We appreciate Dr Cattaneo's interest in our article. We found that individuals with a history of heart disease had an elevated CHD risk at higher homocysteine values during a 13-year follow-up examination. No association was, however, found in individuals free from heart disease at baseline. Because causal inference is difficult in an observational study such as ours, several interpretations for the associations are possible. Of the alternative interpretations, 2 are of special interest: (1) interaction of hyperhomocysteinemia with some other condition is a risk factor for atherothrombosis (as preferred by Dr Cattaneo) and (2) elevated homocysteine level is a marker of the pathogenesis of atherosclerosis.
Knekt P, Reunanen A, Alfthan G, Heliövaara M, Rissanen H, Marniemi J, Aromaa A. Is Hyperhomocysteinemia a Risk Factor or a Consequence of Coronary Heart Disease?—Reply. Arch Intern Med. 2001;161(21):2628–2629. doi: