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CLINICAL STUDY: ENDOTHELIAL FUNCTION ASSESSMENT

Coronary endothelial function in hyperhomocysteinemia: improvement after treatment with folic acid and cobalamin in patients with coronary artery disease

Frank F. Willems, MD^*,*, Wim R. M. Aengevaeren, MD, PhD, Godfried H. J. Boers, MD, PhD, Henk J. Blom, PhD and Freek W. A. Verheugt, MD, PhD, FACC

^* Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands
Heart Center, University Medical Center, Nijmegen, The Netherlands
Department of Internal Medicine, University Medical Center, Nijmegen, The Netherlands
Laboratory of Pediatrics and Neurology, University Medical Center, Nijmegen, The Netherlands

Manuscript received November 30, 2001; revised manuscript received April 16, 2002, accepted May 15, 2002.

^* Reprint requests and correspondence: Dr. Frank F. Willems, Department of Cardiology, Rijnstate Hospital, P.O. Box 9555, Arnhem, The Netherlands.
willemsf{at}xs4all.nl

OBJECTIVES: We evaluated the effect of therapy with folic acid and cobalamin on coronary endothelial function, expressed as a change in volumetric coronary blood flow (CBF), in hyperhomocysteinemic patients with coronary artery disease (CAD).

BACKGROUND: Hyperhomocysteinemia is an independent risk factor for CAD. The mechanism responsible for this increased risk is unclear, but it is generally assumed that hyperhomocysteinemia causes endothelial dysfunction. It is unknown whether lowering plasma homocysteine levels with folic acid and cobalamin improves coronary endothelial function in patients with hyperhomocysteinemia and symptomatic CAD.

METHODS: Fifteen patients scheduled for elective percutaneous transluminal coronary angioplasty (PTCA) with plasma homocysteine levels of 16 µmol/l were randomized for six months of treatment with folic acid 5 mg and cobalamin 400 µg daily or placebo. Coronary endothelial function was evaluated in a non-PTCA vessel using acetylcholine infusion in dosages of 10^–8 M, 10^–7 M, and 10^–6 M. Endothelium- dependent CBF is determined using intracoronary Doppler velocity and quantitative coronary angiography at baseline and after six months.

RESULTS: In the folic acid/cobalamin treated group, CBF increased after acetylcholine infusion with 96% (standard deviation 54; 95% confidence interval [CI]: 44% to 154%) compared with a decrease of 16% (standard deviation 35; 95% CI: –20% to +30%) of the CBF in the placebo-treated group (p < 0.005).

CONCLUSIONS: This is the first prospective randomized placebo-controlled intervention study evaluating coronary endothelial function in hyperhomocysteinemic patients with CAD. Our results suggest that coronary endothelial function improves after treatment with folic acid and cobalamin.

Abbreviations and Acronyms   ACH   acetylcholine   CAD   coronary artery disease   CBF   volumetric coronary blood flow   CI   confidence interval   CVR   coronary velocity range   LAD   left anterior descending artery   MOD   minimal obstruction diameter   MSD   mean segment diameter   PTCA   percutaneous transluminal coronary angioplasty   RCA   right coronary artery   RCX   ramus circumflexus   SD   standard deviation   tHcy   total plasma homocysteine

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