Plasma C₂₀-Sphingolipids predict cardiovascular events independently from conventional cardiovascular risk factors in patients undergoing coronary angiography

Aims: Sphingolipids are emerging as novel players in the pathogenesis of atherosclerosis and cardiovascular disease. Serine palmitoyltransferase (SPT) catalyzes the first and rate-limiting step in the de novo synthesis of sphingolipids-the condensation of palmitoyl-CoA and l-Serine. In addition to these canonical substrates, SPT can also metabolize other acyl-CoAs and amino acids, thus generating a variety of atypical sphingoid bases. In this study, we investigated the association of these atypical sphingoid bases with the presence of angiographically characterized coronary artery disease (CAD) as well as their ability to predict the incidence of cardiovascular events. Methods and results: 349 subjects, who underwent coronary angiography for the evaluation of established or suspected stable CAD, were enrolled in the study at baseline and followed up for cardiovascular events over a period of 8 years (median 7.7 years). The sphingoid base profile in the extracted plasma sphingolipids were determined by LC/MS after acid-base hydrolysis. Plasma levels of C₁₈SAdiene were found to be significantly lower in CAD patients at baseline, while levels for C₁₆SA, C₁₆SO, C₁₇SO, C₁₈SA, C₁₈SO, and C₁₉SO and 1-deoxy sphingoid bases were not different. In the prospective analysis C₂₀SO significantly predicted cardiovascular events (standardized adjusted HR=1.20, CI 95% [1.03-1.41]; p=0.022) after adjusting for traditional risk factors, the use of lipid-lowering drugs and angiographically-determined CAD at baseline. Conclusion: Plasma C₂₀SO levels are independent predictive biomarkers for cardiovascular events, even after adjusting for cardiovascular risk factors including coronary stenosis.