Succinate links atrial dysfunction and cardioembolic stroke

Sarah Nelson, Zsuzsanna Ament, Zoe Wolcott, Robert E. Gerszten, W. Taylor Kimberly

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Abstract

ObjectiveTo 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.MethodsA 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 1 >4,000 V·ms), left atrial enlargement on echocardiography, and frank atrial fibrillation on ECG. Stroke recurrence risk was assessed using CHADS 2 and CHA 2 DS 2 -VASc scores. Associations between metabolites and CE stroke, atrial dysfunction, and stroke recurrence risk were evaluated using logistic regression models.ResultsThree tricarboxylic acid metabolites - succinate (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.36-2.15, p = 1.37 × 10 -6 ), α-ketoglutarate (OR 1.62, 95% CI 1.29-2.04, p = 1.62 × 10 -5 ), and malate (OR 1.58, 95% CI 1.26-1.97, p = 2.57 × 10 -5 ) - were associated with CE stroke. Succinate (OR 1.36, 95% CI 1.31-1.98, p = 1.22 × 10 -6 ), α-ketoglutarate (OR 2.14, 95% CI 1.60-2.87, p = 2.08 × 10 -8 ), and malate (OR 2.02, 95% CI 1.53-2.66, p = 1.60 × 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 × 10 -4 ) and stroke recurrence based on dichotomized CHADS 2 (OR 2.63, 95% CI 1.68-4.13, p = 3.00 × 10 -6 ) and CHA 2 DS 2 -VASc (OR 2.43, 95% CI 1.60-3.68, p = 4.25 × 10 -6 ) scores.ConclusionsMetabolite 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.

Original languageEnglish (US)
Pages (from-to)E802-E810
JournalNeurology
Volume92
Issue number8
DOIs
Publication statusPublished - Feb 19 2019

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ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Nelson, S., Ament, Z., Wolcott, Z., Gerszten, R. E., & Kimberly, W. T. (2019). Succinate links atrial dysfunction and cardioembolic stroke. Neurology, 92(8), E802-E810. https://doi.org/10.1212/WNL.0000000000006957