The Impact of Cognitive Function on the Effectiveness and Safety of Intensive Blood Pressure Control for Patients With Hypertension: A post-hoc Analysis of SPRINT

Background: Poor cognitive function can predict poor clinical outcomes. Intensive blood pressure control can reduce the risk of cardiovascular diseases and all-cause mortality. In this study, we assessed whether intensive blood pressure control in older patients can reduce the risk of stroke, composite cardiovascular outcomes and all-cause mortality for participants in the Systolic Blood Pressure Intervention Trial (SPRINT) with lower or higher cognitive function based on the Montreal Cognitive Assessment (MoCA) cut-off scores.Methods: The SPRINT evaluated the impact of intensive blood pressure control (systolic blood pressure <120 mmHg) compared with standard blood pressure control (systolic blood pressure <140 mmHg). We defined MoCA score below education specific 25th percentile as lower cognitive function. And SPRINT participants with a MoCA score below 21 (<12 years of education) or 22 (≥12 years of education) were having lower cognitive function, and all others were having higher cognitive function. The Cox proportional risk regression was used to investigate the association of treatment arms with clinical outcomes and serious adverse effects in different cognitive status. Additional interaction and stratified analyses were performed to evaluate the robustness of the association between treatment arm and stroke in patients with lower cognitive function.Results: Of the participants, 1,873 were having lower cognitive function at baseline. The median follow-up period was 3.26 years. After fully adjusting for age, sex, ethnicity, body mass index, smoking, systolic blood pressure, Framingham 10-year CVD risk score, aspirin use, statin use, previous cardiovascular disease, previous chronic kidney disease and frailty status, intensive blood pressure control increased the risk of stroke [hazard ratio (HR) = 1.93, 95% confidence interval (CI): 1.04–3.60, P = 0.038)] in patients with lower cognitive function. Intensive blood pressure control could not reduce the risk of composite cardiovascular outcomes (HR = 0.81, 95%CI: 0.59–1.12, P = 0.201) and all-cause mortality (HR = 0.93, 95%CI: 0.64–1.35, P = 0.710) in lower cognitive function group. In patients with higher cognitive function, intensive blood pressure control led to significant reduction in the risk of stroke (HR = 0.55, 95%CI: 0.35–0.85, P = 0.008), composite cardiovascular outcomes (HR = 0.68, 95%CI: 0.56–0.83, P < 0.001) and all-cause mortality (HR = 0.62, 95%CI: 0.48–0.80, P < 0.001) in the fully adjusted model. Additionally, after the full adjustment, intensive blood pressure control increased the risk of hypotension and syncope in patients with lower cognitive function. Rates of hypotension, electrolyte abnormality and acute kidney injury were increased in the higher cognitive function patients undergoing intensive blood pressure control.Conclusion: Intensive blood pressure control might not reduce the risk of stroke, composite cardiovascular outcomes and all-cause mortality in patients with lower cognitive function.

Risk-Based Intensive Blood Pressure Lowering and Prevention of Heart Failure: A SPRINT Post Hoc Analysis

The SPRINT (Systolic Blood Pressure Intervention Trial) demonstrated that intensive blood pressure (BP) lowering (target<120 mm Hg) was more effective in preventing heart failure (HF) compared with standard BP goals (target<140 mm Hg). However, intensive BP lowering also led to an increase in serious adverse events. We aimed to identify a subset of the clinical trial population who might derive the greatest benefit from intensive BP lowering for prevention of HF using a previously validated HF risk prediction model. SPRINT participants without prevalent cardiovascular disease were stratified into HF risk tertiles based on predicted HF risk. We performed Kaplan-Meier Survival analysis and multivariable Cox proportional hazards models to test the effect of intensive versus standard BP lowering on incident HF in each tertile of predicted HF risk. A total of 6911 individuals were included and 77 incident HF events occurred over a median follow-up time of 3.3 (interquartile range, 2.9–3.8) years. A reduction in risk of HF was observed among those randomized to intensive BP lowering in each risk tertile but was significant only in the highest HF risk category (risk tertile 1: hazard ratio, 0.86 [95% CI, 0.29–2.56]; risk tertile 2: 0.54 [0.23–1.30]; risk tertile 3: 0.46 [0.24–0.88]). Serious adverse events were frequent in all groups. While the short follow-up may lead to an underestimation of benefit in the lower predicted risk groups, prioritizing intensive BP lowering in those at highest predicted HF risk may help to reduce the high burden of HF in the United States.