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

Robert Wolk, Marnie Bertolet, Prachi Singh, Maria M. Brooks, Richard E. Pratley, Robert L. Frye, Arshag D. Mooradian, Martin K. Rutter, Andrew D. Calvin, Bernard R. Chaitman, Virend Somers

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)858-866
Number of pages9
JournalMayo Clinic Proceedings
Volume91
Issue number7
DOIs
StatePublished - Jul 1 2016

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Adipokines
Obesity
Leptin
Body Mass Index
Adiponectin
Angioplasty
C-Reactive Protein
Type 2 Diabetes Mellitus
Coronary Artery Disease
Lymphotoxin-beta
Tumor Necrosis Factor-alpha
Chemokine CCL2
Proportional Hazards Models
Interleukin-6
Cardiovascular Diseases
Stroke
Myocardial Infarction

ASJC Scopus subject areas

  • Medicine(all)

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Prognostic Value of Adipokines in Predicting Cardiovascular Outcome : Explaining the Obesity Paradox. / Wolk, Robert; Bertolet, Marnie; Singh, Prachi; Brooks, Maria M.; Pratley, Richard E.; Frye, Robert L.; Mooradian, Arshag D.; Rutter, Martin K.; Calvin, Andrew D.; Chaitman, Bernard R.; Somers, Virend.

In: Mayo Clinic Proceedings, Vol. 91, No. 7, 01.07.2016, p. 858-866.

Research output: Contribution to journalArticle

Wolk, R, Bertolet, M, Singh, P, Brooks, MM, Pratley, RE, Frye, RL, Mooradian, AD, Rutter, MK, Calvin, AD, Chaitman, BR & Somers, V 2016, 'Prognostic Value of Adipokines in Predicting Cardiovascular Outcome: Explaining the Obesity Paradox', Mayo Clinic Proceedings, vol. 91, no. 7, pp. 858-866. https://doi.org/10.1016/j.mayocp.2016.03.020
Wolk, Robert ; Bertolet, Marnie ; Singh, Prachi ; Brooks, Maria M. ; Pratley, Richard E. ; Frye, Robert L. ; Mooradian, Arshag D. ; Rutter, Martin K. ; Calvin, Andrew D. ; Chaitman, Bernard R. ; Somers, Virend. / Prognostic Value of Adipokines in Predicting Cardiovascular Outcome : Explaining the Obesity Paradox. In: Mayo Clinic Proceedings. 2016 ; Vol. 91, No. 7. pp. 858-866.
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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.",
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AU - Brooks, Maria M.

AU - Pratley, Richard E.

AU - Frye, Robert L.

AU - Mooradian, Arshag D.

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N2 - 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.

AB - 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.

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