Blood Pressure Variability and Ischemic Stroke Outcome (BP-VISO) - PROJECT SUMMARY/ABSTRACT Stroke affects 800,000 Americans every year and remains a leading cause of long-term disability. Increased blood pressure variability (BPV) has consistently been associated with two to three times higher risk of disability or mortality after acute ischemic stroke (AIS) in retrospective analyses, independent of mean blood pressure. Our central hypothesis is that increased BPV is harmful after AIS and warrants reduction. However, prior BPV research in AIS patients has been retrospective and limited by non-standardized BP measurement and, therefore, BPV is not mentioned in current stroke guidelines. To address the limitations of prior BPV research, determine mechanisms of BPV's deleterious effect, and identify potentially effective methods to reduce BPV, the proposed study will: 1) prospectively validate that “short-term” and “long-term” BPV after AIS onset is associated with functional outcome and define the effect size of different levels of BPV, 2) utilize portable MRI to confirm that final infarct volume, infarct growth and hemorrhagic transformation between baseline (measured within 12 hours of hospital arrival) and 72 hours are mechanistically related to BPV, and 3) utilize bedside pupillometry to determine how the autonomic nervous system contributes to BPV after AIS and evaluate the class effect of antihypertensive medications on BPV. To achieve these goals, we will enroll 150 patients who have anterior circulation stroke and a baseline NIH Stroke Scale ≥6 within 12 hours of AIS onset at three study sites. With completion of the Aims, we will define the outcome for a future trial (disability at 90 days vs. infarct volume or HT vs. post-stroke cognitive impairment at 12 months vs. composites), the effect size of BPV on individual outcomes and composites, the duration for lowering BPV (24-72 hours vs. weeks or months), and potential interventions to reduce BPV. Pharmacologic BPV reduction would be an inexpensive and widely available intervention, able to be administered in a range of healthcare settings. By completing the proposed Aims, we will be ideally positioned to test accessible targeted interventions to diminish the morbidity and mortality of AIS.