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Convincing experimental evidence indicates a causal relationship between increased plasma levels of total homocysteine (tHcy), endothelial cell dysfunction and accelerated atherosclerosis. However, if this appears to be true for markedly elevated tHcy concentrations, such as those observed in rare inborn disorders of methionine metabolism, it is still controversial as to whether or not moderately elevated tHcy levels contribute independently to increased cardiovascular risk. Some observational studies support this view, whereas others did not find any effect or only in specific subgroups of patients. The best method to answer the question of the causal relationship between homocysteine (Hcy) and cardiovascular disease is to randomise patients at high vascular risk to placebo or Hcy-lowering multivitamin therapy and follow them prospectively for the occurrence of atherothrombotic events. Unfortunately, most of the intervention trials conducted so far have insufficient statistical power to provide conclusive results. …
Competing interests None.