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We aim to examine whether a change in homocysteine (Hcy) levels is associated with risk of stroke in a post-hoc analysis of the China Stroke Primary Prevention Trial (CSPPT).
A total of 16,867 participants with Hcy measurements at both baseline and exit visit in the CSPPT were included in the current analysis. The primary outcome was first stroke. The secondary outcome was a composite of cardiovascular events consisting of cardiovascular death, myocardial infarction (MI) and stroke. The percent decline in Hcy was calculated as [(baseline Hcy-exit Hcy) / baseline Hcy *100].
Over the median treatment duration of 4.5 years, participants with a stroke occurrence had a significantly lower percent decline in Hcy (β=-5.7; 95%CI: -8.8,-2.6). Consistently, a 20% Hcy decline was associated with a reduction in stroke risk of 7% (HR, 0.93; 95%CI: 0.90-0.97). When percent decline in Hcy was assessed as tertiles, a significantly lower stroke risk was found in those in tertiles 2-3 (HR, 0.79; 95%CI: 0.64-0.97) compared with participants in tertile 1. Similar results were observed for the composite of cardiovascular events outcome. The beneficial effect associated with higher Hcy reduction were consistent in a stratified analysis with the subgroups age, sex, treatment group, MTHFR C677T genotypes, serum folate and Hcy levels.
Percent decline in Hcy was significantly associated with a reduction in stroke risk in adults with hypertension. Hcy reduction can be considered a reliable biomarker as an indicator of the beneficial effect of folic acid therapy on stroke prevention.