A Meta-Analysis of Folic Acid in Combination with Anti-Hypertension Drugs in Patients with Hypertension and Hyperhomocysteinemia

Abstract

Folic acid is generally used to lower homocysteine concentrations and prevent stroke and cardiovascular disease (CVD) at present. However, the efficacy of therapies that lower homocysteine concentrations in reducing the risk of CVD and stroke remains controversial. Our objective was to do a meta-analysis of relevant randomized controlled trials (RCTs) to evaluate the efficacy of folic acid supplementation among patients with hypertension and Hyperhomocysteinemia (HT/HHcy). We included RCTs examining the effects of folic acid plus antihypertensive therapy compared to antihypertensive alone. Weighted Mean Difference (WMD) and Relative risk (RR) were used as a measure of the effect of folic acid on the outcome measures with a random effect model. Sixty-five studies including 7887 patients met all inclusion criteria. Among them, 49 trials reported significant effect of combination therapy for reducing SBP (systolic Blood Pressure) and DBP (Diastolic Blood Pressure) levels compared with antihypertensive alone (WMD = −7.85, WMD = −6.77, respectively). Meanwhile, folic acid supplementation apparently reduced the level of total homocysteine (WMD = 5.5). In addition, folic acid supplementation obviously reduced the risk of cardiovascular and cerebrovascular events (CVCE) by 12.9% compared with control groups. In terms of the stratified analyses, a bigger beneficial effect was seen in those RCTs with treatment duration of more than 12 weeks, a decrease in the concentration of total homocysteine of more than 25%, with folic acid fortification. Our findings indicated that folic acid supplementation was effective in the primary prevention of CVCE among HT/HHcy patients, as well as reducing the blood pressure and total homocysteine levels.

Association of total homocysteine with blood pressure in a general population of Chinese adults: a cross-sectional study in Jiangsu province, China

“…It has been reported that higher folate intake is associated with a lower incidence of hypertension as seen in both the Nurses’ Health Study 33 and the Coronary Artery Risk Development in Young Adults study. 34 Williams et al , 35 van Dijk et al 36 and a recent meta-analysis 12 of relevant randomised trials among patients with hypertension and hyperhomocysteinaemia reported that tHcy lowering with folic acid therapy may reduce the blood pressure levels. Our previous study 37 also suggested that elevated tHcy concentration significantly decreased the antihypertensive effect of both short-term and long-term enalapril-based antihypertensive treatment.…”

“… 11 Recently, a meta-analysis of relevant randomised trials, including 7887 participants, also indicated that folic acid therapy was effective in reducing the blood pressure and tHcy levels among patients with hypertension and hyperhomocysteinaemia. 12 However, in the China Stroke Primary Prevention Trial (CSPPT), folic acid therapy had no obvious effect on blood pressures in 20 702 hypertensive participants. 13 In fact, Fakhrzadeh et al 14 and Dinavahi et al 15 found no significant association between tHcy and blood pressure levels.…”

Effects of Multivitamin and Multimineral Supplementation on Blood Pressure: A Meta-Analysis of 12 Randomized Controlled Trials

“…As we have discussed in the third paragraph of the discussion section, the bioavailability of micronutrients decreased and the lowering effect of MVMS on blood pressure became weaker with aging. In the present meta-analysis, no included studies evaluated the effect of MVMS containing folic acid on blood pressure in hypertensive subjects, but one previous meta-analysis based on RCTs indicated that folic acid in combination with antihypertension drugs has a synergic effect on both SBP and DBP in hypertensive subjects compared with antihypertension drugs alone [ 47 ]. The lowering effect of folic acid on blood pressure may be attributed to its important role in homocysteine (Hcy) metabolism.…”

Effect of Moxibustion on Hyperhomocysteinemia and Oxidative Stress Induced by High‐Methionine Diet

“…According to the formation mechanism of HHcy, the current expert guidelines recommend folic acid and vitamin B12 supplementation for treatment [8][9][10][11][12], but meta-analysis results show that folic acid supplementation for more than three years is necessary to reduce the risk of stroke [13].…”