Nilsson-Ehle H. Lowering of plasma homocysteine and reduction of coronary restenosis. Rondel 2002; 10: Debate (www.rondellen.net, jan-mar 2002)

Lowering of plasma homocysteine and reduction in coronary restenosis

Whether lowering of homocysteine (P-tHcys) is clinically beneficial or not, is the subject of ongoing studies, see previous review in the Rondel [1]. Results are expected to emerge within the next years. So far, homocysteine has not been proven to be a causative risk factor for atherothrombotic disease [2]C:\Documents and Settings\Administrator\My Documents\HNE\Refs\b1200.ref #358; in randomised studies, although certain epidemiological and experimental data suggest this. For example, B-vitamin supplementation has been shown to reverse carotid plaques [3]. In a prospective, randomised double-blind study of 205 consecutive coronary patients (mean age 61 years) recently published in the N Engl J Med [4], supplementation with B vitamins affected clinically relevant endpoints. A combination of vitamins (1mg folic acid, 0.4 mg vitamin B₁₂, 10 mg vitamin B₆) given after percutaneous coronary angioplasty lead to fewer restenoses (primary endpoint) and serious cardiac events (secondary endpoints) than placebo during 6 months follow-up. The groups were well balanced for gender, cardiovascular risk factors in the medical history, laboratory analyses (glycosylated Hb, creatinine, lipids) and additional therapy (statins, beta blockers and angiotensin-converting-enzyme inhibitors). Baseline P-tHcys were in the vitamin group mean 11.1 (SD4.3), in the placebo group 10.8 (SD4.0) m mol/l, after six months of vitamin supplementation 7.2 (SD2.4) and 9.5 (SD3.6) m mol/l, respectively (p<0.001). Restenosis occurred in 19.6% of the vitamin group, in 37.6% of the placebo group (p=0.01). The decrease of P-tHcys was more pronounced in subjects without restenosis, 14% showed neither decline in P-tHcys, nor decreased restenoses. In a multivariate analysis of all variables correlating to restenosis, only vitamin supplementation and previous restenosis retained statistical (independent) significance. Serious cardiac events occurred in 12.7% in the vitamin group, in 24.5% in the placebo group (p=0.055), event free survival in the vitamin group was 87%, in the placebo group 75.5% (p=0.02). There were no differences in cardiac deaths or non-fatal myocardial infarctions during the study period, and hopefully, long-term morbidity and mortality for the study population will also be assessed. It’s noteworthy that baseline P-tHcys were not very "high", but declined some 35 % by vitamin therapy. It was concluded that lowering of P-tHcys with supplementation with vitamin B₁₂, folic acid and vitamin B₆ lead to significantly fewer restenoses and cardiac complications after percutaneous coronary angioplasty. This study indicates P-tHcys to be a modifiable cardiovascular risk factor in this very population. Whether this is true also for other populations (with or without cardiovascular disorders) remains to be shown, and forthcoming results from ongoing and planned intervention studies with clinical endpoints will be very interesting.

Herman Nilsson-Ehle

[1]. Hultdin J. Trials of trials - effects of homocystein-lowering regimes on atherothrombotic disease. The Rondel 2000;5.

[2]. Blacher J, Safar ME. Homocysteine, folic acid, B vitamins and cardiovascular risk. J Nutr Health Aging 2001;5(3):196-9.

[3]. Hackam DG, Peterson JC, Spence JD. What level of plasma homocyst(e)ine should be treated? Effects of vitamin therapy on progression of carotid atherosclerosis in patients with homocyst(e)ine levels above and below 14 micromol/L. Am J Hypertens 2000;13(1 PT 1):105-10.

[4]. Schnyder G, Roffi M, Pin R, Flammer Y, Lange H, Eberli FR et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med 2001;345(22):1593-600.

Published January 28, 2002

Published January 6, 2002