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Abstract Background Hyperhomocysteinaemia is an independent risk factor for atherosclerosis and is thought to induce its effects through causing endothelial dysfunction. We studied the effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on urinary and plasma markers of endothelial function, and on plasma C-reactive protein, a marker of chronic inflammation. Design We performed a placebo-controlled 2-year trial among 158 healthy siblings of patients with premature atherosclerotic disease to determine the effect of daily folic acid (5 mg) plus vitamin B6 (250 mg) treatment as compared with placebo medication (n = 80) on markers of endothelial function (urinary albumin-to-creatinine ratio and plasma concentrations of soluble E-selectin, soluble vascular cell adhesion molecule-1, von Willebrand factor, tissue-type plasminogen activator and plasminogen activator inhibitor-1) and inflammation (C-reactive protein). Outcome variables were assessed at baseline and after 1 and 2 years of treatment. Results Fasting homocysteine concentrations (µmol L-1 ) at baseline and after treatment were 14·7 ± 8·2 and 7·4 ± 1·9 in the vitamin and 14·7 ± 8·8 and 12·0 ± 5·4 for the placebo group, respectively. Vitamin treatment was associated with a decreased urinary albumin-to-creatinine ratio at follow up [regression coefficient (β) –0·20 mg mmol-1 (CI: -0·43–0·03); P = 0·09]. After adjustment for age, sex, baseline concentrations of postmethionine total homocysteine plus the baseline albumin-to-creatinine ratio, the β was –0·23 mg mmol-1 (CI: –0·43 to –0·02; P = 0·03), which amounts to a decrease of approximately 20%. There was no apparent effect of vitamin treatment on the other markers. Conclusions Homocysteine-lowering vitamin treatment in healthy siblings of... [ABSTRACT FROM AUTHOR]

Objectives: Mild hyperhomocysteinaemia (HHC), fasting or after methionine loading, is associated with an increased risk and severity of atherosclerotic vascular disease. Post-methionine and fasting HHC are responsive to treatment with vitamin B, and folic acid. We performed a prospective cohort study amongst normohomocysteinaemic and vitamin-treated (vitamin B6, 250 mg plus folic acid, 5 mg daily) hyperhomocysteinaemic patients with premature peripheral arterial occlusive disease and assessed the incidence of cardiovascular events.Design: We studied 273 consecutive patients with clinically manifest peripheral arterial occlusive disease with onset before the age of 56, 79 (28.9%) of whom had postmethionine HHC. Follow-up was obtained in 232 (85'%o) patients. At baseline, 70 (30')/) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B, and folic acid; 162 (70%) were normohomocysteinaemic (reference group).Results: During the follow-up period (median 20, range 1-63 months), 48 (29.6%) and 23 (32.9%) of the normo- and the hyperhomocysteinaemic patients, respectively, had a new cardiovascular event. Most (75%) involved the peripheral arterial system. The crude incidence rate for any cardiovascular event was 0.16 (95% CI, 0.12-0.21) per person per year in the normohomocysteinaemic and 0.16 (95% CI, 0.09-0.22) per person per year in the hyperhomocysteinaemic group. Multivariate Cox regression analyses showed that higher plasma homocysteine levels were associated with an increased risk of new cardiovascular events in the normohomocysteinaemic patients (relative risk [RR] per 1 micromol L(-1), 1.17 [CI, 1.05-1.30] for fasting and 1.06 [CI, 1.01-1.12] for postmethionine levels), but not in the hyperhomocysteinaemic (vitamin-treated) patients. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.76 (CI, 0.33-1.74).Conclusions: These data are consistent with a protective effect of treatment with vitamin B6 and folic acid in patients with premature peripheral arterial occlusive disease and postmethionine HHC. Double-blind randomized trials are necessary to confirm this. [ABSTRACT FROM AUTHOR]