Association of plasma homocysteine with restenosis after percutaneous coronary angioplasty.

AIMS: Restenosis after percutaneous coronary angioplasty remains an important limitation of this procedure. This study evaluates whether elevated total plasma homocysteine levels contribute to the development of restenosis after coronary angioplasty. METHODS AND RESULTS: Two hundred and five patients were recruited after successful angioplasty of at least one coronary stenosis (> or =50%). End-points were restenosis (> or =50%) and a composite of major adverse cardiac events. Of the 205 patients, 183 (89.3%) underwent 6 months angiographic follow-up. Patients with restenosis had significantly higher homocysteine levels than those without (10.9+/- 3.9 micromol x l(-1) vs 9.3+/-3.8 micromol x l(-1), P<0.01). Homocysteine levels were significantly correlated to follow-up diameter stenosis (r=0.24, P=0.0001), especially in small vessels (<3 mm) treated with balloon angioplasty only (r=0.40, P<0.0005). Late lumen loss at follow-up was significantly smaller with homocysteine levels below 9 micromol x l(-1) (0.62+/-0.82 mm vs 0.90+/-0.77 mm, P<0.01). Restenosis rate (25.3% vs 50.0%, P<0.001) and major adverse cardiac events (15.7% vs 28.4%, P<0.05) were also significantly lower in patients with homocysteine levels below 9 micromol x l(-1). Multivariate analysis did not weaken these findings. CONCLUSION: Total plasma homocysteine is a strong predictor of restenosis and major adverse cardiac events after coronary angioplasty. Thus, plasma homocysteine appears to be an important cardiovascular risk factor influencing outcome after successful coronary angioplasty.

Decreased rate of coronary restenosis after lowering of plasma homocysteine levels.

BACKGROUND: We have previously demonstrated an association between elevated total plasma homocysteine levels and restenosis after percutaneous coronary angioplasty. We designed this study to evaluate the effect of lowering plasma homocysteine levels on restenosis after coronary angioplasty. METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD] age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial. The primary end point was restenosis within six months as assessed by quantitative coronary angiography. The secondary end point was a composite of major adverse cardiac events. RESULTS: Base-tine characteristics and initial angiographic results after coronary angioplasty were similar in the two study groups. Folate treatment significantly lowered plasma homocysteine levels from 11.1+/-4.3 to 7.2+/-2.4 micromol per liter (P<0.001). At follow-up, the minimal luminal diameter was significantly larger in the group assigned to folate treatment (1.72+/-0.76 vs. 1.45+/-0.88 mm, P=0.02), and the degree of stenosis was less severe (39.9+/-20.3 vs. 48.2+/-28.3 percent, P=0.01). The rate of restenosis was significantly lower in patients assigned to folate treatment (19.6 vs. 37.6 percent, P=0.01), as was the need for revascularization of the target lesion (10.8 vs. 22.3 percent, P=0.047). CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty. This inexpensive treatment, which has minimal side effects, should be considered as adjunctive therapy for patients undergoing coronary angioplasty.