Increased Levels of Circulating Fatty Acids Are Associated with Protective Effects against Future Cardiovascular Events in Nondiabetics

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.

心血管疾病（Cardiovascular disease, CVD）是全球范围内发病率与死亡率的主要诱因，尤其在糖尿病患者群体中更为突出。本研究旨在明确与未来心血管事件风险相关的循环代谢物谱，并重点关注受试者的糖尿病患病状态。研究采用液相色谱-高分辨质谱（LC–HRMS）结合类二十烷酸与内源性大麻素类靶向定量的方法，完成了非靶向代谢组学分析。本研究纳入了来自IMPROVE泛欧洲队列的375名个体的血浆样本，采用病例对照研究设计开展实验。经数据处理后，将三类代谢物数据集进行合并，最终得到包含267种已鉴定代谢物的单一数据集。因子分析结果显示，共提取出6个因子，可解释该预测变量集合中26.6%的变异度。经校正后，仅1个因子与心血管事件存在显著关联（p = 0.026）。从该因子中，我们鉴定出一组游离脂肪酸特征谱（包含10种脂质，涵盖饱和脂肪酸、单不饱和脂肪酸与多不饱和脂肪酸），该特征谱仅在非糖尿病个体中与更低的未来心血管事件风险相关（比值比OR=0.65，95%置信区间CI：0.27–0.80，p = 0.030），而在糖尿病个体中未观察到此类关联。上述研究结果支持以下假说：循环中ω-6与ω-3脂肪酸水平升高，可对未来心血管事件产生保护作用。但该保护效应仅在非糖尿病人群中得以观察，这进一步凸显了临床研究中对患者进行分层的必要性。