Folic acid supplements atop antihypertensive may help prevent stroke
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Adding folic acid (vitamin B9) to daily treatment of enalapril reduced the risk of first stroke in Chinese adults with hypertension, especially among those with low platelet count (PLT) and high total homocysteine (tHcy), according to post hoc analysis of the CSPPT*.
Both low PLT and high tHcy were known predictors of stroke risk, according to the authors — low PLT is believed to be a marker for endothelial injury and platelet adherence, while high tHcy presents a risk factor for atherosclerosis and cardiovascular disease.
“Our data suggest that identifying those patients with a combination of low PLT and high tHcy (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,” said study principal investigator Dr Yong Huo of Peking University First Hospital in Beijing, China.
The multicommunity double-blind trial involved 10,789 Chinese adults (mean age 59.5 years, 38 percent male) with hypertension (defined as systolic blood pressure [SBP]≥140 mm Hg or diastolic BP ≥90 mm Hg or who were on antihypertensive medication) without prior stroke and myocardial infarction. They were randomized 1:1 to enalapril 10 mg plus folic acid 0.8 mg daily or enalapril alone. [J Am Coll Cardiol 2018;71:2136-2146]
During a median follow-up of 4.2 years, 371 cases of first strokes occurred, of which 210 were in the enalapril-alone group and 161 were in the folic acid group. The lowest stroke rate (3.3 percent) was seen in patients with high PLT (≥210 x 109/L) and low tHcy (<15 µmol/L), while the highest stroke rate (5.6 percent) in those with low PLT (<210 x 109/L) and high tHcy (≥15 µmol/L).
When the analysis was stratified by PLT, the risk of first stroke was significantly reduced by 58 percent with folic acid supplementation vs with enalapril alone among patients in the lowest PLT quartile (<210 x 109/L; adjusted hazard ratio [HR], 0.42; p<0.001), but not in those in the higher quartiles (≥210 x 109/L; p=0.382).
The results were consistent in further stratified analyses defined by sex, age, mean SBP, total fasting cholesterol and glucose at baseline, and MTHFR** C677T genotypes, which are known risk factors of stroke.
In an analysis stratified by stroke subtype, risk of first stroke remained significantly reduced with folic acid supplementation vs enalapril alone in the lowest PLT quartile for ischaemic stroke (HR, 0.43; p=0.001), but not for haemorrhagic stroke. Nonetheless, the researchers noted that the sample size in the latter subgroup was too small to be powered.
Conversely, the greatest benefit — a risk reduction of 73 percent — of folic acid supplementation was seen in patients belonging to the highest stratum of tHcy (≥15µmol/L) who also had low PLT, ie, the high-risk group (HR for first stroke, 0.27; p=0.003). No significant effects were observed in those with high PLT and low tHcy, ie, the low-risk group.
“If the findings are further confirmed by prospective trials ... we can remarkably lower stroke risk among this subgroup of patients with folic acid,” said Huo.
“The widespread belief that B vitamins do not reduce the risk of stroke is mistaken. This study not only invited confirmation of the benefit of B vitamins, but opens the door to wider applications,” raised Dr David Spence of the Stroke Prevention and Atherosclerosis Research Centre, Ontario, Canada, in an editorial.
As stroke and dementia represent risks for each other, identifying patients with low PLT and high tHcy could benefit patients in terms of both conditions, especially in a low folate setting, noted Spence and co-authors. [J Am Coll Cardiol 2018;71:2147-2148]
According to the researchers, the study population was from a background with no folate fortification of grain products, insufficient intake of folate-rich food, and a low rate of folic acid supplementation. Hence, they could not ascertain the generalizability of the results to other setting.
“If confirmed [in further studies], these results have enormous public health implications given the high incident rate of stroke in many developing countries, in addition to China,” said Huo said.
“Based on our findings, we can detect hypertensive adults at particular high risk of stroke and incorporate a folic acid supplement tailored to individual genetic, nutritional, and clinical characteristics.,” he added. “We are on the right path to figuring out cost-effective primary prevention strategies for stroke in China and beyond.”
*ACC/AHA: American College of Cardiology and the American Heart Association
**SPRINT: Systolic PRessure INtervention Trial
