Plasma sphingolipids and risk of cardiovascular diseases: a large-scale lipidomic analysis

Introduction: Sphingolipids are a diverse class of lipids with various roles in cell functions and subclasses such as ceramides have been associated with cardiovascular diseases (CVD) in previous studies.

Objectives: We aimed to measure molecularly-distinct sphingolipids via a large-scale lipidomic analysis and expand the literature to an Asian population.

Methods: We performed a lipidomics evaluation of 79 molecularly distinct sphingolipids in the plasma of 2627 ethnically-Chinese Singaporeans.

Results: During a mean follow-up of 12.9 years, we documented 152 cases of major CVD (non-fatal myocardial infarction, stroke and cardiovascular death). Total ceramide concentrations were not associated with CVD risk [hazard ratio (HR), 0.99; 95% CI 0.81-1.21], but higher circulating total monohexosylceramides (HR, 1.22; 95% CI 1.03, 1.45), total long-chain sphingolipids (C16-C18) (HR, 1.22; 95% CI 1.02, 1.45) and total 18:1 sphingolipids (HR, 1.21; 95% CI 1.01, 1.46) were associated with higher CVD risk after adjusting for conventional CVD risk factors.

Conclusions: Our results do not support the hypothesis that higher ceramide concentrations are linked to higher CVD risk, but suggest that other classes of sphingolipids may affect CVD risk.

Keywords: Cardiovascular mortality; Ceramides; Cerebrosides; Gangliosides; Heart disease; Hexosylceramides; Lipidomics; Sphingomyelin.