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