Abstract 3354: Effect of Homocysteine-Lowering on Recurrent Vascular Risk in Middle-Aged Stroke Patients

Abstract

Background: Cross-sectional studies suggest that the association between elevated homocysteine (HCY) and stroke is strongest in young adults and decreases with age. Furthermore, individuals with coexisting hypertension and elevated HCY have a substantially higher risk of stroke. Although clinical trials have failed to demonstrate a benefit of vitamin therapy for secondary stroke prevention in individuals with high HCY, the trials enrolled subjects in their late 60s and did not specifically assess the effect of HCY lowering in hypertensive subjects. Additional data in support of the aforementioned cross-sectional data may make the case for considering future HCY-lowering trials targeting younger individuals with hypertension. Methods: Post-hoc analysis of individuals aged 45-64 years enrolled in the Vitamin Intervention for Stroke Prevention trial, a multicenter, double-blind, randomized controlled trial of high vs. low dose folic acid, pyridoxine, and cobalamin in ischemic stroke patients with elevated HCY. Time to primary (stroke, myocardial infarction or death from any cause) and secondary (stroke) outcomes were assessed after adjusting for demographic and vascular risk factors. Interaction effects of age vs. treatment category on outcome and baseline hypertension or blood pressure > 140/90 mm Hg vs. treatment category on outcome were assessed. Results: Among 1425 individuals aged 45-64 years, the treatment groups were similar with respect to stroke severity, demographic and vascular risk factors. The only differences between the treatment groups were among individuals aged 45-54 years; those treated with high dose vitamins were more likely to smoke and have a history of prior stroke compared to those treated with low dose vitamins. Among individuals aged 45-54 years, high dose vitamin therapy trended towards a reduced risk of the primary outcome (HR 0.62, 95% CI 0.36-1.06, p=0.08)( Figure ) after adjustment for covariates, but this benefit was not seen in those aged 55-64 years (HR 1.08, 95% CI 0.72-1.63). High dose vitamin therapy did not have an effect on the secondary outcome. Also, subjects with concomitant hypertension did not have different outcomes compared to those without hypertension. Conclusions: Among younger individuals with a history of stroke and elevated HCY, high dose vitamin therapy is linked to a lower trend in risk of subsequent major vascular events. Future randomized clinical trials with adequate power will be necessary to prospectively determine if high dose vitamin therapy reduces the risk of vascular events in individuals <55 years with elevated HCY and stroke.