Time for a randomised controlled trial of plasma homocysteine reduction

It is now accepted that an elevated plasma concentration of homocysteine is a risk factor for atherosclerotic vascular disease affecting the coronary, cerebral, and peripheral arteries.1 Prospective data2 3 4 confirm the findings of casecontrol studies5 6 7 8 and indicate that an elevated plasma homocysteine concentration precedes the development of disease and that there is a dose-response effect.

A 5 μmol/l increase in plasma homocysteine concentration has been estimated to raise the risk of coronary heart disease by as much as an increase in serum cholesterol concentration of 0.5 mmol/l.1 Data from the European Union concerted action project, a case-control study of 750 patients with vascular disease and 800 controls, indicate that a plasma homocysteine concentration above 12 μmol/l (the top fifth of the control distribution) doubles the risk of myocardial infarction and cerebral or peripheral vascular disease in both men and women.9 Additional patients at high risk can be identified by stressing the methionine pathway by means of a methionine loading test, analogous to a glucose tolerance …