E. Vermeulen

Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial

BACKGROUND A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease. METHODS We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography. FINDINGS Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively). INTERPRETATION Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.

Homocysteine-lowering treatment with folic acid plus vitamin B6 lowers urinary albumin excretion but not plasma markers of endothelial function or C-reactive protein: further analysis of secondary end-points of a randomized clinical trial.

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.

Effect of homocysteine‐lowering treatment with folic acid plus vitamin B6 on cerebrovascular atherosclerosis and white matter abnormalities as determined by MRA and MRI: a placebo‐controlled, randomized trial

Background  A high plasma homocysteine concentration is an independent risk factor for large and possibly small vessel disease. We investigated the effects of homocysteine‐lowering treatment with folic acid plus vitamin B6 on markers of cerebrovascular atherosclerosis and cerebral microangiopathy.

Effect of homocysteine-lowering vitamin treatment on electrocardiography stress tests in a randomized, placebo-controlled trial: comparison between ST-segment changes and athen QRS-score

E.G.J. Vermeulen*, M.I.A. van Engeland, F.C. Visser, C.D.A. Stehouwer, J.W.R. Twisk, C.M.C. van Campen, J.A. Rauwerda Department of Surgery, Vascular Surgical Unit, VU University Medical Center, Amsterdam, The Netherlands Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands d Institute for Cardiovascular Research ‘‘Vrije Universiteit’’ (ICaR-VU), Amsterdam, The Netherlands e Institute for Research in Extramural Medicine (EMGO), Amsterdam, The Netherlands