Plasma homocysteine concentrations in the acute and convalescent periods of atherothrombotic stroke

Background and Purpose-Homocysteine is a proposed causal risk factor for atherosclerosis, but this remains controversial. We measured fasting plasma homocysteine concentrations immediately after atherothrombotic stroke and in the convalescent period to investigate this controversy.

Methods-One hundred six patients (59 men and 47 women, mean age 57.2 [25 to 70] and 56.5 [26 to 69] years, respectively) were recruited within 24 hours of admission, and 82 patients were resampled at least 3 months later. Fasting total plasma homocysteine (tHcy) concentrations were measured by high-performance liquid chromatography.

Results-Median tHcy in the acute phase of stroke was not significantly higher than in matched control subjects (men 9.2 [range 4.4 to 22.8] versus 8.7 [4.9 to 20] mu mol/L, P=0.09, Mann-Whitney U test; women 8.1 [4.8 to 32.3] versus 7.6 [3.3 to 14.4] mu mol/L, P=0.58). Median plasma concentrations increased significantly in the convalescent period (from 8.5 [4.8 to 19.2] to 10.1 [4.3 to 31.5] mu mol/L, P<0.001, Wilcoxon signed rank test) and were then significantly higher than in control subjects in both men and women (P=0.03 and 0.05, respectively, Mann-Whitney U test). This did not appear to be explained by alteration in the known covariates red-cell folate, serum B-12, or creatinine concentrations.

Conclusions-Homocysteine concentrations are not elevated after recent atherothrombotic stroke but rise in the convalescent period. These data do not support the hypothesis that raised plasma homocysteine concentrations predate atherothrombotic stroke. Instead, they offer an explanation for the discrepancies between prospective and retrospective studies and suggest that elevated tHcy levels may be caused by the disease process itself.