Plasma glucosylceramides and cardiovascular risk in incident hemodialysis patients

Mark M. Mitsnefes, Jessica Fitzpatrick, Stephen M Sozio, Bernard Jaar, Michelle M. Estrella, Jose Monroy-Trujillo, Wujuan Zhang, Kenneth Setchell, Rulan S. Parekh

Research output: Contribution to journalArticle

Abstract

Background: Recent population-based studies identified plasma sphingolipids as independent predictors of increased cardiovascular disease (CVD) morbidity and mortality. Understanding the impact of sphingolipids on CVD outcomes in patients on dialysis, who suffer from higher risk of these conditions, is important for risk assessment and treatment. Objective: To measure plasma sphingolipid levels and determine their associations with CVD in adults initiating maintenance hemodialysis. Methods: To evaluate associations of plasma sphingolipids with intermediate cardiovascular outcomes (hypertension, left ventricular hypertrophy, and decreased ejection fraction), cardiovascular mortality, and all-cause mortality in patients with end-stage renal disease, we measured plasma levels of ceramides, glucosylceramides, and lactosylceramides from the family of sphingolipids in 368 incident hemodialysis patients enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease study. Results: Glucosylceramide C16GC (per 1 log μM increase) was associated with higher odds of having uncontrolled hypertension (odds ratio [OR]: 1.34; 95% confidential interval [CI]: 1.01–1.76), left ventricular hypertrophy (OR: 1.53; 95% CI: 1.11–2.13), and reduced ejection fraction (OR: 1.05; 95% CI: 1.00–1.11) in fully adjusted models. During a median 2.5 years of follow-up, there were 78 deaths from all causes, of which 33 were from CVD. Mortality was higher among those in the highest tertile of C16GC for all causes (HR: 1.81; 95% CI: 1.02–3.22) and CVD (HR: 2.63, 95% CI: 1.08–6.55). Conclusions: These results suggest that abnormal glycosphingolipid metabolism might contribute to increased CVD risk in end-stage renal disease.

Original languageEnglish (US)
JournalJournal of Clinical Lipidology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Glucosylceramides
Sphingolipids
Renal Dialysis
Cardiovascular Diseases
Chronic Kidney Failure
Mortality
Odds Ratio
Left Ventricular Hypertrophy
Lactosylceramides
Hypertension
Glycosphingolipids
Ceramides
Dialysis
Cause of Death
Maintenance
Morbidity
Population

Keywords

  • Atherosclerosis
  • Cardiomyopathy
  • Cardiovascular disease
  • Dialysis
  • Sphingolipids

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

Cite this

Plasma glucosylceramides and cardiovascular risk in incident hemodialysis patients. / Mitsnefes, Mark M.; Fitzpatrick, Jessica; Sozio, Stephen M; Jaar, Bernard; Estrella, Michelle M.; Monroy-Trujillo, Jose; Zhang, Wujuan; Setchell, Kenneth; Parekh, Rulan S.

In: Journal of Clinical Lipidology, 01.01.2018.

Research output: Contribution to journalArticle

Mitsnefes, Mark M. ; Fitzpatrick, Jessica ; Sozio, Stephen M ; Jaar, Bernard ; Estrella, Michelle M. ; Monroy-Trujillo, Jose ; Zhang, Wujuan ; Setchell, Kenneth ; Parekh, Rulan S. / Plasma glucosylceramides and cardiovascular risk in incident hemodialysis patients. In: Journal of Clinical Lipidology. 2018.
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abstract = "Background: Recent population-based studies identified plasma sphingolipids as independent predictors of increased cardiovascular disease (CVD) morbidity and mortality. Understanding the impact of sphingolipids on CVD outcomes in patients on dialysis, who suffer from higher risk of these conditions, is important for risk assessment and treatment. Objective: To measure plasma sphingolipid levels and determine their associations with CVD in adults initiating maintenance hemodialysis. Methods: To evaluate associations of plasma sphingolipids with intermediate cardiovascular outcomes (hypertension, left ventricular hypertrophy, and decreased ejection fraction), cardiovascular mortality, and all-cause mortality in patients with end-stage renal disease, we measured plasma levels of ceramides, glucosylceramides, and lactosylceramides from the family of sphingolipids in 368 incident hemodialysis patients enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease study. Results: Glucosylceramide C16GC (per 1 log μM increase) was associated with higher odds of having uncontrolled hypertension (odds ratio [OR]: 1.34; 95{\%} confidential interval [CI]: 1.01–1.76), left ventricular hypertrophy (OR: 1.53; 95{\%} CI: 1.11–2.13), and reduced ejection fraction (OR: 1.05; 95{\%} CI: 1.00–1.11) in fully adjusted models. During a median 2.5 years of follow-up, there were 78 deaths from all causes, of which 33 were from CVD. Mortality was higher among those in the highest tertile of C16GC for all causes (HR: 1.81; 95{\%} CI: 1.02–3.22) and CVD (HR: 2.63, 95{\%} CI: 1.08–6.55). Conclusions: These results suggest that abnormal glycosphingolipid metabolism might contribute to increased CVD risk in end-stage renal disease.",
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AU - Mitsnefes, Mark M.

AU - Fitzpatrick, Jessica

AU - Sozio, Stephen M

AU - Jaar, Bernard

AU - Estrella, Michelle M.

AU - Monroy-Trujillo, Jose

AU - Zhang, Wujuan

AU - Setchell, Kenneth

AU - Parekh, Rulan S.

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AB - Background: Recent population-based studies identified plasma sphingolipids as independent predictors of increased cardiovascular disease (CVD) morbidity and mortality. Understanding the impact of sphingolipids on CVD outcomes in patients on dialysis, who suffer from higher risk of these conditions, is important for risk assessment and treatment. Objective: To measure plasma sphingolipid levels and determine their associations with CVD in adults initiating maintenance hemodialysis. Methods: To evaluate associations of plasma sphingolipids with intermediate cardiovascular outcomes (hypertension, left ventricular hypertrophy, and decreased ejection fraction), cardiovascular mortality, and all-cause mortality in patients with end-stage renal disease, we measured plasma levels of ceramides, glucosylceramides, and lactosylceramides from the family of sphingolipids in 368 incident hemodialysis patients enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease study. Results: Glucosylceramide C16GC (per 1 log μM increase) was associated with higher odds of having uncontrolled hypertension (odds ratio [OR]: 1.34; 95% confidential interval [CI]: 1.01–1.76), left ventricular hypertrophy (OR: 1.53; 95% CI: 1.11–2.13), and reduced ejection fraction (OR: 1.05; 95% CI: 1.00–1.11) in fully adjusted models. During a median 2.5 years of follow-up, there were 78 deaths from all causes, of which 33 were from CVD. Mortality was higher among those in the highest tertile of C16GC for all causes (HR: 1.81; 95% CI: 1.02–3.22) and CVD (HR: 2.63, 95% CI: 1.08–6.55). Conclusions: These results suggest that abnormal glycosphingolipid metabolism might contribute to increased CVD risk in end-stage renal disease.

KW - Atherosclerosis

KW - Cardiomyopathy

KW - Cardiovascular disease

KW - Dialysis

KW - Sphingolipids

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