title: Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease.
abstract: Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.
authors.affiliation: Department of Vascular Surgery, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Van den Berg
authors.forename: G H
authors.initials: GH
authors.lastname: Boers
authors.forename: D G
authors.initials: DG
authors.lastname: Franken
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
authors.forename: G J
authors.initials: GJ
authors.lastname: Van Kamp
authors.forename: C
authors.initials: C
authors.lastname: Jakobs
authors.forename: J A
authors.initials: JA
authors.lastname: Rauwerda
authors.forename: C
authors.initials: C
authors.lastname: Kluft
authors.forename: C D
authors.initials: CD
authors.lastname: Stehouwert
mesh_terms: D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D001157:Arterial Occlusive Diseases / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005215:Fasting; D005260:Female; D005492:Folic Acid / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008715:Methionine; D008875:Middle Aged; D011736:Pyridoxine / Q000627:therapeutic use*; D012907:Smoking; D018180:Thrombomodulin / Q000032:analysis; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D015415:Biomarkers; D018180:Thrombomodulin; D014841:von Willebrand Factor; D006710:Homocysteine; D005492:Folic Acid; D002784:Cholesterol; D008715:Methionine; D010959:Tissue Plasminogen Activator; D011736:Pyridoxine