Plasma glucosylceramides and cardiovascular risk in incident hemodialysis patients

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.