Epidemiology and Prevention Associations of Total and High-Molecular-Weight Adiponectin With All-Cause and Cardiovascular Mortality in Older Persons The Cardiovascular Health Study

—In a population-based study of older adults, we examined the relationships of total andhigh-molecular-weight adiponectin with mortality among subgroups defined by baseline cardiovascular status: Nocardiovascular disease, heart failure, or atrial fibrillation (group 1); cardiovascular disease but no heart failure/atrialfibrillation (group 2); and heart failure/atrial fibrillation (group 3). We found significant differences in the associationswith all-cause mortality across the groups. The association in group 1 was U-shaped; increasing levels of totaladiponectin up to 12.4 mg/L were associated with lower mortality after adjustment for confounders (hazard ratio 0.81per 1 SD [95% confidence interval, 0.65–0.95]), but above this cut point, higher levels conferred greater risk (hazardratio 1.19 [95% confidence interval, 1.12–1.27]). Further adjustment for diabetes mellitus or insulin resistance,protection against which has been proposed to mediate the beneficial relationships of adiponectin with outcome,attenuated the association in the lower range. There was no significant association in group 2, but in group 3, totaladiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory interme-diates suggested a direct association for group 2, and magnified the one for group 3 (hazard ratio 1.31 [1.15–1.50]).Results were similar for high-molecular-weight adiponectin and for cardiovascular mortality.