Homocysteine and cardiovascular disease
Research over the past decade has shown that elevated levels of homocysteine have a strong association with all forms of atherothrombotic disease and venous thromboembolism. This association is particularly strong for coronary disease and newer data indicate that screening for homocysteine levels may be warranted in those with unexplained thrombotic tendencies and in young patients who develop coronary events or disease without the usual predisposing factors such as hypertension, smoking, hypercholesterolemia, or diabetes. Although the link between hyperhomocysteinemia and cardiac disease has not been conclusively shown to be causal as yet, data are emerging that lowering homocysteine levels may be beneficial in patients at high risk. Such lowering can be done safely and inexpensively with increased intake of fruits and vegetables and in those patients who are particularly at high risk using supplementation with folic acid and the B vitamins. Preliminary studies have shown that lowering homocysteine levels in this manner may slow the progression of atherosclerosis in coronary and carotid vessels. No mortality data exist yet showing that reducing homocysteine reduces cardiac or total mortality, although it is likely that ongoing and planned trials that are underway will shed light on these important questions soon.
Malinow MR, Bostom AG, Krauss RM: Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association
Wald DS, Law M, Morris JK: Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis
Boushey CJ, Beresford SA, Omenn GS, Motulsky AG: A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes
Nygard O, Nordrehaug JE, Refsum H, et al.
: Plasma homocysteine levels and mortality in patients with coronary artery disease
. N Engl J Med
Anderson JL, Muhlestein JB, Horne BD, et al.
: Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically defined coronary artery disease
Hoogeveen EK, Kostense PJ, Eysink PE, et al.
: Hyperhomocysteinemia is associated with the presence of retinopathy in type 2 diabetes mellitus: the Hoorn study
. Arch Intern Med
Stubbs PJ, Al Obaidi MK, Conroy RM, et al.
: Effect of plasma homocysteine concentration on early and late events in patients with acute coronary syndromes
Schnyder G, Roffi M, Pin R, et al.
: Decreased rate of coronary restenosis after lowering of plasma homocysteine levels
. N Engl J Med
Graham IM, Daly LE, Refsum HM, et al.
: Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project
Nishio E, Watanabe Y: Homocysteine as a modulator of platelet-derived growth factor action in vascular smooth muscle cells: a possible role for hydrogen peroxide
. Br J Pharmacol
Dalton ML, Gadson PF Jr, Wrenn RW, Rosenquist TH: Homocysteine signal cascade: production of phospholipids, activation of protein kinase C, and the induction of c-fos and c-myb in smooth muscle cells
. FASEB J
Woo KS, Sanderson JE, Sun YY, et al.
: Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans.
Van den BM, Boers GH, Franken DG, et al.
: Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease
. Eur J Clin Invest
Chambers JC, Ueland PM, Obeid OA, et al.
: Improved vascular endothelial function after oral B vitamins: An effect mediated through reduced concentrations of free plasma homocysteine
Stein JH, Bushara M, Bushara K, et al.
: Smoking cessation, but not smoking reduction, reduces plasma homocysteine levels
. Clin Cardiol
Schnyder G, Roffi M, Flammer Y, et al.
: Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial
Zairis MN, Ambrose JA, Manousakis SJ, et al.
: The impact of plasma levels of C-reactive protein, lipoprotein (a) and homocysteine on the long-term prognosis after successful coronary stenting: The Global Evaluation of New Events and Restenosis After Stent Implantation Study
. J Am Coll Cardiol
Schnyder G, Rouvinez G: Total plasma homocysteine and restenosis after percutaneous coronary angioplasty: current evidence
. Ann Med
Vasan RS, Beiser A, D’Agostino RB, et al.
: Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction
Mangoni AA, Jackson SH: Homocysteine and cardiovascular disease: current evidence and future prospects
. Am J Med
Carlsson CM, Stein JH: Clinical trials testing the homocysteine hypothesis
. Ann Intern Med
© Current Science Inc 2004