Heart Stress and Blood Pressure Management in Older Adults: Post Hoc Analysis of the ASPREE Trial

BACKGROUND: Blood pressure (BP) management in older adults is complex because of age-related physiological changes and uncertainty around ideal systolic BP (SBP) targets. Heart stress (HS), defined by age-adjusted elevation in NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, may improve cardiovascular disease (CVD) risk stratification and support more individualized BP management. METHODS: We conducted a post hoc analysis of ASPREE (Aspirin in Reducing Events in the Elderly) involving 11 941 community-dwelling older adults without CVD at enrollment (mean age, 75.1 years; 53.5% women). HS was defined by NT-proBNP ≥150 pg/mL for participants 65 to 74 years of age and ≥300 pg/mL for participants ≥75 years of age. Participants were categorized into 4 groups by hypertension and HS status. The primary outcome was total CVD events (a composite of nonfatal myocardial infarction, fatal or nonfatal stroke, coronary heart disease death, or hospitalization for heart failure). Associations between hypertension and SBP with total CVD events were examined by HS status using Cox proportional-hazards models and restricted cubic spline. SBP was evaluated categorically (<120, 120-129, 130-139, 140-159, or ≥160 mm Hg) and continuously. A landmark sensitivity analysis excluded participants with CVD events or censoring in the first 2 years, with follow-up starting at year 3. RESULTS: HS was present in 25.8% of participants. Compared with the reference group (no hypertension or HS), adjusted hazard ratios (95% CI) for total CVD events were 1.41 (1.18-1.70) for hypertension + no HS, 1.79 (1.34-2.39) for no hypertension + HS, and 2.32 (1.89-2.84) for hypertension + HS (Ptrend<0.001). Among participants without HS, the lowest incidence of total CVD events occurred at SBP 130 to 139 mm Hg, showing a U-shaped association across SBP levels (Pnonlinearity=0.011). Among participants with HS, risk increased linearly with SBP (Plinear trend=0.85) and was lowest at SBP <120 mm Hg. Landmark analyses yielded generally consistent findings. CONCLUSIONS: HS is common in older adults and jointly associated with hypertension and increased CVD risk. The SBP-CVD relationship differs by HS status, suggesting a potential value of HS for guiding individualized BP management. Prospective studies are warranted to determine whether HS-guided strategies improve BP control and reduce CVD risk in older adults.