| The biological factors underlying the greater risk of coronary heart disease (CHD) in men than women remain unclear. Endogenous sex hormones, as well as sex-differences in fat distribution and fat-derived hormones, are potential candidates. The goal of this dissertation was to describe the cross-sectional and prospective association of the adipocytokine, adiponectin, with cardiovascular disease and mortality, and its modulation by endogenous sex hormones. Sex-specific analyses were performed using data from 1513 participants of the Rancho Bernardo Study, a population based cohort of older adults.; We observed a favorable association between adiponectin and most CHD risk factors, adiponectin levels were positively related to age, alcohol intake and HDL cholesterol, and negatively associated with male sex, waist girth, body mass index, insulin resistance and triglycerides. Current literature reasons that lower adiponectin levels in men compared to women must be due to either a suppressive effect of testosterone or a stimulatory effect of estrogens. Our results are contrary to both of these hypotheses and provide credible evidence that regulation by sex hormones does not account for the sex difference in serum adiponectin in older adults. Higher testosterone and lower bioavailable estradiol were each associated with higher levels of adiponectin in both sexes, independent of age, adiposity, lifestyle, insulin resistance, or lipoproteins.; Higher adiponectin levels had a protective association with prevalent CHD for both men and women, which seemed to be primarily mediated by HDL cholesterol and triglycerides. In prospective analyses, higher adiponectin concentrations predicted reduced risk of non-fatal myocardial infarction over the following 20 years in men, but not women. Adiponectin was not associated with 20 year CHD mortality in either sex, and adiponectin levels above the 80th percentile for this population were associated with increased risk of cardiovascular death and of death from all causes. We found no evidence that endogenous sex hormones modulated the link between adiponectin and CHD risk.; We conclude that neither adiponectin, nor its interaction with endogenous sex hormones, is likely to provide a foundation for reconciling sex differences in CHD. |
