Plasma Homocysteine and Prognosis of Acute Ischemic Stroke: a Gender-Specific Analysis From CATIS Randomized Clinical Trial

Elevated total homocysteine level (tHcy) has been hypothesized to be associated with morbidity and mortality of stroke; however, results regarding the association between plasma tHcy status and prognosis of acute ischemic stroke are inconsistent. Moreover, the gender effect on this association has yet to be explored. We thus prospectively investigated whether higher tHcy concentrations predicted poor stroke prognosis in Chinese adults. A total of 3309 acute ischemic stroke patients were included in this prospective multicenter study from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). Baseline tHcy concentrations were quantitatively determined via enzymatic cycling assay. The primary outcome was a combination of death and major disability at 3 months (modified Rankin scale scores 3-6) after hospitalization. Multivariate logistic regression models with restricted cubic splines were used to determine the association between baseline plasma tHcy and the subsequent outcome. Higher plasma tHcy concentrations were associated with increased risks of the primary outcome in women but not in men (P (interaction) = 0.016). Adjusted odds ratios comparing two extreme tHcy quartiles were 1.83 (95 % confidence interval 1.12-2.98; P (trend) = 0.02) in women and 0.87 (95 % confidence interval 0.61-1.25; P (trend) = 0.37) in men. The significant association between baseline tHcy status and stroke prognosis in women, but not in men, persisted in further subgroup analyses, stratified by age, baseline systolic blood pressure, and other pre-specified factors. Elevated tHcy is positively associated with poor prognosis of acute ischemic stroke in women, but not in men. Further studies are needed to replicate our findings and to clarify the potential sex-specific mechanisms.