Apparent treatment‐resistant hypertension (aTRH), defined as blood pressure (BP) that remains uncontrolled despite unconfirmed concurrent treatment with three antihypertensives, is associated with an increased risk of developing cardiovascular and renal complications compared with controlled hypertension. We aimed to identify the characteristics of aTRH patients with an elevated risk of major adverse cardiovascular events plus (MACE+; defined as stroke, myocardial infarction, or heart failure hospitalization) and end stage renal disease (ESRD). This retrospective cohort study included aTRH patients (BP ≥140/90 mmHg and taking ≥3 antihypertensives) from the United States–based Optum® de‐identified Electronic Health Record dataset and used machine learning models to identify risk factors of MACE+ or ESRD. Patients had claims for ≥3 antihypertensive classes within 30 days between January 1, 2015 and June 30, 2021, and two office BP measures recorded 1–90 days apart within 30 days to 11 months after the index regimen date. Of a total 18 797 070 patients identified with any hypertension, 71 100 patients had aTRH. During the study period (mean 25.5 months), 4944 (7.0%) patients had a MACE+ and 2403 (3.4%) developed ESRD. In total, 22 risk factors were included in the MACE+ model and 16 in the ESRD model, and most were significantly associated with study outcomes. The risk factors with the largest impact on MACE+ risk were congestive heart failure, stages 4 and 5 chronic kidney disease (CKD), age ≥80 years, and living in the Southern region of the United States. The risk factors with the largest impact on ESRD risk, other than pre‐existing CKD, were anemia, congestive heart failure, and type 2 diabetes. The overall study cohort had a 5‐year predicted MACE+ risk of 13.4%; this risk was increased in those in the top 50% and 25% high‐risk groups (21.2% and 29.5%, respectively). The overall study cohort had a predicted 5‐year risk of ESRD of 6.8%, which was increased in the top 50% and 25% high‐risk groups (10.9% and 17.1%, respectively). We conclude that risk models developed in our study can reliably identify patients with aTRH at risk of MACE+ and ESRD based on information available in electronic health records; such models may be used to identify aTRH patients at high risk of adverse outcomes who may benefit from novel treatment interventions.

中文翻译：

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使用机器学习方法预测美国明显难治性高血压患者的心血管和肾脏风险

表观难治性高血压（aTRH）定义为尽管未经证实同时使用三种抗高血压药物，但血压仍不受控制，与控制性高血压相比，与发生心血管和肾脏并发症的风险增加相关。我们的目的是确定 aTRH 患者的主要不良心血管事件（MACE+；定义为中风、心肌梗塞或心力衰竭住院）和终末期肾病 (ESRD) 风险升高的特征。这项回顾性队列研究纳入了来自美国 Optum 的 aTRH 患者（血压≥140/90 mmHg 且服用≥3 种抗高血压药物）®去识别化电子健康记录数据集，并使用机器学习模型来识别 MACE+ 或 ESRD 的风险因素。患者在2015年1月1日至2021年6月30日期间的30天内要求接受≥3级抗高血压治疗，并且在指数治疗日期后30天至11个月内记录了相隔1-90天的两次办公室血压测量。在总共 18 797 070 名患有高血压的患者中，71 100 名患者患有 aTRH。在研究期间（平均 25.5 个月），4944 名患者 (7.0%) 患有 MACE+，2403 名患者 (3.4%) 发展为 ESRD。总共，MACE+ 模型中包含 22 个危险因素，ESRD 模型中包含 16 个危险因素，并且大多数与研究结果显着相关。对 MACE+ 风险影响最大的危险因素是充血性心力衰竭、4 期和 5 期慢性肾病 (CKD)、年龄≥80 岁以及居住在美国南部地区。除既存 CKD 之外，对 ESRD 风险影响最大的危险因素是贫血、充血性心力衰竭和 2 型糖尿病。整个研究队列的 5 年预测 MACE+ 风险为 13.4%；前 50% 和 25% 的高风险群体（分别为 21.2% 和 29.5%）的这种风险增加。整个研究队列的预测 5 年 ESRD 风险为 6.8%，前 50% 和 25% 高风险组的风险有所增加（分别为 10.9% 和 17.1%）。我们的结论是，我们研究中开发的风险模型可以根据电子健康记录中的可用信息可靠地识别具有 MACE+ 和 ESRD 风险的 aTRH 患者；此类模型可用于识别出现不良后果高风险的 aTRH 患者，这些患者可能会从新的治疗干预措施中受益。