Ilse C Schrieks1, Anna Nozza2, Barbara E Stähli3, John B Buse4, Robert R Henry5, Klas Malmberg6, Bruce Neal7, Stephen J Nicholls8, Lars Rydén9, Linda Mellbin9, Anders Svensson10, Hans Wedel11, Arlette Weichert10, A Michael Lincoff12, Jean-Claude Tardif13, Diederick E Grobbee14, Gregory G Schwartz15. 1. Julius Clinical and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands ilse.schrieks@juliusclinical.com. 2. Montreal Health Innovations Coordinating Center, Montreal Heart Institute, Montreal, Canada. 3. Department of Cardiology, Charité Berlin-University Medicine, Campus Benjamin Franklin, Berlin, Germany. 4. University of North Carolina School of Medicine, Chapel Hill, NC. 5. University of California San Diego, San Diego, CA. 6. Karolinska Institutet and Vicore Pharma, Stockholm, Sweden. 7. The George Institute for Global Health, University of Sydney, Sydney, Australia. 8. South Australian Health and Medical Research Institute, The University of Adelaide, Adelaide, Australia. 9. Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden. 10. F. Hoffmann-La Roche Ltd., Basel, Switzerland. 11. Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 12. Department of Cardiovascular Medicine, Cleveland Clinic Coordinating Center for Clinical Research (C5Research), Cleveland, OH. 13. Montreal Heart Institute, Université de Montréal, Montreal, Canada. 14. Julius Clinical and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands. 15. Division of Cardiology, VA Medical Center and University of Colorado School of Medicine, Denver, CO.
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 contrast to prior 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.
RCT Entities:
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 contrast to prior 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.
Authors: Neil K Huang; Petra Bůžková; Nirupa R Matthan; Luc Djoussé; Calvin H Hirsch; Jorge R Kizer; W T Longstreth; Kenneth J Mukamal; Alice H Lichtenstein Journal: J Am Heart Assoc Date: 2021-03-08 Impact factor: 5.501