Associations of Total and High-Molecular-Weight Adiponectin with All-Cause and Cardiovascular Mortality in Older Persons: The Cardiovascular Health Study
Background—Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk), and cohorts with prevalent cardiovascular disease (CVD), heart failure (HF) or advanced age (higher risk).
Methods and Results—In a population-based study of older adults, we examined the relationships of total and high-molecular-weight (HMW) adiponectin with mortality among subgroups defined by baseline cardiovascular status: no CVD, HF or atrial fibrillation (AF) (Group 1); CVD but no HF/AF (Group 2); and HF/AF (Group 3). We found significant differences in the associations with all-cause mortality across the groups. The association in Group 1 was U-shaped; increasing levels of total adiponectin up to 12.4 mg/L were associated with lower mortality after adjustment for confounders (HR=0.81 per 1-SD [0.65-0.95]), but above this cutpoint, higher levels conferred greater risk (HR=1.19 [1.12-1.27]). Further adjustment for diabetes or insulin resistance, protection against which has been proposed to mediate adiponectin's beneficial relationships with outcome, attenuated the association in the lower range. There was no significant association in Group 2, but in Group 3, total adiponectin showed a direct adjusted association. Additional adjustment for putative metabolic/inflammatory intermediates suggested a direct association for Group 2, and magnified the one for Group 3 (HR=1.31 [1.15-1.50]). Results were similar for HMW adiponectin, and for cardiovascular mortality.
Conclusions—Adiponectin exhibits distinct associations with mortality in elders, which shift from U-shaped to flat to direct with greater baseline cardiovascular dysfunction, but become more consistently adverse after accounting for metabolic/inflammatory factors presumed to be favorably regulated by the adipokine. These findings advance understanding of the adiponectin paradox as relates to older adults.
- Received August 4, 2012.
- Accepted October 26, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited