2006
CHS publications (continued)
• Blood pressure level and outcomes in adults aged 65
and older with prior ischemic stroke. J Am Geriatr
Soc. 9;54 (1309-1316). 2006
• 10-year follow-up of subclinical cardiovascular
disease and risk of coronary heart disease in the
Cardiovascular Health Study. Arch.Intern.Med. 1;166
(71-78). 1-9-2006
• Metabolic syndrome and cardiovascular disease in
older people: The cardiovascular health study. J Am
Geriatr Soc. 9;54 (1317-1324). 2006
• Mortality and cardiovascular risk across the anklearm index spectrum: results from the Cardiovascular
Health Study. Circulation. 3;113 (388-393). 1-242006
CHS publications (cont.)
• The association of microalbuminuria with clinical
cardiovascular disease and subclinical
atherosclerosis in the elderly: The
Cardiovascular Health Study. Atherosclerosis.
10-19-2005
• Increased left ventricular mass is a risk factor for
the development of a depressed left ventricular
ejection fraction within five years: the
Cardiovascular Health Study. J.Am.Coll.Cardiol.
12;43 (2207-2215). 6-16-2004
• The association between lipid levels and the
risks of incident myocardial infarction, stroke,
and total mortality: The Cardiovascular Health
Study. J.Am.Geriatr.Soc. 10;52 (1639-1647).
2004
Possible Topics for Future Papers
• Prognosis associated with echo left atrial
dimension—e.g., in relation to stroke
• Papers examining relation of progression
of LV mass in relation to future risk of
cardiovascular events (CHD, CHF, stroke)
• Predictors of progression of LV mass
• Combination of increased CIMT and LV
mass in relation to CHF or CHD events.
Multiethnic Study of Atherosclerosis
• 6,814 adults aged 45-80 enrolled at 6 field centers,
including Caucasians, African-Americans,
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 (HarborUCLA) and abdominal aortic calcium (UC San
Diego) in full or partial cohorts.
MESA Study Design Features
Four examinations approximately two years apart,
exam 4 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
MESA Key Subclinical Disease
Measures
• Coronary calcium Agatston score and volume
• LV size, thoracic aortic calcium, aortic valve
calcium (ancillary study)
• Abdominal aortic calcium (ancillary study),
including aortic diameter
• Ankle brachial index
• ECG variables (LVH, Q-waves, long QT, AFIB)
• Carotid Ultrasound (Common and Internal CIMT,
max carotid stenosis)
• Cardiac MRI (LV end diastolic mass, volumes,
LVEF, stroke volume, aortic distensibility, cardiac
output)
MESA laboratory variables
• Glucose, insulin, TG, HDL (including 8
subfractions), LDL (incl very small to large
subfractions), mean LDL and HDL size,
• Urinary albumin, creatinine, microalbuminuria,
homocysteine
• CD40 ligand, E-selectin, IL-2, IL-6, HS-CRP,
MMP3, 9, TNF-alpha, PAI-1, HSV, CMV,
H.Pylori, C. Pneumoniae
• CETP activity and mass, SI-cam, Ox-LDL, Ddimer
Other MESA Variables
• Family history of MI, stroke
• Cigarette, cigar, pipe, and chewing
tobacco
• Total light, moderate, and vigorous
physical activity in minutes/wk and MetS
• Medications: Statins, Anti-arrhythmics by
class, beta-blockers, CCBs, Cox2
inhibitors, estrogen replacement therapy,
oral anticoagulants
Cumulative Incidence of Any
Coronary Event: MESA Study
(Detrano et al., NEJM 2008)
Risk Factor-Adjusted Hazard Ratios
by Coronary Calcium Score: MESA
Study (Detrano et al., NEJM 2008)
MESA ongoing papers in progress
here at UCI
• Metabolic syndrome, diabetes, and
progression of coronary calcium
• Abdominal aortic calcification and
systemic atherosclerosis (relation to CAC,
CIMT, and ABI)
• Value of CAC vs. CIMT in predicting CHD
events over FRS in Metabolic Syndrome
and Diabetes (with Dr. Malik)
Multiethnic Study of
Atherosclerosis (MESA): CAC and
CHD Events
(Malik, Wong et al, AHA Nov 2007)
Adjusted Hazard Ratios No MetS/DM
(HRs) (95% CI)
(n= 3,800 )
MetS without
DM
(n =1,996)
DM (n=1018 )
CHD Events
30
21
20
CAC 1-99 vs. 0
2.4 (0.6-9.2)
2.3 (0.4-14.1)
4.4 (0.9-21.5)
CAC 100-399 vs. 0
9.7 (2.9-31.7)
11.2 (2.4-53.2)
5.2 (1.0-27.8)
CAC 400+ vs. 0
13.6 (3.9-47.0) 8.2 (1.5-44.1)
Adjusted for Framingham Risk Score and Ethnicity
6.8 (1.3-34.8)
Multiethnic Study of Atherosclerosis
(MESA): Common CIMT and CHD Events
(Malik, Wong et al AHA Nov. 2007)
Adjusted Hazard
No MetS/DM MetS without
Ratios (HRs) (95% CI) (n= 3,800 )
DM (n =1,996)
DM (n=1018 )
CHD Events
30
20
CIMT 2nd quartile vs
1st quartile
0.8 (0.2-2.4) 0.5 (0.1-3.0)
2.1 (0.2-20.6)
CIMT 3rd quartile vs
1st quartile
0.9 (0.3-2.7) 2.0 (0.6-7.5)
3.9 (0.5-32.2)
CIMT 4th quartile vs
1st quartile
1.7 (0.6-4.7) 0.7 (0.2-3.1)
3.6 (0.5-28.3)
21
Adjusted for Framingham Risk Score and Ethnicity
Results for Internal CIMT were similar.
1.00
ROC Curve Analyses for CVD Events: FRS alone, FRS
plus CIMT, or FRS plus CAC in those with Mets
(without DM): MESA Study (Malik, Wong et al., AHA
2007)
0.75
ROC FRS alone
ROC FRS + CIMT
0.00
0.25
0.50
ROC FRS + CAC
0.00
0.25
0.50
1-Specificity
FRS2 ROC area: 0.6967
CAC2 ROC area: 0.7539
0.75
1.00
CIMT2 ROC area: 0.6925
Reference
ROC area FRS+CAC (0.7539) vs. FRS alone (0.6967), p = 0.0017
ROC area FRS + CIMT (0.6926) vs FRS alone (0.6967), p =0.6354
ROC area FRS+ CAC (0.7539) vs. FRS + CIMT (0.6925), p = 0.002
1.00
ROC Curve Analyses for CVD Events:
FRS alone, FRS plus CIMT, or FRS plus CAC in
those with DM: MESA Study (Malik, Wong et al.,
AHA 2007)
0.75
ROC FRS alone
ROC FRS + CIMT
0.00
0.25
0.50
ROC FRS + CAC
0.00
0.25
0.50
1-Specificity
FRS3 ROC area: 0.6669
CAC3 ROC area: 0.7285
0.75
1.00
CIMT3 ROC area: 0.6809
Reference
ROC area FRS+CAC (0.7285) vs. FRS alone (0.6669), p = 0.0001
ROC area FRS + CIMT (0.6809) vs. FRS alone (0.6669), p =0.3258
ROC area FRS+ CAC (0.7285) vs. FRS + CIMT (0.6809), p = 0.0037
Incidence and Progression of Coronary Calcium
(mean 2.4 years between scans): Multiethnic Study
of Atherosclerosis (n=5570)
(Wong et al., AHA 2006)
P<0.01 to p<0.001
between each group
158
160
140
110
120
P<0.001
across groups
100
80
60
P<0.001 across
groups
40
20
12
21
56
90
No MetS/DM
MetS w/o DM
DM
64
45
24
0
A. New CAC (%) B. Progression
(%)
C. Progression
w/baseline CAC
A. % with new CAC among those free of CAC at baseline
B. % with progression of CAC (score change >0)
C. Mean adjusted change in CAC score among those with CAC at baseline
Abdominal Aortic Calcium
(5cm from iliac bifurcation)
Prevalence of AAC (>0), CAC (>0), ABI (<0.9),
and common and internal IMT (>1mm) by Age in
Men (Wong et al., AHA 2006)
96
Prevalence (%)
100
89
75
80
86
73
59
60
64
45.7
40
51
39
34
22
20
36
20
8
45-54
AAC
8
6
1
0
50
CAC
1
55-64
CCA-IMT
65-74
75-84
ICA-IMT
ABI
P<0.001 across age groups, n=971 (except 969 for common IMT)
Prevalence of AAC (>0), CAC (>0), ABI (<0.9),
and common and internal IMT (>1mm) by Age in
Women (Wong et al., AHA 2006)
Prevalence (%)
100
93
88
76
80
67
60
50
55
42
49
34
40
20
26
24
14
14
1
0
13
11
6
45-54
AAC
39
CAC
3
1
55-64
CCA-IMT
65-74
75-84
ICA-IMT
P<0.001 across age groups (n=933 except 931 for common IMT)
ABI
Prevalence of CAC, Increased CIMT, and
Low ABI by Presence of AAC – Men
(Wong et al., AHA 2006)
70
70
Prevalence (%)
60
48
50
40
30
28
30
20
11
11
10
4.2
0
0
CAC
CCA-IMT
No AAC
ICA-IMT
Any AAC
Prevalence of CAC >0, CCA-IMT or ICA-IMT >1mm, or ABI <0.9
P<0.001 for those with vs. without AAC for all measures
ABI
Prevalence of CAC, Increased CIMT, and
Low ABI by Presence of AAC – Women
(Wong et al., AHA 2006)
60
Prevalence (%)
51
50
42
40
30
20
23
11
10
6
10
1.4
3.8
0
CAC
CCA-IMT
No AAC
ICA-IMT
ABI
Any AAC
Prevalence of CAC >0, CCA-IMT or ICA-IMT >1mm, or ABI <0.9
P<0.001 for those with vs. without AAC for all measures except p=0.06 for ABI
Counts of Events
MI
CHF
Stroke
Hard
CHD
All
CHD
All
CVD
Currently
Available
73
74
59
91
165
230
Available
12/07
90
89
59
118
205
269
All
recorded
91
90
59
119
210
274
Other possible ideas for papers
• Hypertension and BP categories and
progression of MRI LV mass or LVEF
• Progression of CIMT vs. progression of
MRI LV mass or LVEF
• Alcohol intake and MRI LV dimensions,
mass, and LVEF
• LDL and HDL subfractions and subclinical
atherosclerosis
Other Prospective Epidemiologic
Studies
• Atherosclerosis Risk in Communities –
approximately 10,000 adults aged 45-64 years,
half African-American enrolled at 4 field centers,
ongoing follow-up for CVD events and mortality
• Epidemiology of Diabetes Interventions and
Complications (EDIC) – Follow-up of original
DCCT cohort of approximately 1,400 adults with
Type 1 diabetes. Standard and novel risk factor
assessments and measures of carotid IMT (2
measures), ABI, and coronary calcium by CT.
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)
Other Studies
Antihypertensive Lipid-Lowering to Prevent Heart
Attack Trial (ALLHAT)
• Blood Pressure Control in Hispanics in the Antihypertensive
and Lipid-Lowering Treatment to Prevent Heart Attack Trial.
• Margolis KL, Piller LB, Ford CE, Henriquez MA, Cushman WC,
Einhorn PT, Colon PJ Sr, Vidt DG, Christian R, Wong ND,
Wright JT Jr, Goff DC Jr; Antihypertensive Lipid-Lowering
Treatment to Prevent Heart Attack Trial Collaborative Research
Group.
Women’s Health Initiative Observational Study and
Clinical Trial
• Panic Attacks and Risk of Incident Cardiovascular Events
Among Postmenopausal Women in the Women's Health
Initiative Observational Study.
• Smoller JW, Pollack MH, Wassertheil-Smoller S, Jackson RD,
Oberman A, Wong ND, Sheps D.
NHANES Cross-Sectional and
Mortality Follow-up Studies
• NHANES 2003-2004 (and 2005-2006
becoming available) cross-sectional health
survey and clinic exam data
• NHANES 3 Mortality Follow-up
– Abdominal obesity and mortality from CHD,
CVD, all-causes
– Combined HTN – Dyslipidemia and mortality
– Pulmonary function (% predicted FVC), Creactive protein, and mortality
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 and DBP 90 mm Hg)
100
17%
16%
<40
40-49
16%
20%
20%
11%
50-59 60-69
Age (y)
70-79
80+
80
Frequency of
hypertension 60
subtypes in all
untreated
40
hypertensives
(%)
20
0
Numbers at top of bars represent the overall percentage distribution of untreated hypertension by
age.
Franklin et al. Hypertension 2001;37: 869-874.
Cardiovascular Disease (CVD) and Total Mortality:
US Men and Women Ages 30-74
(age, gender, and risk-factor adjusted Cox regression) NHANES II
Follow-Up (n=6255)(Malik and Wong, et al., Circulation 2004; 110: 12451250)
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
Odds of CVD Stratified by CRP Levels in U.S.
Persons (Malik and Wong et al., Diabetes Care 2005;
28: 690-3)
6
O
d
d
s
R
a
t
i
o
***
5
4
3
2
***
*
*
**
1
0
High CRP
No
Metabolic
disease
Syndrome
Low CRP
Diabetes
–*p<.05, **p<.01, **** p<.0001 compared to no disease, low CRP
–CRP categories: >3 mg/l (High) and <3 mg/L (Low)
–age, gender, and risk-factor adjusted logistic regression (n=6497)
Diabetes Care
2008; 31: 1405-9
Estimated CHD Risk by Gender and Ethnicity
(Hoang, Wong et al., Diabetes Care 2008)
Control (all treated) (%) of HTN in US
Adults, by Disease Status (Wong et al., Arch
Intern Med 2007)
Control of HTN (%)
100
80
60
64.6
*
63.7 61.2
49.3
48.8
**
42.2
40
**
**
46.7 50.3
34.9
20
0
No-Disease
Dyslipidemia
Mets
DM
CKD
Stroke
**P<0.05**P<0.01 when compared to No-Disease Group
Control is in persons with HTN defined as BP < 140/90
If DM and CKD is based on BP<130/80 control is **35.3% and **23.2%, respectively.
If MetS is based on BP<130/85 control is **46.7%
CHF
PAD
CAD
Mean BP and Distance to Goal Among HTN Pts Not at Goal
(Wong et al., Arch Intern Med 2007)
No Disease
Dyslipidemia
MetS
DM
CKD
Stroke
CHF
PAD
CAD
SBP mm Hg
DBP mm Hg
(Distance to Goal)
(Distance to Goal)
154 (14)
93
(3)
154 (19)
90* (7)
154 (16)
94
149* (14)
87** (6)
155 (18)
87** (7**)
155 (22*)
87** (6)
154 (22**)
89** (6)
157 (23**)
89* (7)
155 (21*)
90
(5)
(6)
Minimum BP distance from goal of < 140/90 in parenthesis, even with DM & CKD
*p<0.05 **p<0.01 compared to no disease
UCI Heart Disease Prevention
Program Resources
• SAS and Stata Statistical Software and
computing resources
• Affiliated faculty: Stanley Franklin, MD,
FACC, John Zamarra, MD, FACC, and
Shaista Malik, MD
• Statistical Staff: Heli Ghandehari, Victor
Lopez
• Research Student Staff: Alejandro Perez,
May Song, Vy Le