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.