Continuous Blood Pressure Variability and Small Vessel Disease in Acute Ischemic Stroke (COMPASS)

Design and population: This is a single-center, prospective, observational cohort study. Adults (>=19 years) with acute ischemic stroke presenting within 24 hours of symptom onset are enrolled. Patients with atrial fibrillation are excluded because it degrades the accuracy of photoplethysmography (PPG)-based blood pressure estimation. A total of 450 participants are planned over three years.

Blood pressure monitoring: As soon as possible after enrollment, a cuffless, PPG-based ring-type wearable device is applied to a finger and records blood pressure continuously for up to 72 hours without disturbing sleep. Wearing the device does not interfere with standard care, and blood pressure management follows standard clinical guidelines. The device data are used for research analysis only and do not guide real-time treatment.

Imaging: Baseline white matter hyperintensity (WMH) is graded on MRI FLAIR using the Fazekas scale (total 0-6), with severe WMH defined as a total score of 3 or higher.

Exposures: The primary exposure is systolic blood pressure variability over the first 72 hours (primary metric: standard deviation of systolic blood pressure). Secondary exposures include the coefficient of variation and maximum-minimum difference of systolic and diastolic blood pressure, and the nocturnal dipping pattern (dipper, non-dipper, reverse-dipper).

Outcome: The primary outcome is poor functional outcome, defined as a modified Rankin Scale score of 3-6, assessed at hospital discharge.

Hypotheses: (1) Increased systolic blood pressure variability and a nocturnal non-dipping pattern independently predict poor functional outcome at discharge. (2) Severe WMH amplifies the association between blood pressure variability and poor outcome (synergistic effect).

Statistical analysis: The primary analysis uses multivariable logistic regression relating systolic blood pressure variability (standard deviation) to poor outcome (mRS 3-6), adjusted for mean blood pressure, age, sex, baseline comorbidities, and initial NIHSS. Incremental model performance is assessed by AUC, net reclassification improvement (NRI), and integrated discrimination improvement (IDI).

A prespecified interaction analysis tests effect modification by severe WMH (blood pressure variability x severe WMH; P for interaction), with subgroup analysis by WMH severity (Fazekas >=3 vs <3).

Prespecified secondary analyses re-examine the primary finding using alternative variability metrics and the nocturnal dipping pattern.

Prespecified exploratory analyses include nonlinear dose-response modeling of blood pressure variability and mean blood pressure using restricted cubic splines, including spline curves stratified by WMH severity. Analyses beyond those prespecified are reported as exploratory.