J-Curve trend in long-term blood pressure management: time in therapeutic range among elderly hypertensive patients from the STEP trials

Background Accumulating evidence supports the benefits of strict BP control. However, existing studies primarily relied on mean achieved blood pressure (BP) or time-point measurements, which fail to capture the cumulative burden of longitudinal BP exposure. Time in therapeutic range (TTR) offers a dynamic and integrative metric to quantify the proportion of time a patient's BP remains below a specified threshold. Purpose We aimed to investigate the dose-response relationship between TTR at different BP thresholds (<140, <130, and <120 mmHg) during the medication maintenance phase and primary cardiovascular outcomes. Methods In this post-hoc analysis of the STEP and STEP2 trials, both treatment arms were pooled. BP data during two dose-titration periods were excluded: the initial 3 months after enrolment and the first 3 months upon entry into STEP2. TTR was calculated using a consecutive 3-month intervals. Time-dependent Cox proportional hazards models, adjusted for baseline demographic and clinical covariates, were utilised to evaluate the risk of primary cardiovascular events in subsequent intervals. Restricted cubic splines (RCS) and categorical analyses were applied to explore potential non-linear relationships. Sensitivity analyses using a 6-month window were also conducted. Results After excluding patients who experienced a primary event during the dose-titration period, a total of 8142 patients with 478 primary events were included. Higher TTRs for standard (<140 mmHg) and intensive (<130 mmHg) targets were linearly associated with decreased cardiovascular risk. Every 10% increase in TTR <140 mmHg and TTR <130 mmHg was associated with risk reductions of 5.2% (HR= 0.948, 95% CI 0.926-0.971; p<0.001) and 2.1% (HR=0.979, 95% CI 0.960-0.998; p=0.031), respectively. However, when assessing the strictly intensive threshold (<120 mmHg), RCS and tertile analyses suggested a J-curve trend. Compared with the lowest tertile, moderate TTR <120 mmHg (34%-66%) showed a protective trend (HR=0.53, 95% CI 0.26-1.07), whereas the highest tertile (67%-100%) demonstrated attenuation of benefits (HR=0.96, 95% CI 0.69-1.34). Conclusion Longitudinal BP management targeting <140 mmHg and <130 mmHg provides consistent cardiovascular benefits in the elderly. However, maintaining BP strictly below 120 mmHg for prolonged periods showed a suggestive J-curve pattern of cardiovascular risk, suggesting that the optimal long-term BP target in older adults may lie between 120 and 130 mmHg. These findings underscore the importance of vigilant longitudinal monitoring to balance cardiovascular benefits and avoid sustained overtreatment.