Systolic Blood Pressure Burden: A Novel Metric for Predicting Cardiovascular Outcomes in High Cardiovascular Risk Patients - Insights from the SPRINT Study.

Abstract

Conventional systolic blood pressure (SBP) indices, such as mean SBP or variability indices, fail to capture control consistency. SBP time in target range (TTR) improves risk prediction by measuring SBP control duration. However, it neglects the magnitude of SBP elevation, treating minor and severe elevations equally. We developed and validated the SBP burden, a novel metric integrating both the duration and magnitude of SBP elevation, to enhance cardiovascular risk prediction. This post hoc analysis of the SPRINT included 9,017 high-risk, nondiabetic participants (age, 67.0 [61.0-76.0] years; 64.7% men). SBP burden was calculated as the proportion of the over-target time multiplied by the over-target part proportion of SBP area under the curve [AUC] during that time, using SBP records in months 0-6 (target: 130 mm Hg). Its prediction performance was compared with mean SBP, SBP standard deviation (SD), SBP average real variability (ARV), SBP TTR, and SBP AUC. The primary outcome was the first occurrence of major adverse cardiovascular events (MACEs), including cardiovascular death (CVD death), myocardial infarction, stroke, and heart failure (HF) hospitalization. Over a median follow-up of 3.89 years, 568 MACEs occurred. After adjusting for traditional risk co-variables, the SBP burden showed an independent linear association with MACEs (hazard ratio [HR], 95% confidence interval [CI]: 1.17, 1.09-1.26; <i>p</i> &lt; 0.01) and this association remained even after further adjustment for SBP SD and ARV. Mean SBP (HR, 95% CI: 1.13, 1.03-1.23; <i>p</i> &lt; 0.01), SBP SD (HR, 95% CI: 1.10, 1.01-1.19; <i>p</i> = 0.03), SBP ARV (HR, 95% CI: 1.10, 1.01-1.18; <i>p</i> = 0.02), SBP AUC (HR, 95% CI: 1.15, 1.05-1.26; <i>p</i> &lt; 0.01), and SBP TTR (HR, 95% CI: 0.88, 0.80-0.97; <i>p</i> = 0.01) were also independent risk predictors. Further, we confirmed SBP burden acheived the greatest improvement in discrimination and reclassification (Net reclassification improvement as 0.12 [0.03-0.22]; integrated discrimination improvement as 0.0032 [0.0006-0.0076]), and feature importance (relative informativeness and LASSO ranking as top 1) among tested SBP indices. In high-risk, nondiabetic patients, SBP burden is an independent predictor of cardiovascular outcomes. It overcomes the limitations of SBP TTR, outperforming other SBP indices in predictive performance and feature importance for cardiovascular outcomes. High systolic blood pressure (SBP) is a major risk factor for heart attacks, strokes, and heart failure (HF). While current measures assess average blood pressure levels, variability, or time spent within a safe range, each reflects only one dimension of blood pressure control. We developed &#x201c;systolic blood pressure burden&#x201d; (SBP burden), a metric that accounts for both the duration and magnitude of blood pressure elevation above a set threshold. We tested this measure in over 9,000 adults at high cardiovascular risk who were followed for approximately 4 years. Patients with a higher SBP burden faced significantly greater risks of heart attacks, strokes, HF, and CVD death, independent of other known risk factors and blood pressure fluctuations. Among all measures tested, blood pressure burden proved to be the strongest predictor of future heart-related events and offered the most significant improvement in identifying at-risk patients. These findings suggest that evaluating both the duration and severity of blood pressure elevation may better capture cardiovascular risk than conventional measures. Consequently, blood pressure burden could help doctors identify high-risk patients earlier and guide more timely treatment decisions.