Many studies have demonstrated a strong association between elevated plasma total homocyst(e)ine levels and vascular diseases. Consequently, hyperhomocyst(e)inemia is now generally accepted as an independent risk factor for coronary artery disease. We critically reviewed the results of 35 human studies in which the levels of plasma total homocysteine were measured in patients with atherosclerotic diseases (n=4338) and in controls (n=22) 593). Total homocysteine levels were consistently higher in patients than in controls. The average of this increment among 23 case-control studies was 26%. New insights into the biochemical pathways of total homocysteine metabolism, the factors that influence total homocysteine levels, genetic contributions to hyperhomocyst(e)inemia, the pathogenesis of homocyst(e)ine-induced vascular damage, and current recommendations for treatment of hyperhomocyst(e)inemia were also reviewed. Various lines of evidence now link hyperhomocyst(e)inemia with vascular diseases. Although there are no data from double-blind, placebo-controlled clinical trials of treatment for hyperhomocyst(e)inemia, the strong epidemiologic and experimental evidence argues for treatment of hyperhomocyst(e)inemia; in fact, its treatment with low doses of vitamins is thought to be safe and is inexpensive.
Arch Intern Med. 1997;157:2299-2308