Stability of Plasma Homocyst(e)ine in Acute Stroke Patients (SHASP)
INTRODUCTION. Elevated plasma homocyst(e)ine concentration [H(e)] has been associated with an increased risk of stroke. Clinical trials such as the Vitamin Intervention for Stroke Prevention trial (VISP) are underway to determine whether lowering H(e) will reduce recurrent stroke. VISP limits enrollment to stroke patients who meet the H(e) criterion of > 9.5 μmol/L for men and > 8.5 μmol/L for women. VISP allows blood for H(e) analysis to be drawn up to 100 days following the qualifying stroke, however the appropriate earliest time is not known. The literature suggests that H(e)levels increase from the acute to the convalescent phase after stroke but changes during the acute phase have not been studied. METHODS. A prospective, multicenter study was conducted to examine changes in H(e)over two-weeks following an incident stroke. Blood samples for H(e) analysis were collected at days 1 (24–48 hrs), 3, 5, 7, and between 10–14 days after the stroke. Total plasma H(e) was determined by high-performance liquid chromatography and electrochemical detection at a Central Lab. Analyses were performed using the mixed models of Laird and Ware. RESULTS. Eighty-one patients (54 men, 27 women, mean age 66.8) were enrolled at 9 sites from 02/97 to 06/98. The estimated mean H(e) level at the five time periods increased with time from stroke (see table). Differences between any two time periods were significant (p<0.02) with the exception of days 3 vs. 5 and days 7 vs. 10–14. Change in H(e) was not affected by age group (< 67 vs. ≥ 68), sex, current smoker, alcohol use, hypertension, diabetes, or Rankin Score (< 2 vs. ≥ 3). CONCLUSONS. Plasma H(e) levels are frequently measured following stroke. These data suggest that: 1) interpretation of observed values of H(e) require an adjustment for time since stroke; 2) case-control studies assessing H(e) after stroke may be biased in overestimating its impact as a risk factor.