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

被引:257
作者
Vermeulen, EGJ
Stehouwer, CDA
Twisk, JWR
van den Berg, M
de Jong, SC
Mackaay, AJC
van Campen, CMC
Visser, FC
Jakobs, CAJM
Bulterijs, EJ
Rauwerda, JA
机构
[1] Univ Hosp Vrije Univ, Dept Internal Med, NL-1007 MB Amsterdam, Netherlands
[2] Univ Hosp Vrije Univ, Dept Gen Surg, Vasc Surg Unit, NL-1007 MB Amsterdam, Netherlands
[3] Univ Hosp Vrije Univ, Dept Cardiol, NL-1007 MB Amsterdam, Netherlands
[4] Univ Hosp Vrije Univ, Dept Clin Chem, Metab Unit, NL-1007 MB Amsterdam, Netherlands
[5] Vrije Univ Amsterdam, Inst Cardiovasc Res, Amsterdam, Netherlands
[6] Inst Res Extramural Med, Amsterdam, Netherlands
关键词
D O I
10.1016/S0140-6736(99)07391-2
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 B-6) 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 B-6 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 mu mol/L vs from 14.7 to 12.0 mu mol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 mu mol/L vs from 64.8 to 50.3 mu mol/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 Be 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.
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页码:517 / 522
页数:6
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