Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide, particularly in individuals with diabetes. The current study objective was to determine the circulating metabolite profiles associated with the risk of future cardiovascular events, with emphasis on diabetes status. Nontargeted metabolomics analysis was performed by LC–HRMS in combination with targeted quantification of eicosanoids and endocannabinoids. Plasma from 375 individuals from the IMPROVE pan-European cohort was included in a case-control study design. Following data processing, the three metabolite data sets were concatenated to produce a single data set of 267 identified metabolites. Factor analysis identified six factors that described 26.6% of the variability in the given set of predictors. An association with cardiovascular events was only observed for one factor following adjustment (p = 0.026). From this factor, we identified a free fatty acid signature (n = 10 lipids, including saturated, monounsaturated, and polyunsaturated fatty acids) that was associated with lower risk of future cardiovascular events in nondiabetics only (OR = 0.65, 0.27–0.80 95% CI, p = 0.030), whereas no association was observed among diabetic individuals. These observations support the hypothesis that increased levels of circulating omega-6 and omega-3 fatty acids are associated with protective effects against future cardiovascular events. However, these effects were only observed in the nondiabetic population, further highlighting the need for patient stratification in clinical investigations.

中文翻译：

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循环脂肪酸水平的增加与非糖尿病患者未来心血管事件的保护作用有关

心血管疾病 (CVD) 是全球发病率和死亡率的主要原因，尤其是在糖尿病患者中。目前的研究目标是确定与未来心血管事件风险相关的循环代谢物谱，重点是糖尿病状态。通过 LC-HRMS 结合类花生酸和内源性大麻素的靶向定量进行非靶向代谢组学分析。来自 IMPROVE 泛欧洲队列的 375 名个体的血浆被纳入病例对照研究设计。在数据处理之后，将三个代谢物数据集连接起来，生成一个包含 267 种已鉴定代谢物的单一数据集。因素分析确定了六个因素，这些因素描述了给定预测变量集中 26.6% 的变异性。p = 0.026)。根据这个因素，我们确定了一个游离脂肪酸特征（n = 10 种脂质，包括饱和脂肪酸、单不饱和脂肪酸和多不饱和脂肪酸），该特征仅与非糖尿病患者未来心血管事件的风险降低相关（OR = 0.65, 0.27–0.80 95% CI，p = 0.030），而在糖尿病个体中未观察到相关性。这些观察结果支持这样的假设，即循环 omega-6 和 omega-3 脂肪酸水平的增加与对未来心血管事件的保护作用有关。然而，这些影响仅在非糖尿病人群中观察到，进一步强调了在临床研究中对患者进行分层的必要性。