Department of Neurology and Institute of Neurology, Huashan Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Shanghai Medical College, Fudan University, National Center for Neurological Disorders, Shanghai, China.
The Institute of Science and Technology for Brain-inspired Intelligence, Fudan University, Shanghai, China.
J Neurochem. 2022 Aug;162(4):371-384. doi: 10.1111/jnc.15659. Epub 2022 Jul 15.
The relevance between circulating metabolites and vascular events remains controversial and comprehensive studies are lacking. We sought to investigate the prospective associations of plasma metabolomics with risks of incident stroke, ischemic stroke (IS), hemorrhagic stroke (HS), and myocardial infarction (MI). Within the UK Biobank cohort, 249 circulating metabolites were measured in 90 438 participants without baseline vascular diseases. Cox proportional hazards regressions were applied to estimate adjusted hazard ratios (HRs) for per 1 standard deviation increment in metabolites. The least absolute shrinkage and selection operator algorithm was used for selecting metabolite subsets. During a median of 9.0 years of follow-up, we documented 833 incident stroke and 1256 MI cases. Lipid constituents, comprising cholesterol, cholesteryl esters, free cholesterol, phospholipids, and total lipids, in very low- (VLDL), intermediate- (IDL), and low-density lipoprotein (LDL) particles were positively associated with MI risk (HR = 1.12 to 1.36; 95% CI = 1.06 to 1.44), while in high-density lipoprotein (HDL) particles showed inverse associations (HR = 0.68 to 0.81; 95% CI = 0.63 to 0.87). Similar association pattern with MI was also observed for VLDL, IDL, LDL, and HDL particles themselves. In contrast, triglycerides within all lipoproteins, including most HDL particles, were positively associated with MI risk (HR = 1.14 to 1.28; 95% CI = 1.08 to 1.35) and, to a slightly lesser extent, with stroke and IS. Unsaturation of fatty acids and albumin were inversely associated with risks of stroke, IS, and MI. In contrast, the linear association for HS is absent. When combining multiple metabolites, the metabolite risk score captured a drastically elevated risk of all vascular events, about twice that of any single metabolite. Taken together, circulating metabolites showed remarkably widespread associations with incident MI, but substantially weakened associations with risks of stroke and its subtypes. Exhaustive metabolomics profiling may shed light on vascular risk prediction and, in turn, guide pertinent strategies of intervention and treatment.
循环代谢物与血管事件之间的相关性仍存在争议，且缺乏全面的研究。我们旨在探究血浆代谢组学与卒中、缺血性卒中（IS）、出血性卒中（HS）和心肌梗死（MI）事件风险之间的前瞻性关联。在英国生物库队列中，对 90438 名无基线血管疾病的参与者测量了 249 种循环代谢物。应用 Cox 比例风险回归估计代谢物每标准差增加的调整后危险比（HR）。使用最小绝对收缩和选择算子算法选择代谢物子集。在中位 9.0 年的随访期间，我们记录了 833 例卒中事件和 1256 例 MI 病例。极低密度脂蛋白（VLDL）、中间密度脂蛋白（IDL）和低密度脂蛋白（LDL）颗粒中的脂质成分，包括胆固醇、胆固醇酯、游离胆固醇、磷脂和总脂质，与 MI 风险呈正相关（HR=1.12-1.36；95%CI=1.06-1.44），而高密度脂蛋白（HDL）颗粒则呈负相关（HR=0.68-0.81；95%CI=0.63-0.87）。VLDL、IDL、LDL 和 HDL 颗粒本身也观察到与 MI 类似的关联模式。相反，所有脂蛋白中的甘油三酯，包括大多数 HDL 颗粒，与 MI 风险呈正相关（HR=1.14-1.28；95%CI=1.08-1.35），与卒中和 IS 的相关性略低。脂肪酸和白蛋白的不饱和程度与卒中、IS 和 MI 的风险呈负相关。相反，HS 的线性关联不存在。当结合多种代谢物时，代谢物风险评分可捕捉到所有血管事件的风险大大升高，大约是任何单个代谢物的两倍。总之，循环代谢物与 MI 事件发生有显著广泛的关联，但与卒中及其亚型的风险的关联显著减弱。全面的代谢组学分析可能有助于血管风险预测，并进而指导相关的干预和治疗策略。
