Coronary endothelial function in hyperhomocysteinemia: improvement after treatment with folic acid and cobalamin in patients with coronary artery disease.
OBJECTIVE
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 >or=16 micromol/l were randomized for six months of treatment with folic acid 5 mg and cobalamin 400 microg 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.
Department of Cardiology, Rijnstate Hospital, Arnhem, The Netherlands. willemsf@xs4all.nl
Frank F
FF
Willems
Wim R M
WR
Aengevaeren
Godfried H J
GH
Boers
Henk J
HJ
Blom
Freek W A
FW
Verheugt
D000328:Adult; D000368:Aged; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005492:Folic Acid / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014805:Vitamin B 12 / Q000494:pharmacology* / Q000627:therapeutic use
D005492:Folic Acid; D014805:Vitamin B 12