Obesity Epidemiology

188 EPIDEMIOLOGIC STUDIES OF CONSEQUENCES OF OBESITYObesity and CHFConsiderable evidence indicates that obesity is an independent risk factor for CHF. 60-65In the NHANES I epidemiologic follow-up study, 60 after adjustment for hypertension,diabetes, CHD, and other cardiovascular risk factors at baseline, overweight was associatedwith a 23% (95% CI: 9% to 38%) higher risk of CHF. In that hypertension, diabetes,and CHD are all strongly related to obesity, a model adjusted for these variables wouldcertainly underestimate the effects of BMI.In the Framingham Heart Study, Kenchaiah et al. 62 reported a 39% (12% to 72%)increased risk of CHF in the overweight group and a nearly 2-fold (1.54 to 2.56)increased risk among the obese compared to the normal-weight group. After adjustmentfor other cardiovascular risk factors at baseline (e.g., hypertension, diabetes, left ventricularhypertrophy, and MI), each unit increment in BMI was associated with a 5% increasein CHF risk for men and a 7% increase for women. Clearly, this is overadjustment as theadjusted factors are intermediate variables in the pathway between obesity and CHF. Theestimated population-attributable risk of CHF due to overweight and obesity was 28% inwomen and 30% in men.Nicklas et al. 63 examined overall and abdominal obesity in relation to risk of CHF inolder men and women in the Health, Aging and Body Composition study. In the analysesadjusting for demographic variables and smoking, all adiposity measurements—includingBMI, percentage of body fat, total fat mass, waist circumference, and visceral and subcutaneousabdominal adipose tissue measured by CT scans—significantly predicted CHFrisk. However, waist circumference appeared to be the most robust predictor of CHFwhen included with other adiposity variables in multivariate models. Further adjustmentfor inflammation, hypertension, insulin resistance, and diabetes mellitus did not materiallyalter the association for waist circumference. This study underscores the importanceof abdominal obesity in the development of CHF.The observed link between obesity and CHF is not surprising given that major riskfactors for CHF (e.g., CHD, hypertension, and diabetes) are all strongly associated withobesity. The association between obesity and CHF remained significant, however, evenafter adjustment for these risk factors, suggesting additional mechanisms. Obesity hasbeen associated with left ventricular hypertrophy and dilatation, both important precursorsto CHF. 66,67 In a Swedish study, Ingelsson et al. 64 reported that insulin resistancemeasured by euglycemic insulin clamp significantly predicted incidence of CHF independentof BMI and waist circumference, whereas positive associations between BMI orwaist circumference and CHF became nonsignificant after adjustment for insulin resistance.This study suggests that at least part of the association between excess adiposityand CHF is mediated through insulin resistance.“Obesity Paradox” in CHFObesity is clearly an important risk factor for the development of CHF, but it has alsobeen associated with improved survival in patients with established CHF—a phenomenonreferred to as “reverse epidemiology” 68 or “obesity paradox.” 69 In CHF, the direction ofassociation between other cardiovascular risk factors (e.g., blood pressure and serumcholesterol) and mortality is also reversed. In other words, hypercholesterolemia andhigh blood pressure are associated with improved rather than decreased survival amongpatients with CHF. 68 The inverse association between higher BMI and lower mortality