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Metabolic Syndrome and Health
Disparities:
Addressing Unmet Needs
Luther T. Clark, MD
Chief, Division of Cardiovascular Medicine
Professor of Clinical Medicine
State University of New York
Downstate Medical Center
Brooklyn, New York
March 30, 2007
Estimated Life Expectancy: 2001
82
80
78
80.2
75
76
74
72
70
AA Male
75.5
68.6
68
66
64
62
White Male
AA Female
White Female
National Vital Statistics Reports. 2004;52(14):33-34.
Risk for Cardiovascular Disease
CVD Death Rate per 100,000 Persons
Death Rates per 100,000 Persons among US Ethnicities
600
500
400
479.6
359.1
354.8
300
256.2
219.8
201.2
200
123.6
149.7
100
0
African
African
American American
Men
Women
White
Women
White Men American American
Indian
Indian
Women
Men
Hispanic
Women
Hispanic
Men
American Heart Association. Heart Disease and Stroke
Statistics – 2006 Update. Dallas, Tex.: American Heart Association; 2006.
Coronary Heart Disease and Stroke Death
Rates, 1980-2000
Age-adjusted rate per 100,000
400
300
Coronary Heart Disease
200
Stroke
100
0
1980
1985
1990
1995
2000
Coronary Heart Disease and Stroke Death
Rates, 1980-2000
Age-adjusted rate per 100,000
400
300
Coronary Heart Disease
200
CHD 2010 target
Stroke
100
Stroke 2010 target
0
1980
1985
1990
1995
2000
Annual Rate of First Heart Attacks
by Age, Sex and Race
ARIC: 1987-2000
Source: NHLBI’s ARIC surveillance study, 1987-2000.
Coronary Heart Disease Death Rates, 2000
Age-adjusted rate per 100,000
250
200
2010
target
150
100
50
0
Total
IOM Report, 2002: Assessing the Quality
of Minority Health Care
“Disparities in the health care
delivered to racial and ethnic
minorities are real and are
associated with worse outcomes in
many cases, which is
unacceptable.”
-- Alan Nelson, retired physician, former
president of the American Medical Association
and chair of the committee that wrote the
Institute of Medicine report, Unequal
Treatment: Confronting Racial and Disparities
in Health Care
Figure 1: Differences, Disparities, and Discrimination: Populations with
Equal Access to Health Care
Clinical Appropriateness
and Need
Patient Preferences
The Operation of Healthcare
Systems and the Legal and
Regulatory Climate
Disparity
Minority
Non-Minority
Difference
Populations with Equal Access to Health Care
Discrimination: Biases and
Prejudice, Stereotyping, and
Uncertainty
Cardiac Care:
The Weight of the Evidence
“Of all forms of inequality in our society,
injustice in health care is the most shocking
and the most inhumane.”
Martin Luther King, Jr.
Second National Convention of the
Medical Committee for Human Rights
Chicago, March 25, 1966
DISPARITIES: Historical Perspective
1895
National Medical Association Founded: as the voice of black physicians and the patients they serve,
one of the key objectives of the group was improving the health status and outcomes of African
Americans and the disadvantaged
1927: Stone CT and Vanzant FR. Heart disease as seen in a southern clinic: clinical and pathological
survey. JAMA. 1927;89:1473-1477: hypertensive heart disease was twice as frequent among blacks as
whites; arteriosclerotic heart disease and angina pectoris uncommon in Blacks
1985: Report of the Secretary’s Task Force On Black and Minority Health (Heckler-Malone) Report:
identified that, nationally, 60,000 African Americans die needlessly due to lack of access and quality
health care (“excess mortality”).
1998:
United States Department of Health and Human Services launches Healthy People 2010:
Identified as two overarching goals for the first decade of the 21st century: 1) increasing the quality and
years of healthy life; and 2) eliminating health disparities
2002: Institute of Medicine published report Unequal Treatment: Confronting Racial and Ethnic
Disparities in Health: Highlighted the health disparities between Blacks and Whites and the impact of
racial attitudes on health disparities
2004: Eliminating Disparities in Cardiovascular Care and Outcomes: Roadmap to 2010: Report of the
Special Emphasis Panel and Working Group (Association of Black Cardiologists, Inc, NIBIB, NHLBI,
NCMHD, NIDDK)
A Continuing National Paradox
Although there have been tremendous scientific
achievements in terms of improvement in overall
health status for the general population, significant
health inequities persist among African Americans
and other minorities.
A Continuing National Paradox
Although there have been tremendous scientific
achievements in terms of improvement in overall
health status for the general population, significant
health inequities persist among African Americans
and other minorities.
1985 Secretary of Health and Human Services
Report on Black and Minority Health
Excess CVD Morbidity and Mortality among
African Americans
Excess burden of risk factors
 Patient delay in seeking medical care
 Under-treatment of high risk individuals

 Under-utilization
of primary and secondary risk reduction strategies
 Limited access to modern/invasive/high tech services: thrombolytics,
cath, percutaneous coronary interventions (PCI), bypass surgery
 Under-treatment of chronic cardiac conditions (ie heart failure)
INTERHEART: 9 Modifiable factors
account for 90% of first-MI risk worldwide
100
90
80
PAR
(%)
60
50
40
36
20
33
14
20
18
12
10
7
0
Smoking
Fruits/
veg
Exercise
Alcohol
Hypertension
Diabetes
Abdominal
obesity
Psychosocial
Lipids
All 9 risk
factors
Lifestyle factors
N = 15,152 patients and 14,820 controls in 52 countries
PAR = population attributable risk, adjusted for all risk factors
Yusuf S et al. Lancet. 2004;364:937-52.
Risk Factors More Prevalent in
African-Americans than Whites
• Associated with Increased Risk
– Hypertension
– Type 2 diabetes mellitus
– Obesity
– Cigarette smoking
– Physical inactivity
– Left ventricular hypertrophy
• Associated With Decreased Risk
– Higher high-density lipoprotein cholesterol
• Association with CHD risk unclear
– Higher Lp(a)
CHD risk factors in Hispanics and African Americans
compared to Non-Hispanic Whites
More Prevalent in Non-Hispanic
Blacks than NHW
–
–
–
–
Hypertension
Type 2 diabetes mellitus
Obesity
Metabolic Syndrome
(females)
– Cigarette smoking
– Physical inactivity
Ford, et al. JAMA. 2002;287:356-359.
Clark LT. Med Clin NA. 2005;89 (5):977-1001.
Liao, et al J Am Coll Cardiol 30: 1200–1205, 1997
More Prevalent in Hispanics
than NHW
– Type 2 diabetes mellitus
– Obesity
– Lower HDL-Cholesterol
(females)
– Elevated Triglycerides
– Metabolic Syndrome
– Physical Inactivity
Obesity, Metabolic Syndrome, Type 2
Diabetes and Cardiovascular Disease
Insulin resistance
Obesity
Metabolic syndrome
Diabetes
2 Risk
Cardiovascular disease
Luscher et al. Circulation. 2003;108:1655.
Reilly and Rader. Circulation. 2003;108:1546.
4 Risk
Abdominal Adiposity:
The Critical Adipose Depot
Subcutaneous fat
Abdominal muscle
layer
Intra-abdominal fat
Is this where you measure?
M. Davidson, MD.
Multiple Cardiometabolic Risk
AKA: Insulin Resistance Syndrome; Syndrome X; Dysmetabolic Syndrome; Multiple Metabolic Syndrome; Cardiometabolic
Syndrome; The Deadly Quartet
1923: Kylin describes clustering of hypertension, gout, and hyperglycemia
1988: Reaven describes “Syndrome X” – hypertension, hyperglycemia,
glucose intolerance, elevated triglycerides, and low HDL cholesterol
1998: WHO defines “metabolic syndrome” as clustering of hypertension,
low HDL, hypertriglyceridemia, insulin resistance, glucose intolerance or
type 2 diabetes, high waist-to-hip ratio, and microalbuminuria
2001: NCEP ATP III provides clinical definition of “metabolic syndrome”
Isomaa B et al. Diabetes Care. 2001;24:683-689.
Grundy, et al. Circulation 2002;106:3143
Clinical Identification of the Metabolic Syndrome*
Risk Factor
• Abdominal obesity
(waist circumference)
Men
Women
• Triglycerides
• HDL Cholesterol
Men
Women
• Blood pressure
• Fasting glucose
Defining Level
> 102 cm (>40 in)
> 88 cm (>35 in)
 150 mg/dl
< 40 mg/dl
< 50 mg/dl
 130/ 85 mm Hg
 100 mg/dl
* Diagnosis requires three or more criteria present
Circulation. 2002;106:3143.
Circulation. 2005;112: 2735-2752.
Definitions of the Metabolic Syndrome
Components
NCEP ATP III
IDF
AHA-NHLBI
≥3
WC + ≥2
≥3
Europid
WC, cm
>102 (m) >88 (f)
≥94 (m) ≥80 (f)
S. Asian* ≥90 (m) ≥80 (f)
>102 (m) >88 (f)‡
Japanese ≥85 (m) ≥90 (f)
TG, mg/dL
150
150†
150†
HDL-C, mg/dL
<40 (m) <50 (f)
<40 (m) <50 (f)†
<40 (m) <50 (f)†
BP, mm Hg
130/85
130 OR 85†
130 OR 85†
FPG, mg/dL
110
100†
100†
*
Based on a Chinese, Malay, and Asian-Indian population
† Or on drug treatment
‡ ≥90cm (m) ≥80cm (f) for Asian Americans
Metabolic syndrome ICD-9-CM code: 277.7
National Cholesterol Education Program Expert Panel on Detection,
Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP
III). 2002;106:3143-3421.
International Diabetes Federation. 2005. www.idf.org
Grundy SM, et al. Circulation. 2005;112:2735-2752.
NHANES III: Age-adjusted Prevalence of
³3 Risk Factors for Metabolic Syndrome*
40
Men
Women
35
25.7%
difference
35.6
56.7%
difference
28.3
30
25
%
25.7
24.8
22.8
20
16.4
15
10
5
0
White
African-American
Mexican-American
NHANES III=third National Heath and Nutrition Examination Survey; ATP=Adult Treatment Panel.
*Criteria based on ATP III; diabetics were included in diagnosis; overall unadjusted prevalence was 21.8%.
Ford, et al. JAMA. 2002;287:356-359.
Age-Adjusted Prevalence of Obesity* in Americans
Aged 20-74, Men and Women
Men
Women
33%
Percentage of Population
35
30
28%
26%
25
21%
20
15
12%
13%
19711974
19761980
17%
17%
19711974
19761980
10
5
0
19881994
19992002
19881994
19992002
Since 1971, obesity has doubled in both men and women
*Obesity is defined as a BMI of 30.0 or higher
Source: NHANES, 1971-1974, 1976-1980, 1988-1994, 1999-2000,
National Center for Health Statistics, CDC, 2002.
NHANES: Age-Adjusted Prevalence of Metabolic
Syndrome Abnormalities
NHANES 1999-2000
50
Prevalence, %
40
30
20
10
0
Abdominal High TG
Obesity
NHANES 1999-2000, N=1677
Low HDL-C
High BP
Glucose
≥100 mg/L
ADA
Glucose
≥110 mg/L
ATP III
Ford ES, et al. Diabetes Care. 2004;24:2444-2449.
Wilson PWF, et al. Circulation. 2003;108:1422-1425.
NHANES III: Age-Specific Prevalence
of the Metabolic Syndrome
Age-adjusted prevalence of the metabolic syndrome is 23.7%
Approximately 47 million US residents have the metabolic syndrome
50
45
Prevalence, %
40
35
Men
30
Women
25
20
15
10
5
0
20-29
30-39
NHANES III, 1988-1994
Data are presented as percentage (SE)
40-49
50-59
60-69
70
Age, years
Ford ES, et al. JAMA. 2002;287:356-359.
CVD and All-cause Mortality are Increased in Men
with the Metabolic Syndrome*
Coronary Heart Disease Mortality
Cumulative Hazard, %
20
Metabolic Syndrome
Yes
No
15
Cardiovascular Disease Mortality
All-Cause Mortality
20
20
15
15
RR (95% CI), 3.77 (1.74-8.17)
RR (95% CI), 2.43 (1.64-3.51)
RR (95% CI), 3.55 (1.96-6.43)
10
10
10
5
5
5
0
0
0
2
No. at Risk
Metabolic Syndrome
Yes
No
4
6
8
Follow-up, y
866
867
852
279
10
12
834
234
*As defined by NCEP ATP III.
Lakka H, et al. JAMA. 2002;288:2709-2716.
0
0
292
100
2
866
288
4
6
8
Follow-up, y
852
279
10
834
234
12
292
100
0
866
288
2
4
6
8
Follow-up, y
852
279
834
234
10
292
100
12
The Metabolic Syndrome Is a Predictor of New
CVD Events in Women with CAD
Patients with significant CAD
Patients without significant CAD
100
100
Normal (n = 85)
90
P=.007
80
Met Syn (n = 62)
70
Diabetes (n = 137)
Event-Free Survival, %
Event-Free Survival, %
Normal (n = 237)
90
Met Syn (n = 125)
Diabetes (n = 103)
80
P=NS for all
comparisons
70
60
60
0
1
2
3
4
Year
Marroquin OC, et al. Circulation. 2004;109:714-721.
0
1
2
Year
3
4
Association of MI and Stroke With Components of
the Metabolic Syndrome
Men
2.5
2.2
Women
2.1
2.0
Odds Ratio
1.47
1.5
1.38
1.3
1.16
1.32
1.18
1.3
1.0
1.0
0.5
0.0
Abdominal
Obesity
High TG
Low HDL-C
HTN
IR
Ninomiya JK, et al. Circulation. 2004;109:142-46.
Elevated Risk of CVD Prior to Clinical Diagnosis
of Type 2 Diabetes
6
5.02
Relative Risk
5
3.71
4
2.82
3
2
1
1
0
Nondiabetic
throughtout the
study
Prior to diagnosis
of diabetes
Hu FB, et al. Diabetes Care 2002;25(7) :1129-1134.
After diagnosis of
diabetes
Diabetic at
baseline
Previous MI and Diabetes are Strong Predictors of
Mortality (MRFIT; N = 9434)
All CVD Death
CHD Death
No MI
300
Mortality Rate*
264
MI
250
208
194
200
159
144
150
104
100
50
43
29
0
No DM
DM
No DM
MRFIT, Multiple Risk Factor Intervention Trial
*Median 25 years of follow-up, age-adjusted rate per 10,000 person-years
Vaccaro O, et al. Arch Intern Med. 2004;164:1438:1443.
DM
Diabetes Has a Greater Impact on CVD
in Women than in Men
Age-Adjusted Relative CVD Risk*
10
9
Relative Risk
8
Men
Women
8.0
7
6.4
6
5
4.4
3.7
4
3.4
3
2
1.5
1
0
CHD
*Relative CVD risk for persons with diabetes
versus those without
Kannel WB, et al. Adv Intern Med. 1997;42:39-66.
Peripheral
Cardiac Failure
Artery Disease
Therapeutic Approach To Cardiometabolic Risk
Reduction
Diagnosis of ≥ 3 of the following:
Abdominal obesity
Elevated TGs
Low HDL-C
Elevated BP
IFG/IGT/diabetes
CHD or CHD equivalent (10year risk >20%) Goal: <70
mg/dL
Reduce underlying
causes:
Overweight and obesity
Physical inactivity
Clark, Ferdinand, Ferdinand, Gavin.
Contemporary Management of the Metabolic Syndrome.
Achieve LDL-C goal
Multiple risk factors and 10year risk <20% Goal: <130
mg/dL
Treat associated lipid
and nonlipid risk
factors
Intensify weight
management and
physical activity
Therapeutic Approach To Cardiometabolic Risk Reduction
Diagnosis of the metabolic syndrome: ≥ 3
of the following:
Abdominal obesity
Elevated TGs
Low HDL-C
Elevated BP
IFG/IGT/diabetes
CHD or CHD equivalent (10year risk >20%) Goal: <70
mg/dL
Multiple risk factors and 10year risk <20% Goal: <130
mg/dL
Achieve LDL-C goal
Treat associated lipid
and nonlipid risk
factors
Reduce underlying
causes:
Overweight and obesity
Physical inactivity
Elevated TGs
Achieve non-HDL-C goal (LDL-C
goal +30)
Intensify weight
management and
physical activity
Low HDL-C
LDL-C is the primary target.
Emphasize weight loss and
increasing
physical activity.
*Drug therapy should not be routinely used in patients
with IFG/IGT or to prevent diabetes pending the results ofConsider drug therapy in highongoing clinical trials.
risk patients (CHD/CHD
ASA, aspirin; BP, Blood pressure; CHD, coronary heart
disease; HDL-C, high density lipoprotein cholesterol; IFG,
equivalents)*
impaired fasting glucose; IGT, impaired glucose
tolerance; LDL-C, low-density lipoprotein cholesterol; TG,
triglycerides
(Clark, Ferinand: Cardiology Special Edition, 2003)
Elevated BP
Prothrombotic state
IFG/IGT/diabetes
Achieve BP goal:
<130/80 mm Hg
Antiplatelet therapy (ASA ±
clopidogrel)
Weight loss, increased
physical activity,
counseling. Drug therapy
not routinely
recommended. If diabetic,
optimized glycemic control
Clark, Ferdinand, Ferdinand, Gavin.
Contemporary Management of the Metabolic Syndrome.
Cardiometabolic Risk:
Strategies for Treatment
• Professionals/Patients
– Patients with CMR should increase their physical activity level,
lose weight (if overweight) and have their BP and lipid
abnormalities treated to recommended goals
– If one cardiometabolic risk factor is present, others should be
looked at
– Information on obesity, HBP, and metabolic risk factors for CVD
and diabetes should be widely disseminated
– Information on the benefits of physical activity and nutrition
should be widely disseminated
– A special campaign to prevent and control childhood obesity
should be carried out
Cardiometabolic Risk:
Strategies for Treatment
• Professional/lay education
– Targeted health promotional programs for various population
groups at cardiometabolic risk
– Partner with CBO for information dissemination
– Integration of individual risk factors for patients with multiple risk
factors
Cardiometabolic Risk:
Strategies for Treatments
• Research
– Addition of metabolic syndrome as an end point in clinical trials
– Assess the benefits of interventions targeting multiple RF in
clinical trials
– Randomized clinical trials to assess the effects of treatment of
the metabolic syndrome on clinical events and survival
– Improved strategies for management of multiple RF
Unanswered Questions
• What is the incremental risk added by CV risk factors not in
the FHS (obesity, elevated TG, IFG)?
• What are the treatment goals (beyond LDL) in patients with
multiple risk factors (BP, IFG/IGT, low HDL-C, high TG,
overweight/obese)?
• Are there gene-gene and/or gene-environment interactions
that predict metabolic syndrome or other clusters of RF and
CV risk?
Conclusions
 CVD is the leading cause of morbidity/mortality in African
Americans
 Disparities in cardiovascular health continue to exist, due to:




Excessive risk factor burden
Patient delays in seeking medical care
Under-recognition and under-treatment of high risk individuals
Lack of access to routine and modern cardiac medical/procedural care
 Prevention of CVD, improving outcomes and decreasing
disparities in AA maybe difficult but is not a mystery
 A high prevalence of modifiable RF provides great
opportunity for prevention
Conclusions:
Addressing Unmet Needs




Increase physician awareness of racial disparities in health care
Improve compliance and adherence to evidence-based treatment
guidelines
Increase educational programs to improve knowledge concerning
cultural competency and sensitivity in clinical settings
Increase patient educational programs to


improve knowledge of CVD and available therapies
Decrease delays in seeking medical care
Identify and address barriers that limit access to appropriate
cardiac services (institutional, provider, health care coverage, etc)
 Improve efforts to make cardiovascular care available,
accessible,affordable, and acceptable
 Increase training of minority clinicians and investigators
