Data from: Succinate links atrial dysfunction and cardioembolic stroke

Objective: To determine whether altered metabolic profiles represent a
link between atrial dysfunction and cardioembolic (CE) stroke, and thus
whether underlying dysfunctional atrial substrate may contribute to
thromboembolism risk in CE stroke. Methods: One hundred forty-four
metabolites were measured using liquid chromatography-tandem mass
spectrometry in plasma samples collected within 9 hours of stroke onset in
367 acute stroke patients. Stroke subtype was assigned using the causative
classification of stroke, and CE stroke (n=181) was compared to non-CE
stroke (n=186). Markers of left atrial dysfunction included abnormal
atrial function (P-wave terminal force in lead V1, PTFV1 >4000
µV•ms), left atrial enlargement on echocardiography, and frank atrial
fibrillation on electrocardiograms. Stroke recurrence risk was assessed
using CHADS2 and CHA2DS2-VASc scores. Associations between metabolites and
CE stroke, atrial dysfunction, and stroke recurrence risk were evaluated
using logistic regression models. Results: Three tricarboxylic acid (TCA)
cycle acids, succinate (OR 1.71, 95% CI 1.36-2.15, P=1.37x10-6),
alpha-ketoglutarate (OR 1.62, 95% CI 1.29-2.04, P=1.62x10-5), and malate
(OR 1.58, 95% CI 1.26-1.97, P=2.57x10-5), were associated with CE stroke.
Succinate (OR 1.36, 95% CI 1.31-1.98, P=1.22x10-6), alpha-ketoglutarate
(OR 2.14, 95% CI 1.60-2.87, P=2.08x10-8), and malate (OR 2.02, 95% CI
1.53-2.66, P=1.60x10-7) were among metabolites also associated with
subclinical atrial dysfunction. Of these, succinate was also associated
with left atrial enlargement (OR 1.54, 95% CI 1.23-1.94, P=1.06x10-4) and
stroke recurrence based on dichotomized CHADS2 (OR 2.63, 95% CI 1.68-4.13,
P=3.00x10-6) and CHA2DS2-VASc (OR 2.43, 95% CI 1.60-3.68, P=4.25x10-6)
scores. Conclusions: Metabolite profiling identified changes in succinate
associated with CE stroke, atrial dysfunction, and stroke recurrence,
revealing a putative underlying link between CE stroke and energy
metabolism.

【研究目的】明确异常代谢谱是否可作为心房功能障碍与心源性栓塞性（cardioembolic, CE）卒中之间的关联纽带，进而探究潜在的功能异常心房底物是否会增加心源性栓塞性卒中的血栓栓塞风险。【研究方法】本研究纳入367例急性卒中患者，在其卒中发作后9小时内采集血浆样本，采用液相色谱-串联质谱法（liquid chromatography-tandem mass spectrometry）对144种代谢物进行定量检测。依据卒中病因分类标准对卒中亚型进行划分，将181例心源性栓塞性卒中患者与186例非心源性栓塞性卒中患者进行对照分析。左心房功能障碍的评估指标包括：异常心房功能（V1导联P波终末电势PTFV1＞4000 µV•ms）、超声心动图显示左心房扩大，以及心电图确诊的心房颤动。采用CHADS2评分与CHA2DS2-VASc评分评估卒中复发风险。通过逻辑回归模型分析代谢物与心源性栓塞性卒中、心房功能障碍及卒中复发风险之间的关联。【研究结果】三种三羧酸循环（tricarboxylic acid, TCA）相关代谢物与心源性栓塞性卒中存在显著关联：琥珀酸（OR=1.71，95%置信区间CI=1.36~2.15，P=1.37×10^-6）、α-酮戊二酸（OR=1.62，95%CI=1.29~2.04，P=1.62×10^-5）以及苹果酸（OR=1.58，95%CI=1.26~1.97，P=2.57×10^-5）。此外，上述三种代谢物同样与亚临床心房功能障碍相关：琥珀酸（OR=1.36，95%CI=1.31~1.98，P=1.22×10^-6）、α-酮戊二酸（OR=2.14，95%CI=1.60~2.87，P=2.08×10^-8）、苹果酸（OR=2.02，95%CI=1.53~2.66，P=1.60×10^-7）。其中，琥珀酸还与左心房扩大（OR=1.54，95%CI=1.23~1.94，P=1.06×10^-4）以及基于二分法CHADS2评分（OR=2.63，95%CI=1.68~4.13，P=3.00×10^-6）与CHA2DS2-VASc评分（OR=2.43，95%CI=1.60~3.68，P=4.25×10^-6）评估的卒中复发风险显著相关。【研究结论】代谢组学分析发现琥珀酸的水平变化与心源性栓塞性卒中、心房功能障碍及卒中复发均存在关联，揭示了心源性栓塞性卒中与能量代谢之间潜在的病理生理联系。