Homocysteine-Lowering Therapy and Stroke Risk, Severity, and Disability Additional Findings From the HOPE 2 Trial

被引:212
作者
Saposnik, Gustavo [1 ,2 ,3 ]
Ray, Joel G. [3 ]
Sheridan, Patrick [4 ]
McQueen, Matthew [4 ,5 ]
Lonn, Eva [4 ]
机构
[1] Univ Toronto, St Michaels Hosp, Dept Med, Stroke Res Unit,Div Neurol, Toronto, ON M5C 1R6, Canada
[2] Univ Toronto, St Michaels Hosp, Dept Hlth Policy Management & Evaluat, Div Neurol, Toronto, ON M5C 1R6, Canada
[3] Univ Toronto, St Michaels Hosp, Dept Obstet & Gynecol, Toronto, ON M5C 1R6, Canada
[4] McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada
[5] McMaster Univ, Hamilton Gen Hosp, Dept Pathol & Mol Med, Hamilton, ON, Canada
关键词
cardiovascular disease; folate; folic acid; homocysteine; primary stroke; randomized clinical trial; secondary stroke; stroke prevention; vitamin B12; FOLIC-ACID SUPPLEMENTATION; VITAMIN INTERVENTION; PREVENTION; EFFICACY;
D O I
10.1161/STROKEAHA.108.529503
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Elevated total homocysteine is associated with a higher risk of cerebrovascular disease. It is not known whether lowering homocysteine impacts on stroke risk, both in terms of severity and ischemic vs hemorrhagic stroke subtypes. Our aim was to determine whether vitamin therapy reduces the risk of ischemic and hemorrhagic stroke, as well as stroke-related disability. Methods-We analyzed stroke outcomes among participants of the Heart Outcomes Prevention Evaluation 2 (HOPE 2) trial that randomized 5522 adults with known cardiovascular disease to a daily combination of 2.5 mg of folic acid, 50 mg of vitamin 136, and I mg of vitamin 1312, or matching placebo, for 5 years. Results-Among 5522 participants, stroke occurred in 258 (4.7%) individuals during a mean of 5 years of follow-up. The geometric mean homocysteine concentration decreased by 2.2 mu mol/L in the vitamin therapy group and increased by 0.80 mu mol/L in the placebo group. The incidence rate of stroke was 0.88 per 100 person-years in the vitamin therapy group and 1.15 per 100 person-years in the placebo group (hazard ratio [HR], 0.75; 95% CI, 0.59-0.97). Vitamin therapy also reduced the risk of nonfatal stroke (HR, 0.72; 95% CI, 0.54-0.95) but did not impact on neurological deficit at 24 hours (P=0.45) or functional dependence at discharge or at 7 days (OR, 0.95; 95% CI, 0.57-1.56). In subgroup analysis, patients aged younger than 69 years, from regions without folic acid food fortification, with higher baseline cholesterol and homocysteine levels, and those not receiving antiplatelet or lipid-lowering drugs at enrollment had a larger treatment benefit. Conclusions-Lowering of homocysteine with folic acid and vitamins 136 and B12 did reduce the risk of overall stroke, but not stroke severity or disability. (Stroke. 2009;40:1365-1372.)
引用
收藏
页码:1365 / 1372
页数:8
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