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

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

作者信息

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

机构信息

Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK.

Bloomsbury Institute of Intensive Care Medicine, University College London, London, UK; UCL Hospitals NHS Foundation Trust, London, UK; NIHR University College London Hospitals Biomedical Research Centre, London, UK.

出版信息

Br J Anaesth. 2025 May;134(5):1300-1307. doi: 10.1016/j.bja.2024.10.040. Epub 2024 Dec 20.

DOI:10.1016/j.bja.2024.10.040

PMID:39709293

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12106892/

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, 95% CI 576-820 pg ml) and higher renin concentration (mean difference 350 pg ml, 95% CI 123-577 pg ml), 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.

摘要

背景

老年患者的高血压治疗往往未达最佳效果，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RAAS激活的不同内型与心肌损伤风险增加相关。

方法

这是一项对多中心随机对照试验（ISRCTN17251494）的预先指定的探索性分析，该试验将60岁及以上接受择期非心脏手术的患者随机分为继续或停用RAAS抑制剂（根据药代动力学特征确定）两组。无监督分层聚类分析从麻醉诱导前采集的样本中识别出具有相似RAAS激活的不同患者组，通过酶联免疫吸附测定法对血浆肾素、醛固酮、血管紧张素转换酶2和二肽基肽酶-3进行定量。主要结局对研究人员和参与者设盲，为心肌损伤（血浆高敏肌钙蛋白T）。

结果

我们识别出三个聚类，随机分配至停用或继续使用RAAS抑制剂的比例相似。聚类1（n = 52；平均年龄[标准差]，75岁[8岁]；54%为女性）和聚类3（n = 25；75岁[6岁]；44%为女性）的心肌损伤发生率较高（分别为23/52[44%]和13/25[52%]），而聚类2为51/164（31.1%；n = 153；70岁[6岁]；46%为女性；比值比：1.95，95%置信区间（CI）1.12 - 3.39，P = 0.018）。与心肌损伤发生率较高的聚类1和聚类3相比，聚类2的特征是N末端B型利钠肽原（NT-proBNP）浓度较低（平均差异698 pg/ml，95% CI 576 - 820 pg/ml）且肾素浓度较高（平均差异350 pg/ml，95% CI 123 - 577 pg/ml）。