Dataset Information

Ceramide Remodeling and Risk of Cardiovascular Events and Mortality.

ABSTRACT: BACKGROUND:Recent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to determine the relations between the most abundant plasma ceramide species of differing acyl chain lengths and the risk of coronary heart disease (CHD) and mortality in community-based samples. METHODS AND RESULTS:We developed a liquid chromatography/mass spectrometry assay to quantify plasma C24:0, C22:0, and C16:0 ceramides and ratios of these very-long-chain/long-chain ceramides in 2642 FHS (Framingham Heart Study) participants and in 3134 SHIP (Study of Health in Pomerania) participants. Over a mean follow-up of 6 years in FHS, there were 88 CHD and 90 heart failure (HF) events and 239 deaths. Over a median follow-up time in SHIP of 5.75 years for CHD and HF and 8.24 years for mortality, there were 209 CHD and 146 HF events and 377 deaths. In meta-analysis of the 2 cohorts and adjusting for standard CHD risk factors, C24:0/C16:0 ceramide ratios were inversely associated with incident CHD (hazard ratio per average SD increment, 0.79; 95% confidence interval, 0.71-0.89; P<0.0001) and inversely associated with incident HF (hazard ratio, 0.78; 95% confidence interval, 0.61-1.00; P=0.046). Moreover, the C24:0/C16:0 and C22:0/C16:0 ceramide ratios were inversely associated with all-cause mortality (C24:0/C16:0: hazard ratio, 0.60; 95% confidence interval, 0.56-0.65; P<0.0001; C22:0/C16:0: hazard ratio, 0.65; 95% confidence interval, 0.60-0.70; P<0.0001). CONCLUSIONS:The ratio of C24:0/C16:0 ceramides in blood may be a valuable new biomarker of CHD risk, HF risk, and all-cause mortality in the community.

SUBMITTER: Peterson LR

PROVIDER: S-EPMC6015315 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Ceramide Remodeling and Risk of Cardiovascular Events and Mortality.

Peterson Linda R LR Xanthakis Vanessa V Duncan Meredith S MS Gross Stefan S Friedrich Nele N Völzke Henry H Felix Stephan B SB Jiang Hui H Sidhu Rohini R Nauck Matthias M Jiang Xuntian X Ory Daniel S DS Dörr Marcus M Vasan Ramachandran S RS Schaffer Jean E JE

Journal of the American Heart Association 20180503 10

<h4>Background</h4>Recent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to determine the relations between the most abundant plasma ceramide species of differing acyl chain lengths and the risk of coronary heart disease (CHD) and mortality in community-based samples.<h4>Methods and results</h4>We developed a liquid chromatography/mass spectrometry assay to quantify plasma C24:0, C22:0, and C16:0 ceramide ...[more]

PMID: 29728014

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Project description:RATIONALE & OBJECTIVE:Inflammation, cardiac remodeling, and fibrosis may explain in part the excess risk for cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Growth differentiation factor 15 (GDF-15), galectin 3 (Gal-3), and soluble ST2 (sST2) are possible biomarkers of these pathways in patients with CKD. STUDY DESIGN:Observational cohort study. SETTING & PARTICIPANTS:Individuals with CKD enrolled in either of 2 multicenter CKD cohort studies: the Seattle Kidney Study or C-PROBE (Clinical Phenotyping and Resource Biobank Study). EXPOSURES:Circulating GDF-15, Gal-3, and sST2 measured at baseline. OUTCOMES:Primary outcome was all-cause mortality. Secondary outcomes included hospitalization for physician-adjudicated heart failure and the atherosclerotic CVD events of myocardial infarction and cerebrovascular accident. ANALYTIC APPROACH:Cox proportional hazards models used to test the association of each biomarker with each outcome, adjusting for demographics, CVD risk factors, and kidney function. RESULTS:Among 883 participants, mean estimated glomerular filtration rate was 49±19mL/min/1.73m2. Higher GDF-15 (adjusted HR [aHR] per 1-SD higher, 1.87; 95% CI, 1.53-2.29), Gal-3 (aHR per 1-SD higher, 1.51; 95% CI, 1.36-1.78), and sST2 (aHR per 1-SD higher, 1.36; 95% CI, 1.17-1.58) concentrations were significantly associated with mortality. Only GDF-15 level was also associated with heart failure events (HR per 1-SD higher, 1.56; 95% CI, 1.12-2.16). There were no detectable associations between GDF-15, Gal-3, or sST2 concentrations and atherosclerotic CVD events. LIMITATIONS:Event rates for heart failure and atherosclerotic CVD were low. CONCLUSIONS:Adults with CKD and higher circulating GDF-15, Gal-3, and sST2 concentrations experienced greater mortality. Elevated GDF-15 concentration was also associated with an increased rate of heart failure. Further work is needed to elucidate the mechanisms linking these circulating biomarkers with CVD in patients with CKD.

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Dataset Information

Ceramide Remodeling and Risk of Cardiovascular Events and Mortality.

Publications

Ceramide Remodeling and Risk of Cardiovascular Events and Mortality.

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