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


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).


CONCLUSIONS
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."


BACKGROUND
clinicaltrials.gov Identifier: NCT00006305.
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN; Pfizer Inc., Groton, CT. Electronic address: Robert.Wolk@pfizer.com.
Robert
R
Wolk
University of Pittsburgh, Pittsburgh, PA.
Marnie
M
Bertolet
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
Prachi
P
Singh
University of Pittsburgh, Pittsburgh, PA.
Maria M
MM
Brooks
Florida Hospital Diabetes and Translational Research Institutes, Orlando.
Richard E
RE
Pratley
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
Robert L
RL
Frye
Division of Endocrinology, College of Medicine-Jacksonville, University of Florida, Jacksonville.
Arshag D
AD
Mooradian
Endocrinology and Diabetes Research Group, Institute of Human Development, University of Manchester, Manchester, UK; Manchester Diabetes Centre, Manchester Academic Health Science Centre, Manchester, UK.
Martin K
MK
Rutter
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
Andrew D
AD
Calvin
Division of Cardiology, St. Louis University School of Medicine, St. Louis, MO.
Bernard R
BR
Chaitman
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN.
Virend K
VK
Somers
D054392:Adipokines / Q000097:blood*; D017677:Age Distribution; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality / Q000503:physiopathology; D015897:Comorbidity; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D006801:Humans; D016014:Linear Models; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018570:Risk Assessment; D017678:Sex Distribution; D013318:Stroke Volume; D016277:Ventricular Function, Left
D054392:Adipokines; D015415:Biomarkers