doi: 10.1161/hq1201.100223
© 2001 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Long-Term Homocysteine-Lowering Treatment With Folic Acid Plus Pyridoxine Is Associated With Decreased Blood Pressure but Not With Improved Brachial Artery Endothelium-Dependent Vasodilation or Carotid Artery Stiffness
A 2-Year, Randomized, Placebo-Controlled Trial
From the Institute for Cardiovascular Research Vrije Universiteit (R.A.J.M.v.D., J.A.R., M.S., J.W.R.T., C.D.A.S.) and Department of Internal Medicine (R.A.J.M.v.D., M.S., C.D.A.S.), University Hospital Vrije Universiteit, Department of Surgery (J.A.R.), University Hospital Vrije Universiteit, and Institute for Research in Extramural Medicine (J.W.R.T.), Vrije Universiteit, Amsterdam, Netherlands.
Reprint requests to Professor Coen D.A. Stehouwer, University Hospital Vrije Universiteit, Department of Internal Medicine, De Boelelaan 1117, 1081 HV Amsterdam, Netherlands, and PO Box 7057, 1007 MB Amsterdam, Netherlands. E-mail cda.stehouwer{at}vumc.nl
Homocysteine is associated with atherothrombotic disease, which may be mediated through associations of homocysteine levels with blood pressure, endothelial function, or arterial stiffness. In a placebo-controlled, randomized clinical trial, we measured blood pressure, brachial artery endothelium-dependent vasodilation, and common carotid artery stiffness in 158 clinically healthy siblings of patients with premature atherothrombotic disease at baseline and after 1 and 2 years of homocysteine-lowering treatment with folic acid (5 mg) plus pyridoxine (250 mg). Intention-to-treat analyses limited to participants (n=130) who underwent at least 1 measurement after the baseline visit showed that compared with placebo, treatment with folic acid plus pyridoxine was associated with a 3.7-mm Hg (95% CI -6.8 to -0.6 mm Hg) lower systolic and a 1.9-mm Hg (95% CI -3.7 to -0.02 mm Hg) lower diastolic blood pressure over the 2-year trial period. Together with the decreased occurrence of abnormal exercise electrocardiography tests reported previously, our results support the hypothesis that homocysteine-lowering treatment with folic acid plus pyridoxine has beneficial vascular effects. Because no effects could be demonstrated on brachial artery endothelium-dependent vasodilation or on common carotid artery stiffness, the present study does not support the hypothesis that the cardiovascular effects of homocysteine are mediated through these factors, at least in clinically healthy individuals.
Key Words: homocysteine • blood pressure • common carotid artery stiffness • brachial artery flow-mediated vasodilation • folic acid • pyridoxine
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