Hyperhomocysteinemia in Young Adults with Ischemic Stroke: Association with Stroke Etiology

Background: Hyperhomocysteinemia has been implicated in ischemic stroke through endothelial dysfunction, oxidative stress, thrombogenicity, and vascular injury. However, its relationship with specific etiologic subtypes of ischemic stroke in young adults remains incompletely defined. This study evaluated the prevalence of hyperhomocysteinemia and its association with stroke etiology in young adults with first-ever ischemic stroke. Material and Methods: In this prospective observational study, 150 consecutive patients aged <50 years with first-ever acute ischemic stroke were enrolled. Demographic characteristics, vascular risk factors, biochemical parameters, and neurovascular and cardiac findings were systematically recorded. Fasting serum total homocysteine, vitamin B12, and folate concentrations were measured. Stroke etiology was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Hyperhomocysteinemia was defined as homocysteine >15 μmol/L. Multivariable logistic regression was performed to assess associations with stroke etiology after adjustment for age, sex, hypertension, diabetes mellitus, dyslipidemia, smoking, vitamin B12, folate, and renal function. Results: Hyperhomocysteinemia was present in 61 (40.7%) patients, with a mean homocysteine concentration of 18.6 ± 9.4 μmol/L. Mean concentrations were highest in large-artery atherosclerosis (23.4 ± 10.2 μmol/L), followed by small-vessel occlusion (18.7 ± 7.9), undetermined etiology (17.6 ± 8.6), cardioembolism (14.9 ± 6.3), and other determined etiologies (13.8 ± 5.7; P<0.001). Hyperhomocysteinemia was more frequent in large-artery atherosclerosis than in other etiologic subtypes (60.0% vs 35.0%; P=0.012). After adjustment, hyperhomocysteinemia remained independently associated with large-artery atherosclerosis (adjusted OR, 2.84; 95% CI, 1.31–6.16; P=0.008). Each 5-μmol/L increase in homocysteine was associated with higher odds of large-artery atherosclerosis (adjusted OR, 1.31; 95% CI, 1.08–1.59; P=0.006). Conclusion: Hyperhomocysteinemia was common among young adults with ischemic stroke and was independently associated with large-artery atherosclerosis. These findings support an association between elevated homocysteine and the atherosclerotic stroke phenotype in young adults and highlight homocysteine as a potentially relevant metabolic marker for etiologic characterization.

Keywords: Hyperhomocysteinemia, Homocysteine, Ischemic stroke, Young adults, Large-artery atherosclerosis, Stroke etiology, TOAST.