Plasma Ceramide C24:0/C16:0 Relates to Outcomes in Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Ceramides are complex sphingolipids with pleiotropic effects. The ratio of specific ceramides (plasma C24:0/C16:0) is inversely related to incident heart failure (HF) and all-cause death in large, community-based cohorts without pre-existing HF. Whether plasma C24:0/C16:0 relates to outcomes in patients with HF with preserved ejection fraction (HFpEF) is unclear. We hypothesized plasma C24:0/C16:0 would be inversely related to, and independently predict, outcomes in HFpEF patients. OBJECTIVES: To test our hypothesis, we used plasma samples, baseline, and outcomes data from the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Findings were extended to a community-based cohort of HFpEF patients from the SHIP (Study of Health in Pomerania). METHODS: Plasma C24:0/C16:0 was measured using well-validated liquid chromatography/tandem mass spectrometry. For TOPCAT, our primary endpoint was the composite of time to cardiovascular disease (CVD) death, hospitalization for HF, or aborted cardiac death episode. Secondary endpoints were time to CVD death and to HF hospitalization. For SHIP, CVD death was the primary endpoint and total mortality a secondary endpoint. RESULTS: In 419 TOPCAT subjects (mean follow-up 3.3 years), lower plasma C24:0/C16:0 was associated with a higher risk of the primary endpoint; and HF hospitalization. In SHIP (N = 292; median follow-up 15.7 years), lower plasma C24:0/C16:0 was associated with a higher risk of CVD death and all-cause mortality in the SHIP cohort. CONCLUSIONS: Low plasma C24:0/C16:0 is independently associated with CVD death, all-cause mortality, and HF hospitalization in patients with HFpEF and may provide insight into novel treatment targets.