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.
Highlights
Prospective previous researches had confirmed a solid, graded, and independent positive association between blood pressure and risk of stroke and cardiovascular disease (CVD) (Chobanian et al, 2003)
In our current meta-analysis, we provided coherent evidence and found apparent benefit of folic acid paratherapy antihypertensive treatments on the risk of cardiovascular and stroke events in primary prevention compared with antihypertensive alone in HT/HHcy
65 trials with the total of 7,887 subjects that met the inclusion criteria to process the analysis and the results suggested that folic acid plus antihypertensive combination therapy could reduce the systolic blood pressure (SBP) and DBP levels compared to antihypertensive alone
Summary
Prospective previous researches had confirmed a solid, graded, and independent positive association between blood pressure and risk of stroke and cardiovascular disease (CVD) (Chobanian et al, 2003). The latest epidemiological data showed that hypertension is the biggest single contributor to the global burden of disease, leading to approximately nine million deaths each year (Lim et al, 2012), which was largely mediated through CVD and stroke (Poulter et al, 2015). It was interesting to note that several carefully conducted studies to date have showed hyperhomocysteinemia often accompany with hypertension in many experimental models, as well as in patients with primary hypertension, especially systolic blood pressure (SBP) (Lim and Cassano, 2002; Huo et al, 2015). Hyperhomocysteinemia associated hypertension patients (HT/HHcy) are common in clinic, the precise mechanism by which tHcy results in vascular dysfunction and contributes to hypertension are largely unknown (Sen et al, 2010). Hyperhomocysteinemia related changes in vascular biology such as increased arterial stiffness, vascular smooth muscle cell proliferation and endothelial dysfunction could lead to an increase in blood pressure (Stehouwer and van Guldener, 2003)
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