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

Area of Science:

• Cardiovascular Medicine
• Biochemistry
• Metabolomics

Background:

• Sphingolipids, including ceramides, have diverse biological roles.
• The ratio of plasma C24:0/C16:0 ceramides is linked to heart failure (HF) and mortality in general populations.
• The prognostic value of plasma C24:0/C16:0 in HF with preserved ejection fraction (HFpEF) remains undetermined.

Purpose of the Study:

• To investigate the association between plasma C24:0/C16:0 ratios and clinical outcomes in patients with HFpEF.
• To determine if plasma C24:0/C16:0 independently predicts adverse events in HFpEF.

Main Methods:

• Plasma samples from the TOPCAT trial and the Study of Health in Pomerania (SHIP) cohort were analyzed.
• Plasma C24:0/C16:0 was quantified using liquid chromatography/tandem mass spectrometry.
• Clinical outcomes included cardiovascular disease death, HF hospitalization, and all-cause mortality.

Main Results:

• In the TOPCAT cohort, lower plasma C24:0/C16:0 was associated with increased risk of cardiovascular death, HF hospitalization, and aborted cardiac death.
• In the SHIP cohort, lower plasma C24:0/C16:0 correlated with higher risks of cardiovascular death and all-cause mortality.
• These associations remained significant after adjusting for other risk factors.

Conclusions:

• Reduced plasma C24:0/C16:0 is an independent predictor of adverse outcomes in HFpEF patients.
• This ceramide ratio may serve as a valuable biomarker for risk stratification in HFpEF.
• Targeting ceramide metabolism could represent a novel therapeutic strategy for HFpEF.