Plasma concentrations of molecular lipid species predict long-term clinical outcome in coronary artery disease patients

Abstract

Purpose: 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 (MACE) during a median follow-up of 4.7 years in patients with coronary artery disease (CAD). Methods: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 MACE, comprising all-cause mortality, nonfatal ACS or unplanned coronary revascularization. The secondary endpoint comprised all-cause mortality or nonfatal ACS. Conclusion:Altogether, the circulating ceramide lipids we investigated here are associated with adverse cardiac outcome during long-term follow-up independent of clinical risk factors.

A Review of Lipidomics of Cardiovascular Disease Highlights the Importance of Isolating Lipoproteins

“…The findings were first documented in the LURIC study [23] and replicated in the ATHEROREMO-IVUS study [28,29]. FINRISK 2002 study, Corogene study, PREDIMED trial, ADVANCE study, and LIPID study consistently confirmed the findings [24,26,[30][31][32].…”

“…As to methods of lipid measurement, two early studies used shotgun lipidomics [19,20], two studies used NMR measuring total lipids, triglycerides, and cholesterol within l4 lipoprotein subclasses [21,22], and the majority of studies used LC-MS, measuring hundreds of lipids [16][17][18][19][20][21][22][23][24][25][26][27]. Eight of the 16 studies were lipidomics/metabolomics-wide association studies that assessed associations of all measured lipids with CVD outcomes [19][20][21][22][23][24][25][26], six studies used a candidate-lipid approach by focusing on specific lipids such as ceramides [27][28][29][30][31][32], and two studies classified lipids into groups and examined global associations of lipid species with CVD outcomes [33,34]. Of the 16 studies, 6 studies included participants with a history of coronary heart disease (CHD) and focused on secondary prevention [23,24,26,28,29,31], and 10 studies focused on primary prevention of CVD [19][20][21][22]25,…”

“…Eight of the 16 studies were lipidomics/metabolomics-wide association studies that assessed associations of all measured lipids with CVD outcomes [19][20][21][22][23][24][25][26], six studies used a candidate-lipid approach by focusing on specific lipids such as ceramides [27][28][29][30][31][32], and two studies classified lipids into groups and examined global associations of lipid species with CVD outcomes [33,34]. Of the 16 studies, 6 studies included participants with a history of coronary heart disease (CHD) and focused on secondary prevention [23,24,26,28,29,31], and 10 studies focused on primary prevention of CVD [19][20][21][22]25,27,30,[32][33][34]. Most of the included studies adjusted for lipid biomarkers such as total cholesterol and HDL-c as covariates in the model.…”

“…The lipidomic-wide association LURIC study first showed that the three ceramides were positively associated with the risks of recurrent CHD and mortality and that Cer (d18:1/24:0) was inversely associated [23]; however, these associations were eliminated after adjusting for multiple testing. The ATHEROREMO-IVUS study measured ceramides that were identified in the LURIC study and showed that Cer (d18:1/16:0) and the Cer (d18:1/24:1)/Cer (d18:1/24:0) ratio were positively associated with major adverse cardiac events [28,29]. Thereafter, the FINRISK 2002 study [30], the Corogene study [31], and the PREDIMED trial [32] specifically focused on the four mentioned ceramides and consistently found that Cer (d18:1/16:0), Cer (d18:1/18:0), and Cer (d18:1/24:1) were positively associated with CVD outcomes.…”

Circulating ceramide ratios and risk of vascular brain aging and dementia

“…Recent cardiovascular studies have consistently shown an increased risk of adverse vascular events and mortality in individuals with increased ratios of long-chain to very long-chain ceramides in plasma. 5,17,[31][32][33] In a murine model of ceramide synthase 2 haploinsufficiency, a reduction in levels of very long-chain (C22:0 and C24:0) ceramides and a compensatory increase in levels of longchain ceramides (C16:0) was noted, resulting in an increased susceptibility to insulin resistance and hepatocyte apoptosis. 30 Given the role of ceramides in pancreatic b-cell dysfunction, insulin resistance and vascular reactivity, 34 increased cardiometabolic risk could potentially mediate the association with dementia.…”