Department of Cardiology, Amsterdam University Medical Centers, Location VU Medical Center, Amsterdam, the Netherlands.
Department of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, Rotterdam, the Netherlands.
Atherosclerosis. 2022 Apr;347:47-54. doi: 10.1016/j.atherosclerosis.2022.03.017. Epub 2022 Mar 17.
In this study, we investigated whether increased renin angiotensin aldosterone system (RAAS) activation and endothelin-1 levels are related to coronary artery calcium (CAC) score, total plaque volume (TPV), high risk plaque, hyperemic myocardial blood flow (MBF) and coronary microvascular dysfunction (CMD).
In a prospective, observational, cross-sectional cohort, renin as a marker for RAAS activation and endothelin-1 were measured in peripheral venous blood of 205 patients (64% men; age 58 ± 8.7 years) with suspected coronary artery disease (CAD) who underwent coronary computed tomography angiography (CCTA), [O]HO positron emission tomography (PET) perfusion imaging and invasive fractional flow reserve (FFR) measurements. Patients were categorized into three groups based on FFR (≤0.80) and hyperemic MBF <2.3 ml/min/g: [1] obstructive CAD (n = 92), [2] CMD (n = 26) or [3] no or non-obstructive CAD (n = 85).
After correction for baseline characteristics, including RAAS inhibiting therapy, renin associated positively with CAC score and TPV, but not with hyperemic MBF (p < 0.01; p = 0.02 and p = 0.23). Patients with high risk plaque displayed higher levels of renin (mean logarithmic renin 1.25 ± 0.43 vs. 1.12 ± 0.35 pg/ml; p = 0.04), but not endothelin-1. Compared to no or non-obstructive CAD patients, renin was significantly elevated in obstructive CAD patients but not in CMD patients (mean logarithmic renin 1.06 ± 0.34 vs. 1.23 ± 0.36; p < 0.01 and 1.06 ± 0.34 vs. 1.16 ± 0.41 pg/ml; p = 0.65). Endothelin-1 did not differ between the three patient groups.
Our report provides evidence that RAAS activity measured by renin concentration is elevated in patients with coronary atherosclerosis and high risk plaque but not in patients with CMD, whereas endothelin-1 is not related to either.
在本研究中，我们研究了肾素血管紧张素醛固酮系统（RAAS）激活和内皮素-1 水平的增加是否与冠状动脉钙（CAC）评分、总斑块体积（TPV）、高危斑块、充血性心肌血流（MBF）和冠状动脉微血管功能障碍（CMD）有关。
在一项前瞻性、观察性、横断面队列研究中，我们测量了 205 名疑似冠心病（CAD）患者（64%为男性；年龄 58±8.7 岁）外周静脉血中的肾素作为 RAAS 激活的标志物和内皮素-1，这些患者接受了冠状动脉计算机断层扫描血管造影（CCTA）、[O]HO 正电子发射断层扫描（PET）灌注成像和有创性血流储备分数（FFR）测量。根据 FFR（≤0.80）和充血性 MBF <2.3 ml/min/g，患者分为三组：[1]阻塞性 CAD（n=92）、[2]CMD（n=26）或[3]无或非阻塞性 CAD（n=85）。
在校正基线特征后，包括 RAAS 抑制治疗，肾素与 CAC 评分和 TPV 呈正相关，但与充血性 MBF 无关（p<0.01;p=0.02 和 p=0.23）。高危斑块患者的肾素水平较高（平均对数肾素 1.25±0.43 与 1.12±0.35 pg/ml;p=0.04），但内皮素-1 无差异。与无或非阻塞性 CAD 患者相比，阻塞性 CAD 患者的肾素水平显著升高，但 CMD 患者的肾素水平无差异（平均对数肾素 1.06±0.34 与 1.23±0.36;p<0.01 和 1.06±0.34 与 1.16±0.41 pg/ml;p=0.65）。三组患者的内皮素-1 无差异。
我们的报告提供了证据表明，用肾素浓度测量的 RAAS 活性在冠状动脉粥样硬化和高危斑块患者中升高，但在 CMD 患者中不升高，而内皮素-1与两者均无关。
