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Succinate links atrial dysfunction and cardioembolic stroke.

Authors :: Nelson SE
Ament Z
Wolcott Z
Gerszten RE
Kimberly WT
Source :: Neurology [Neurology] 2019 Feb 19; Vol. 92 (8), pp. e802-e810. Date of Electronic Publication: 2019 Jan 23.
Publication Year :: 2019
Abstract: 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.<br />Methods: 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, PTFV <subscript>1</subscript> >4,000 μV·ms), left atrial enlargement on echocardiography, and frank atrial fibrillation on ECG. Stroke recurrence risk was assessed using CHADS <subscript>2</subscript> and CHA <subscript>2</subscript> DS <subscript>2</subscript> -VASc scores. Associations between metabolites and CE stroke, atrial dysfunction, and stroke recurrence risk were evaluated using logistic regression models.<br />Results: Three tricarboxylic acid metabolites-succinate (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.36-2.15, p = 1.37 × 10 <superscript>-6</superscript> ), α-ketoglutarate (OR 1.62, 95% CI 1.29-2.04, p = 1.62 × 10 <superscript>-5</superscript> ), and malate (OR 1.58, 95% CI 1.26-1.97, p = 2.57 × 10 <superscript>-5</superscript> )-were associated with CE stroke. Succinate (OR 1.36, 95% CI 1.31-1.98, p = 1.22 × 10 <superscript>-6</superscript> ), α-ketoglutarate (OR 2.14, 95% CI 1.60-2.87, p = 2.08 × 10 <superscript>-8</superscript> ), and malate (OR 2.02, 95% CI 1.53-2.66, p = 1.60 × 10 <superscript>-7</superscript> ) 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 × 10 <superscript>-4</superscript> ) and stroke recurrence based on dichotomized CHADS <subscript>2</subscript> (OR 2.63, 95% CI 1.68-4.13, p = 3.00 × 10 <superscript>-6</superscript> ) and CHA <subscript>2</subscript> DS <subscript>2</subscript> -VASc (OR 2.43, 95% CI 1.60-3.68, p = 4.25 × 10 <superscript>-6</superscript> ) scores.<br />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.<br /> (© 2019 American Academy of Neurology.)