Department of Internal Medicine II (G.-H. Schernthaner, C. Plank, E. Minar, R. Koppensteiner), Department of Radiology (C. Plank), Department of Medical and Chemical Laboratory Diagnostics (C. Bieglmayer), Medical University of Vienna; Department of Internal Medicine I, Rudolfstiftung Hospital (G. Schernthaner), Vienna, Austria.
No effect of homocysteine-lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease
Article first published online: 18 APR 2006
European Journal of Clinical Investigation
Volume 36, Issue 5, pages 333–339, May 2006
How to Cite
Schernthaner, G.-H., Plank, C., Minar, E., Bieglmayer, C., Koppensteiner, R. and Schernthaner, G. (2006), No effect of homocysteine-lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease. European Journal of Clinical Investigation, 36: 333–339. doi: 10.1111/j.1365-2362.2006.01639.x
- Issue published online: 18 APR 2006
- Article first published online: 18 APR 2006
- Received 2 January 2006; accepted 7 March 2006
- Folic acid;
- 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.
Materials and 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 µmol L−1−12·6 ± 2·8 µmol 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.
Conclusion 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.