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
14.0 13.2
12.0 11.0 10.9
10.7
Percent of Population
10.0
8.0 6.7
5.6
6.0
4.0
2.0
0.0
Men Women
NH Whites NH Blacks Mexican Americans
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
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)
10
10 9
8 Men Women
11
Risk 6
ratio 30
4 19
38 9 6
20 3*
2
0
Total CHD Cardiac Intermittent Stroke
CVD failure claudication
Age-adjusted annual rate/1,000
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
Endothelial
Complex Systemic
Dysfunction Inflammation
Dyslipidemia
TG, LDL
HDL
Insulin Athero-
Disordered
Fibrinolysis
Resistance sclerosis
Hypertension Visceral
Type 2 Diabetes Obesity
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
Risk Factor Defining Level
Abdominal obesity†
(Waist circumference‡)
Men >102 cm (>40 in)
Women >88 cm (>35 in)
TG 150 mg/dL or Rx for ↑ TG
HDL-C
Men <40 mg/dL
Women <50 mg/dL or Rx for ↓ HDL
Blood pressure 130/85 mm Hg or on HTN
Fasting glucose 100 mg/dL Rx
or Rx for ↑ glucose
*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.
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 1988-1994
45
40 Men
Women
Prevalence (%)
35
30
25
20
15
10
5
0
20-29 30-39 40-49 50-59 60-69 > 70
Ford E et al. JAMA. 2002(287):356. Age (years)
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
Prevalence of the NCEP Metabolic Syndrome:
NHANES III by Sex and Race/Ethnicity
White
African American
40% Mexican American 36%
Other
28%
30%
Prevalence, %
25% 26%
23%
21% 20%
20% 16%
10%
0%
Men Women
Ford ES et al. JAMA 2002;287:356-359.
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)
7 ***
6 ***
5
Relative Risk
***
None
4 MetS
***
***
3
*** Diabetes
*** ***
*** CVD
*
2 **
CVD+Diabetes
1
0
CHD Mortality CVD Mortality Total Mortality
* 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)
