You are here

Associations of total and high-molecular-weight adiponectin with all-cause and cardiovascular mortality in older persons: the Cardiovascular Health Study.

TitleAssociations of total and high-molecular-weight adiponectin with all-cause and cardiovascular mortality in older persons: the Cardiovascular Health Study.
Publication TypeJournal Article
Year of Publication2012
AuthorsKizer, JR, Benkeser, D, Arnold, AM, Mukamal, KJ, Ix, JH, Zieman, SJ, Siscovick, DS, Tracy, RP, Mantzoros, CS, deFilippi, CR, Newman, AB, Djoussé, L
JournalCirculation
Volume126
Issue25
Pagination2951-61
Date Published2012 Dec 18
ISSN1524-4539
KeywordsAdiponectin, Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Female, Health Surveys, Humans, Male, Molecular Weight
Abstract<p><b>BACKGROUND: </b>Adiponectin shows opposite associations with adverse outcomes in healthy middle-aged populations (lower risk) and cohorts with prevalent cardiovascular disease, heart failure, or advanced age (higher risk).</p><p><b>METHODS AND RESULTS: </b>In a population-based study of older adults, we examined the relationships of total and high-molecular-weight adiponectin with mortality among subgroups defined by baseline cardiovascular status: No cardiovascular disease, heart failure, or atrial fibrillation (group 1); cardiovascular disease but no heart failure/atrial fibrillation (group 2); and heart failure/atrial fibrillation (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 (hazard ratio=0.81 per 1 SD [95% confidence interval, 0.65-0.95]), but above this cut point, higher levels conferred greater risk (hazard ratio=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, 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 (hazard ratio=1.31 [1.15-1.50]). Results were similar for high-molecular-weight adiponectin and for cardiovascular mortality.</p><p><b>CONCLUSIONS: </b>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 it relates to older adults.</p>
DOI10.1161/CIRCULATIONAHA.112.135202
Alternate JournalCirculation
PubMed ID23159554
PubMed Central IDPMC3968250
Grant ListR01 AG015928 / AG / NIA NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
R56 AG020098 / AG / NIA NIH HHS / United States
R01 HL-094555 / HL / NHLBI NIH HHS / United States
AG-20098 / AG / NIA NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
R01 HL094555 / HL / NHLBI NIH HHS / United States
N01-HC-85086 / HC / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
AG-027058 / AG / NIA NIH HHS / United States
N01 HC-55222 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
N01-HC-75150 / HC / NHLBI NIH HHS / United States
R01 HL080295 / HL / NHLBI NIH HHS / United States
R01 AG020098 / AG / NIA NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
HL080295 / HL / NHLBI NIH HHS / United States
N01-HC-85239 / HC / NHLBI NIH HHS / United States
AG-023629 / AG / NIA NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 AG027058 / AG / NIA NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
R56 AG023629 / AG / NIA NIH HHS / United States