Short-term high-dose folic acid does not alter markers of endothelial cell damage in patients with coronary heart disease.
OBJECTIVE
Endothelial dysfunction is an early, pre-clinical manifestation of coronary heart disease and is associated with increased plasma levels of von Willebrand factor (vWF), soluble E-selectin, and thrombomodulin, markers of endothelial cell damage/activation and reduced nitric oxide bioavailability. Homocysteine is associated with an increased risk of cardiovascular disease and mortality. High-dose folic acid treatment lowers plasma homocysteine by 25% and improves nitric oxide bioavailability; however, the effects on other indices of endothelial cell activation/damage has not been examined in patients with coronary heart disease and normal renal function.


METHODS
In a randomised, double-blind, cross-over study in 50 patients with coronary heart disease and normal serum creatinine, folic acid (5 mg/daily) was administered for 6 weeks and blood was analysed for von Willebrand factor, soluble E-selectin, and thrombomodulin. Endothelial nitric oxide bioavailability was assessed by flow-mediated dilatation.


RESULTS
Plasma folate levels increased (9.1+/-3.4 vs. 310+/-235 microg/l; p<0.001) and nitric oxide bioavailability improved (47+/-35 vs. 110+/-43 microm; p<0.001) following active treatment. However, markers of endothelial cell injury were not significantly influenced (von Willebrand factor 118+/-33 vs. 119+/-34%; E-selectin 52+/-17 vs. 51+/-16 microg/l; thrombomodulin 3.94+/-1.81 vs. 3.94+/-1.51 microg/l; p=NS comparing post-placebo with post-folate). No correlation was observed between improvement in flow-mediated dilatation and change in endothelial marker proteins.


CONCLUSIONS
These data suggest that endothelial markers are not useful surrogates of endothelial nitric oxide bioavailability in coronary heart disease and may be a less sensitive marker of endothelial function than nitric oxide.
Doshi
Sagar N
SN
Cardiovascular Sciences Research Group, Department of Pharmacology, Wales Heart Research Institute, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, UK. Sagar.Doshi@msnyuhealth.org
Moat
Stuart J
SJ
Lewis
Malcolm J
MJ
McDowell
Ian F W
IF
Giddings
John C
JC
Goodfellow
Jonathan
J
D000368:Aged; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000503:physiopathology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D005492:Folic Acid / Q000494:pharmacology*; D006397:Hematinics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D018180:Thrombomodulin / Q000097:blood; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D019040:E-Selectin; D006397:Hematinics; D018180:Thrombomodulin; D014841:von Willebrand Factor; D009569:Nitric Oxide; D005492:Folic Acid