OBJECTIVES This study investigated the relationship between plasma angiotensin-converting enzyme 2 (ACE2) activity levels and the severity of stenosis and myocardial remodeling in patients with aortic stenosis (AS) and determined if plasma ACE2 levels offered incremental prognostic usefulness to predict all-cause mortality. BACKGROUND ACE2 is an integral membrane protein that degrades angiotensin II and has an emerging role as a circulating biomarker of cardiovascular disease. METHODS Plasma ACE2 activity was measured in 127 patients with AS; a subgroup had myocardial tissue collected at the time of aortic valve replacement. RESULTS The median plasma ACE2 activity was 34.0 pmol/ml/min, and levels correlated with increased valvular calcification (p = 0.023) and the left ventricular (LV) mass index (r = 0.34; p < 0.001). Patients with above-median plasma ACE2 had higher LV end-diastolic volume (57 ml/m2 vs. 48 ml/m2; p = 0.021). Over a median follow-up of 5 years, elevated plasma ACE2 activity was an independent predictor of all-cause mortality after adjustment for relevant clinical, imaging, and biochemical parameters (HR: 2.28; 95% CI: 1.03 to 5.06; p = 0.042), including brain natriuretic peptide activation (integrated discrimination improvement: 0.08; p < 0.001). In 22 patients with plasma and tissue, increased circulating ACE2 was associated with reduced myocardial ACE2 gene expression (0.7-fold; p = 0.033) and severe myocardial fibrosis (p = 0.027). CONCLUSIONS In patients with AS, elevated plasma ACE2 was a marker of myocardial structural abnormalities and an independent predictor of mortality with incremental value over traditional prognostic markers. Loss of ACE2 from the myocardium was associated with increased fibrosis and higher circulating ACE2 levels.

中文翻译：

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血浆ACE2活性可预测主动脉瓣狭窄的死亡率，并与严重的心肌纤维化相关。

目的本研究调查了血浆血管紧张素转化酶2（ACE2）活性水平与主动脉瓣狭窄（AS）患者的狭窄程度和心肌重塑之间的关系，并确定血浆ACE2水平是否可提供增加的预后价值以预测全因死亡率。背景技术ACE2是降解血管紧张素II的完整膜蛋白，并且具有作为心血管疾病的循环生物标记物的新兴作用。方法对127例AS患者进行血浆ACE2活性测定。一个亚组在主动脉瓣置换时收集了心肌组织。结果血浆ACE2活性中值为34.0 pmol / ml / min，且水平与瓣膜钙化（p = 0.023）和左心室（LV）质量指数（r = 0.34; p <0.001）相关。血浆ACE2高于中值的患者的舒张末期左室容积较高（57 ml / m2对48 ml / m2； p = 0.021）。经过5年的中位随访，调整了相关的临床，影像和生化参数后，血浆ACE2活性升高是全因死亡率的独立预测因子（HR：2.28； 95％CI：1.03至5.06； p = 0.042 ），包括脑利钠肽的活化（综合辨别力改善：0.08； p <0.001）。在22名血浆和组织患者中，循环中的ACE2升高与心肌ACE2基因表达降低（0.7倍； p = 0.033）和严重的心肌纤维化（p = 0.027）相关。结论在AS患者中，血浆ACE2升高是心肌结构异常的标志，并且是死亡率的独立预测因子，其价值比传统的预后指标高。