Succinate links atrial dysfunction and cardioembolic stroke

Area of Science:

• Biochemistry
• Cardiology
• Neurology

Background:

• Cardioembolic (CE) stroke is a significant cause of morbidity and mortality.
• Atrial dysfunction is a known risk factor for CE stroke.
• The underlying mechanisms linking atrial dysfunction to CE stroke remain incompletely understood.

Purpose of the Study:

• To investigate whether altered metabolic profiles mediate the relationship between atrial dysfunction and CE stroke.
• To explore the association between specific metabolites, atrial dysfunction markers, and stroke recurrence risk.

Main Methods:

• Plasma samples from 367 acute stroke patients were analyzed for 144 metabolites using liquid chromatography-tandem mass spectrometry.
• Patients were categorized into CE stroke and non-CE stroke groups.
• Associations between metabolites, atrial dysfunction (including P-wave terminal force, left atrial enlargement, and atrial fibrillation), and stroke recurrence scores (CHADS2, CHA2DS2-VASc) were assessed using logistic regression.

Main Results:

• Three tricarboxylic acid cycle metabolites—succinate, α-ketoglutarate, and malate—were significantly associated with CE stroke.
• These metabolites were also linked to markers of subclinical atrial dysfunction, including left atrial enlargement.
• Succinate levels were particularly associated with increased stroke recurrence risk, as indicated by CHADS2 and CHA2DS2-VASc scores.

Conclusions:

• Metabolite profiling revealed significant alterations in succinate, α-ketoglutarate, and malate in patients with CE stroke and atrial dysfunction.
• These findings suggest a potential link between impaired energy metabolism and the pathogenesis of CE stroke.
• Succinate may serve as a potential biomarker for CE stroke risk and recurrence.