Beyond atherosclerosis: Investigating the significant association between hyperhomocysteinemia and cardioembolic stroke subtypes in young patients

Abstract

Background: Hyperhomocysteinemia (HHcy) is traditionally viewed as a driver of arteriopathy. However, clinical observations increasingly suggest a "cardio-toxic" role. This study evaluates the specific link between elevated total Homocysteine (tHcy) and cardioembolic stroke in a cohort of young adults, where traditional atherosclerotic burdens are typically lower.

Methods: A 12-month prospective study of 196 ischemic stroke patients (<50 years) was conducted. Stroke aetiology was categorised via modified TOAST criteria. Fasting tHcy levels were analysed, with HHcy defined as >15\mu mol/L. Results: HHcy was present in 38.7% of the cohort. While Large Artery Atherosclerosis was present in only 6% of cases, Cardioembolic strokes accounted for 9%. Statistical analysis revealed a significant positive correlation between tHcy levels and cardioembolic events (p < 0.05). Notably, patients with tHcy >30 \mu mol/L showed a higher propensity for cardioembolic origins compared to other subtypes.

Discussion: Our findings suggest that HHcy may serve as a biomarker for a prothrombotic endocardial environment. The association with cardioembolism— historically less explored than the Hcy-atherosclerosis link—points toward Hcyinduced atrial remodelling or endocardial oxidative stress as potential drivers of embolus formation in young patients.

Conclusion: The significant relationship between increased Hcy levels and cardioembolic stroke warrants a re-evaluation of current screening protocols. In regions like Ukraine, where Hcy testing is not yet obligatory, the "Hcy-Cardiac Axis" may represent a major undiagnosed contributor to the young stroke burden