Abstract 16033: A Paradoxical Relationship of Plasma Adiponectin to Cardiovascular Risk in Patients With Diabetes and Recent Acute Coronary Syndrome - the Alecardio Trial
Introduction: Adiponectin (Adn), a hormone secreted by adipocytes, modulates insulin action and sensitivity, and has putative anti-atherogenic effects. Observational cohort studies show an inverse association of Adn levels with incident cardiovascular (CV) disease risk. Adn levels are generally reduced in type 2 diabetes (T2D). PPAR-γ agonists are among the most effective agents to raise Adn concentrations. Therefore, we investigated the relation between Adn concentrations and total mortality and CV events in the AleCardio trial that compared the PPAR-α/γ agonist aleglitazar with placebo in patients with T2D and acute coronary syndrome (ACS).
Methods: Data for baseline and change in Adn concentrations were available in 6998 and 6325 patients, respectively. Using Cox regression adjusted for 28 clinical, laboratory, and pharmacologic variables, we examined the association of Adn with total mortality and CV events (CV death or nonfatal myocardial infarction or stroke).
Results: At baseline, median (IQR) Adn was 4 (3-6) μg/ml. Baseline Adn was associated with total mortality (P<.001, Figure). Doubling of baseline Adn was associated with HR 1.83 (95% CI 1.63-2.01, P<.001) and adjusted HR 1.54 (95% CI 1.36-1.75, P<.001) for mortality, and with HR 1.31 (95% CI 1.21-1.42, P<.001) and adjusted HR 1.17 (95% CI 1.08-1.27, P<.001) for CV events. At 3 months’ randomized treatment, median Adn increased to 12 (7-19) μg/ml with aleglitazar, but did not change from baseline with placebo. In the aleglitazar group, each 1 μg/ml increase in Adn from baseline to Month 3 was associated with higher risk for both total mortality and CV events (HR 1.02, 95% CI 1.00-1.04, P=.038 and HR 1.02, 95% CI 1.00-1.03, P= .051, respectively).
Conclusions: Higher Adn shortly after ACS is independently associated with an increased risk of mortality and CV events in patients with T2D. These findings are in contrast to the favorable association of Adn with CV risk observed in cohorts without prior CV events.
Author Disclosures: I.C. Schrieks: Employment; Significant; Julius Clinical. A. Nozza: None. B.E. Stähli: Research Grant; Significant; Godfried and Julia Bangerter-Rhyner Foundation, Novartis Foundation for medical-biomedical research, Swiss Foundation for Medical-Biological Scholarships. J.B. Buse: Research Grant; Modest; AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Eli Lilly, GI Dynamics, Intarcia, Johnson & Johnson, Lexicon, Medtronic, Novo Nordisk, Orexigen, Sanofi, Scion NeuroStim, Takeda, Theracos. Ownership Interest; Modest; PhaseBio. Consultant/Advisory Board; Modest; Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, Elycylex, F. Hoffman-LaRoche, GI Dynamics, Lexicon, Merck, Metavention, Novo Nordisk, Orexigen, PhaseBio, Quest, Takeda, vTv Therapeutics. K. Malmberg: Employment; Modest; Roche. Employment; Significant; Antaros Medical. B. Neal: Research Grant; Significant; Abbvie, Dr Reddy’s Laboratories, Janssen, Roche, Servier. Honoraria; Significant; Abbott, AstraZeneca, Novartis, Pfizer, Roche, Servier. S.J. Nicholls: Research Grant; Significant; Anthera, Amgen, AstraZeneca, Cerenis, Eli Lilly, F. Hoffmann-La Roche, InfraReDx, LipoScience, Novartis, Resverlogix, Sanofi-Regeneron. Consultant/Advisory Board; Modest; Abbott, Amgen, AstraZeneca, Atheronova, Boehringer Ingelheim, CSL Behring, Esperion, LipoScience, Merck, Novartis, Omthera, Pfizer Roche, sanofi-aventis, Takeda. L. Rydén: Research Grant; Significant; AFA Insurance Company, Bayer AG, Karolinska Institutet Funds, Roche, the Swedish Diabetes Association, the Swedish Heart Lung Foundation. Honoraria; Modest; AstraZeneca, Bristol-Myers Squibb, Roche, sanofi-aventis. A. Svensson: Employment; Significant; F. Hoffmann-La Roche. Ownership Interest; Significant; F. Hoffmann-La Roche. H. Wedel: Honoraria; Modest; AstraZeneca, Roche, Pfizer. A. Weichert: Employment; Significant; F. Hoffmann-La Roche. A. Lincoff: Research Grant; Modest; F. Hoffmann-La Roche. J. Tardif: Research Grant; Modest; Amarin, Eli Lilly, Isis, Merck, Pfizer, Roche, sanofi-aventis, Servier. Research Grant; Significant; DalCor. Honoraria; Modest; Servier. D.E. Grobbee: Research Grant; Significant; F. Hoffmann-La Roche. G.G. Schwartz: Research Grant; Modest; Cerenis, Resverlogix, The Medicines Company. Research Grant; Significant; F. Hoffmann-La Roche, Sanofi.
- © 2016 by American Heart Association, Inc.