Folic acid supplementation and biomarkers of progression of sub-clinical coronary atherosclerosis in patients with stable angina pectoris. A WENBIT sub-study based on coronary angiography and intravascular ultrasound

Abstract

Background: Coronary artery disease (CAD) is the leading cause of death in the world. Total plasma homocysteine (tHcy) is an independent risk factor for CAD, and while tHcy is lowered by folic acid (FA)/vitamin B12 (B12) treatment – such therapy has failed to result in clinical benefit. Aim: Investigate the connection between treatment with FA/ B12 and progression of sub-clinical CAD in patients with stable angina pectoris (SAP) with invasive measurements of CAD progression and associated metabolic changes. Materials and methods: Patients included in Sub-group studies from the Western Norway B Vitamin Intervention Trial (WENBIT) undergoing percutaneous coronary intervention were randomized to daily treatment with FA/B12 or placebo. Coronary angiograms and quantitative coronary angiography (QCA) were obtained at baseline and follow-up along with virtual histology intravascular ultrasound. Plasma levels of asymmetric dimethylarginine (ADMA), trimethyllysine (TML) and monocyte chemoattractant protein-1 (MCP-1) were collected. Results: Paper I demonstrated that treatment with FA/B12 was associated with a potential risk of rapid progression of CAD by QCA. Paper II showed that while FA/B12 did not affect levels of ADMA, TML or MCP-1, ADMA and TML predicted progression of CAD by QCA. In paper III MCP-1 was associated with unstable coronary plaques. Conclusion and implications: Vitamin B treatment showed a potential adverse effect on angiographic progression of CAD. While the methylated amino acids ADMA and TML adversely affected CAD – FA/B12 intervention did not affect either ADMA/TML levels or plaque stability as measured by VH-IVUS.