Dataset Information

Association of Circulating Ceramides With Cardiac Structure and Function in the Community: The Framingham Heart Study.

ABSTRACT: Background A higher circulating plasma ceramide ratio (C16:0/C24:0) is associated with an increased risk of heart failure, even after accounting for standard risk factors including lipid markers. However, the pathobiological mechanisms that underlie this association are incompletely understood. We tested the hypothesis that plasma ceramide ratio (C16:0/C24:0) is associated with adverse cardiac remodeling in the community. Methods and Results We evaluated 2652 Framingham Offspring Study participants (mean age, 66±9 years; 55% women) who attended their eighth examination cycle and underwent routine echocardiography and liquid chromatography-tandem mass spectrometry-based assays for circulating ceramide concentrations. We used multivariable linear regression models to relate C16:0/C24:0 (independent variable) to the following echocardiographic measures (dependent variables; separate models for each): left ventricular mass, left ventricular ejection fraction, left atrial emptying fraction, left atrial end-systolic volume, E/e' (a measure of left ventricular diastolic function), and left ventricular global circumferential and longitudinal strain by speckle-tracking echocardiography. In multivariable-adjusted analyses, higher C16:0/C24:0 per standard deviation increment was associated with lower left ventricular ejection fraction (0.991-fold change in left ventricular ejection fraction; P=0.0004), worse global circumferential strain (?=0.34, P=0.004), higher left atrial end-systolic volume (?=2.48, p<0.0001), and lower left atrial emptying fraction (0.99-fold change; P<0.0001). The C16:0/C24:0 ratio was not associated with either E/e' or global longitudinal strain, and the association with higher left ventricular mass was rendered statistically nonsignificant upon correction for multiple comparisons. Conclusions Our cross-sectional observations in a large community-based sample are consistent with a potential detrimental impact of higher ceramide ratio (C16:0/24:0) on cardiac remodeling traits, which may partly explain the associations of these molecular species with clinical heart failure.

SUBMITTER: Nwabuo CC

PROVIDER: S-EPMC6806035 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Association of Circulating Ceramides With Cardiac Structure and Function in the Community: The Framingham Heart Study.

Nwabuo Chike C CC Duncan Meredith M Xanthakis Vanessa V Peterson Linda R LR Mitchell Gary F GF McManus David D Cheng Susan S Vasan Ramachandran S RS

Journal of the American Heart Association 20190924 19

Background A higher circulating plasma ceramide ratio (C16:0/C24:0) is associated with an increased risk of heart failure, even after accounting for standard risk factors including lipid markers. However, the pathobiological mechanisms that underlie this association are incompletely understood. We tested the hypothesis that plasma ceramide ratio (C16:0/C24:0) is associated with adverse cardiac remodeling in the community. Methods and Results We evaluated 2652 Framingham Offspring Study participa ...[more]

PMID: 31549564

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Project description:Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease (COPD) and are highly heritable. We conducted genome-wide association (GWA) analyses (Affymetrix 100K SNP GeneChip) for measures of lung function in the Framingham Heart Study.Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow from the 25th to 75th percentile (FEF25-75), the FEV1/FVC ratio, and the FEF25-75/FVC ratio were examined. Percent predicted phenotypes were created using each participant's latest exam with spirometry. Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index (BMI). All modeling was performed stratified by sex and cohort. Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years. Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years.Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency > or = 10%, genotype call rate > or = 80%, and Hardy-Weinberg equilibrium p-value > or = 0.001. A SNP in the interleukin 6 receptor (IL6R) on chromosome 1 was among the best results for percent predicted FEF25-75. A non-synonymous coding SNP in glutathione S-transferase omega 2 (GSTO2) on chromosome 10 had top-ranked results studying the mean FEV1 and FVC measurements from two examinations. SNPs nearby the SOD3 and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes.GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA. These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 webcite.

Project description:Adipokines mediate cardiometabolic risk associated with obesity but their role in the pathogenesis of obesity-associated heart failure remains uncertain. We investigated the associations between circulating adipokine concentrations and echocardiographic measures in a community-based sample. We evaluated 3514 Framingham Heart Study participants (mean age 40 years, 53.8% women) who underwent routine echocardiography and had select circulating adipokines measured, ie, leptin, soluble leptin receptor, fatty acid-binding protein 4, retinol-binding protein 4, fetuin-A, and adiponectin. We used multivariable linear regression, adjusting for known correlates (including weight), to relate adipokine concentrations (independent variables) to the following echocardiographic measures (dependent variables): left ventricular mass index, left atrial diameter in end systole, fractional shortening, and E/e'. In multivariable-adjusted analysis, left ventricular mass index was inversely related to circulating leptin and fatty acid-binding protein 4 concentrations but positively related to retinol-binding protein 4 and leptin receptor levels (P≤0.002 for all). Left atrial end-systolic dimension was inversely related to leptin but positively related to retinol-binding protein 4 concentrations (P≤0.0001). E/e' was inversely related to leptin receptor levels (P=0.0002). We observed effect modification by body weight for select associations (leptin receptor and fatty acid-binding protein 4 with left ventricular mass index, and leptin with left atrial diameter in end systole; P<0.05 for interactions). Fractional shortening was not associated with any of the adipokines. No echocardiographic trait was associated with fetuin-A or adiponectin concentrations. In our cross-sectional study of a large, young to middle-aged, relatively healthy community-based sample, key indices of subclinical cardiac remodeling were associated with higher or lower circulating concentrations of prohypertrophic and antihypertrophic adipokines in a context-specific manner. These observations may offer insights into the pathogenesis of the cardiomyopathy of obesity.

Project description:Background Data are limited on the association of mildly reduced estimated glomerular filtration rate (eGFR 60-89 mL/min per 1.73 m2) with cardiovascular disease (CVD) in the community. Methods and Results We evaluated 3066 Framingham Offspring Study participants (55% women, mean age 58 years), without clinical CVD. Using multivariable regression, we related categories of mildly reduced eGFR (80-89, 70-79, or 60-69 versus ≥90 mL/min per 1.73 m2 [referent]) to prevalent coronary artery calcium, carotid intima media thickness, and left ventricular hypertrophy, and to circulating concentrations of cardiac stress biomarkers. We related eGFR categories to CVD incidence and to progression to ≥Stage 3 chronic kidney disease (eGFR <60 mL/min per 1.73 m2) using Cox regression. Individuals with eGFR 60-69 mL/min per 1.73 m2 (n=320) had higher coronary artery calcium score (odds ratio 1.69; 95% CI 1.02-2.80) compared with the referent group. Individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 had higher blood growth differentiating factor-15 concentrations (β=0.131 and 0.058 per unit-increase in log-biomarker, respectively). Participants with eGFR 60-69 and 80-89 mL/min per 1.73 m2 had higher blood B-type natriuretic peptide concentrations (β=0.119 and 0.116, respectively). On follow-up (median 16 years; 691 incident CVD and 252 chronic kidney disease events), individuals with eGFR 60-69 and 70-79 mL/min per 1.73 m2 experienced higher CVD incidence (hazard ratio [HR], 1.40; 95% CI, 1.02-1.93 and 1.45, 95% CI, 1.05-2.00, respectively, versus referent). Participants with eGFR 60-69 mL/min per 1.73 m2 experienced higher chronic kidney disease incidence (HR, 2.94; 95% CI, 1.80-4.78 versus referent). Conclusions Individuals with mildly reduced eGFR 60-69 mL/min per 1.73 m2 have a higher burden of subclinical atherosclerosis cross-sectionally, and a greater risk of CVD and chronic kidney disease progression prospectively. Additional studies are warranted to confirm our findings.

Dataset Information

Association of Circulating Ceramides With Cardiac Structure and Function in the Community: The Framingham Heart Study.

Publications

Association of Circulating Ceramides With Cardiac Structure and Function in the Community: The Framingham Heart Study.

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