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.
A total of 144 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 System, 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 >4,000 μV·ms), left atrial enlargement on echocardiography, and frank atrial fibrillation on ECG. 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.
Three tricarboxylic acid metabolites—succinate (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.36–2.15, p = 1.37 x 10–6), α-ketoglutarate (OR 1.62, 95% CI 1.29–2.04, p = 1.62 x 10–5), and malate (OR 1.58, 95% CI 1.26–1.97, p = 2.57 x 10–5)—were associated with CE stroke. Succinate (OR 1.36, 95% CI 1.31–1.98, p = 1.22 x 10–6), α-ketoglutarate (OR 2.14, 95% CI 1.60–2.87, p = 2.08 x 10–8), and malate (OR 2.02, 95% CI 1.53–2.66, p = 1.60 x 10–7) 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 = 1.06 x 10–4) and stroke recurrence based on dichotomized CHADS2 (OR 2.63, 95% CI 1.68–4.13, p = 3.00 x 10–6) and CHA2DS2-VASc (OR 2.43, 95% CI 1.60–3.68, p = 4.25 x 10–6) scores.
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.