Abstract

Hyperhomocysteinaemia is a well-known risk factor for venous thromboembolic disease (VTD). However, it is not clear whether homocysteine (Hc) itself or a related metabolite or a cofactor is primarily responsible for VTD. We carried out a case-control study to investigate whether vitamin concentrations that are involved in the Hc metabolism are associated or not with an elevated risk of VTD. Case-control study. We measured serum vitamin B12, folate, creatinine and albumin concentrations and plasma Hc concentrations in 101 consecutive patients with VTD, diagnosed by image tests and 101 control subjects, matched for age and sex. Serum vitamin B12 concentrations were significantly lower in VTD patients than in the control subjects. There were no differences in plasma Hc or serum folate concentrations between the groups. Among the male subgroup aged more than 70 years, serum vitamin B12 concentrations were significantly lower (240.88 +/- 103.07 vs. 421.20 +/- 314.31 pmol L(-1); P = 0.03) and plasma Hc concentrations were significantly higher (13.1 +/- 4.18 vs. 10.56 +/- 3.06 micromol L(-1); P =0.04) in VTD patients than in the control group. On multivariate analysis, in patients aged more than 70 years, serum vitamin B12 concentrations were independently associated with VTD. Compared with the highest quartile of vitamin B12 (>512.6 pmol L(-1)) the odds ratio (OR) for VTD in the lowest quartile (<230.9 pmol L(-1)) was 3.8 (95% CI 1.44-10.18; P = 0.01). In the VTD group, lowest vitamin B12 concentrations (percentile 10 <152.8 pmol L(-1)) were associated with the factor V Leiden mutation (OR = 6.07, 95% CI 0.93-38.55; P = 0.04). Measuring vitamin B12 concentrations in elderly males may help in identifying people at risk of venous thromboembolism in our population.

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