Background & 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 [clot] vs. hemorrhagic [bleeding] 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 5,522 adults with known cardiovascular disease to a daily combination of 2.5 mg of folic acid [vitamin B9], 50 mg of vitamin B6, and 1 mg of vitamin B12, or matching placebo [fake supplements], for 5 years.
• Among 5,522 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 micromol/L in the vitamin therapy group and increased by 0.80 micromol/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). [Note: The difference between an incidence rate of 0.88 and one of 1.15 would be 27%.]
• 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 B6 and B12 did reduce the risk of overall stroke, but not stroke severity or disability.
Source: Stroke, Feb 19, 2009. [Epub ahead of print] PMID: 19228852 Saposnik G, Ray JG, Sheridan P, McQueen M, Lonn E; the HOPE 2 Investigators. Division of Neurology, Departments of Medicine, and Health Policy Management and Evaluation, St. Michael's Hospital, University of Toronto, Ontario; Population Health Research Institute and Department of Pathology and Molecular Medicine, Hamilton General Hospital, McMaster University, Ontario; Department of Medicine, Division of Cardiology, Hamilton Health Sciences, Hamilton, Ontario, Canada. [E-mail: firstname.lastname@example.org]