HDL Phospholipids, but Not Cholesterol Distinguish Acute Coronary Syndrome From Stable Coronary Artery Disease

Abstract

Background Although acute coronary syndromes (ACS) are a major cause of morbidity and mortality, relationships with biologically active lipid species potentially associated with plaque disruption/erosion in the context of their lipoprotein carriers are indeterminate. The aim was to characterize lipid species within lipoprotein particles which differentiate ACS from stable coronary artery disease. Methods and Results Venous blood was obtained from 130 individuals with de novo presentation of an ACS (n=47) or stable coronary artery disease (n=83) before coronary catheterization. Lipidomic measurements (533 lipid species; liquid chromatography electrospray ionization/tandem mass spectrometry) were performed on whole plasma as well as 2 lipoprotein subfractions: apolipoprotein A1 (apolipoprotein A, high‐density lipoprotein) and apolipoprotein B. Compared with stable coronary artery disease, ACS plasma was lower in phospholipids including lyso species and plasmalogens, with the majority of lipid species differing in abundance located within high‐density lipoprotein (high‐density lipoprotein, 113 lipids; plasma, 73 lipids). Models including plasma lipid species alone improved discrimination between the stable and ACS groups by 0.16 (C‐statistic) compared with conventional risk factors. Models utilizing lipid species either in plasma or within lipoprotein fractions had a similar ability to discriminate groups, though the C‐statistic was highest for plasma lipid species (0.80; 95% CI, 0.75–0.86). Conclusions Multiple lysophospholipids, but not cholesterol, featured among the lipids which were present at low concentration within high‐density lipoprotein of those presenting with ACS. Lipidomics, when applied to either whole plasma or lipoprotein fractions, was superior to conventional risk factors in discriminating ACS from stable coronary artery disease. These associative mechanistic insights elucidate potential new preventive, prognostic, and therapeutic avenues for ACS which require investigation in prospective analyses.

Structure-function relationships of HDL in diabetes and coronary heart disease

“…Sphingomyelins were reported to be decreased in HDL of patients with metabolic syndrome in 1 study but not in another (18,22). An increased content of HDL in (polyunsaturated) PEs was previously reported for acute coronary syndrome patients and associated with increased thrombogenicity (23)(24)(25).…”

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

“…In total, we identified eight studies using NMR or LC-MS for lipidomic analyses, all based on a relatively small sample size (number of participants ranging from 20 to 159). Most of the studies were conducted in hospital settings using cross-sectional or case-control designs [59][60][61][62][63][64][65]. Three studies conducted lipidomics of HDL and non-HDL particles [51,52,64], while five studies specifically focused on the lipidome of HDLs [61][62][63]65,66].…”

“…Most of the studies were conducted in hospital settings using cross-sectional or case-control designs [59][60][61][62][63][64][65]. Three studies conducted lipidomics of HDL and non-HDL particles [51,52,64], while five studies specifically focused on the lipidome of HDLs [61][62][63]65,66]. Of the five studies, two studies examined varieties in HDL lipid content, comparing participants with high HDL-c to those with low HDL-c [61,66], and the other studies focused on the lipidome of lipoproteins and CHD diagnosis and progression [51,52,[62][63][64][65].…”

“…Three studies conducted lipidomics of HDL and non-HDL particles [51,52,64], while five studies specifically focused on the lipidome of HDLs [61][62][63]65,66]. Of the five studies, two studies examined varieties in HDL lipid content, comparing participants with high HDL-c to those with low HDL-c [61,66], and the other studies focused on the lipidome of lipoproteins and CHD diagnosis and progression [51,52,[62][63][64][65]. Only one study included LDL-c as a covariate [62], and only three studies corrected for multiple testing [63][64][65].…”

“…Another study found that, compared to participants without CHD or at the initial stages of CHD, participants with severe CHD had higher levels of SFA chains in both HDL and non-HDL particles, lower levels of PC and SM in HDL particles, and lower levels of PUFA in non-HDL particles [60]. Additionally, two studies showed that lower levels of PC-plasmalogens were associated with a higher risk of CHD, particularly acute CHD [63,64]. Plasmalogens contain a vinyl ether-linked alkyl chain at the sn-1 position of the glycerol backbone and a polyunsaturated fatty acyl chain at the sn-2 position.…”