Effect Of Intermittent Folic Acid Supplementation On Short-term Cardio-cerebral Vascular Events In Patients With H-type Hypertension

Objective: Increased total homocysteine levels are a risk factor for cardio-cerebral vascular disease and.However,the efficacy of therapies that lower homocysteine concentrations with of folic acid supplementation in reducing the risk of cardiocerebral vascular diseases in patients with H-type hypertension remains controversial.The purpose of this study was to evaluate the effect of folic acid supplementation on homocysteine level and cardio-cerebral vascular events prevention in patients with Htype hypertension.Methods: A total of 397 patients who had H-type hypertension participated in the study and all patients were given routine antihypertensive drugs therapy according to the individual clinical condition.Eligible participants were randomly assigned to either a package of non-pharmacological preventive interventions alone or together with a weekly 5 mg of folic acid tablet.The non-pharmacological preventive interventions include educational training about healthy lifestyle.Plasma levels of folate and total plasma homocysteine were measured at randomization,at 1 month,at 3 months,at 6months,and then every 6 months thereafter.The changes of plasma homocysteine and serum folate levels were observed.After randomization,patients were evaluated every three months to determine their adherence to treatment and identify adverse events and clinical outcomes.The primary end point was a composite of death from cardiovascular causes,myocardial infarction,and stroke during the follow-up.The secondary end points were total ischemic events,death from any cause,hospitalization for unstable angina,hospitalization for congestive heart failure,revascularization,the incidence of cancer.The hazard ratio and the cumulative incidence of the clinical outcomes in the two groups were observed.Meanwhile,the gene polymorphism of methylenetetrahydrofolate reductase(MTHFR)was measured in the intervention group.According to the MTHFR C677 T gene polymorphism results,patients were included in the CT group,CC group and TT group.The changes of plasma homocysteine and serum folate levels,the incidence of primary and secondary end points and the hazard ratio were observed in patients with different genotypes.Results: During an average treatment duration of 15 months,compared with the control group,the total homocysteine levels was lowered by a mean of 31.72%,from17.31μmol/l at baseline to 11.82μmol/l at the end of the intervention;and the serum folate levels had approximately doubled,from 11.63ng/ml at baseline to 20.52ng/ml at the end of the intervention among patients given folic acid.There were significant differences in baseline Hcy levels and baseline folic acid levels among the CC,CT,and TT groups.Baseline Hcy levels in the TT group were significantly higher than those in the CC and CT groups(P <0.05).Baseline folate levels in the TT group were significantly higher than those in the CC group in the post-hoc multiple comparisons of baseline folate levels in the three groups(P <0.05).After treatment with folic acid5mg/w orally for 15 months,participants with the TT genotype exhibited a lower decrease in total homocysteine levels following folic acid supplementation than did participants with the CC or CT genotype among the intervention group.But such treatment had no significant effect on the primary end point(HR,1.23;95% CI,0.56-2.73;P = 0.60)and the risk of the total ischemic events(HR,0.94;95% CI,0.65-1.35;P =0.73).There was no beneficial treatment effect in any of the subgroups evaluated.Also,supplementation with folic acid was not associated with any significant benefit on the primary and secondary end points by MTHFR C677 T genotypes.Conclusion: Supplementation with folic acid 5 mg per week could also effectively lower homocysteine concentrations in patients with H-type hypertension,especially in TT genotype.Due to the small sample size,the short follow-up period,and the influence of basic folic acid level,supplementation with folic acid 5 mg per week has no significant effect on cardio-cerebral vascular events prevention in patients with Htype hypertension in the short term,which needs further study.