Prognostic importance of long-term SBP variability in high-risk hypertension

Objective: In addition to high blood pressure variability (BPV), low BPV was associated with adverse cardiovascular prognosis in selected high-risk patients. We explored this issue in the Systolic Blood Pressure Intervention Trial (SPRINT) using a nonlinear approach with BPV as a continuous variable. Methods: Long-term systolic BPV (SBPV) (coefficient of variation, CoV %) was calculated on quarterly visits until a fatal/nonfatal cardiovascular event or all-cause mortality, excluding titration period and patients with missing visits. We used Cox proportional hazard models with penalized smoothing splines to shape the risk of outcomes against the continuum of SBPV (independent variable). Adjusted hazard ratios (aHR, 95% CI) were calculated using the reference range derived from the nonlinear model. Sensitivity analysis based on propensity score matching (PSM) was performed. Results: The association of SBPV with fatal/nonfatal cardiovascular events was J-shaped, whereas that with all-cause mortality was linear. After multivariate adjustment, however, the only significant associations remained that of low SBPV (CoV <5%) with cardiovascular events (hazard ratio 1.85, 95% CI 1.24-2.75, P = 0.003), and of high SBPV (CoV >10%) with the composite of cardiovascular events and all-cause mortality (hazard ratio 1.35, 95% CI 1.02-1.80; P = 0.037). Low SBPV was associated with ischemic heart disease (hazard ratio 2.76, 95% CI 1.55-4.91; P < 0.001). There was a significant U-shaped association of SBPV with cardiovascular events in the PSM cohort. Conclusion: Nonlinear modeling indicates that low and high long-term SBPV have prognostic relevance in high-risk hypertensive individuals from SPRINT. Randomized trials are needed to test these findings and their potential therapeutic implications.