부산대학교 도서관

Introduction: The vast majority of healthy individuals who develop symptomatic coronary artery disease (CAD) have low-to-intermediate risk serum cholesterol profiles. Mass spectrometry has enabled the profiling of a diverse array of circulating non-cholesterol lipids that may be implicated in CAD pathogenesis. Hypothesis: We hypothesized that specific sphingolipid species correlate with lipid and plaque volumes and are potential predictors of early coronary plaque formation in asymptomatic individuals. Methods: We serially profiled 306 plasma lipids at 6 timepoints over 24 hours (circadian phenotype) and monthly over 6 months (longitudinal phenotype) using MRM in 79 middle-aged asymptomatic individuals with median LDL-C of 3.2 mmol/l (2.7, 3.6), HDL-C of 1.4 mmol/l (1.1, 1.7) and triglyceride of 1.3 mmol/l (0.9, 1.8). All subjects underwent 384-slice coronary computed tomography angiogram (CCTA) to quantify the burden of lipid-rich, fibrous and calcified coronary plaques (Syngovia Frontier coronary plaque analysis version 2.0.3). The average abundance of the lipids on circadian and longitudinal measurements was correlated to traditional cardiovascular risk factors and plaque characteristics. P < 0.01 was considered statistically significant. Results: The median (IQR) age of volunteers was 57 years and 33% were women, with 40% of subjects having detectable lipid-rich and fibrous plaques. Circadian and longitudinal lipidomic profiles revealed 31 lipid species that were significantly associated with total lipid plaque volume (two Cers, LPC 20:3, PC 38:3, PE 38:3, PI 38:3, seven DGs and 18 TGs), 11 lipid species (CE 18:, Hex3Cer d18:1/22:0, SM 34:1, two GM3s, two PE-Ps, three DGs and TG 52:4) that were significantly associated with total fibrotic plaque burden and only two lipid species that were significant associated with total calcified plaque burden (LPI 18:2, LPI 20:4). Surprisingly, C-reactive protein has much weaker associations with the circadian and longitudinal lipidomic profiles (only CE 18:0) while 77 lipids were significantly associated with Framingham risk score. Conclusions: Circadian and longitudinal lipidomic phenotypes report on the severity of presymptomatic CAD in healthy adults. Numerous non-cholesterol lipids deserve greater consideration in CAD risk stratification and as potential therapeutic targets. [ABSTRACT FROM AUTHOR]