Key result
Progression from robust to frail status over 12 months was associated with a 70% increased risk of cardiovascular disease (HR 1.70) compared to remaining stable-robust, while intensive blood pressure treatment reduced CVD risk regardless of frailty changes.
Why the study?
Frailty status changes over time, but the impact of these changes on clinical outcomes and whether they modify the effects of intensive blood pressure treatment was unknown.
Does intensive blood pressure treatment reduce cardiovascular disease and mortality regardless of frailty status changes in older adults with hypertension and high cardiovascular risk?
Cohort (n=7,924)
Open-label
Yes
Does intensive blood pressure treatment reduce cardiovascular disease and mortality regardless of frailty status changes in older adults with hypertension and high cardiovascular risk?
Hazard Ratio: 1.7 (95% CI 1.2–2.41)
Absolute Event Rate: 6.38% vs 3.08%
Intensive blood pressure lowering reduces cardiovascular events and mortality in older adults with hypertension, regardless of whether their frailty status worsens, improves, or remains stable over time.
May support intensive BP lowering across frailty trajectories in older hypertensives; hypothesis-generating and requires RCT confirmation before practice change.
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.
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Zhang et al. (2025) conducted a cohort in Hypertension and increased cardiovascular risk (n=7,924). Progression from robust to frail status vs. Stable-robust status was evaluated on Major cardiovascular disease (CVD) events (HR 1.70, 95% CI 1.20-2.41). Progression from robust to frail status over 12 months was associated with a 70% increased risk of cardiovascular disease (HR 1.70) compared to remaining stable-robust, while intensive blood pressure treatment reduced CVD risk regardless of frailty changes.
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