Ceramide Remodeling and Risk of Cardiovascular Events and Mortality

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 dis...

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Published inJournal of the American Heart Association Vol. 7; no. 10
Main Authors Peterson, Linda R., Xanthakis, Vanessa, Duncan, Meredith S., Gross, Stefan, Friedrich, Nele, Völzke, Henry, Felix, Stephan B., Jiang, Hui, Sidhu, Rohini, Nauck, Matthias, Jiang, Xuntian, Ory, Daniel S., Dörr, Marcus, Vasan, Ramachandran S., Schaffer, Jean E.
Format Journal Article
LanguageEnglish
Published England John Wiley and Sons Inc 15.05.2018
Wiley
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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.
AbstractList 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.
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. 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; <0.0001) and inversely associated with incident HF (hazard ratio, 0.78; 95% confidence interval, 0.61-1.00; =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; <0.0001; C22:0/C16:0: hazard ratio, 0.65; 95% confidence interval, 0.60-0.70; <0.0001). 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.
BackgroundRecent 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 ResultsWe 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). ConclusionsThe 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.
BACKGROUNDRecent 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 RESULTSWe 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). CONCLUSIONSThe 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.
Author Gross, Stefan
Vasan, Ramachandran S.
Völzke, Henry
Felix, Stephan B.
Jiang, Hui
Dörr, Marcus
Sidhu, Rohini
Ory, Daniel S.
Peterson, Linda R.
Duncan, Meredith S.
Friedrich, Nele
Xanthakis, Vanessa
Jiang, Xuntian
Schaffer, Jean E.
Nauck, Matthias
AuthorAffiliation 7 Department of Internal Medicine B University Medicine Greifswald Greifswald Germany
4 Section of Cardiology Department of Medicine Boston University Boston MA
1 Diabetic Cardiovascular Disease Center and Department of Medicine Washington University St Louis MO
2 Framingham Heart Study Framingham MA
8 DZHK (German Centre for Cardiovascular Research), partner site Greifswald Germany
10 Institute for Community Medicine University Medicine Greifswald Germany
11 DZD (German Centre for Diabetes Research), partner site Greifswald Germany
9 Institute of Clinical Chemistry and Laboratory Medicine University Medicine Greifswald Germany
5 Department of Biostatistics Boston University School of Public Health Boston MA
3 Section of Preventive Medicine and Epidemiology Department of Medicine Boston University Boston MA
6 Department of Epidemiology Boston University School of Public Health Boston MA
AuthorAffiliation_xml – name: 2 Framingham Heart Study Framingham MA
– name: 3 Section of Preventive Medicine and Epidemiology Department of Medicine Boston University Boston MA
– name: 6 Department of Epidemiology Boston University School of Public Health Boston MA
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– name: 9 Institute of Clinical Chemistry and Laboratory Medicine University Medicine Greifswald Germany
– name: 11 DZD (German Centre for Diabetes Research), partner site Greifswald Germany
– name: 8 DZHK (German Centre for Cardiovascular Research), partner site Greifswald Germany
– name: 10 Institute for Community Medicine University Medicine Greifswald Germany
– name: 5 Department of Biostatistics Boston University School of Public Health Boston MA
– name: 7 Department of Internal Medicine B University Medicine Greifswald Greifswald Germany
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/29728014$$D View this record in MEDLINE/PubMed
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ContentType Journal Article
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Issue 10
Keywords mortality
ceramides
cardiovascular disease risk factors
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2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
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Meredith S. Duncan is currently located at the Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN.
Dr Peterson, Dr Xanthakis, and Ms Duncan contributed equally to this work.
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PublicationTitle Journal of the American Heart Association
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Snippet Background Recent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to...
Recent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to determine...
BACKGROUNDRecent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to...
BackgroundRecent studies suggest that circulating concentrations of specific ceramide species may be associated with coronary risk and mortality. We sought to...
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SubjectTerms cardiovascular disease risk factors
ceramides
mortality
Original Research
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Title Ceramide Remodeling and Risk of Cardiovascular Events and Mortality
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