Preventive cardiology
Effect of Homocysteine-Lowering B Vitamin Treatment on Angiographic Progression of Coronary Artery Disease: A Western Norway B Vitamin Intervention Trial (WENBIT) Substudy

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Total plasma homocysteine (tHcy) is an independent risk factor for coronary artery disease, and tHcy is lowered by B vitamins. To assess the effect of homocysteine-lowering B-vitamin treatment on angiographic progression of coronary artery disease, this substudy of the Western Norway B Vitamin Intervention Trial (WENBIT) included patients who had undergone percutaneous coronary intervention. The patients were randomized to daily oral treatment with folic acid, vitamin B12, and vitamin B6 or placebo in a 2 × 2 factorial design. The coronary angiograms obtained at baseline and follow-up were evaluated. The primary angiographic end points were the changes in minimum lumen diameter and diameter stenosis. A total of 348 subjects (288 men) with a mean ± SD age of 60 ± 10.2 years were followed up for a median of 10.5 months (twenty-fifth, seventy-fifth percentile 9.2, 11.8). The baseline median plasma tHcy level was 10.0 μmol/L (twenty-fifth, seventy-fifth percentile 8.1, 11.0), and treatment with folic acid/vitamin B12 lowered the tHcy levels by 22%. At follow-up, we found 309 lesions with a significant decrease from baseline in the minimum lumen diameter of a mean of −0.16 ± 0.4 mm and an increase in the diameter stenosis of 4.4 ± 0.7%. Treatment with folic acid/vitamin B12 or vitamin B6 was not associated with a change in diameter stenosis or minimum lumen diameter. In a post hoc analysis, folic acid/vitamin B12 treatment was significantly associated with rapid progression (odds ratio 1.84, 95% confidence interval 1.07 to 3.18). In conclusion, vitamin B treatment showed no beneficial effect on the angiographic progression of coronary artery disease, and the post hoc analyses suggested that folic acid/vitamin B12 treatment might promote more rapid progression.

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Methods

The subjects included in the present study participated in the Western Norway B Vitamin Intervention Trial (WENBIT), a double-blinded, placebo-controlled, 2-center trial that included 3,090 adult patients (20.5% women) who had undergone coronary angiography for suspected CAD. The details and the main results of the trial have been previously described.7 To simultaneously evaluate the effect of folic acid/vitamin B12 and vitamin B6, the patients were randomly assigned to 1 of 4 groups, using a 2

Results

Figure 1 shows the numbers of patients eligible for and included in the present study. Of the 570 WENBIT participants who underwent PCI after baseline coronary angiography at Haukeland University Hospital, 371 (65%) underwent repeat angiography. Of these, 342 patients (92%) underwent scheduled repeat angiography and 29 (8%) had a clinical indication for repeat angiography. A total of 23 participants (6%) were excluded from the analysis because of inadequate angiograms. Of the remaining 348

Discussion

In the present substudy of a large randomized clinical trial of homocysteine-lowering vitamin B treatment, a total of 348 patients were available for serial QCA analysis after baseline coronary angiography. Of these, 183 patients had 309 coronary lesions at baseline or follow-up that fulfilled the angiographically defined inclusion criteria. The patients were followed up for a median of 10 months for the assessment of CAD progression using QCA. The baseline homocysteine levels were relatively

Acknowledgment

We especially thank study nurse Janne Dyngeland, RN, and statistician Tore Wentzel-Larsen, MSc, for their invaluable help.

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    The Western Norway B Vitamin Intervention Trial was funded by the Advanced Research Program and Research Council of Norway, Oslo, Norway; the Norwegian Foundation for Health and Rehabilitation, the Norwegian Heart and Lung Patient Organisation, Oslo, Norway; the Norwegian Ministry of Health and Care Services, Oslo, Norway; the Western Norway Regional Health Authority, Stavanger, Norway; the Department of Heart Disease at Haukeland University Hospital, Bergen, Norway; the Locus for Homocysteine and Related Vitamins at the University of Bergen, Bergen, Norway; the Locus for Cardiac Research at the University of Bergen, Bergen, Norway; the Foundation to Promote Research Into Functional Vitamin B12 Deficiency, Bergen, Norway, and Alpharma Inc., Copenhagen, Denmark.

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