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To the Editor:
Unlike randomized controlled trials, meta-analysis of observational studies remains controversial because bias and confounding contribute to between-study heterogeneity. The meta-analysis by Kelly et al.1 is further complicated by other methodological shortcomings.
A meta-analysis of a continuous exposure should standardize the estimate of effect for a uniform change in that exposure. For example, other meta-analyses of total plasma homocysteine (tHcy) and cardiovascular disease have expressed the pooled odds ratio (OR) in terms of a 5-μmol change in tHcy.2,3⇓ Kelly et al.1 state that it is clinically useful to express the risk of stroke associated with tHcy in a dichotomous manner. However, they do not state the chosen cut-off for defining hyperhomocysteinaemia. In the supplementary tables on the Neurology website, the definition of hyperhomocysteinaemia is different for each study. By combining estimates based on these different definitions, the authors have rendered their pooled effect estimate meaningless.
They also pooled studies based on the reported measure (e.g., ORs, hazard ratio, or arithmetic means) rather than on methodological rigour or study design. For example, case-control studies and nested case-control …
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