摘要: Background: Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated with diabetes or cardiovascular disease. Lipidomics enables the assessment of hundreds of lipid species as potential markers for disease risk. Methods: Plasma lipid species (310) were measured by a targeted lipidomic analysis with liquid chromatography electrospray ionisation-tandem mass spectrometry on a case-cohort (n=3,779) subset from the ADVANCE (Action in Diabetes and Vascular disease: preterAx and diamicroN- MR Controlled Evaluation) trial. The-case cohort was 61% male with a mean age of 67. All participants had type 2 diabetes mellitus with one or more additional cardiovascular risk factors and 35% had a history of macrovascular disease. Weighted Cox regression was used to identify lipid species associated with future cardiovascular events (non-fatal myocardial infarction, non- fatal stroke and cardiovascular death) and cardiovascular death during a five year follow-up period. Multivariable models combining traditional risk factors with lipid species were optimized using the Akaike information criteria. C-statistics and net reclassification indices (NRI) were calculated within a five-fold cross validation framework. Results: Sphingolipids, phospholipids (including lyso- and ether- species), cholesteryl esters, and glycerolipids were associated with future cardiovascular events and cardiovascular death. The addition of 7 lipid species to a base model (14 traditional risk factors and medications) to predict cardiovascular events increased the C statistic from 0.680 (95% confidence interval [CI], 0.678–0.682) to 0.700 (95% CI, 0.698–0.702; P<0.0001) with a corresponding continuous NRI of 0.227 (95% CI, 0.219–0.235). The prediction of cardiovascular death was improved with the incorporation of 4 lipid species into the base model, showing an increase in the C statistic from 0.740 (95% CI, 0.738–0.742) to 0.760 (95% CI, 0.757–0.762; P<0.0001) and a continuous net reclassification index of 0.328 (95% CI, 0.317–0.339). The results were validated in a subcohort with type 2 diabetes mellitus (n=511) from the LIPID trial (Long-Term Intervention With Pravastatin in Ischemic Disease). Conclusions: The improvement in the prediction of cardiovascular events, above traditional risk factors, demonstrates the potential of plasma lipid species as biomarkers for cardiovascular risk stratification in diabetes mellitus.
Keywords: lipids, biomarker, mass spectrometry, cardiovascular outcomes, diabetes mellitus.
脂质组学案例分析疾病研究:血浆靶向脂质组学轮廓谱研究提高二型糖尿病病人中患心血管疾病的传统风险因子的预测能力研究对象:人分析检测平台:LC ESI-MS/MS期刊:Circulation影响因子:17.047发表时间:2016摘要:Background: Clinical lipid measurements do not show the full complexity of the altered lipid metabolism associated