Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial
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 cardiovas...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-12-01
|
| Series: | ESC Heart Failure |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ehf2.12885 |
| _version_ | 1818683089243602944 |
|---|---|
| author | Giovanni Targher Gianluigi Lunardi Alessandro Mantovani Jennifer Meessen Stefano Bonapace Pier Luigi Temporelli Enrico Nicolis Deborah Novelli Antonio Conti Luigi Tavazzi Aldo Pietro Maggioni Roberto Latini |
| author_facet | Giovanni Targher Gianluigi Lunardi Alessandro Mantovani Jennifer Meessen Stefano Bonapace Pier Luigi Temporelli Enrico Nicolis Deborah Novelli Antonio Conti Luigi Tavazzi Aldo Pietro Maggioni Roberto Latini |
| author_sort | Giovanni Targher |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T10:29:11Z |
| format | Article |
| id | doaj.art-68e2281f859c4ac6b40ab30ca090be74 |
| institution | Directory Open Access Journal |
| issn | 2055-5822 |
| language | English |
| last_indexed | 2024-12-17T10:29:11Z |
| publishDate | 2020-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | ESC Heart Failure |
| spelling | doaj.art-68e2281f859c4ac6b40ab30ca090be742022-12-21T21:52:34ZengWileyESC Heart Failure2055-58222020-12-01763288329710.1002/ehf2.12885Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trialGiovanni Targher0Gianluigi Lunardi1Alessandro Mantovani2Jennifer Meessen3Stefano Bonapace4Pier Luigi Temporelli5Enrico Nicolis6Deborah Novelli7Antonio Conti8Luigi Tavazzi9Aldo Pietro Maggioni10Roberto Latini11Division of Endocrinology, Diabetes and Metabolism, Department of Medicine University and Azienda Ospedaliera Universitaria Integrata of Verona Piazzale Stefani, 1 Verona 37126 ItalyMedical Analysis Laboratory ‘IRCCS Sacro Cuore—Don Calabria’ Hospital Negrar ItalyDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine University and Azienda Ospedaliera Universitaria Integrata of Verona Piazzale Stefani, 1 Verona 37126 ItalyDepartment of Cardiovascular Medicine Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan ItalyDivision of Cardiology ‘IRCCS Sacro Cuore—Don Calabria’ Hospital Negrar ItalyDivision of Cardiology Istituti Clinici Scientifici Maugeri, IRCCS Veruno ItalyDepartment of Cardiovascular Medicine Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan ItalyDepartment of Cardiovascular Medicine Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan ItalyMedical Analysis Laboratory ‘IRCCS Sacro Cuore—Don Calabria’ Hospital Negrar ItalyMaria Cecilia Hospital, GVM Care & Research Cotignola ItalyANMCO Research Center Florence ItalyDepartment of Cardiovascular Medicine Istituto di Ricerche Farmacologiche Mario Negri IRCCS Milan ItalyAbstract 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.https://doi.org/10.1002/ehf2.12885CeramidesHeart failureCardiovascular mortalityRisk factors |
| spellingShingle | Giovanni Targher Gianluigi Lunardi Alessandro Mantovani Jennifer Meessen Stefano Bonapace Pier Luigi Temporelli Enrico Nicolis Deborah Novelli Antonio Conti Luigi Tavazzi Aldo Pietro Maggioni Roberto Latini Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial ESC Heart Failure Ceramides Heart failure Cardiovascular mortality Risk factors |
| title | Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial |
| title_full | Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial |
| title_fullStr | Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial |
| title_full_unstemmed | Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial |
| title_short | Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI‐HF trial |
| title_sort | relation between plasma ceramides and cardiovascular death in chronic heart failure a subset analysis of the gissi hf trial |
| topic | Ceramides Heart failure Cardiovascular mortality Risk factors |
| url | https://doi.org/10.1002/ehf2.12885 |
| work_keys_str_mv | AT giovannitargher relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT gianluigilunardi relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT alessandromantovani relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT jennifermeessen relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT stefanobonapace relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT pierluigitemporelli relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT enriconicolis relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT deborahnovelli relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT antonioconti relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT luigitavazzi relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT aldopietromaggioni relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial AT robertolatini relationbetweenplasmaceramidesandcardiovasculardeathinchronicheartfailureasubsetanalysisofthegissihftrial |