Effect of Long-Term Homocysteine Reduction with B Vitamins on Arterial Wall Inflammation Assessed by Fluorodeoxyglucose Positron Emission Tomography: A Randomised Double-Blind, Placebo-Controlled Trial

Abstract

Background: Homocysteine may promote atherosclerosis by exacerbating inflammatory processes within the arterial wall. B-vitamin supplements reduce total plasma homocysteine concentrations (tHcy), but it is not known whether the treatment also reduces arterial wall inflammation. We used ¹⁸F-fluorodeoxygluose positron emission tomography (¹⁸F-FDG PET) to investigate whether long-term homocysteine-lowering treatment alters arterial wall inflammation in patients with a history of ischemic stroke. Methods: 30 stroke patients were randomly assigned to B-vitamin therapy (folic acid 2 mg, vitamin B₆ 25 mg and vitamin B₁₂ 0.5 mg) or placebo in a double-blind clinical trial. After a mean treatment period of 4.0 ± 0.7 years, all subjects had tHcy, carotid intima-medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery measured and underwent an ¹⁸F-FDG PET scan. Standardised uptake values (SUV) were measured at six sites in the carotid, femoral and aortic arteries. Areas of locally increased tracer uptake in the arterial wall (‘hot spots’) were also identified and counted. Results: Long-term B-vitamin treatment significantly reduced tHcy compared with placebo (8.4 μmol/l, 95% confidence interval, CI, 7.2–9.6 vs. 11.6 μmol/l, 95% CI 10.0–13.4, p = 0.002). The treatment did not affect mean arterial SUV (2.0 ± 0.3 vitamins vs. 2.1 ± 0.3 placebo, p = 0.65) or the number of hot spots (n = 1.1 ± 1.0 vitamins vs. n = 1.2 ± 1.0 placebo, p = 0.65). There was no significant correlation between mean arterial SUV and CIMT or FMD. Conclusions: These results suggest that a long-term Hcy reduction with B vitamins does not affect arterial wall inflammation assessed by ¹⁸F-FDG PET.