Effect of Postural Hypotension on Recurrent Stroke: Secondary Prevention of Small Subcortical Strokes (SPS3) Study

Abstract

Orthostatic hypotension (OH) has been independently associated with increased risk of stroke and other cardiovascular events. We sought to investigate the relationship between OH at follow up and recurrent stroke risk in SPS3 (Secondary Prevention of Small Subcortical Strokes) trial patient cohort. This is a retrospective cohort analysis. We included all SPS3 trial participants with blood pressure measurements in both sitting and standing position per protocol at baseline, with at least 1 follow up visit to establish the relationship between OH at follow up and recurrent stroke risk (primary outcome). Secondary outcomes included major vascular events, myocardial infarction (MI), all-cause mortality, and, ischemic and hemorrhagic stroke subtypes. Participants were classified as having OH at baseline and at each follow up visit based on a systolic BP decline ≥ 20 mm Hg or a diastolic BP decline ≥ 10 mm Hg on position change from sitting to standing. We used Cox proportional hazards regression modeling to compare the risk of outcomes among those with and without OH. A total of 2275 patients were included with a mean follow up time 3.2 years (standard deviation = 1.6 years). 39% (881/2275) had OH at some point during their follow up. Of these, 41% (366/881) had orthostatic symptoms accompanying the BP drop. In a fully adjusted model, those with OH had a 1.8 times higher risk of recurrent stroke than those without OH (95% CI: 1.1–3.0). The risk of ischemic stroke, major vascular events, and all-cause mortality was similarly elevated among the OH group. Orthostatic hypotension was associated with increased recurrent stroke risk, vascular events, and all-cause death in this large cohort of lacunar stroke patients. Whether minimizing OH in the management of post-stroke hypertension in patients with lacunar stroke reduces recurrent stroke risk deserves further study.