Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention

Background: Diabetes is a known risk factor for stroke, but data on its prospective association with first stroke are limited. Folic acid supplementation has been shown to protect against first stroke, but its role in preventing first stroke in diabetes is unknown.Objectives: This post hoc analysis of the China Stroke Primary Prevention Trial tested the hypotheses that the fasting blood glucose (FBG) concentration is positively associated with first stroke risk and that folic acid treatment can reduce stroke risk associated with elevated fasting glucose concentrations.Design: This analysis included 20,327 hypertensive adults without a history of stroke or myocardial infarction, who were randomly assigned to a double-blind daily treatment with 10 mg enalapril and 0.8 mg folic acid (n = 10,160) or 10 mg enalapril alone (n = 10,167). Kaplan-Meier survival analysis and Cox proportionate hazard models were used to test the hypotheses with adjustment for pertinent covariables.Results: During a median treatment duration of 4.5 y, 616 participants developed a first stroke (497 ischemic strokes). A high FBG concentration (≥7.0 mmol/L) or diabetes, compared with a low FBG concentration (<5.0 mmol/L), was associated with an increased risk of first stroke (6.0% compared with 2.6%, respectively; HR: 1.9; 95% CI: 1.3, 2.8; P < 0.001). Folic acid treatment reduced the risk of stroke across a wide range of FBG concentrations ≥5.0 mmol/L, but risk reduction was greatest in subjects with FBG concentrations ≥7.0 mmol/L or with diabetes (HR: 0.66; 95% CI: 0.46, 0.97; P < 0.05). There was a significant interactive effect of FBG and folic acid treatment on first stroke (P = 0.01).Conclusions: In Chinese hypertensive adults, an FBG concentration ≥7.0 mmol/L or diabetes is associated with an increased risk of first stroke; this increased risk is reduced by 34% with folic acid treatment. These findings warrant additional investigation. This trial was registered at clinicaltrials.gov as NCT00794885.