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Lowering plasma homocysteine with folic acid in cardiovascular disease: what will the trials tell us?

2002; Elsevier BV; Volume: 165; Issue: 1 Linguagem: Inglês

10.1016/s0021-9150(02)00191-0

1879-1484

Sagar N. Doshi, Stuart J. Moat, Ian McDowell, Malcolm Lewis, Jonathan Goodfellow,

Cerebrovascular and Carotid Artery Diseases

Homocysteine, is an amino acid present in plasma under normal conditions,which is now regarded as a risk factor for the development of coronary heart disease (CHD) [ [1] Boushey C.J. Beresford S.A. Omenn G.S. Motulsky A.G. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. J. Am. Med. Assoc. 1995; 274: 1049-1057 Crossref Scopus (3561) Google Scholar ] and also for mortality in established CHD [ [2] Anderson J.L. Muhlestein J.B. Horne B.D. Carlquist J.F. Bair T.L. Madsen T.E. Pearson R.R. Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease. Circulation. 2000; 102: 1227-1232 Crossref PubMed Scopus (213) Google Scholar ] largely independent of other traditional risk factors. However, the association between homocysteine and CHD risk remains controversial and not all studies have been positive [ 3 Alfthan G. Pekkanen J. Jauhiainen M. Pitkaniemi J. Karvonen M. Tuomilehto J. Salonen J.T. Ehnholm C. Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study. Atherosclerosis. 1994; 106: 9-19 Abstract Full Text PDF PubMed Scopus (523) Google Scholar , 4 Evans R.W. Shaten B.J. Hempel J.D. Cutler J.A. Kuller L.H. Homocyst(e)ine and risk of cardiovascular disease in the Multiple Risk Factor Intervention Trial. Arterioscler. Thromb. Vasc. Biol. 1997; 17: 1947-1953 Crossref PubMed Scopus (333) Google Scholar , 5 Folsom A.R. Nieto F.J. McGovern P.G. Tsai M.Y. Malinow M.R. Eckfeldt J.H. Hess D.L. Davis C.E. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1998; 98: 204-210 Crossref PubMed Scopus (593) Google Scholar ]. Furthermore, evidence supporting a link between homocysteine and cardiovascular disease in humans comes largely from observational studies and it is therefore unclear whether homocysteine is directly causal or merely an association of the atherosclerotic process.