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Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial
Aims Ceramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mor...
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| Published in: | ESC Heart Failure 2020-12, Vol.7 (6), p.3288-3297 |
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| creator | Targher, Giovanni Lunardi, Gianluigi Mantovani, Alessandro Meessen, Jennifer Bonapace, Stefano Temporelli, Pier Luigi Nicolis, Enrico Novelli, Deborah Conti, Antonio Tavazzi, Luigi Maggioni, Aldo Pietro Latini, Roberto |
| description | Aims
Ceramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.
Methods and results
In a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure (GISSI‐HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow‐up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high‐risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P |
| doi_str_mv | 10.1002/ehf2.12885 |
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Ceramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.
Methods and results
In a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure (GISSI‐HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow‐up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high‐risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer(d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin‐3 levels, and, especially, plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P‐threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23).
Conclusions
Higher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT‐proBNP concentrations.</description><identifier>ISSN: 2055-5822</identifier><identifier>EISSN: 2055-5822</identifier><identifier>DOI: 10.1002/ehf2.12885</identifier><identifier>PMID: 32627354</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Acute coronary syndromes ; Biomarkers ; Body mass index ; Cardiovascular disease ; Cardiovascular mortality ; Ceramides ; Chromatography ; Creatinine ; Diabetes ; Ejection fraction ; Heart failure ; Hypertension ; Hypotheses ; Laboratories ; Lipids ; Morbidity ; Mortality ; Original ; Original s ; Plasma ; Risk factors</subject><ispartof>ESC Heart Failure, 2020-12, Vol.7 (6), p.3288-3297</ispartof><rights>2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5425-199d301a01e2fdad85714b077422b771452c31a62ff7794da89cdbce743cc37e3</citedby><cites>FETCH-LOGICAL-c5425-199d301a01e2fdad85714b077422b771452c31a62ff7794da89cdbce743cc37e3</cites><orcidid>0000-0002-4325-3900</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2628048905/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2628048905?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,11562,25753,27924,27925,37012,37013,44590,46052,46476,53791,53793,75126</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32627354$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Targher, Giovanni</creatorcontrib><creatorcontrib>Lunardi, Gianluigi</creatorcontrib><creatorcontrib>Mantovani, Alessandro</creatorcontrib><creatorcontrib>Meessen, Jennifer</creatorcontrib><creatorcontrib>Bonapace, Stefano</creatorcontrib><creatorcontrib>Temporelli, Pier Luigi</creatorcontrib><creatorcontrib>Nicolis, Enrico</creatorcontrib><creatorcontrib>Novelli, Deborah</creatorcontrib><creatorcontrib>Conti, Antonio</creatorcontrib><creatorcontrib>Tavazzi, Luigi</creatorcontrib><creatorcontrib>Maggioni, Aldo Pietro</creatorcontrib><creatorcontrib>Latini, Roberto</creatorcontrib><title>Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial</title><title>ESC Heart Failure</title><addtitle>ESC Heart Fail</addtitle><description>Aims
Ceramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.
Methods and results
In a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure (GISSI‐HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow‐up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high‐risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer(d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin‐3 levels, and, especially, plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P‐threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23).
Conclusions
Higher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT‐proBNP concentrations.</description><subject>Acute coronary syndromes</subject><subject>Biomarkers</subject><subject>Body mass index</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular mortality</subject><subject>Ceramides</subject><subject>Chromatography</subject><subject>Creatinine</subject><subject>Diabetes</subject><subject>Ejection fraction</subject><subject>Heart failure</subject><subject>Hypertension</subject><subject>Hypotheses</subject><subject>Laboratories</subject><subject>Lipids</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Original</subject><subject>Original s</subject><subject>Plasma</subject><subject>Risk factors</subject><issn>2055-5822</issn><issn>2055-5822</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9ktFqFDEUhgdRbFl74wNIwBspbE0yySTjhVBKt7tQEKxehzOZM50s2cmazLTsjfgIPqNP4mynllbQqxxyvnycE_4se83oCaOUv8e24SeMay2fZYecSjmXmvPnj-qD7CilNaWUyYJJLl5mBzkvuMqlOMy-f0YPvQsdqbC_RezI1kPaALEYYeNqTAS6mliItQs3kOzgIZIaoW-J64htY-icJS1C7EkDzg8RP5BTkoYqYT--Bb9LLpHQkL5FcrG6ulr9-vFzuSB9dOBfZS8a8AmP7s9Z9nVx_uVsOb_8dLE6O72cWym4nLOyrHPKgDLkTQ21loqJiiolOK_UWEtucwYFbxqlSlGDLm1dWVQitzZXmM-y1eStA6zNNroNxJ0J4MzdRYjXZlzAWY-m0Mi5Zo2WpRVgi0pQqHJqgZa02htn2cfJtR2qDdYWuz6CfyJ92ulca67DjVFKipLKUfDuXhDDtwFTbzYuWfQeOgxDMlxwWuS8zPMRffsXug5DHD91pAquqdCT8N-UUEwxSfV-7uOJsjGkFLF5GJlRs8-S2WfJ3GVphN88XvIB_ZOcEWATcOs87v6jMufLBZ-kvwEuhdNc</recordid><startdate>202012</startdate><enddate>202012</enddate><creator>Targher, Giovanni</creator><creator>Lunardi, Gianluigi</creator><creator>Mantovani, Alessandro</creator><creator>Meessen, Jennifer</creator><creator>Bonapace, Stefano</creator><creator>Temporelli, Pier Luigi</creator><creator>Nicolis, Enrico</creator><creator>Novelli, Deborah</creator><creator>Conti, Antonio</creator><creator>Tavazzi, Luigi</creator><creator>Maggioni, Aldo Pietro</creator><creator>Latini, Roberto</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><general>Wiley</general><scope>24P</scope><scope>WIN</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-4325-3900</orcidid></search><sort><creationdate>202012</creationdate><title>Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial</title><author>Targher, Giovanni ; Lunardi, Gianluigi ; Mantovani, Alessandro ; Meessen, Jennifer ; Bonapace, Stefano ; Temporelli, Pier Luigi ; Nicolis, Enrico ; Novelli, Deborah ; Conti, Antonio ; Tavazzi, Luigi ; Maggioni, Aldo Pietro ; Latini, Roberto</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5425-199d301a01e2fdad85714b077422b771452c31a62ff7794da89cdbce743cc37e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acute coronary syndromes</topic><topic>Biomarkers</topic><topic>Body mass index</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular mortality</topic><topic>Ceramides</topic><topic>Chromatography</topic><topic>Creatinine</topic><topic>Diabetes</topic><topic>Ejection fraction</topic><topic>Heart failure</topic><topic>Hypertension</topic><topic>Hypotheses</topic><topic>Laboratories</topic><topic>Lipids</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Original</topic><topic>Original s</topic><topic>Plasma</topic><topic>Risk factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Targher, Giovanni</creatorcontrib><creatorcontrib>Lunardi, Gianluigi</creatorcontrib><creatorcontrib>Mantovani, Alessandro</creatorcontrib><creatorcontrib>Meessen, Jennifer</creatorcontrib><creatorcontrib>Bonapace, Stefano</creatorcontrib><creatorcontrib>Temporelli, Pier Luigi</creatorcontrib><creatorcontrib>Nicolis, Enrico</creatorcontrib><creatorcontrib>Novelli, Deborah</creatorcontrib><creatorcontrib>Conti, Antonio</creatorcontrib><creatorcontrib>Tavazzi, Luigi</creatorcontrib><creatorcontrib>Maggioni, Aldo Pietro</creatorcontrib><creatorcontrib>Latini, Roberto</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library Free Content</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>ESC Heart Failure</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Targher, Giovanni</au><au>Lunardi, Gianluigi</au><au>Mantovani, Alessandro</au><au>Meessen, Jennifer</au><au>Bonapace, Stefano</au><au>Temporelli, Pier Luigi</au><au>Nicolis, Enrico</au><au>Novelli, Deborah</au><au>Conti, Antonio</au><au>Tavazzi, Luigi</au><au>Maggioni, Aldo Pietro</au><au>Latini, Roberto</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial</atitle><jtitle>ESC Heart Failure</jtitle><addtitle>ESC Heart Fail</addtitle><date>2020-12</date><risdate>2020</risdate><volume>7</volume><issue>6</issue><spage>3288</spage><epage>3297</epage><pages>3288-3297</pages><issn>2055-5822</issn><eissn>2055-5822</eissn><abstract>Aims
Ceramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.
Methods and results
In a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure (GISSI‐HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow‐up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high‐risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer(d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin‐3 levels, and, especially, plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P‐threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23).
Conclusions
Higher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT‐proBNP concentrations.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>32627354</pmid><doi>10.1002/ehf2.12885</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-4325-3900</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | ESC Heart Failure, 2020-12, Vol.7 (6), p.3288-3297 |
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| subjects | Acute coronary syndromes Biomarkers Body mass index Cardiovascular disease Cardiovascular mortality Ceramides Chromatography Creatinine Diabetes Ejection fraction Heart failure Hypertension Hypotheses Laboratories Lipids Morbidity Mortality Original Original s Plasma Risk factors |
| title | Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial |
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