TY - JOUR
T1 - Adiponectin, free fatty acids, and cardiovascular outcomes in patients with type 2 diabetes and acute coronary syndrome
AU - Schrieks, Ilse C.
AU - Nozza, Anna
AU - Stähli, Barbara E.
AU - Buse, John B.
AU - Henry, Robert R.
AU - Malmberg, Klas
AU - Neal, Bruce
AU - Nicholls, Stephen J.
AU - Rydén, Lars
AU - Mellbin, Linda
AU - Svensson, Anders
AU - Wedel, Hans
AU - Weichert, Arlette
AU - Lincoff, A. Michael
AU - Tardif, Jean Claude
AU - Grobbee, Diederick E.
AU - Schwartz, Gregory G.
N1 - Funding Information:
was supported by F. Hoffmann-La Roche (Basel, Switzerland). J.B.B. has received research grants from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GI Dynamics, Intarcia, Johnson & Johnson, Lexicon, Medtronic, Novo Nordisk, Orexigen, Sanofi, Scion NeuroStim, Takeda, and Theracos; has ownership interest in PhaseBio; and has been a consultant for or served on the advisory board for Adocia, AstraZeneca, Dance Biopharm, Eli Lilly, Elcelyx, F. Hoffman-LaRoche, GI Dynamics, Lexicon, Merck, Metaven-tion, Novo Nordisk, Orexigen, PhaseBio, Quest, Takeda, and vTv Therapeutics. R.R.H. has received research grants from AstaReal, Eli Lilly, Hitachi, F. Hoffman-LaRoche, Lexicon, and Viacyte and has been a consultant for or served on the advisory board for Alere, AstraZeneca, Boehringer Ingelheim, Elcelyx, Eli Lilly, Intarcia, Ionis, Johnson & Johnson/Janssen, Sanofi, and REMD. K.M. has been employed by Roche and is currently employed by Vicore Pharma. B.N. has received research grants from Abbvie, Dr. Reddy’s Laboratories, Janssen, Roche, and Servier and has received honoraria from Abbott, AstraZeneca, Novartis, Pfizer, Roche, and Servier. S.J.N. has received research grants from Anthera, Amgen, AstraZeneca, Cerenis, Eli Lilly, F. Hoffmann-La Roche, InfraReDx, LipoScience, Novartis, Resverlogix, and Sanofi-Regeneron and has been a consultant for or served on the advisory board for Abbott, Amgen, AstraZeneca, Atheronova, Boehringer Ingelheim, CSL Behring, Esperion, LipoScience, Merck, Novartis, Omthera, Pfizer, Roche, Sanofi, and Takeda. L.R. has received research grants from AFA Insurance Company, Bayer AG, Karolinska Institutet Funds, Roche, the Swedish Diabetes Association, and the Swedish Heart Lung Foundation and has received honoraria from AstraZeneca, Bristol-Myers Squibb, Roche, and Sanofi. L.M. has received research grants from Bayer AG and has been a consultant for or received honoraria from Merck, Sanofi, Boehringer Ingelheim, and Novo Nordisk. A.S. is employed by F. Hoffmann-La Roche and has ownership interest in F. Hoffmann-La Roche. H.W. has received honoraria from AstraZeneca, Roche, and Pfizer. A.W. is employed by F. Hoffmann-La Roche. A.M.L. has received a research grant from F. Hoffmann-La Roche. J.-C.T. has received research grants from Amarin, Eli Lilly, Ionis, Merck, Pfizer, Roche, Sanofi, Servier, and DalCor and has received honoraria from Servier. D.E.G. has received a research grant from F. Hoffmann-La Roche. G.G.S. has received institutional research support from Cerenis, Resverlogix, F. Hoffmann-La Roche, and Sanofi. No other potential conflicts of interest relevant to this article were reported. Author Contributions. I.C.S. designed the study and wrote the manuscript. A.N. conducted statistical analysis and reviewed and edited the manuscript. B.E.S., J.B.B., R.R.H., K.M., B.N., S.J.N., L.R., L.M., A.S., H.W., A.W., A.M.L., J.-C.T., and D.E.G. reviewed and edited the manuscript. G.G.S. designed the study and wrote and edited the manuscript. I.C.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the
Publisher Copyright:
© 2018 by the American Diabetes Association.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
KW - Acute Coronary Syndrome/complications
KW - Adiponectin/blood
KW - Aged
KW - Coronary Disease/complications
KW - Diabetes Mellitus, Type 2/blood
KW - Diabetic Angiopathies/blood
KW - Fatty Acids, Nonesterified/blood
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/complications
KW - Oxazoles/therapeutic use
KW - Retrospective Studies
KW - Stroke/complications
KW - Thiophenes/therapeutic use
KW - Treatment Outcome
UR - http://www.scopus.com/inward/record.url?scp=85053491032&partnerID=8YFLogxK
U2 - 10.2337/dc18-0158
DO - 10.2337/dc18-0158
M3 - Article
C2 - 29903845
AN - SCOPUS:85053491032
SN - 0149-5992
VL - 41
SP - 1792
EP - 1800
JO - Diabetes Care
JF - Diabetes Care
IS - 8
ER -