King's British Heart Foundation Centre (C.S., S.R.L., U.M., M. Mayr) and Department of Twin Research & Genetic Epidemiology (M. Mangino, C.M., A.M., T.D.R.), King's College London, London, UK; Department of Neurology, Medical University Innsbruck, Innsbruck, Austria (R.P., P.W., J.W., S.K.); Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK (P.W.); and Departments of Laboratory Medicine and Neurology, Bruneck Hospital, Bruneck, Italy (P.S., G.R.).
Circulation. 2014 May 6;129(18):1821-31. doi: 10.1161/CIRCULATIONAHA.113.002500. Epub 2014 Mar 12.
The bulk of cardiovascular disease risk is not explained by traditional risk factors. Recent advances in mass spectrometry allow the identification and quantification of hundreds of lipid species. Molecular lipid profiling by mass spectrometry may improve cardiovascular risk prediction.
Lipids were extracted from 685 plasma samples of the prospective population-based Bruneck Study (baseline evaluation in 2000). One hundred thirty-five lipid species from 8 different lipid classes were profiled by shotgun lipidomics with the use of a triple-quadrupole mass spectrometer. Levels of individual species of cholesterol esters (CEs), lysophosphatidylcholines, phosphatidylcholines, phosphatidylethanolamines (PEs), sphingomyelins, and triacylglycerols (TAGs) were associated with cardiovascular disease over a 10-year observation period (2000-2010, 90 incident events). Among the lipid species with the strongest predictive value were TAGs and CEs with a low carbon number and double-bond content, including TAG(54:2) and CE(16:1), as well as PE(36:5) (P=5.1 × 10⁻⁷, 2.2 × 10⁻⁴, and 2.5 × 10⁻³, respectively). Consideration of these 3 lipid species on top of traditional risk factors resulted in improved risk discrimination and classification for cardiovascular disease (cross-validated ΔC index, 0.0210 [95% confidence interval, 0.0010-0.0422]; integrated discrimination improvement, 0.0212 [95% confidence interval, 0.0031-0.0406]; and continuous net reclassification index, 0.398 [95% confidence interval, 0.175-0.619]). A similar shift in the plasma fatty acid composition was associated with cardiovascular disease in the UK Twin Registry (n=1453, 45 cases).
This study applied mass spectrometry-based lipidomics profiling to population-based cohorts and identified molecular lipid signatures for cardiovascular disease. Molecular lipid species constitute promising new biomarkers that outperform the conventional biochemical measurements of lipid classes currently used in clinics.
大量心血管疾病风险无法用传统风险因素来解释。质谱技术的最新进展使得数百种脂质种类的鉴定和定量成为可能。通过质谱进行分子脂质谱分析可能会改善心血管风险预测。
从前瞻性人群为基础的 Bruneck 研究（2000 年基线评估）的 685 个血浆样本中提取脂质。使用三重四极杆质谱仪通过 shotgun 脂质组学对 8 种不同脂质类别的 135 种脂质种类进行了分析。在 10 年的观察期间（2000-2010 年，90 例事件），胆固醇酯（CE）、溶血磷脂酰胆碱、磷脂酰胆碱、磷脂酰乙醇胺（PE）、神经鞘磷脂和三酰基甘油（TAG）等单个脂质种类的水平与心血管疾病相关。在具有最强预测价值的脂质种类中，包括 TAG(54:2)和 CE(16:1)，以及 PE(36:5)在内的具有低碳数和双键含量的 TAG 和 CE 以及具有低碳数和双键含量的 TAG 和 CE （TAG(54:2)和 CE(16:1)，以及 PE(36:5)（P=5.1×10⁻⁷，2.2×10⁻⁴和 2.5×10⁻³，分别）。在传统危险因素的基础上考虑这 3 种脂质种类，可改善心血管疾病的风险分层和分类（经交叉验证的ΔC 指数增加 0.0210[95%置信区间，0.0010-0.0422]；综合鉴别改善指数增加 0.0212[95%置信区间，0.0031-0.0406]；连续净重新分类指数增加 0.398[95%置信区间，0.175-0.619]）。在英国双胞胎登记处（n=1453，45 例）中，与心血管疾病相关的血浆脂肪酸组成也发生了类似的变化。
本研究应用基于质谱的脂质组学分析方法对人群为基础的队列进行了分析，并确定了心血管疾病的分子脂质特征。分子脂质种类是有前途的新型生物标志物，其性能优于目前临床应用的常规脂质类别的生化测量。
