Kurczina Anita, Ráduly Arnold Péter, Siket Ivetta Mányiné, Pólik Zsófia, Kracskó Bertalan, Kertész Attila Béla, Balogh Ágnes, Molnár Andrea, Fülöp Tibor, Antal Laura, Ötvös Csaba, Fagyas Miklós, Szerafin Tamás, Tóth Attila, Papp Zoltán, Csanádi Zoltán, Borbély Attila
Division of Cardiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Móricz Zsigmond str. 22., H-4032, Debrecen, Hungary.
Division of Clinical Physiology, Department of Cardiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Geroscience. 2025 Jul 15. doi: 10.1007/s11357-025-01792-6.
Aortic stenosis (AS) is the most prevalent valve disease in developed countries, with its incidence rising in the aging population. The current criteria for aortic valve replacement (AVR) are based on subjective symptoms and left ventricular ejection fraction (LVEF), which may not adequately reflect left ventricular (LV) dysfunction. This highlights the necessity for objective biomarkers to evaluate subclinical LV dysfunction. Serum angiotensin-converting enzyme 2 (sACE2) has emerged as a promising novel biomarker for cardiovascular diseases. To investigate the association between sACE2 activity and different flow-grade categories of severe AS, compare it with the traditional biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP), and assess the utility of sACE2 as a biomarker for AS. sACE2 and NT-proBNP were measured in 175 patients (97 male, 78 female, mean age 75 ± 8 years) diagnosed with severe AS (aortic valve area, AVA ≤ 1 cm). Patients were classified into 5 groups depending on LV flow state and pressure gradient levels: normal flow-low gradient (NF-LG), normal flow-high gradient (NF-HG), low flow-high gradient (LF-HG), low flow-low gradient (LF-LG), and paradoxical low flow-low gradient (PLF-LG) AS. Both biomarkers showed a general increase with advanced stages of severe AS (NF-LG: 65.0 ± 3.5 U/ml; LF-LG: 148.1 ± 16.8 U/ml; P < 0.05 for sACE2 and NF-LG: 687 ± 193 pg/ml; LF-LG: 5966 ± 1076 pg/ml; P < 0.05 for NT-proBNP). Notably, PLF-LG patients exhibited NT-proBNP levels similar to NF groups (PLF-LG: 1010 ± 218 pg/ml). Both biomarkers negatively correlated with LVEF and AVA. Receiver operating characteristic (ROC) analysis revealed that sACE2 provides incremental value over NT-proBNP in detecting subclinical LV dysfunction, with a 44% specificity for sACE2 compared to 6% for NT-proBNP at 98,67% sensitivity. The assessment of sACE2 activity in patients with AS provides valuable insights into disease stage and progression, supporting clinical decision-making and optimizing the timing of AVR. Furthermore, sACE2 activity serves as a moderately sensitive blood biomarker for identifying patients at risk of AS.
主动脉瓣狭窄（AS）是发达国家最常见的瓣膜疾病，其发病率在老年人群中呈上升趋势。目前主动脉瓣置换术（AVR）的标准基于主观症状和左心室射血分数（LVEF），这可能无法充分反映左心室（LV）功能障碍。这凸显了使用客观生物标志物评估亚临床LV功能障碍的必要性。血清血管紧张素转换酶2（sACE2）已成为一种有前景的心血管疾病新型生物标志物。为了研究sACE2活性与重度AS不同血流分级类别之间的关联，将其与传统生物标志物N端前脑钠肽（NT-proBNP）进行比较，并评估sACE2作为AS生物标志物的效用。对175例诊断为重度AS（主动脉瓣面积，AVA≤1 cm）的患者（97例男性，78例女性，平均年龄75±8岁）进行了sACE2和NT-proBNP检测。根据LV血流状态和压力梯度水平，患者被分为5组：正常血流-低梯度（NF-LG）、正常血流-高梯度（NF-HG）、低血流-高梯度（LF-HG）、低血流-低梯度（LF-LG）和矛盾性低血流-低梯度（PLF-LG）AS。两种生物标志物均显示随着重度AS病情进展总体升高（sACE2：NF-LG为65.0±3.5 U/ml；LF-LG为148.1±16.8 U/ml；P<0.05；NT-proBNP：NF-LG为687±193 pg/ml；LF-LG为5966±1076 pg/ml；P<0.05）。值得注意的是，PLF-LG患者的NT-proBNP水平与NF组相似（PLF-LG：1010±218 pg/ml）。两种生物标志物均与LVEF和AVA呈负相关。受试者工作特征（ROC）分析显示，在检测亚临床LV功能障碍方面，sACE2比NT-proBNP具有更高的价值，在灵敏度为98.67 %时，sACE2的特异性为44%，而NT-proBNP为6%。评估AS患者的sACE2活性可为疾病阶段和进展提供有价值的见解，支持临床决策并优化AVR时机。此外，sACE2活性可作为一种中度敏感的血液生物标志物，用于识别有AS风险的患者。
