Interaction of serum calcium and folic acid treatment on first stroke in hypertensive males

Abstract

Background & aims: The role of serum calcium on the risk of stroke is still uncertain. We aimed to evaluate the effect of serum calcium on first stroke risk, and on the efficacy of folic acid treatment in prevention of first stroke among hypertensive patients.

Methods: Our analyses included a total of 19,644 eligible hypertensive adults from the China Stroke Primary Prevention Trial (CSPPT). In the CSPPT, a total of 20,702 hypertensive patients were randomly assigned to a double-blind, daily treatment with either 10 mg enalapril and 0.8 mg folic acid or 10 mg enalapril alone. The primary outcome was a first stroke.

Results: Over a median of 4.5 years, among those not receiving folic acid, a significantly higher risk of first stroke was found in hypertensive males with baseline albumin-corrected serum calcium ≥2.43 mmol/L (median) (vs. <2.43 mmol/L; 6.5% vs. 2.3%; adjusted HR, 2.47; 95% CI: 1.72, 3.55). For those with enalapril and folic acid treatment, compared with the enalapril only group, the risk of first stroke was reduced from 6.5% to 3.0% (adjusted HR, 0.49; 95% CI: 0.35, 0.68) in hypertensive males with baseline albumin-corrected serum calcium ≥2.43 mmol/L, whereas there was no significant effect among hypertensive males with baseline albumin-corrected serum calcium <2.43 mmol/L. However, among hypertensive females, serum calcium did not significantly affect the first stroke risk and the efficacy of folic acid in prevention of first stroke.

Conclusions: Among Chinese hypertensive males, those with elevated serum calcium levels had increased risk of first stroke, and this risk was reduced by 51% with folic acid treatment.

Keywords: First stroke; Folic acid; Hypertension; Serum calcium; Sex.