Adiponectin, free fatty acids, and cardiovascular outcomes in patients with type 2 diabetes and acute coronary syndrome

Ilse C. Schrieks, Anna Nozza, Barbara E. Stähli, John B. Buse, Robert R. Henry, Klas Malmberg, Bruce Neal, Stephen J. Nicholls, Lars Rydén, Linda Mellbin, Anders Svensson, Hans Wedel, Arlette Weichert, A. Michael Lincoff, Jean Claude Tardif, Diederick E. Grobbee, Gregory G. Schwartz

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Abstract

OBJECTIVE: In observational cohorts, adiponectin is inversely associated and free fatty acids (FFAs) are directly associated with incident coronary heart disease (CHD). Adiponectin tends to be reduced and FFAs elevated in type 2 diabetes. We investigated relationships of adiponectin and FFA and major adverse cardiovascular events (MACEs) and death in patients with acute coronary syndrome (ACS) and type 2 diabetes using data from the AleCardio (Effect of Aleglitazar on Cardiovascular Outcomes After Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus) trial, which compared the PPAR-α/γ agonist aleglitazar with placebo. RESEARCH DESIGN AND METHODS: Using Cox regression adjusted for demographic, laboratory, and treatment variables, we determined associations of baseline adiponectin and FFAs, or the change in adiponectin and FFAs from baseline, with MACEs (cardiovascular death, myocardial infarction, or stroke) and death. RESULTS: A twofold higher baseline adiponectin (n = 6, 998) was directly associated with risk of MACEs (hazard ratio [HR] 1.17 [95% CI 1.08-1.27]) and death (HR 1.53 [95% CI 1.35-1.73]). A doubling of adiponectin from baseline to month 3 (n = 6, 325) was also associated with risk of death (HR 1.20 [95%CI 1.03-1.41]). Baseline FFAs(n=7,038), but not change in FFAs from baseline (n = 6, 365), were directly associated with greater risk of MACEs and death. There were no interactions with study treatment. CONCLUSIONS: In contrasttoprior observational data for incident CHD, adiponectin is prospectively associated with MACEs and death in patients with type 2 diabetes and ACS, and an increase in adiponectin from baseline is directly related to death. These findings raise the possibility that adiponectin has different effects in patients with type 2 diabetes and ACS than in populations without prevalent cardiovascular disease. Consistent with prior data, FFAs are directly associated with adverse outcomes.

Original languageEnglish
Pages (from-to)1792-1800
Number of pages9
JournalDiabetes Care
Volume41
Issue number8
DOIs
Publication statusPublished - 1 Aug 2018
Externally publishedYes

Cite this

Schrieks, I. C., Nozza, A., Stähli, B. E., Buse, J. B., Henry, R. R., Malmberg, K., Neal, B., Nicholls, S. J., Rydén, L., Mellbin, L., Svensson, A., Wedel, H., Weichert, A., Lincoff, A. M., Tardif, J. C., Grobbee, D. E., & Schwartz, G. G. (2018). Adiponectin, free fatty acids, and cardiovascular outcomes in patients with type 2 diabetes and acute coronary syndrome. Diabetes Care, 41(8), 1792-1800. https://doi.org/10.2337/dc18-0158