Effects of Lowering Homocysteine Levels With B Vitamins on Cardiovascular Disease, Cancer, and Cause-Specific Mortality<subtitle>Meta-analysis of 8 Randomized Trials Involving 37 485 Individuals</subtitle><alt-title>Effects of Lowering Homocysteine Levels</alt-title>

Abstract

Elevated plasma homocysteine levels have been associated with higher risks of cardiovascular disease, but the effects on disease rates of supplementation with folic acid to lower plasma homocysteine levels are uncertain. Individual participant data were obtained for a meta-analysis of 8 large, randomized, placebo-controlled trials of folic acid supplementation involving 37 485 individuals at increased risk of cardiovascular disease. The analyses involved intention-to-treat comparisons of first events during the scheduled treatment period. There were 9326 major vascular events (3990 major coronary events, 1528 strokes, and 5068 revascularizations), 3010 cancers, and 5125 deaths. Folic acid allocation yielded an average 25% reduction in homocysteine levels. During a median follow-up of 5 years, folic acid allocation had no significant effects on vascular outcomes, with rate ratios (95% confidence intervals) of 1.01 (0.97-1.05) for major vascular events, 1.03 (0.97-1.10) for major coronary events, and 0.96 (0.87-1.06) for stroke. Likewise, there were no significant effects on vascular outcomes in any of the subgroups studied or on overall vascular mortality. There was no significant effect on the rate ratios (95% confidence intervals) for overall cancer incidence (1.05 [0.98-1.13]), cancer mortality (1.00 [0.85-1.18]) or all-cause mortality (1.02 [0.97-1.08]) during the whole scheduled treatment period or during the later years of it. Dietary supplementation with folic acid to lower homocysteine levels had no significant effects within 5 years on cardiovascular events or on overall cancer or mortality in the populations studied.

Secondary Prevention After Coronary Artery Bypass Graft Surgery

“…421 This was confirmed in a meta-analysis of >37 000 participants that demonstrated that high-dose B vitamins and folic acid are not effective as a secondary prevention measure for cardiovascular disease. 422 Finally, a meta-analysis of 50 randomized, controlled trials with nearly 300 000 participants showed no benefit of vitamin and antioxidant supplementation in reducing the risk of major cardiovascular events, including subgroup meta-analyses examining the effects of individual vitamins. 423 Undergoing cardiac surgery leads to considerable stress on the body, which plays a key factor in determining outcome.…”

Homocysteine — is it still an important risk factor for cardiovascular disease?

“…The 2006 meta-analysis of 12 randomised clinical trials by Bazzano et al [45], which included 16,958 subjects with CV disease, showed no significant reduction in the risk of CV disease, IHD, stroke, and all-cause mortality. Similarly, in the meta-analysis by Clarke et al [46] (8 clinical trials; 37,485 participants), no significant reduction in CV risk was observed despite reduction in Hcy level by on average 25%.…”

Predictors of Residual Cardiovascular Risk in Patients on Statin Therapy for Primary Prevention

“…Although an increasing body of evidence suggests that Hcy reduction using vitamin supplementation is not accompanied by a reduction in the occurrence of future events, the patient populations considered in these studies had pre-existing CVD unlike the population studied in our analyses [8,9]. Of note, data on Hcy as a primary prevention target or its utility in reclassifying the intermediate risk population is sparse at best [10].…”