Metabolic Syndrome and Health Disparities:

Addressing Unmet Needs

Metabolic Syndrome and Health Disparities:

Addressing Unmet Needs

Chief, Division of Cardiovascular Medicine

Professor of Clinical MedicineState University of New YorkDownstate Medical Center

Brooklyn, New York

March 30, 2007

Chief, Division of Cardiovascular Medicine

Professor of Clinical MedicineState University of New YorkDownstate Medical Center

Brooklyn, New York

March 30, 2007

Luther T. Clark, MDLuther T. Clark, MD

Estimated Life Expectancy: Estimated Life Expectancy: 20012001

68.6

75 75.5

80.2

62

64

66

68

70

72

74

76

78

80

82AA Male

White Male

AA Female

White Female

National Vital Statistics Reports. 2004;52(14):33-34.

Risk for Cardiovascular DiseaseDeath Rates per 100,000 Persons among US Ethnicities

479.6

256.2

359.1

123.6

201.2149.7

219.8

354.8

0

100

200

300

400

500

600

AfricanAmerican

Men

AfricanAmericanWomen

WhiteWomen

White Men AmericanIndian

Women

AmericanIndianMen

HispanicWomen

HispanicMen

CV

D D

eath

Rat

e p

er 1

00,0

00 P

erso

ns

American Heart Association. Heart Disease and Stroke Statistics – 2006 Update. Dallas, Tex.: American Heart Association; 2006.

0

100

200

300

400

1980 19901985 20001995

Stroke

Coronary Heart Disease

Coronary Heart Disease and Stroke Death Rates, 1980-2000

Age-adjusted rate per 100,000

0

100

200

300

400

1980 19901985 20001995

Stroke

Coronary Heart Disease

CHD 2010 target

Stroke 2010 target

Coronary Heart Disease and Stroke Death Rates, 1980-2000

Age-adjusted rate per 100,000

Annual Rate of First Heart Attacks Annual Rate of First Heart Attacks by Age, Sex and Race by Age, Sex and Race

ARIC: 1987-2000ARIC: 1987-2000

Source: NHLBI’s ARIC surveillance study, 1987-2000.

Coronary Heart Disease Death Rates, 2000

0

50

100

150

200

250

TotalBla

ck, N

ot

Hispan

ic

Hispan

ic

Asian

or

Pac

ific Is

lande

r

Amer

ican

India

n

or Ala

ska

Nativ

e

White

, Not

Hispan

ic Mal

e

Femal

e

2010target

Age-adjusted rate per 100,000

“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

IOM Report, 2002: Assessing the Quality of Minority Health Care

Non

-Min

orit

y

Min

orit

yDifference

Clinical Appropriateness and Need

Patient Preferences

The Operation of Healthcare Systems and the Legal and Regulatory Climate

Discrimination: Biases andPrejudice, Stereotyping, andUncertainty

Disparity

Qua

li ty

o f H

e al th

Car

eFigure 1: Differences, Disparities, and Discrimination: Populations with Equal Access to Health Care

Populations with Equal Access to Health Care

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 RightsChicago, 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)

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.

A Continuing National Paradox

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

Yusuf S et al. Lancet. 2004;364:937-52.N = 15,152 patients and 14,820 controls in 52 countriesPAR = population attributable risk, adjusted for all risk factors

36

127 10

20

33

0

20

40

60

80

100

Smoking Fruits/veg

Exercise Alcohol Psycho-social

Lipids All 9 risk factors

PAR(%)

14 18

50

90

Diabetes Abdominalobesity

Hyper-tension

Lifestyle factors

Risk Factors More Prevalent inAfrican-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)

More Prevalent in Non-Hispanic More Prevalent in Non-Hispanic Blacks than NHWBlacks than NHW

– Hypertension– Type 2 diabetes mellitus– Obesity– Metabolic Syndrome

(females)– Cigarette smoking– Physical inactivity

– Type 2 diabetes mellitus– Obesity– Lower HDL-Cholesterol

(females)– Elevated Triglycerides– Metabolic Syndrome– Physical Inactivity

More Prevalent in Hispanics More Prevalent in Hispanics than NHWthan NHW

CHD risk factors in Hispanics and African Americans CHD risk factors in Hispanics and African Americans compared to Non-Hispanic Whitescompared to Non-Hispanic Whites

Clark LT. Med Clin NA. 2005;89 (5):977-1001.Liao, et al J Am Coll Cardiol 30: 1200–1205, 1997

Ford, et al. JAMA. 2002;287:356-359.

Obesity, Metabolic Syndrome, Type 2 Diabetes and

Cardiovascular Disease

Obesity, Metabolic Syndrome, Type 2 Diabetes and

Cardiovascular Disease

Obesity

Cardiovascular disease

Metabolic syndrome

Insulin resistance

2 Risk 4 Risk

Luscher et al. Circulation. 2003;108:1655.Reilly and Rader. Circulation. 2003;108:1546.

Diabetes

Subcutaneous fat

Abdominal muscle layer

Intra-abdominal fat

Abdominal Adiposity:The Critical Adipose Depot

M. Davidson, MD.

Is this where you measure?

Multiple Cardiometabolic Risk

Isomaa B et al. Diabetes Care. 2001;24:683-689.Grundy, et al. Circulation 2002;106:3143

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”

Clinical Identification of the Metabolic Syndrome*Clinical Identification of the Metabolic Syndrome*

Risk Factor Defining Level • Abdominal obesity (waist circumference) Men > 102 cm (>40 in) Women > 88 cm (>35 in)• Triglycerides 150 mg/dl• HDL Cholesterol Men < 40 mg/dl Women < 50 mg/dl• Blood pressure 130/ 85 mm Hg• Fasting glucose 100 mg/dl

Circulation. 2002;106:3143.Circulation. 2005;112: 2735-2752.

* Diagnosis requires three or more criteria present

Definitions of the Metabolic Syndrome

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.orgGrundy SM, et al. Circulation. 2005;112:2735-2752.

* Based on a Chinese, Malay, and Asian-Indian population

† Or on drug treatment

Metabolic syndrome ICD-9-CM code: 277.7

Components

NCEP ATP III

≥3

IDF

WC + ≥2

AHA-NHLBI

≥3

WC, cm >102 (m) >88 (f)

Europid ≥94 (m) ≥80 (f)

S. Asian* ≥90 (m) ≥80 (f)

Japanese ≥85 (m) ≥90 (f)

>102 (m) >88 (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†

‡ ≥90cm (m) ≥80cm (f) for Asian Americans

NHANES III: Age-adjusted Prevalence of ³3 Risk Factors for Metabolic Syndrome*

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.

%%

24.8

16.4

28.3

22.825.7

35.6

0

5

10

15

20

25

30

35

40

White African-American Mexican-American

Men

Women

25.7% difference

56.7%difference

Source: NHANES, 1971-1974, 1976-1980, 1988-1994, 1999-2000, National Center for Health Statistics, CDC, 2002.

Age-Adjusted Prevalence of Obesity* in Americans Aged 20-74, Men and Women

12%

17%

13%

17%

21%

26%28%

33%

0

5

10

15

20

25

30

35

Perc

en

tag

e o

f P

op

ula

tio

n

1971-1974

1976-1980

1988-1994

1999-2002

1971-1974

1976-1980

1988-1994

1999-2002

Since 1971, obesity has doubled in both men and women

*Obesity is defined as a BMI of 30.0 or higher

Men Women

NHANES: Age-Adjusted Prevalence of Metabolic Syndrome Abnormalities

NHANES 1999-2000, N=1677Ford ES, et al. Diabetes Care. 2004;24:2444-2449.

Wilson PWF, et al. Circulation. 2003;108:1422-1425.

0

10

20

30

40

50

Abdominal High TG Low HDL-C High BP Glucose Glucose Obesity ≥100 mg/L ≥110 mg/L

ADA ATP III

Pre

vale

nce

, %

NHANES 1999-2000

NHANES III: Age-Specific Prevalence of the Metabolic Syndrome

NHANES III, 1988-1994Data are presented as percentage (SE)

20-29 30-39 40-49 50-59 60-69 70

Age, years

50

45

40

35

30

25

20

15

10

5

0

Pre

vale

nce

, %

Men

Women

Ford ES, et al. JAMA. 2002;287:356-359.

Age-adjusted prevalence of the metabolic syndrome is 23.7%

Approximately 47 million US residents have the metabolic syndrome

CVD and All-cause Mortality are Increased in Men CVD and All-cause Mortality are Increased in Men with the Metabolic Syndrome*with the Metabolic Syndrome*

Coronary Heart Disease Mortality Cardiovascular Disease Mortality All-Cause Mortality

RR (95% CI), 3.77 (1.74-8.17) RR (95% CI), 3.55 (1.96-6.43) RR (95% CI), 2.43 (1.64-3.51)

Follow-up, y Follow-up, y Follow-up, y

Cu

mu

lati

ve H

azar

d, %

No. at Risk

Metabolic Syndrome

Yes

No

866 852 834 292 866 852 834 292 866 852 834 292

867 279 234 100 288 279 234 100 288 279 234 100

0

5

10

15

20

0 2 4 6 8 10 120

5

10

15

20

0 2 4 6 8 10 120

5

10

15

20

0 2 4 6 8 10 12

Metabolic SyndromeYesNo

*As defined by NCEP ATP III.Lakka H, et al. JAMA. 2002;288:2709-2716.

The Metabolic Syndrome Is a Predictor of New The Metabolic Syndrome Is a Predictor of New CVD Events in Women with CADCVD Events in Women with CAD

Marroquin OC, et al. Circulation. 2004;109:714-721.

Patients with significant CAD

60

70

80

90

100

0 1 2 3 4

P=.007

Normal (n = 85)

Met Syn (n = 62)

Diabetes (n = 137)

Year

Eve

nt-

Fre

e S

urv

ival

, %

60

70

80

90

100

0 1 2 3 4

Patients without significant CAD

Normal (n = 237)

Met Syn (n = 125)

Diabetes (n = 103)

Year

P=NS for allcomparisons

Eve

nt-

Fre

e S

urv

ival

, %

Association of MI and Stroke With Components of the Metabolic Syndrome

Ninomiya JK, et al. Circulation. 2004;109:142-46.

1.16

1.471.38

1.181.32

1.0

2.1

1.3

2.2

1.3

0.0

0.5

1.0

1.5

2.0

2.5

Abdominal Obesity

High TG Low HDL-C HTN IR

Od

ds

Rat

io

Men

Women

Elevated Risk of CVD Prior to Clinical Diagnosis Elevated Risk of CVD Prior to Clinical Diagnosis of Type 2 Diabetesof Type 2 Diabetes

Hu FB, et al. Diabetes Care 2002;25(7) :1129-1134.

1

2.82

3.71

5.02

0

1

2

3

4

5

6

Nondiabeticthroughtout the

study

Prior to diagnosisof diabetes

After diagnosis ofdiabetes

Diabetic atbaseline

Rel

ativ

e R

isk

4329

194

159144

104

264

208

0

50

100

150

200

250

300

Previous MI and Diabetes are Strong Predictors of Previous MI and Diabetes are Strong Predictors of Mortality (MRFIT; N = 9434)Mortality (MRFIT; N = 9434)

MRFIT, Multiple Risk Factor Intervention Trial*Median 25 years of follow-up, age-adjusted rate per 10,000 person-years

Mo

rtal

ity

Rat

e*

Vaccaro O, et al. Arch Intern Med. 2004;164:1438:1443.

All CVD Death CHD Death

No DM DM

No MI

MI

No DM DM

Diabetes Has a Greater Impact on CVD Diabetes Has a Greater Impact on CVD in Women than in Menin Women than in Men

Kannel WB, et al. Adv Intern Med. 1997;42:39-66.

1.5

3.4

4.43.7

6.4

8.0

0

1

2

3

4

5

6

7

8

9

10

CHD PeripheralArtery Disease

Cardiac Failure

Rela

tive R

isk

MenWomen

Age-Adjusted Relative CVD Risk*

*Relative CVD risk for persons with diabetes versus those without

Treat associated lipid and nonlipid risk

factors

Treat associated lipid and nonlipid risk

factors

Intensify weight management and physical activity

Intensify weight management and physical activity

Reduce underlying causes:Overweight and obesityPhysical inactivity

Reduce underlying causes:Overweight and obesityPhysical inactivity

Therapeutic Approach To Cardiometabolic Risk Reduction

CHD or CHD equivalent (10-year risk >20%) Goal: <70 mg/dLCHD or CHD equivalent (10-year risk >20%) Goal: <70 mg/dL

Achieve LDL-C goalAchieve LDL-C goal Multiple risk factors and 10-year risk <20% Goal: <130 mg/dL

Multiple risk factors and 10-year risk <20% Goal: <130 mg/dL

Diagnosis of ≥ 3 of the following:Abdominal obesityElevated TGsLow HDL-CElevated BPIFG/IGT/diabetes

Diagnosis of ≥ 3 of the following:Abdominal obesityElevated TGsLow HDL-CElevated BPIFG/IGT/diabetes

Clark, Ferdinand, Ferdinand, Gavin.

Contemporary Management of the Metabolic Syndrome.

Therapeutic Approach To Cardiometabolic Risk Reduction

IFG/IGT/diabetesIFG/IGT/diabetesProthrombotic stateProthrombotic stateElevated BPElevated BPLow HDL-CLow HDL-CElevated TGsElevated TGs

Weight loss, increased physical activity, counseling. Drug therapy not routinely recommended. If diabetic, optimized

glycemic control

Weight loss, increased physical activity, counseling. Drug therapy not routinely recommended. If diabetic, optimized

glycemic control

Antiplatelet therapy (ASA ± clopidogrel)

Antiplatelet therapy (ASA ± clopidogrel)

Achieve BP goal:<130/80 mm Hg

Achieve BP goal:<130/80 mm Hg

LDL-C is the primary target. Emphasize weight loss and increasing physical activity. Consider

drug therapy in high-risk patients (CHD/CHD equivalents)*

LDL-C is the primary target. Emphasize weight loss and increasing physical activity. Consider

drug therapy in high-risk patients (CHD/CHD equivalents)*

Achieve non-HDL-C goal (LDL-C goal +30)

Achieve non-HDL-C goal (LDL-C goal +30)

*Drug therapy should not be routinely used in patients with IFG/IGT or to prevent diabetes pending the results of ongoing clinical trials.ASA, aspirin; BP, Blood pressure; CHD, coronary heart disease; HDL-C, high density lipoprotein cholesterol; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; LDL-C, low-density lipoprotein cholesterol; TG, triglycerides(Clark, Ferinand: Cardiology Special Edition, 2003)

Intensify weight management and physical

activity

Intensify weight management and physical

activity

Diagnosis of the metabolic syndrome: ≥ 3 of the following:

Abdominal obesityElevated TGsLow HDL-CElevated BPIFG/IGT/diabetes

Diagnosis of the metabolic syndrome: ≥ 3 of the following:

Abdominal obesityElevated TGsLow HDL-CElevated BPIFG/IGT/diabetes

Treat associated lipid and nonlipid risk factors

Treat associated lipid and nonlipid risk factors

Reduce underlying causes:Overweight and obesityPhysical inactivity

Reduce underlying causes:Overweight and obesityPhysical inactivity

CHD or CHD equivalent (10-year risk >20%) Goal: <70 mg/dLCHD or CHD equivalent (10-year risk >20%) Goal: <70 mg/dL

Achieve LDL-C goalAchieve LDL-C goal Multiple risk factors and 10-year risk <20% Goal: <130 mg/dL

Multiple risk factors and 10-year risk <20% Goal: <130 mg/dL

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

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

Conclusions: Addressing Unmet Needs