Good news for adults with hypertension with a study finding that combining folic acid with a conventional blood pressure medication enalapril significantly reduced the risk of a stroke.
Heart attacks are China’s leading cause of death and the second leading cause of death worldwide. Intervention prior to a first heart attack is critical as 77 percent of strokes are first events.
Results from a study of 20,000 Chinese adults suffering from high blood pressure but who had not suffered a stroke were released to coincide with the American College of Cardiology Annual Scientific Session. Led by Yong Huo, M.D. of Peking University First Hospital, Beijing, and colleagues had 20,702 adults with hypertension without history of heart attack randomly assigned to receive daily treatment with a single-pill combination containing enalapril (10 mg) and folic acid (0.8 mg; n = 10,348), or a tablet containing enalapril alone (10 mg; n = 10,354). The trial was conducted from May 2008 to August 2013 in 32 communities in China’s Jiangsu and Anhui provinces. Participants were tested for variations in the MTHFR C677T gene (CC, CT, and TT genotypes) that may affect folate levels.
Over a median term treatment span of 4.5 years only 282 patients (2.7 percent) in the enalapril-folic acid study stream suffered a first stroke compared with 355 (3.4 percent) in the enalapril only study stream. In relative terms this represents a 21 per cent reduction in the risk of stroke.
Data analysis also pointed to significant declines in the risk of ischemic stroke (2.2 percent vs 2.8 percent) and composite cardiovascular events (cardiovascular death, heart attack and stroke) (3.1 percent vs 3.9 percent) amongst the enalapril-folic acid study stream. No significant difference was discovered between the two study streams for risk associated with hemorrhagic stroke, heart attack, toe spacers, or all-cause death, or in the frequency of hypertension related health issues.
The study’s authors concluded that there was convincing evidence that baseline data on foliate levels and associated MTHFR geneotyoes indicate that baseline foliate levels are a crucial factor in the effectiveness of foliate therapy in stroke prevention, “The CSPPT is the first large-scale randomized trial to test the hypothesis using individual measures of baseline folate levels. In this population without folic acid fortification, we observed considerable individual variation in plasma folate levels and clearly showed that the beneficial effect appeared to be more pronounced in participants with lower folate levels.”
“We speculate that even in countries with folic acid fortification and widespread use of folic acid supplements such as in the United States and Canada, there may still be room to further reduce stroke incidence using more targeted folic acid therapy — in particular, among those with the TT genotype and low or moderate folate levels.”
Conclusion
Meir Stampfer, M.D., Dr.P.H and Walter Willett, M.D., Dr.P.H., of the Harvard T. H. Chan School of Public Health and Channing Division of Network Medicine, Boston, in an accompanying editorial to the study wrote, “The trial by Huo et al has important implications for stroke prevention worldwide.” They added, “Although the trial participants all had hypertension, there is little reason to doubt that the results would apply to normotensive persons, although the absolute effect would be smaller.
It is possible to debate the ethics of whether a replication trial should be performed, especially because folic acid supplementation (or fortification) is safe and inexpensive, and carries other benefits. Large segments of the world’s population, potentially billions of people, including those living in northern China, Bangladesh, and Scandinavia, have low levels of folate.”
“Individuals with the TT genotype might particularly benefit, although it seems unlikely that genotyping for that purpose would be cost-effective. Also, some persons in the United States on the low end of the distribution of folate intake may benefit; effects in this subgroup would not have been detected in previous trials. Ideally, adequate folate levels would be achieved from food sources such as vegetables (especially dark green leafy vegetables), fruits and fruit juices, nuts, beans, and peas.
However, for many populations, achieving adequate levels from diet alone is difficult because of expense or availability. This study seems to support fortification programs where feasible, and supplementation should be considered where fortification will take more time to implement.”
