Blood Pressure Complexity Discriminates Pathological Beat‐to‐Beat Variability as a Marker of Vascular Aging

Background Beat‐to‐beat blood pressure variability (BPV) is associated with an increased risk of stroke but can be driven by both healthy physiological processes and failure of compensatory mechanisms. Blood pressure (BP) complexity measures structured, organized variations in BP, as opposed to random fluctuations, and its reduction may therefore identify pathological beat‐to‐beat BPV. Methods and Results In the prospective, population‐based OXVASC (Oxford Vascular Study) Phenotyped Cohort with transient ischemic attack or minor stroke, patients underwent at least 5 minutes of noninvasive beat‐to‐beat monitoring of BP (Finometer) and ECG to derive the following: BPV (coefficient of variation) and complexity (modified multiscale entropy) of systolic BP and diastolic BP, heart rate variability (SD of R‐R intervals), and baroreflex sensitivity (BRS; Welch's method), in low‐ (0.04–0.15 Hz) and high‐frequency (0.15–0.4 Hz) bands. Associations between BPV or BP complexity with autonomic indexes and arterial stiffness were determined (linear regression), unadjusted, and adjusted for age, sex, and cardiovascular risk factors. In 908 consecutive, consenting patients, BP complexity was inversely correlated with BPV coefficient of variation (P <0.001) and was similarly reduced in patients with hypertension or diabetes (P <0.001). However, although BPV coefficient of variation had a U‐shaped relationship with age, BP complexity fell systematically across age quintiles (quintile 1: 15.1 [14.0–16.1] versus quintile 5: 13.8 [12.4–15.1]) and was correlated with markers of autonomic dysfunction (heart rate variability SD of R‐R intervals:r  = 0.20; BRS low frequency: 0.19; BRS high frequency: 0.26) and arterial stiffness (pulse wave velocity: −0.21; allP <0.001), even after adjustment for clinical variables (heart rate variability SD of R‐R intervals: 0.12; BRS low frequency and BRS high frequency: 0.13 and 0.17; and pulse wave velocity: −0.07; allP <0.05).Conclusions Loss of BP complexity discriminates BPV because of pathological failure of compensatory mechanisms and may represent a less confounded and potentially modifiable risk factor for stroke.