Determinants of soluble angiotensin-converting enzyme 2 concentrations in adult patients with complex congenital heart disease

Abstract

Background Angiotensin-converting enzyme (ACE) 2 is known to be a functional receptor for SARS-CoV-2 in the current pandemic. Soluble ACE2 (sACE2) concentrations are elevated in patients with various cardiovascular disorders including heart failure. Methods In a total of 182 consecutive adult patients with complex congenital heart disease (CHD) and 63 healthy controls, sACE2 concentrations were measured in serum using the Human ACE2® assay by Cloud-Clone Corporation and associated with clinical, laboratory and echocardiographic parameters. Results Median sACE2 levels were increased in patients with complex CHD as compared to healthy controls (761.9 pg/ml vs 365.2 pg/ml, p < 0.001). Moreover, sACE2 concentrations were significantly elevated in patients with a higher NYHA class ≥ III (1856.2 pg/ml vs 714.5 pg/ml in patients with NYHA class I/II, p < 0.001). Using linear regression analysis, higher sACE2 levels were associated with a higher NYHA class ≥ III, more severe CHD, a morphological left systemic ventricle, higher creatinine and the use of mineralocorticoid receptor antagonists (MRA) in the univariable model. The use of ACE inhibitors or angiotensin receptor blockers (ARB) was associated with lower sACE2 levels. In the multivariable model, higher sACE2 levels were independently associated with a higher NYHA class ≥ III (p = 0.002) and lower sACE2 levels with the use of ACE inhibitors or ARB (p = 0.001). Conclusion Soluble ACE2 concentrations were significantly increased in all types of complex CHD with highest levels found in patients with NYHA class ≥ III. Moreover, a higher NYHA class ≥ III was the most significant determinant that was independently associated with elevated sACE2 concentrations. Graphic abstract

Effects of SARS-CoV-2 on Cardiovascular System: The Dual Role of Angiotensin-Converting Enzyme 2 (ACE2) as the Virus Receptor and Homeostasis Regulator-Review

“…The reason for this discrepancy could be explained by the enhanced ADAM17 expression and activity in pathologic conditions, which corresponds to the increase of sACE2 concentration in plasma samples [ 30 , 51 ]. sACE2 concentration increases in patient cohorts with heart failure, mostly in males, and in patients with worse New York Heart Association functional class (NYHA) [ 18 , 51 , 52 , 53 ]. In patients with CVDs, the relation between the reduction of ACE2 protein on membranes and the susceptibility toward SARS-CoV-2 is still unclear.…”

The Relationship between Soluble Angiotensin-Converting Enzyme Level and Coronavirus Disease 2019 in Children: A Prospective Cohort Study

“…20 Some studies have shown positive prognostic results with the use of human recombinant sACE2 in COVID-19. 10,21 However, previous studies suggest that high blood ACE2 concentration is associated with COVID-19 severity 10,22 and also some comorbidities 22,23 that influence the prognosis of COVID-19. 5, 24 Ciaglia et al 7 speculated that the reason for these paradoxes may lie in posttranslational events that regulate protein levels and their balance between membrane-bound and soluble forms of ACE2.…”

“…On the 5th day, patients with moderate disease had higher CRP, D-dimer, and troponin levels than mild and asymptomatic patients. In several studies, extremes of age, 28 male sex, 5 obesity, 25 comorbid conditions, 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 high inflammatory markers (ferritin, CRP, procalcitonin, D-dimer, B-type natriuretic peptide and IL-6) 5 25 28 increased viral loads, 29 immune system genetic defects, 30 immunocompromised status, and lymphopenia 5 were identified as factors associated with COVID-19 severity in children. In a nationwide cohort study, children with confirmed COVID-19 were older and had higher rates of obesity compared with children with negative tests.…”

Concentrations of Soluble Angiotensin Converting Enzyme 2 (sACE2) in Children and Adults with and without COVID-19

“…Therefore, high sACE2 could be a risk factor for severe COVID-19. We have demonstrated that sACE2 concentration in serum was associated with the severity of congenital heart diseases and heart failure in adults [16].…”