Effect of homocysteine interventions on the risk of cardiocerebrovascular events: a meta-analysis of randomised controlled trials

Abstract

Aims: To evaluate the effects of homocysteine lowering intervention on the risk of cardiocerebrovascular events and all-cause mortality in randomised controlled trials among people with preexisting cardiocerebrovascular or renal disease.

Methods: Studies were retrieved by searching MEDLINE and OVID (from January 1966 to December 2008) using the following keywords: homocysteine, hyperhomocysteinaemia, cardiovascular disease, coronary disease, cerebrovascular disease, B vitamins, folic acid, randomised controlled trial. References of all retrieved articles were also searched. Randomised controlled trials which compared folic acid or plus B vitamins supplementation with either placebo or usual care were evaluated with cardiocerebrovascular disease events or all-cause mortality reported as an end-point. Data on study design, characteristics of participants, changes in homocysteine levels, and cardiocerebrovascular events and all-cause mortality were independently abstracted by two investigators using a standardised protocol.

Results: Seventeen trials involving 39,107 patients with preexisting cardiocerebrovascular or renal disease were included. Results of meta-analyses showed that no significant differences were identified between the intervention group and the control group. The overall relative risks (95% confidence intervals) of outcomes for patients treated with folic acid or plus B vitamins supplementation compared with controls were 1.01 (0.97-1.05) for cardiovascular events, 1.01 (0.94-1.07) for coronary heart disease, 0.94 (0.85-1.04) for stroke and 1.00 (0.95-1.05) for all-cause mortality. In the exclusion of low-quality trials and seven trials in grain fortification countries respectively, sensitivity analyses did not change the overall results.

Conclusion: There is no sufficient evidence to show that homocysteine lowering intervention can reduce the risk of cardiocerebrovascular diseases or all-cause mortality among people with preexisting vascular disease. Folic acid supplementation should not be recommended for the secondary prevention of cardiocerebrovascular diseases. More evidence from large-scale randomised controlled trials is needed to confirm this.