Match!

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

Published on Jul 1, 2016
· DOI :10.1016/J.MAYOCP.2016.03.020
Robert Wolk32
Estimated H-index: 32
(Pfizer),
Marnie Bertolet17
Estimated H-index: 17
(University of Pittsburgh)
+ 8 AuthorsVirend K. Somers100
Estimated H-index: 100
(Mayo Clinic)
Abstract
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.
  • References (40)
  • Citations (8)
📖 Papers frequently viewed together
2018
20152.78PLOS ONE
7 Authors (Ekim Seven, ..., Jørgen Jeppesen)
23 Citations
42 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References40
Newest
#1Prachi Singh (Mayo Clinic)H-Index: 17
#2Pragya Sharma (Mayo Clinic)H-Index: 3
Last. Virend K. Somers (Mayo Clinic)H-Index: 100
view all 11 authors...
Adiponectin exerts beneficial effects by reducing inflammation and improving lipid metabolism and insulin sensitivity. Although the adiponectin level is lower in obese individuals, whether weight gain reduces adiponectin expression in humans is controversial. We sought to investigate the role of weight gain, and consequent changes in leptin, on altering adiponectin expression in humans. Forty-four normal-weight healthy subjects were recruited (mean age 29 years; 14 women) and randomized to eithe...
21 CitationsSource
#1Robert Wolk (Pfizer)H-Index: 32
#2Marnie Bertolet (University of Pittsburgh)H-Index: 17
Last. Virend K. SomersH-Index: 100
view all 11 authors...
AimsTo determine the effects of insulin sensitization (IS) and insulin provision (IP) treatment strategies on adipokines associated with cardiovascular disease in patients with type 2 diabetes mellitus and coronary artery disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (BARI 2D).Methods and resultsChanges in adipokine levels were compared in patients with type 2 diabetes mellitus and coronary artery disease randomized to IS (n = 1037) versus IP (n = 1019) treat...
7 CitationsSource
#1Connie M. Rhee (UCI: University of California, Irvine)H-Index: 33
#2Danh V. Nguyen (UCI: University of California, Irvine)H-Index: 38
Last. Kamyar Kalantar-Zadeh (UCI: University of California, Irvine)H-Index: 100
view all 10 authors...
Background In the general population, circulating adiponectin is associated with a favorable cardiovascular risk profile (eg, lower triglycerides and body fat) and decreased mortality. Hemodialysis (HD) patients have comparatively higher adiponectin concentrations, but prior studies examining the adiponectin-mortality association in this population have not accounted for body composition or shown a consistent relationship. Study Design Prospective cohort study. Settings & Participants We examine...
35 CitationsSource
#1Zhi Zhang (SJTU: Shanghai Jiao Tong University)H-Index: 6
#2Fang Wang (SJTU: Shanghai Jiao Tong University)H-Index: 1
Last. Qiuyan Dai (SJTU: Shanghai Jiao Tong University)H-Index: 7
view all 7 authors...
Vascular extracellular matrix (ECM) remodelling, which is the result of disruption in the balance of ECM synthesis and degradation, induces vessel fibrosis and thereby leads to hypertension. Leptin is known to promote tissue fibrosis, while adiponectin has recently been demonstrated to be anti-fibrogenic in tissue fibrosis. In this study, we aimed to evaluate the leptin-antagonist function of adiponectin and to further elucidate the mechanisms through which adiponectin dampens leptin signalling ...
15 CitationsSource
#1Zhen-Jie Wu (Guangxi Medical University)H-Index: 6
#1Zhenjie Wu (Guangxi Medical University)H-Index: 10
Last. Lynn Htet Htet Aung (Guangxi Medical University)H-Index: 15
view all 4 authors...
Abstract Background The overall quantitative estimate on the possible association of adiponectin concentrations with mortality in patients with cardiovascular diseases (CVD) has not been reported. Methods We performed a systematic review and meta-analysis of prospective studies to evaluate the overall quantitative estimates on the adiponectin levels for risk of mortality in patients with CVD. MEDLINE, EMBASE, CINAHL, and the Cochrane Library (up to Mar 22, 2014) were used to search for studies e...
61 CitationsSource
#1Carl J. Lavie (Pennington Biomedical Research Center)H-Index: 86
#2Paul A. McAuley (WSSU: Winston-Salem State University)H-Index: 18
Last. Steven N. Blair (USC: University of South Carolina)H-Index: 144
view all 5 authors...
Obesity has been increasing in epidemic proportions, with a disproportionately higher increase in morbid or class III obesity, and obesity adversely affects cardiovascular (CV) hemodynamics, structure, and function, as well as increases the prevalence of most CV diseases. Progressive declines in physical activity over 5 decades have occurred and have primarily caused the obesity epidemic. Despite the potential adverse impact of overweight and obesity, recent epidemiological data have demonstrate...
314 CitationsSource
#1Kazuto Nakamura (BU: Boston University)H-Index: 13
#2José J. Fuster (BU: Boston University)H-Index: 21
Last. Kenneth Walsh (BU: Boston University)H-Index: 91
view all 3 authors...
Obesity is a risk factor for various cardiovascular diseases including hypertension, atherosclerosis, and myocardial infarction. Recent studies aimed at understanding the microenvironment of adipose tissue and its impact on systemic metabolism have shed light on the pathogenesis of obesity-linked cardiovascular diseases. Adipose tissue functions as an endocrine organ by secreting multiple immune-modulatory proteins known as adipokines. Obesity leads to increased expression of pro-inflammatory ad...
217 CitationsSource
#1Marjorie Bastien (Laval University)H-Index: 8
#2Paul Poirier (Laval University)H-Index: 57
Last. Jean-Pierre Després (Laval University)H-Index: 113
view all 4 authors...
Abstract The prevalence of obesity has increased worldwide and is a source of concern since the negative consequences of obesity start as early as in childhood. The most commonly used anthropometric tool to assess relative weight and classify obesity is the body mass index (BMI); BMI alone shows a U- or a J-shaped association with clinical outcomes and mortality. Such an inverse relationship fuels a controversy in the literature, named the ‘obesity paradox', which associates better survival and ...
530 CitationsSource
#1Johan Van de Voorde (UGent: Ghent University)H-Index: 24
#2Bart Pauwels (UGent: Ghent University)H-Index: 9
Last. Kelly Decaluwé (UGent: Ghent University)H-Index: 10
view all 4 authors...
Abstract Adipose tissue can be considered as a huge gland producing paracrine and endocrine hormones, the adipo(cyto)kines. There is growing evidence that these adipo(cyto)kines may link obesity to cardiovascular diseases. The excessive adipocyte hypertrophy in obesity induces hypoxia in adipose tissue. This leads to adiposopathy, the process that converts “healthy” adipose tissue to “sick” adipose tissue. This is accompanied by a change in profile of adipo(cyto)kines released, with less product...
130 CitationsSource
#1Ryan K. Masters (UNC: University of North Carolina at Chapel Hill)H-Index: 12
#2Eric N. Reither (USU: Utah State University)H-Index: 16
Last. Bruce G. Link (Columbia University)H-Index: 84
view all 6 authors...
Objectives. To estimate the percentage of excess death for US Black and White men and women associated with high body mass, we examined the combined effects of age variation in the obesity–mortality relationship and cohort variation in age-specific obesity prevalence.Methods. We examined 19 National Health Interview Survey waves linked to individual National Death Index mortality records, 1986–2006, for age and cohort patterns in the population-level association between obesity and US adult mort...
187 CitationsSource
Cited By8
Newest
#1Taher M. Mandviwala (University of Texas at Austin)H-Index: 1
#2Sukhdeep S. Basra (University of Texas at Austin)H-Index: 1
Last. Anita Deswal (BCM: Baylor College of Medicine)H-Index: 1
view all 9 authors...
Limited data exist on the association of obesity with both hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF), especially in the real-world ambulatory setting. We hypothesized that increasing body-mass index (BMI) in ambulatory heart failure with preserved ejection fraction would have a protective effect on these patients leading to decreased mortality and hospitalizations. We studied the relationship between BMI and the time to all-cause mortal...
1 CitationsSource
#1Vijayakumar Javalkar (LSU Health Sciences Center Shreveport)H-Index: 11
#2Okkes Kuybu (LSU Health Sciences Center Shreveport)H-Index: 1
Last. Roger E. Kelley (LSU Health Sciences Center Shreveport)H-Index: 25
view all 4 authors...
Abstract Background: To use a nationwide database of hospital admissions to assess for trends in inpatient mortality from acute spontaneous intracerebral hemorrhage as well as associated potentially contributing factors. Methods: Adults with intracerebral hemorrhage in the US National Inpatient Sample database from 2012 to 2015 were included in this study. We assessed for mortality rate as well as potential impact of various comorbidities and demographic factors such as ethnicity and median hous...
2 CitationsSource
Summary Background Chronic inflammation is a process sustained by the augmentation of circulating cytokines level and C-reactive protein (CRP). Adipocytes and adipose tissue infiltration with inflammatory cells, are an important source of adipokines production, and their expansion due to overnutrition is responsible for increased in inflammation. The reduction of body fat following both controlled diets or gastric surgery can be favorable in the reduction of pro-inflammatory cytokines. Methods A...
20 CitationsSource
#1Niki Katsiki (A.U.Th.: Aristotle University of Thessaloniki)H-Index: 30
#2Dimitri P. Mikhailidis (UCL: University College London)H-Index: 79
Last. Maciej Banach (Medical University of Łódź)H-Index: 53
view all 3 authors...
Leptin, an adipokine that is implicated in the control of food intake via appetite suppression, may also stimulate oxidative stress, inflammation, thrombosis, arterial stiffness, angiogenesis and atherogenesis. These leptin-induced effects may predispose to the development of cardiovascular diseases. In the present review we discuss the evidence linking leptin levels with the presence, severity and/or prognosis of both coronary artery disease and non-cardiac vascular diseases such as stroke, car...
26 CitationsSource
#1Krzysztof Tojek (UMK: Nicolaus Copernicus University in Toruń)H-Index: 3
#2Beata Wustrau (UMK: Nicolaus Copernicus University in Toruń)H-Index: 2
Last. Jacek Budzyński (UMK: Nicolaus Copernicus University in Toruń)H-Index: 10
view all 7 authors...
Summary Background Overweight and obesity are, on the one hand, recognized as risk factors for many health-related disorders, and, on the other, as favorable prognostic factors in various patients treated for several different conditions; what is called the “obesity paradox”. Until now, the existence of this phenomenon among a general population of consecutive inpatients has not been evaluated. We decided, therefore, to perform an evaluation. Patients and methods Historical prospective analysis ...
3 CitationsSource
#1Mitra Nadali (University of Gothenburg)H-Index: 2
#2Rille Pullerits (University of Gothenburg)H-Index: 17
Last. Maria Bokarewa (University of Gothenburg)H-Index: 36
view all 6 authors...
Despite the predominance of female patients and uncommon obesity, rheumatoid arthritis (RA) is tightly connected to increased cardiovascular morbidity. The aim of this study was to investigate transcriptional activity in the subcutaneous white adipose tissue (WAT) with respect to this disproportionate cardiovascular risk (CVR) in RA. CVR was estimated in 182 female patients, using the modified Systematic Coronary Risk Evaluation scale, and identified 93 patients with increased CVR. The overall t...
2 CitationsSource
#1Massimiliano Ruscica (University of Milan)H-Index: 29
#2Andrea Baragetti (University of Milan)H-Index: 13
Last. Giuseppe Danilo Norata (University of Milan)H-Index: 47
view all 4 authors...
Abstract Aim Critically discuss the available data, to identify the current gaps and to provide key concepts that will help clinicians in translating the biology of adipokines in the context of atherosclerosis and cardio-metabolic diseases. Data synthesis Adipose tissue is nowadays recognized as an active endocrine organ, a function related to the ability to secrete adipokines (such as leptin and adiponectin) and pro-inflammatory cytokines (tumor necrosis factor alpha and resistin). Studies in v...
25 CitationsSource
#1Rohan Samson (Tulane University)H-Index: 5
#2Andrea Qi (Tulane University)H-Index: 1
Last. Suzanne Oparil (UAB: University of Alabama at Birmingham)H-Index: 97
view all 5 authors...
Purpose of Review The present obesity epidemic particularly affects African-American women. Whether the obesity epidemic will alter the hypertension phenotype in African-American women is entertained.
6 CitationsSource