BACKGROUND The rote of platelets and important effect modifiers on the risk of first stroke is unknown. OBJECTIVES This study examined whether low platelet count (PLT) and elevated total homocysteine (tHcy) levels jointly increase the risk of first stroke, and, if so, whether folic add treatment is particularly effective in stroke prevention in such a setting. METHODS A total of 10,789 Chinese hypertensive adults (mean age 59.5 years; 38% mate, with no history of stroke and myocardial infarction) were analyzed from the China Stroke Primary Prevention Trial, where participants were randomly assigned to daily treatments of 10 mg enalapril and 0.8 mg folic acid (n = 5,408) or 10 mg enalapril alone (n = 5,381). The primary endpoint was first stroke. RESULTS During 4.2 years of follow-up, a total of 371 first strokes occurred. In the enalapril-atone group, the lowest rate of first stroke (3.3%) was found in patients with high PIT (quartiles 2 to 4) and tow tHcy (<15 mu mol/l) and the highest rate (5.6%) was in patients with tow PLT (quartile 1) and high tHcy (>= 15 mu mol/l) levels. Following folic acid treatment, the high-risk group had a 73% reduction in stroke (hazard ratio: 0.27; 95% confidence interval: 0.11 to 0.64; p 0.003), whereas there was no significant effect among the low-risk group. CONCLUSIONS Among Chinese hypertensive adults, the subgroup with low PLT and high tHcy had the highest risk of first stroke, and this risk was reduced by 73% with folic acid treatment. If confirmed, PLT and tHcy could serve as biomarkers to identify high-risk individuals who would particularly benefit from folic add treatment. (C) 2018 by the American College of Cardiology Foundation.