Changes in frailty, intensive blood pressure treatment, and risks of adverse clinical outcomes: a post hoc analysis of the SPRINT trial.

Abstract

Background: Frailty is becoming a common health issue and its status changes overtime. However, the impact of the frailty status changes on clinical outcomes is unknown. We aimed to evaluate the association between changes in frailty status and adverse clinical outcomes, and to determine whether the changes modify the effects of intensive blood pressure (BP) treatment.

Methods: Using frailty index (FI) defined by the Systolic Blood Pressure Intervention Trial (SPRINT), participants were categorized as frail (FI > 0.21) or robust (FI ≤ 0.21). Changes in frailty were evaluated by frailty status at baseline and at 12 months. Participants were categorized as stable-robust, robust-to-frail, frail-to-robust, and stable-frail. Outcomes included incident cardiovascular disease (CVD), all-cause mortality, and serious adverse events (SAEs). Cox proportional hazard models were used to evaluate the association between frailty changes and outcomes, and potential modifications of the changes on intensive BP-lowering treatment.

Results: Overall, 7924 eligible SPRINT participants were included. Compared with stable-robust participants, robust-to-frail participants had 70%, 103%, and 47% increased risks of CVD (hazard ratio [HR] = 1.70, 95% confidence interval [CI] 1.20-2.41), all-cause mortality (HR = 2.03, 95% CI 1.22-3.37), and SAEs (HR = 1.47, 95% CI 1.17-1.84), respectively. Compared with stable-frail participants, a 52% decreased risk of all-cause mortality (HR = 0.48, 95% CI 0.24-0.95) was observed in frail-to-robust participants. Changes in frailty did not modify the effects of intensive BP-lowering treatment on CVD, mortality, and SAEs (all P values for interaction > 0.05). In stable-robust participants, intensive BP-lowering treatment was associated with a reduced risk of major CVD events by 41% (HR = 0.59, 95% CI 0.42-0.83), a reduced risk of all-cause mortality by 46% (HR = 0.54, 95% CI 0.31-0.95), and an increased risk of SAEs by 22% (HR = 1.22, 95% CI 1.00-1.48) compared with standard BP-lowering treatment. Similar effects of intensive vs. standard BP-lowering treatment were found in participants with robust-to-frail, frail-to-robust, and stable-frail status.

Conclusions: Changes in frailty were associated with changed risks of clinical outcomes. Intensive BP-lowering treatment reduced CVD and mortality regardless of frailty status changes.