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.
Abbreviations and Acronyms:
BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes), BMI (body mass index), CAD (coronary artery disease), CRP (C-reactive protein), CV (cardiovascular), DM (type 2 diabetes), HR (hazard ratio), IL-6 (interleukin 6), IP (insulin providing), IS (insulin sensitizing), MCP-1 (monocyte chemoattractant protein-1), MI (myocardial infarction), TNF-α (tumor necrosis factor α)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: June 09, 2016
Footnotes
Grant Support: This work was supported by National Heart, Lung and Blood Institute and National Institute of Diabetes and Digestive and Kidney Disease (grants R01HL087214 , U01HL061744 , U01HL061746 , U01HL061748 , U01HL063804 , R21HL121495 ), American Heart Association (grant 11SDG7260046 to P.S. ), Glaxo Smith Kline, Lantheus Medical Imaging (formerly Bristol-Myers Squibb Medical Imaging), Astellas Pharma US, Merck & Co., Abbott Laboratories, Pfizer, MediSense Productions, Bayer Diagnostics, Becton Dickinson & Co., JR Carlson Laboratories, Centocor, Eli Lilly & Co., LipoScience, Sante, Novartis Pharmaceuticals, NovoNordisk.
Potential Competing Interests: Dr Wolk is an employee of Pfizer and owns Pfizer stock; there is no conflict of interest in connection with the submitted manuscript. Dr Somers is working with Mayo Foundation on intellectual property related to obesity.
Identification
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© 2016 Mayo Foundation for Medical Education and Research
