Metabolic Syndrome, Diabetes, and Cardiovascular Disease: Implications

for Preventive Cardiology

Nathan D. Wong, PhD, FACC, FAHA

Professor and Director

Heart Disease Prevention Program

Division of Cardiology

University of California, Irvine

Overview of Diabetes in the United States

Diabetes Prevalence, 1990-1998

Age-adjusted prevalence of physician-diagnosed diabetes in Adults age 18 and older by race/ethnicity and sex (NHANES: 1999-2004). Source: NCHS and NHLBI. NH – non-Hispanic.

Risk of Cardiovascular Events in Diabetics Framingham Study

Age-adjusted

Biennial Rate Age-adjusted

Per 1000 Risk Ratio

Cardiovascular Event Men Women Men Women

Coronary Disease 39 21 1.5** 2.2***

Stroke 15 6 2.9*** 2.6***

Peripheral Artery Dis. 18 18 3.4*** 6.4***

Cardiac Failure 23 21 4.4*** 7.8***

All CVD Events 76 65 2.2*** 3.7***

Subjects 35-64 36-year Follow-up **P<.001,***P<.0001

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Insulin Resistance

Natural History of Type 2 Diabetes

Development of Type 2 Diabetes

Hyperglycemia in Type 2 Diabetes Results From Three

Major Metabolic Defects

Relationship Between Obesity and

Insulin Resistance and Dyslipidemia

Insulin Resistance: Associated Conditions

New Cases of ESRD in the United States

New Cases of ESRD in the United States

by Cause and Ethnicity, 1998

Microalbuminuria

Cardiovascular Disease and Diabetes

Probability of Death From CHD in Patients With Type 2 Diabetes With

or Without Previous MI

Framingham Heart Study 30-Year Follow-Up:CVD Events in Patients With Diabetes (Ages 35-64)

109

20

11

9 63819

3*

30

0

2

4

6

8

10

Age-adjusted annual rate/1,000

Men Women

Total CVD

CHD Cardiac failure

Intermittent claudication

Stroke

Riskratio

P<0.001 for all values except *P<0.05.

Wilson PWF, Kannel WB. In: Hyperglycemia, Diabetes and Vascular Disease. Ruderman N et al, eds. Oxford; 1992.

Presentation• Name: WJC • Age: 54 years old • Professional: former chief executive • Personal: wife lives principally in

Washington, DC; he has a personal cook in his suburban NY home

• Lifestyle: – Occasional use of cigars– has had a long-term weight problem– likes to play golf

Presentation (cont’d)

• Examination:– Height: 6 ft 2 in– Weight: 220 lb (BMI 28 kg/m2)– Waist circumference: 41 in– BP: 150/88 mm Hg– P: 64 bpm – RR: 12 breaths/min

• Cardiopulmonary exam: normal

Presentation (cont’d)

• Medications: – sildenafil 50 mg prn– amlodipine 5 mg/d

• Laboratory results: – TC: 220 mg/dL– HDL-C: 36 mg/dL– LDL-C: 140 mg/dL– TG: 220 mg/dL– FBS: 120 mg/dL

The Metabolic Syndrome

InsulinResistance

Hypertension

Type 2 Diabetes

DisorderedFibrinolysis

ComplexDyslipidemia

TG, LDL

HDL

EndothelialDysfunction

SystemicInflammation

Athero-sclerosis

VisceralObesity

Adapted from the ADA. Diabetes Care. 1998;21:310-314;Pradhan AD et al. JAMA. 2001;286:327-334.

Revised ATP III Metabolic Syndrome Oct 2005

*Diagnosis is established when 3 of these risk factors are present.†Abdominal obesity is more highly correlated with metabolic risk factors than is BMI. ‡Some men develop metabolic risk factors when circumference is only marginally increased.

<40 mg/dL<50 mg/dL or Rx for ↓ HDL

MenWomen

>102 cm (>40 in)>88 cm (>35 in)

MenWomen

100 mg/dL or Rx for ↑ glucoseFasting glucose130/85 mm Hg or on HTN RxBlood pressure

HDL-C150 mg/dL or Rx for ↑ TGTG

Abdominal obesity† (Waist circumference‡)

Defining LevelRisk Factor

International Diabetes Federation Definition:

Abdominal obesity plus two other components: elevated BP, low HDL, elevated TG, or impaired fasting glucose

Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994Prevalence of the Metabolic Syndrome Among US Adults NHANES 1988-1994

Pre

vale

nc

e (

%)

P

reva

len

ce

(%

)

05

10

15

2025

3035

40

45

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

MenMenWomenWomen

Age (years)Age (years)Ford E et al. JAMA. 2002(287):356.Ford E et al. JAMA. 2002(287):356.

1999-2002 Prevalence by IDF vs. NCEP Definitions (Ford ES, Diabetes Care 2005; 28: 2745-9) (unadjusted, age 20+)NCEP : 33.7% in men and 35.4% in women IDF: 39.9% in men and 38.1% in women

0%

10%

20%

30%

40%

Prevalence of the NCEP Metabolic Syndrome: NHANES III by Sex and Race/Ethnicity

Pre

vale

nce

, %

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

Women

WhiteAfrican AmericanMexican AmericanOther

25%25%

16%16%

28%28%

21%21%23%23%

26%26%

36%36%

20%20%

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: 1245-

1250)

0

1

2

3

4

5

6

7

Rel

ativ

e R

isk

CHD Mortality CVD Mortality Total Mortality

None

MetS

Diabetes

CVD

CVD+Diabetes

* p<.05, ** p<.01, **** p<.0001 compared to none

*

***

***

***

**

***

***

***

******

***

Metabolic Syndrome, CVD Events, and Mortality• European cohort studies (6156 men and 5356 women): Modified

WHO definition of MetS associated with all-cause mortality (RR=1.44 [1.17-1.84] in men and 1.38 [1.02-1.87] in women) and CVD mortality (RR=2.26 [1.61-3.17] in men and 2.78 [1.57-4.94 in women) (Hu et al. Arch Intern Med 2004; 164: 1066-76)

• Atherosclerosis Risk in Communities (ARIC) study (12,089 men and women): 11 year follow-up, ATP III MetS associated with 1.5-2-fold greater likelihood of developing CHD and stroke, but MetS did not improve prediction over FRS (McNeill et al. Diab Care 2005; 28: 385-90)

• Cardiovascular Health Study (CHS) (2,175 elderly subjects): ATP III definition associated with 38% increased risk (p<0.01) of coronary/cerebrovascular events (Scuteri et al., Diab Care 2005; 28: 882-7)