Preoperative activation of the renin-angiotensin system and myocardial injury in noncardiac surgery: exploratory mechanistic analysis of the SPACE randomised controlled trial.

IF 9.1 1区医学 Q1 ANESTHESIOLOGY

British journal of anaesthesia Pub Date : 2024-12-20 DOI:10.1016/j.bja.2024.10.040

Ana Gutierrez Del Arroyo, Tom E F Abbott, Akshaykumar Patel, Salma Begum, Priyanthi Dias, David Brealey, Rupert M Pearse, Vikas Kapil, Gareth L Ackland

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引用次数: 0

Abstract

Background: Hypertension therapy in older adults is often suboptimal, in part because of inadequate suppression of the renin-angiotensin-aldosterone system (RAAS). We hypothesised that distinct endotypes of RAAS activation before noncardiac surgery are associated with increased risk of myocardial injury.

Methods: This was a prespecified exploratory analysis of a multicentre randomised controlled trial (ISRCTN17251494) which randomised patients ≥60 yr old undergoing elective noncardiac surgery to either continue or stop RAAS inhibitors (determined by pharmacokinetic profiles). Unsupervised hierarchical cluster analysis identified distinct groups of patients with similar RAAS activation from samples obtained before induction of anaesthesia, quantified by enzyme-linked immunoassays for plasma renin, aldosterone, angiotensin-converting enzyme 2, and dipeptidyl peptidase-3. The primary outcome, masked to investigators and participants, was myocardial injury (plasma high-sensitivity troponin-T).

Results: We identified three clusters, with similar proportions of RAAS inhibitors randomised to stop or continue. Cluster 1 (n=52; mean age [standard deviation], 75 yr [8 yr]; 54% female) and cluster 3 (n=25; 75 yr [6 yr]; 44% female) had higher rates of myocardial injury (23/52 [44%] and 13/25 [52%], respectively), compared with cluster 2 with 51/164 (31.1%; n=153; 70 yr [6] yr; 46% female; odds ratio: 1.95, 95% confidence interval (CI) 1.12-3.39, P=0.018). Cluster 2 was characterised by lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration (mean difference 698 pg ml^-1, 95% CI 576-820 pg ml^-1) and higher renin concentration (mean difference 350 pg ml^-1, 95% CI 123-577 pg ml^-1), compared with clusters 1 and 3 which had higher rates of myocardial injury.

Conclusions: This mechanistic exploratory analysis suggests that effective preoperative RAAS inhibition is associated with lower risk of myocardial injury after noncardiac surgery, independent of stopping or continuing RAAS inhibitors before surgery.

Clinical trial registration: ISRCTN17251494.

查看原文本刊更多论文

非心脏手术中肾素-血管紧张素系统的术前激活与心肌损伤：SPACE随机对照试验的探索性机制分析

背景：老年人高血压治疗通常是次优的，部分原因是肾素-血管紧张素-醛固酮系统（RAAS）抑制不足。我们假设，非心脏手术前不同类型的RAAS激活与心肌损伤风险增加有关。方法：这是一项预先指定的多中心随机对照试验（ISRCTN17251494）的探索性分析，该试验随机分配≥60岁接受选择性非心脏手术的患者继续或停止RAAS抑制剂（由药代动力学谱决定）。通过血浆肾素、醛固酮、血管紧张素转换酶2和二肽基肽酶3的酶联免疫测定，无监督的分层聚类分析从麻醉诱导前获得的样本中识别出具有相似RAAS激活的不同患者组。研究者和参与者不知道的主要结局是心肌损伤（血浆高敏感性肌钙蛋白- t）。结果：我们确定了三个集群，随机停止或继续使用RAAS抑制剂的比例相似。集群1 (n=52；平均年龄[标准差]，75岁[8岁]；54%女性)和聚类3 (n=25；75年[6年]；心肌损伤发生率（分别为23/52[44%]和13/25[52%]）高于聚类2的51/164 (31.1%；n = 153;70年，100年；46%的女性;优势比：1.95,95%可信区间（CI） 1.12-3.39， P=0.018)。与心肌损伤率较高的聚类1和聚类3相比，聚类2的n端前b型利钠肽（NT-proBNP）浓度较低（平均差值698 pg ml-1, 95% CI 576-820 pg ml-1），肾素浓度较高（平均差值350 pg ml-1, 95% CI 123-577 pg ml-1）。结论：这项机制探索性分析表明，术前有效的RAAS抑制与非心脏手术后心肌损伤风险降低相关，与术前停止或继续使用RAAS抑制剂无关。临床试验注册：ISRCTN17251494。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British journal of anaesthesia 医学-麻醉学

CiteScore

13.50

自引率

7.10%

发文量

488

审稿时长

27 days

期刊介绍： The British Journal of Anaesthesia (BJA) is a prestigious publication that covers a wide range of topics in anaesthesia, critical care medicine, pain medicine, and perioperative medicine. It aims to disseminate high-impact original research, spanning fundamental, translational, and clinical sciences, as well as clinical practice, technology, education, and training. Additionally, the journal features review articles, notable case reports, correspondence, and special articles that appeal to a broader audience. The BJA is proudly associated with The Royal College of Anaesthetists, The College of Anaesthesiologists of Ireland, and The Hong Kong College of Anaesthesiologists. This partnership provides members of these esteemed institutions with access to not only the BJA but also its sister publication, BJA Education. It is essential to note that both journals maintain their editorial independence. Overall, the BJA offers a diverse and comprehensive platform for anaesthetists, critical care physicians, pain specialists, and perioperative medicine practitioners to contribute and stay updated with the latest advancements in their respective fields.