Abstract
We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACEs) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). Between 2008 and 2011, 581 patients underwent diagnostic coronary angiography or percutaneous coronary intervention for stable angina pectoris (SAP) or acute coronary syndrome (ACS). Blood was drawn prior to the index procedure and lipid species were determined. The primary endpoint was the occurrence of a MACE, comprising all-cause mortality, nonfatal ACS, or unplanned coronary revascularization. The secondary endpoint comprised all-cause mortality or nonfatal ACS. During a median follow-up of 4.7 [IQR: 4.2-5.6] years, 155 patients (27%) had MACEs. In multivariable analyses, Cer(d18:1/16:0) concentration was associated with MACEs {hazard ratio 2.32; 95% CI [1.09-4.96] per natural logarithm (ln) (pmol/ml) P = 0.030} after adjustment for cardiac risk factors, clinical presentation, statin use at baseline, and admission nonHDL cholesterol level. Furthermore, after multivariable adjustment, concentrations of Cer(d18:1/16:0), Cer(d18:1/20:0), Cer(d18:1/24:1), and their ratios to Cer(d18:1/24:0) were associated with the composite endpoint death or nonfatal ACS. The data together show the circulating ceramide lipids we investigated here are associated with adverse cardiac outcome during long-term follow-up independent of clinical risk factors.
Highlights
We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACEs) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD)
The baseline clinical characteristics and the lipid concentrations of the ATHEROREMO study are summarized in Table 1 and Table 2
We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with clinical cardiovascular outcome during longterm follow-up in 581 patients
Summary
We investigated the associations of ten previously identified high risk molecular lipid species and three ceramide ratios with the occurrence of major adverse cardiac events (MACEs) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). The other authors declare no conflict of interest Established lipid markers such as total cholesterol, LDL cholesterol, triglycerides (TGs), and HDL cholesterol have long formed the cornerstone of lipid-based risk stratification in coronary artery disease (CAD) [1,2,3,4]. In its most advanced form, lipidomics is able to quantify hundreds of diverse molecular lipid species across multiple lipid classes such as sphingolipids, phospholipids, sterol esters, and acylglycerols [7], many of which play an integral role in modulation of biological function such as formation of cellular membranes, energy storage, and cell signaling [8, 9] Because lipidomics provides such detailed lipid profiles, it may further improve risk stratification of CAD patients and provide novel mechanistic insights into CAD [4]. In line with this hypothesis, we have recently performed lipidomics in the Ludwigshafen Risk and Cardiovascular
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