The Relation of Angiotensin-Converting Enzyme 2, Renin-Angiotensin-Aldosterone System Inhibitors, and Arterial Stiffness in Acute COVID-19 Emergency Department Patients-A Prospective Observational Study

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) can damage the endothelium and increase arterial stiffness, potentially leading to adverse cardiovascular events. In parallel, systemic inflammation in COVID-19 also impacts endothelial function. Angiotensin-converting enzyme 2 (ACE2) promotes vasodilation and anti-inflammatory effects, but also facilitates SARS-CoV-2 entry into human cells. Thus, concerns have been raised about the use of RAAS inhibitors (RAASi) in COVID-19 patients due to potential ACE2 upregulation. However, the clinical significance of increased plasma ACE2 (sACE2) in RAASi-treated COVID-19 patients remains unclear. Methods: This prospective, single-centre study evaluated RAASi, sACE2, and vascular function in acutely ill patients with COVID-19 in comparison with acutely ill patients without COVID-19. Adult emergency department patients with confirmed or suspected COVID-19 were enrolled and underwent pulse wave velocity, ankle brachial index, and sACE2 measurements. Results: In the 152 included patients (50% female, median age 62 years, 68% COVID-19 positive), the sACE2 values were slightly higher in the COVID-19 (0.485 [0.364-1.329]) than in the non-COVID-19 subgroup (0.458 [0.356-1.138]; p = 0.70). No significant differences in sACE2 were observed between patients with and without RAASi, regardless of COVID-19 status. Pulse wave velocity values differed significantly between groups (p = 0.015). Conclusions: In emergency department patients, sACE2 was upregulated in COVID-19 patients, probably due to oxidative stress and inflammation. RAASi did not increase sACE2, but may have protective effects against inflammation. Elevated sACE2 appeared to have a beneficial effect on arterial stiffness in all patients. These findings support continued RAASi therapy in COVID-19 patients to protect against chronic inflammation and apoptosis.

Keywords: ACE2; COVID-19; RAAS inhibitors; ankle-brachial index; arterial stiffness; pulse-wave velocity.

Figure 1

Overview of ABI and PWV values in all cohorts. ABI = ankle-brachial index; PWV = pulse-wave velocity; baPWV = brachial-ankle pulse-wave velocity; m/s = meters per second; cfPWV = carotid-femoral pulse-wave velocity 2; RAASi = renin−angiotensin−aldosterone system inhibitors.

Figure 2

sACE2 values of COVID-19 and non-COVID-19 patients with and without RAASi. sACE2 = soluble angiotenin-converting enzyme 2; RAASi = renin−angiotensin−aldosterone system inhibitors.