Differential Associations of On-Treatment Average Blood Pressure (BP) Control with Cardiovascular Outcomes in Each Vascular Territory: Should We Move Beyond One-Size-fits-all BP Targets?

Background: Most BP guidelines suggest universal systolic BP (SBP) targets for reducing cardiovascular (CV) events. We hypothesised that the link between average mean SBP levels on treatment differs for CV events in different vascular territories, and this relationship is more pronounced in specific sub-groups. Using data from hypertensive patients in 3 trials (ASCOT, ALLHAT and SPRINT; n >50,000), we examined, separately, the relationship between cumulative mean SBP achieved after 1y of treatment (cum_avg_SBP1y) and the risk of 3 outcomes: Coronary heart disease (CHD), stroke and peripheral arterial disease (PAD) in those with/without previous CVD (example sub-group). Methods: For each trial and outcome, separate Cox models were used to model cum_avg_SBP1y using restricted cubic splines. HRs (95%CI) adjusted for other CV risk factors, treatment allocation and incident non-outcome events, were estimated with reference to the cum_avg_SBP1y of 120 mmHg. Relationships were categorised as potentially harmful when HR>1, lower CI≤1; and clearly harmful when HR>1, lower CI>1. Results: At 1y, cum_avg_SBP1y was 152mmHg (SD14) in ASCOT, 130mmHg (SD9.5) in SPRINT, and 140mmHg (SD13) in ALLHAT. Amongst CVD-free participants at 1y (N~14500 in ASCOT, 6500 in SPRINT, 19300 in ALLHAT): As per fig 1-3, for CHD outcome, potential harm appeared at cum_avg_SBP1y >120mmHg in ALLHAT and >160mmHg in ASCOT. For stroke events, potential harm was apparent at cum_avg_SBP1y > 120 mmHg in ALLHAT and ASCOT; clear harm only at SBP> 130 mmHg in ALLHAT, > 140 mmHg in SPRINT. For PAD event , cum_avg_SBP1y < 120 mmHg was potentially harmful in ALLHAT, with clear harm beyond ~145 mmHg in ASCOT and ALLHAT. Among participants with CVD (N~2900 in ASCOT, 1700 in SPRINT, 6000 in ALLHAT): For CHD , cum_avg_SBP1y <120mmHg was harmful in all 3 trials, while between 120–160mmHg was protective in ALLHAT. For stroke , cum_avg_SBP1y < 120 mmHg was clearly harmful in ASCOT and SPRINT. For PAD , cum_avg_SBP1y < 120 mmHg and > 130 mmHg were associated with potential harm in ALLHAT; potential harm was also apparent with cum_avg_SBP1y > 120 mmHg in ASCOT and SPRINT. Conclusion: Harmful levels of BP control (especially lower range ones) differ for different CV events and are influenced by participant characteristics, such as prior CVD history. These findings suggest that SBP targets for primary and secondary prevention of CVD may need to be personalised using existing comorbidities and vascular territories of concern.