No effect of homocysteine-lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease.
BACKGROUND
Although peripheral arterial occlusive disease (PAOD) is significantly associated with elevated homocysteine levels, the clinical relevance of hyperhomocysteinaemia for the prevention and progression of PAOD is still unknown.


METHODS
A total of 65 patients suffering from symptomatic PAOD with elevated homocysteine levels were randomized onto placebo or B-vitamins (50 mg thiaminhydrochlorid, 50 mg pyridoxine, and 0.05 mg cyanocobalamin), plus 5 mg folic acid daily for 6 weeks. Serum levels of folic acid, vitamin B12, creatinine, ultra-sensitive C-reactive protein (usCRP), interleukin (IL)-6, IL-8, IL-18, monocyte-chemo-attractant-protein-1 (MCP-1) and plasma levels of homocysteine, tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were determined on the 1st day and 42nd day. Primary outcome was reduction of homocysteine, secondary outcomes were reduction of usCRP, IL-6, IL-8, Il-18, MCP-1, TF and TFPI.


RESULTS
The mean reduction of homocysteine concentration was 33% (95%CI 33.36-55.76, or 18.9+/-5.4 micromol L-1-12.6+/-2.8 micromol L-1, P=0) in the B-vitamin group compared with 1% in the placebo group. Folic acid (P=0) and vitamin B12 (P=0) increased significantly in the verum group, but both remained unchanged in the control group. No treatment effect of lowering of homocysteine on any markers of haemostasis (TF, TFPI) or inflammation (usCRP, IL-6, IL-8, IL-18 and MCP-1) was observed.


CONCLUSIONS
Although homocysteine is associated with vascular disease risk in the general population and in particular with PAOD, marked lowering of homocysteine concentrations by folic acid and B-vitamin supplementation does not influence inflammatory responses involving usCRP, IL-6, IL-8, IL-18 and MCP-1, nor tissue factor. These results provide evidence against a major effect of hyperhomocysteinaemia on vascular chronic inflammation or coagulation in patients with symptomatic peripheral arterial occlusive disease.
Schernthaner
G-H
GH
Department of Internal Medicine II, Medical University of Vienna, and Department of Internal Medicine I, Rudolfstiftung Hospital, Vienna, Austria. gerit.schernthaner@meduniwien.ac.at
Plank
C
C
Minar
E
E
Bieglmayer
C
C
Koppensteiner
R
R
Schernthaner
G
G
D000368:Aged; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use; D006487:Hemostasis / Q000187:drug effects; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000150:complications / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000209:etiology*; D014657:Vasculitis / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D014803:Vitamin B Complex / Q000627:therapeutic use
D015415:Biomarkers; D018836:Inflammation Mediators; D006710:Homocysteine; D014803:Vitamin B Complex; D005492:Folic Acid