Prognostic Value of Adipokines in Predicting Cardiovascular Outcome: Explaining the Obesity Paradox

Abstract

Objective: To evaluate the cardiovascular (CV) prognostic value of adipokines in a large prospective cohort of patients participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial.

Patients and methods: The effects of the adipokine levels at baseline and change from baseline on the composite outcome (CV death, myocardial infarction, and stroke) were analyzed using unadjusted and fully adjusted Cox models in 2330 patients with type 2 diabetes and coronary artery disease who had participated in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (from January 1, 2001, through December 1, 2008).

Results: In a fully adjusted model, baseline leptin and change from baseline leptin were protective for CV events, whereas baseline adiponectin, baseline tumor necrosis factor α (TNF-α), change from baseline TNF-α, baseline C-reactive protein (CRP), and change from baseline CRP were harmful. The effect of baseline leptin on CV events depended on the body mass index (BMI), such that the hazard ratios (HRs) varied between 0.6 and 1.4 across the BMI quintiles (interaction P=.03). The same was true for baseline adiponectin (HR varied from 0.7 to 1.7; interaction P=.01), change from baseline monocyte chemoattractant protein-1 (HR varied from 0.8 to 1.8; interaction P=.03), change from baseline TNF-α (HR varied from 0.9 to 1.4; interaction P=.02), and change from baseline IL-6 (HR varied from 0.7 to 1.8; interaction P=.005).

Conclusion: Adipokines are independent predictors of CV events in patients with type 2 diabetes and coronary artery disease. The association between the specific adipokines and CV outcome varies depending on BMI. This reflects the complex pathophysiology of CV disease in obesity and may help explain the "obesity paradox."

Trial registration: clinicaltrials.gov Identifier: NCT00006305.

Conflict of interest statement

CONFLICT OF INTEREST:

Authors report no conflict of interest in connection with this manuscript.

Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Hazard Ratios (HRs) for baseline (solid line) or change from baseline (dotted line) in leptin (a), adiponectin (b) and leptin/adiponectin ratio (c) by BMI quintiles. Error bars indicate 95% confidence intervals (CIs). When the CIs do not include 1 for a given HR estimate, the effect is statistically significant.

Figure 2

Hazard Ratios (HRs) for baseline (solid line) or change from baseline (dotted line) in leptin (a) and adiponectin (b) by leptin/adiponectin ratio quintiles. Error bars indicate 95% confidence intervals (CIs). When the CIs do not include 1 for a given HR estimate, the effect is statistically significant.