HYPERINSULINEMIA AND CARDIOVASCULAR-DISEASE IN ELDERLY MEN - THE HONOLULU HEART PROGRAM

Hyperinsulinemia has been associated with cardiovascular disease (CVD) , but whether this relation is independent of other CVD risk factors i s uncertain. Most studies have focused on coronary heart disease (CHD) , but few have included peripheral vascular disease (PVD) and stroke. Moreover, evidence in elderly and minority populations is limited. Bet ween 1991 and 1993, 3562 elderly (71 to 93 years) Japanese-American me n form the Honolulu Heart Program were examined and had fasting insuli n levels measured. Hyperinsulinemia, defined as a fasting insulin grea ter than or equal to 95th percentile among nonobese men with normal gl ucose tolerance and no diabetic history or medication use, was observe d in 22% of the population. Subjects with hyperinsulinemia had a more adverse CVD risk factor profile and had higher age-adjusted prevalence s of CHD, angina, PVD, thromboembolic stroke, and hemorrhagic stroke c ompared with those without hyperinsulinemia. Age-adjusted fasting insu lin levels but not 2-hour levels were also significantly elevated (P<. 01) in those with prevalent CVD compared with those without. In logist ic regression analyses, adjustment for multiple CVD risk factors atten uated the relations of hyperinsulinemia with CHD, angina, and PVD to n onsignificant levels, whereas those involving thromboembolic and hemor rhagic stroke were strengthened and remained significant (odds ratios= 2.27 and 7.53, 95% confidence intervals=1.25 to 4.13 and 1.65 to 34.25 , respectively). When multivariate analyses were restricted to nondiab etic subjects, associations were slightly weaker and in general nonsig nificant. Nondiabetic men with thromboembolic stroke were twice as lik ely to have hyperinsulinemia as those who were stroke-free, although t his association was of borderline significance (odds ratio=1.99, 95% c onfidence interval=0.95 to 4.17, P=.069). In subjects with elevated to tal cholesterol levels, somewhat stronger associations were observed f or PVD and stroke, these cross-sectional results are consistent with a n indirect role for insulin in CVD, wherein hyperinsulinemia or an und erlying insulin-resistant state may adversely affect other CVD risk fa ctors or serve as a marker for an atherogenic or thrombogenic state.