Use of Obesity Biomarkers in Cardiovascular Epidemiology

Pischon, Tobias

doi:10.1155/2009/757683

Cited by 27 publications

(18 citation statements)

References 169 publications

(223 reference statements)

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“…However, these associations were no longer significant after multivariate adjustment, and in mediation analysis both adipokines (considered separately and together) did not appear to significantly modify the relationship between VAT and LV diastolic function. Clinical and experimental data on leptin and adiponectin effects on the heart are not entirely consistent [5, 14], and their prognostic significance is controversial, especially in elderly adults and people with chronic diseases [14, 29]. Hyperleptinemia may confer antisteatosis protection to the myocardium by increasing FAs oxidation in early stages of obesity, but this effect may be lost with the progression of leptin resistance that occurs in late stage obesity, leading to lipotoxicity that promotes cardiomyocyte contractile dysfunction and apoptosis [5].…”

Section: Discussionmentioning

confidence: 99%

“…Circulating SHBG is mostly produced by the liver, and has been strongly and inversely correlated with liver fat content in both genders [13]. Leptin and adiponectin are cytokine hormones produced by adipose cells and have gained much attention as mediators of obesity in the regulation of energy homeostasis and lipid metabolism within the heart [4, 5, 14]. Plasma triglycerides were determined by an enzymatic method (ABA-200 ATC Biochromatic Analyzer, Abbott Laboratories).…”

Section: Methodsmentioning

confidence: 99%

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The relationship between visceral adiposity and left ventricular diastolic function: Results from the Baltimore Longitudinal Study of Aging

Canepa¹,

Strait²,

Milaneschi

et al. 2013

Nutrition, Metabolism and Cardiovascular Diseases

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BACKGROUND AND AIMS It is unclear whether subcutaneous and visceral fat are differentially correlated to the decline in left ventricular (LV) diastolic function with aging. This study sought to examine the hypothesis that age-related changes in the regional fat distribution account for changes in LV diastolic function and to explore potential mediators of this association. METHODS AND RESULTS In this cross-sectional study, we evaluated 843 participants of the Baltimore Longitudinal Study of Aging with echocardiogram, dual-energy x-ray absorptiometry (DEXA), abdominal computed tomography (CT) and blood tests performed at the same visit. LV diastolic function was assessed by parameters of LV relaxation (E/A ratio, Em and Em/Am ratio) and LV filling pressures (E/Em ratio). Total body fat was computed by DEXA, while visceral and subcutaneous fat were determined from abdominal CT. In multivariate models adjusted for demographics, cardiovascular risk factors, antihypertensive medications, physical activity and LV mass, both visceral and subcutaneous fat were associated with LV diastolic dysfunction. When both measures of adiposity were simultaneously included in the same model, only visceral fat was significantly associated with LV diastolic dysfunction. Triglycerides and sex-hormone binding globulin, but not adiponectin and leptin, were found to be significant mediators of the relationship between visceral fat and LV diastolic function, explaining 28 to 47% of the association. Bootstrapping analyses confirmed the significance of these findings. CONCLUSIONS Increased visceral adiposity is associated with LV diastolic dysfunction, possibly through a metabolic pathway involving blood lipids and ectopic fat accumulation rather than adipokines.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The relationship between visceral adiposity and left ventricular diastolic function: Results from the Baltimore Longitudinal Study of Aging

Canepa¹,

Strait²,

Milaneschi

et al. 2013

Nutrition, Metabolism and Cardiovascular Diseases

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“…This underscores the importance of adiponectin as an emerging marker of vascular disease risk and potentially modifiable risk factor, and the need for evaluating approaches to control this biomarker with medications, diet and lifestyle modifications. 61 …”

Section: Gardener Et Almentioning

confidence: 99%

Serum Adiponectin in Relation to Race–Ethnicity and Vascular Risk Factors in the Northern Manhattan Study

Gardener

Crisby

Sjoberg

et al. 2013

Metabolic Syndrome and Related Disorders

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Background: Population-based data on serum adiponectin levels, an adipocytokine secreted from adipose tissue, are lacking, particularly across race-ethnic groups. Studies have suggested an inverse association between adiponectin and vascular risk factors, but data are limited and inconsistent. We examined the cross-sectional association between adiponectin, vascular risk factors and race-ethnicity in the population-based Northern Manhattan Study (NOMAS). Methods: Blood samples, anthropomorphics, and vascular risk factors were collected at baseline. Multivariable linear regression analysis was conducted with log-transformed adiponectin as the dependent variable. Results: Adiponectin was measured among 2900 participants (age 69 -10 years, body mass index (BMI) 28.0 -5.6, 37% male, 21% white, 53% Hispanic, 24% black). The mean adiponectin was 11.4 -6.2 mg/mL (median = 9.8, range = 2.1-53.3). After multivariable adjustment, adiponectin levels were greatest among whites, followed by Hispanics, and lowest among blacks. Lower adiponectin levels were observed in participants with the following characteristics: Male, former smoking, hypertension, diabetes, homeostasis model assessment of insulin resistance (HOMA-IR), metabolic syndrome, moderate alcohol use, elevated waist circumference, BMI, estimated glomerular filtration rate (eGFR), triglycerides, low-density lipoprotein cholesterol (LDL-C), lower high-density lipoprotein cholesterol (HDL-C), and younger age. Obesity was a stronger risk factor for decreased adiponectin among blacks than among whites or Hispanics. The associations for several vascular risk factors, including hypertension, triglycerides, and low HDL-C, with low adiponectin were stronger among individuals who were not obese than among those who were obese. Conclusions: Adiponectin levels were lower among blacks and Hispanics and among those with various vascular risk factors, and greater with older age. The association between BMI and adiponectin varied across raceethnic groups. Investigation of whether differences in body fat distribution may explain race-ethnic differences in adiponectin is needed.

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“…Finally, we apply C-JAMP in a substudy of the large European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam cohort study (Boeing, Wahrendorf, & Becker, 1999;Riboli & Kaaks, 1997) with 200 probands, and perform-to our knowledge-the first GWAS of high-molecular-weight (HMW) and mediummolecular-weight (MMW) adiponectin plasma concentrations, which are different biologically active isoforms of the hormone adiponectin and have been associated with obesity and a number of chronic diseases (Aleksandrova et al, 2012;Pischon, 2009). Finally, we apply C-JAMP in a substudy of the large European Prospective Investigation into Cancer and Nutrition (EPIC) Potsdam cohort study (Boeing, Wahrendorf, & Becker, 1999;Riboli & Kaaks, 1997) with 200 probands, and perform-to our knowledge-the first GWAS of high-molecular-weight (HMW) and mediummolecular-weight (MMW) adiponectin plasma concentrations, which are different biologically active isoforms of the hormone adiponectin and have been associated with obesity and a number of chronic diseases (Aleksandrova et al, 2012;Pischon, 2009).…”

Section: Introductionmentioning

confidence: 99%

Powerful rare variant association testing in a copula‐based joint analysis of multiple phenotypes

Konigorski

Yilmaz

Janke

et al. 2019

Genetic Epidemiology

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In genetic association studies of rare variants, the low power of association tests is one of the main challenges. In this study, we propose a new single-marker association test called C-JAMP (Copula-based Joint Analysis of Multiple Phenotypes), which is based on a joint model of multiple phenotypes given genetic markers and other covariates. We evaluated its performance and compared its empirical type I error and power with existing univariate and multivariate single-marker and multi-marker rare-variant tests in extensive simulation studies. C-JAMP yielded unbiased genetic effect estimates and valid type I errors with an adjusted test statistic. When strongly dependent traits were jointly analyzed, C-JAMP had the highest power in all scenarios except when a high percentage of variants were causal with moderate/small effect sizes. When traits with weak or moderate dependence were analyzed, whether C-JAMP or competing approaches had higher power depended on the effect size. When C-JAMP was applied with a misspecified copula function, it still achieved high power in some of the scenarios considered. In a real-data application, we analyzed sequencing data using C-JAMP and performed the first genome-wide association studies of high-molecular-weight and medium-molecular-weight adiponectin plasma concentrations. C-JAMP identified 20 rare variants with pvalues smaller than 10 −5 , while all other tests resulted in the identification of fewer variants with higher p-values. In summary, the results indicate that C-JAMP is a powerful, flexible, and robust method for association studies, and we identified novel candidate markers for adiponectin. C-JAMP is implemented as an R package and freely available from https://cran.r-project.org/package= CJAMP.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

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Use of Obesity Biomarkers in Cardiovascular Epidemiology

Cited by 27 publications

References 169 publications

The relationship between visceral adiposity and left ventricular diastolic function: Results from the Baltimore Longitudinal Study of Aging

The relationship between visceral adiposity and left ventricular diastolic function: Results from the Baltimore Longitudinal Study of Aging

Serum Adiponectin in Relation to Race–Ethnicity and Vascular Risk Factors in the Northern Manhattan Study

Powerful rare variant association testing in a copula‐based joint analysis of multiple phenotypes

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