Folic acid supplementation may help prevent first stroke in high-risk patients with hypertension

Among patients with low platelet count and high total homocysteine levels, receiving folic acid reduced the risk of first stroke by 73%, whereas there was no significant effect of folic acid among low-risk patients.


Supplementation with folic acid may help prevent a first stroke in patients with hypertension whose platelet count is low and whose total homocysteine level is elevated, a recent study found.

Researchers analyzed a subgroup of 10,789 adults with hypertension and no history of stroke or myocardial infarction (mean age, 59.5 years; 38% male) who were enrolled in the multicenter China Stroke Primary Prevention Trial, which found that folic acid can reduce stroke risk by an average of 21% in populations with hypertension and no folic acid fortification.

In the double-blind, randomized controlled trial, participants received daily treatments of enalapril, 10 mg, and folic acid, 0.8 mg (n=5,408), or of 10 mg of enalapril alone (n=5,381). Participants were from one study center and had baseline measures of platelet count and total homocysteine level, with no antiplatelet drug usage. The primary endpoint was first stroke.

Results were published online on May 7 by the Journal of the American College of Cardiology.

During a median follow-up of 4.2 years, 371 first strokes occurred (161 in the enalapril/folic acid group and 210 in the enalapril group). The highest rate of first stroke occurred in patients with low platelet count and high total homocysteine levels, and the lowest rate of first stroke was in patients with high platelet count and low total homocysteine levels. Among patients with low platelet count and high total homocysteine levels, receiving folic acid reduced the risk of first stroke by 73% (hazard ratio, 0.27; 95% CI, 0.11 to 0.64; P=0.003), whereas there was no significant effect of folic acid among low-risk patients.

The study authors noted limitations, such as how they only examined platelet levels at baseline and that only a fixed dosage (0.8 mg/d) of folic acid was used. In addition, there is a possibility of residual confounding, and the study participants were from a low-folate region, they said, emphasizing that the results are hypothesis generating.

“Our data suggest that identifying those patients with a combination of low [platelet count] and high total homocysteine (both biomarkers are easy to obtain) could help detect those individuals who are at high risk of stroke and who would particularly benefit from folic acid supplementation, a treatment that is simple, safe, and inexpensive,” the authors concluded.

While the findings may seem surprising at first, especially because thrombocythemia increases the risk of stroke, they are not surprising for three reasons, according to an accompanying editorial. First, the efficacy of any therapy is greater in high-risk patients; second, there are credible reasons why a low platelet count may predict higher risk; and third, the common belief that B vitamins do not reduce the risk of stroke is a misconception, the editorialists said.

“This study not only invites confirmation, but opens the door to wider applications” of folic acid supplementation in patients with low platelet count and high total homocysteine levels to potentially reduce the risk of not only clinical stroke but also silent cerebrovascular disease and dementia, they wrote.