Letters Section Editor: Stephen J. Lurie,
MD, PhD, Senior Editor.
To the Editor: Dr Toole and colleagues1 concluded that reduction of serum homocysteine
levels had no effect on recurrent cerebral infarction, coronary heart disease,
and death after 2 years of follow-up. As the authors acknowledged, the trial
lacked statistical power to show the reduction in risk that would be expected
from the observed changes in serum homocysteine levels. The average difference
in serum homocysteine levels in the trial between the treated and control
groups after 1 year was 2.2 µmol/L. It has been estimated2 that
a 3-µmol/L reduction in serum homocysteine level is associated with
a relative risk of stroke of 0.76 (95% confidence interval [CI], 0.67-0.85)
and a relative risk of coronary heart disease events of 0.84 (95% CI, 0.80-0.89).
Therefore, a 2.2-µmol/L difference in serum homocysteine levels would,
over enough time, be expected to result in an 18% (95% CI, 11%-25%) reduction
in risk of stroke and a 12% (95% CI, 8%-15%) reduction in the risk of coronary
heart disease events. The trial found a 10% reduction in risk of coronary
heart disease (relative risk, 0.9 [95% CI, 0.7-1.2]) but no decrease in stroke
(relative risk, 1.0 [95% CI, 0.8-1.3]). The result for coronary heart disease
is close to that expected from the reduction in serum homocysteine levels,
and the result for stroke is within the expected 95% CIs. One cannot, therefore,
conclude no effect of homocysteine reduction; the trial result is consistent
both with no effect and with the expected effect.
Wald DS. Vitamin Supplementation and Risk of Stroke. JAMA. 2004;291(18):2191-2192. doi:10.1001/jama.291.18.2191-b