Table_1_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.DOCX

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.

背景：认知功能受损可预示不良临床结局。强化血压控制可降低心血管疾病及全因死亡风险。本研究基于蒙特利尔认知评估量表（Montreal Cognitive Assessment, MoCA）的截断值，针对收缩压干预试验（Systolic Blood Pressure Intervention Trial, SPRINT）中的老年受试者，按认知功能高低分组，探讨强化血压控制能否降低卒中、复合心血管结局及全因死亡风险。

方法：SPRINT研究对比了强化血压控制（收缩压<120 mmHg）与标准血压控制（收缩压<140 mmHg）的干预效果。本研究将按受教育程度分层的第25百分位数以下的MoCA评分定义为认知功能低下：对于受教育年限不足12年的受试者，MoCA评分<21分即判定为认知功能低下；受教育年限≥12年者，MoCA评分<22分判定为认知功能低下，其余则为认知功能正常。采用Cox比例风险回归模型，分析不同认知状态下，干预组与临床结局及严重不良反应的关联。此外，针对认知功能低下的卒中患者，进一步开展交互作用与分层分析，以验证干预组与卒中风险关联的稳健性。

结果：本研究纳入的受试者中，1873例基线时存在认知功能低下。中位随访时间为3.26年。经年龄、性别、种族、体质量指数、吸烟情况、收缩压、弗雷明汉10年心血管疾病风险评分、阿司匹林使用情况、他汀类药物使用情况、既往心血管疾病史、既往慢性肾脏病史及衰弱状态全面校正后，强化血压控制可升高认知功能低下患者的卒中风险[风险比（HR）=1.93，95%置信区间（CI）：1.04~3.60，P=0.038]。在认知功能低下组中，强化血压控制未能降低复合心血管结局（HR=0.81，95%CI：0.59~1.12，P=0.201）与全因死亡风险（HR=0.93，95%CI：0.64~1.35，P=0.710）。而在认知功能正常的患者中，经全面校正后，强化血压控制可显著降低卒中风险（HR=0.55，95%CI：0.35~0.85，P=0.008）、复合心血管结局风险（HR=0.68，95%CI：0.56~0.83，P<0.001）及全因死亡风险（HR=0.62，95%CI：0.48~0.80，P<0.001）。此外，经全面校正后，强化血压控制可升高认知功能低下患者的低血压与晕厥风险；在认知功能正常的受试者中，接受强化血压控制者的低血压、电解质异常及急性肾损伤发生率均升高。

结论：对于认知功能低下的患者，强化血压控制或许无法降低其卒中、复合心血管结局及全因死亡风险。