Lipidomics Profiling and Risk of Cardiovascular Disease in the Prospective Population-Based Bruneck Study
Lipidomics Profiling and Risk of Cardiovascular Disease in the Prospective Population-Based Bruneck Study
复制标题
DOI：
10.1161/circulationaha.113.002500
复制
发表时间：
2014-05-06
期刊：
影响因子：
37.8
通讯作者：
Mayr, Manuel
中科院分区：
文献类型：
--
作者：
Stegemann, Christin;Pechlaner, Raimund;Mayr, Manuel
大部分心血管疾病的风险不能用传统的危险因素来解释。质谱法的最新进展允许鉴定和定量数百种脂质物质。分子脂质谱质谱法可以提高心血管疾病的风险prediction.Methods和结果脂质提取685血浆样本的前瞻性人群为基础的Bruneck研究（基线评价在2000年）。来自8个不同脂质类的135种脂质通过鸟枪脂质组学与使用三重四极杆质谱仪进行了分析。在10年的观察期内（2000-2010年，90起事件），胆固醇酯（CE）、溶血磷脂酰胆碱、磷脂酰胆碱、磷脂酰乙醇胺（PE）、鞘磷脂和三酰甘油（TAG）的单个物质水平与心血管疾病相关。预测价值最强的脂质种类是碳数和双键含量较低的TAG和CE，包括TAG（54：2）和CE（16：1）以及PE（36：5）（P分别为5.1x10（-7）、2.2x10（-4）和2.5x10（-3））。在传统风险因素之上考虑这3种脂质导致心血管疾病的风险区分和分类得到改善（交叉验证的C指数，0.0210 [95%可信区间，0.0010-0.0422];综合辨别力改善，0.0212 [95%可信区间，0.0031-0.0406];和连续净再分类指数，0.398 [95%置信区间，0.175-0.619]）。一个类似的转变，在血浆脂肪酸组成与心血管疾病在英国双登记处（n=1453，45例）。结论本研究采用基于质谱的脂质组学分析，以人口为基础的队列，并确定了心血管疾病的分子脂质签名。分子脂质种类构成了有前途的新生物标志物，其优于目前临床上使用的脂质类的常规生物化学测量。
Background 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.Methods and Results 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=5.1x10(-7), 2.2x10(-4), and 2.5x10(-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 C 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).Conclusions 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.