Assessment of adiponectin and the risk of recurrent cardiovascular events in patients presenting with an acute coronary syndrome: observations from the Pravastatin Or atorVastatin Evaluation and Infection Trial-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22)

Abstract

Background: Adiponectin, an adipocytokine, is secreted by fatty cells and exerts a regulatory role in atherogenesis, modulating foam cell formation and cellular adhesion. In stable atherosclerosis, plasma adiponectin has been reported to be associated with both increased and decreased cardiovascular risk. Recent data have suggested a possible discordant adverse risk relationship in acute coronary syndrome (ACS). Therefore, we investigated the association between adiponectin and cardiovascular events in patients with ACS.

Methods: We measured plasma adiponectin in 3,931 patients stabilized following ACS and assessed the relationship with 2-year outcome. Patients were followed for all-cause death and major cardiovascular events. Using multivariable Cox regression, we adjusted for age, sex, race, ACS type, diabetes, smoking status, triglycerides, blood pressure, body mass index, estimated glomerular filtration rate, treatment group (atorvastatin), B-type natriuretic peptide, and C-reactive protein.

Results: Adiponectin correlated negatively with age, diabetes, body mass index, and triglycerides (each, P < .001) but showed a positive relationship with the risk of death (P = .01), myocardial infarction (P = .01), and heart failure (P < .001). After adjusting for clinical risk factors, B-type natriuretic peptide, and C-reactive protein, adiponectin greater than the median (4,477 ng/mL) was independently associated with an increased risk of death or myocardial infarction (hazard ratio 1.58, 95% CI 1.10-2.28, P = .013) and congestive heart failure (hazard ratio 2.17, 95% CI 1.21-3.89, P = .010).

Conclusions: Higher adiponectin concentrations early after ACS are independently associated with a higher risk of recurrent cardiovascular events. This finding is directionally opposite to that observed in patients at risk for atherosclerosis and reveals the need for investigation to elucidate differences in the pathobiology of adiponectin in stable versus unstable coronary artery disease.

Trial registration: ClinicalTrials.gov NCT00382460.