Abstract 3902: Adiponectin and Risk of Coronary Heart Disease in Older Men and Women: The Cardiovascular Health Study
Reduced adiponectin levels have been reported to predict development of insulin resistance, and to have atherogenic and prothrombotic effects. The results of longitudinal studies evaluating adiponectin and risk of CHD are conflicting, however, with one study finding an inverse association in men, and separate studies in older women or individuals of either sex failing to document a significant relationship. We sought to investigate the relationship between serum adiponectin and incident CHD in older men and women, while accounting for a range of potential confounders and mediating factors, including insulin resistance and leptin. To this end, we conducted a nested case-control study among participants in the population-based Cardiovascular Health Study who were free of prevalent cardiovascular disease in 1992–93. During follow-up through June 2001, there were 280 men and 320 women with first-ever CHD. Controls were frequency-matched to these cases at a ratio of 1.25:1 by age, sex, race, subclinical disease status (by carotid wall thickness, ankle-brachial index, Rose questionnaire, ECG abnormalities) and center, yielding 1386 participants. The homeostasis model assessment (HOMA) was used as a measure of insulin resistance. Adiponectin and leptin were measured in stored blood samples. CHD included angina, myocardial infarction, revascularization and coronary death. After adjustment for matching factors and hypertension, diabetes, waist-hip ratio, smoking, LDL, HDL, triglycerides, creatinine, CRP, fibrinogen, and leptin or HOMA, there was a significant relationship between quintiles (Q) of adiponectin and CHD in men (Q2 vs. Q1: OR 0.80, 95% CI 0.48–1.32; Q3 vs. Q1: OR 0.65, 95% CI 0.38–1.10; Q4 vs. Q1: OR 0.69, 95% CI 0.41–1.15; Q5 vs. Q1: OR 0.54, 95% CI 0.32–0.91; P for trend 0.020) but not women. When assessed as a continuous variable, adiponectin was also significantly associated with CHD in men only (adjusted OR 0.81 per two-fold increase, P=0.007). These findings underscore the independent role of adiponectin as a strong protective factor for CHD in older men, with potentially important therapeutic implications in this high-risk group. Further research is needed to determine the basis for sex differences in the actions of this adipokine.