Aim and Design

　　Our aims were to characterize overall visit-to-visit blood pressure variability (BPV) in the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and to examine the association between BPV and stroke recurrence and other vascular outcomes in SPS3.

　　SPS3 was an international， randomized trial examining secondary prevention strategies in patients with MRI-proven symptomatic lacunar stroke. Briefly， participants aged 30 or older were randomized within 180 days of their event to two interventions in a factorial design: ① antiplatelet therapy (double-blinded): aspirin 325 mg daily plus placebo vs. aspirin 325 mg daily plus clopidogrel 75 mg daily; ② systolic blood pressure targets (open-label): “regular” (130-149 mm Hg) vs. “intensive” (<130 mm Hg). Patients with evidence of a cortical infarct， cervical carotid stenosis >50% in the symptomatic territory of the infarct， or a major-risk cardioembolic source were excluded. The primary outcome was all recurrent stroke; secondary outcomes included acute myocardial infarction and death.

　　Variability of systolic and diastolic blood pressure was explored using standard deviation (SD)， coefficient of variation (CV; SD/mean) and average real variability (ARV)， which is the mean absolute difference between measurements.

　　All-cause variability was examined using all quarterly blood pressure measurements beginning at the six-month visit and beyond. Readings prior to the six-month visit were excluded from the analysis due to the fact that blood pressures were at their most dynamic during this period both due to a combination of active antihypertensive medication adjustment， and possibly other factors including physiological changes.

　　A mean of 13.7 followup visits per patient (36498 visits overall; mean followup 3.4 y) were included in the analysis. Mean visit-to-visit systolic blood pressure was 131.60 mm Hg (SD 11.15) and diastolic was 72.36 (SD 8.23). Average real variability from visit to visit was 11.61 mm Hg (SD 5.93) systolic and 7.07 (SD 3.03) diastolic.

　　Results

　　There was no relationship between systolic variability and all recurrent strokes， nor was there a relationship between systolic variability and recurrent ischemic stroke， or hemorrhagic stroke. Increased systolic variability was associated with increased all-cause mortality， with an increased hazard of 5% for every 1 mm Hg increase in absolute visit-to-visit variability (HR 1.05， 95%CI: 1.025～1.076， P=0.0001)， though there was no definite association between recurrent myocardial infarction or vascular death and BPV that helped to explain the excess in mortality with increased variability.

　　Participants assigned to the higher blood pressure target were taking a mean of 1.8 (SD 1.4) antihypertensive medications at one year after randomization and 1.8 (1.4) at the end of the study; lower target participants were on 2.4 (1.3) medications at one year and 2.4 (1.4) at end of study. When results were stratified by assigned blood pressure target， there was no additional relationship noted between variability and the primary outcome. There was no difference in the range of average real variability by quartile between the higher and lower target groups.

　　In this ongoing analysis， we found no relationship between average real variability and stroke recurrence. The dynamic and intense natural of blood pressure control， as well as reduced blood pressure variability in SPS3 as compared with other historical stroke cohorts， may have precluded us from detecting an association between BPV and vascular risk.