Meta-analysis causality assessments

To assess the relationship of Hey concentrations with vascular disease risk, a meta-analysis of observational studies was carried out, showing that elevated Hey is at most a modest independent predictor of ischemic heart disease and stroke risk in healthy populations. Studies of the impact on disease risk of genetic variants that affect blood Hey concentrations will help determine whether Hey is causally related to vascular disease, as may large randomized trials of the effects on ischemic heart disease and stroke of vitamin supplementation to lower blood Hey concentrations (Homocysteine Studies Collaboration 2002). 

Although the observational studies suggested modest associations of homocysteine with risk of vascular disease that were biologically plausible, such studies could not establish if these associations were causal. The randomized trials assessed the effectiveness of dietary supplementation with B vitamins to lower homocysteine levels on risk of cardiovascular morbidity and mortality. The initial trials were designed in the mid-1990s before the results of the Homocysteine Studies Collaboration meta-analysis (Homocysteine Studies Collaboration 2002) were reported in 2002. Consequently, few of the individual trials had sufficient statistical power to confirm or refute the 10% difference in... 

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