Association of systolic blood pressure time in target range with heart failure risk and mediating roles of NT-proBNP, hs-cTnI, and eGFR: novel findings from the SPRINT trial

Abstract Aims Although achieving lower systolic blood pressure (SBP) targets reduces HF risk, the role and mechanisms of SBP time in target range (TTR) in heart failure (HF) risk and related biomarkers remain unclear. This study investigates the relationship between SBP TTR and HF risk, along with changes in biomarkers over one year and their potential mediating roles. Methods This post-hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) examined the association between SBP TTR and HF risk among 7962 participants with intensive (120 mmHg) or standard (140 mmHg) SBP targets. SBP TTR was calculated using the Rosendaal method. Biomarker changes in high-sensitivity cardiac troponin I (hs-cTnI), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and estimated glomerular filtration rate (eGFR) over one year were analyzed as potential mediators. Cox proportional hazards models and mediation analyses assessed relationships between SBP TTR, biomarkers, and HF outcomes. Results Participants with higher SBP TTR (66% to 100%) exhibited significantly lower risks of HF (adjusted HR: 0.74; 95% confidence interval CI: 0.56–0.98; P=0.034) and the composite outcome of HF and all-cause mortality (adjusted HR: 0.77; 95% CI: 0.64–0.92; P=0.004) compared to lower SBP TTR (66%). High SBP TTR was associated with favorable changes in NT-proBNP and eGFR, but not hs-cTnI. Mediation analyses revealed that NT-proBNP mediated 4.305% of the effect of SBP TTR on HF or death risk (P=0.006), while eGFR mediated 3.489% (P=0.002). Conclusions Higher SBP TTR is independently associated with reduced HF risk, with this effect partially mediated by NT-proBNP and eGFR. These findings may support SBP TTR as a potential therapeutic target for HF prevention.