Folic Acid Therapy Reduces the First Stroke Risk Associated With Hypercholesterolemia Among Hypertensive Patients

Abstract

Background and Purpose-We sought to determine whether folic acid supplementation can independently reduce the risk of first stroke associated with elevated total cholesterol levels in a subanalysis using data from the CSPPT (China Stroke Primary Prevention Trial), a double-blind, randomized controlled trial. Methods-A total of 20 702 hypertensive adults without a history of major cardiovascular disease were randomly assigned to a double-blind daily treatment of an enalapril 10-mg and a folic acid 0.8-mg tablet or an enalapril 10-mg tablet alone. The primary outcome was first stroke. Results-The median treatment duration was 4.5 years. For participants not receiving folic acid treatment (enalapril-only group), high total cholesterol (≥200 mg/dL) was an independent predictor of first stroke when compared with low total cholesterol (<200 mg/dL; 4.0% versus 2.6%; hazard ratio, 1.52; 95% confidence interval, 1.18-1.97; P=0.001). Folic acid supplementation significantly reduced the risk of first stroke among participants with high total cholesterol (4.0% in the enalapril-only group versus 2.7% in the enalapril-folic acid group; hazard ratio, 0.69; 95% confidence interval, 0.56-0.84; P<0.001; number needed to treat, 78; 95% confidence interval, 52-158), independent of baseline folate levels and other important covariates. By contrast, among participants with low total cholesterol, the risk of stroke was 2.6% in the enalapril-only group versus 2.5% in the enalapril-folic acid group (hazard ratio, 1.00; 95% confidence interval, 0.75-1.30; P=0.982). The effect was greater among participants with elevated total cholesterol (P for interaction=0.024). Conclusions-Elevated total cholesterol levels may modify the benefits of folic acid therapy on first stroke. Folic acid supplementation reduced the risk of first stroke associated with elevated total cholesterol by 31% among hypertensive adults without a history of major cardiovascular diseases. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00794885.

Recent advances in preventing stroke recurrence

“…Among participants with LDL-C above 2 mmol/L, the benefit of folic acid was greater: a 31% reduction in stroke 47 . Importantly, folic acid was beneficial in participants with impaired renal function 48 .…”

WITHDRAWN: Association of homocysteine-metabolizing enzyme gene polymorphisms and lipid profiles: an investigation of a geneenvironment interaction

“…Recently, our China Stroke Primary Prevention Trial (CSPPT) subgroup analysis [3] found that, for participants not receiving folic acid treatment, high total cholesterol (TC) (≥ 200 mg/dL) was an independent predictor of first stroke when compared with low TC. Folic acid supplementation for 4.5 years significantly reduced the risk of first stroke by 31% among hypertensive participants with high TC.…”

Lack of association between serum homocysteine level and middle cerebral artery stenosis

“…Therefore, the use of B vitamins and folic acid as secondary prevention in patients with vascular diseases was not supported. However, in the primary prevention clinical trials, folic acid supplementation significantly reduced the risk of first stroke (Huo et al., ; Qin et al., ). Why is lowering HCY useful in primary prevention and useless in secondary prevention?…”