Circulating Plasma Concentrations of ACE2 in Primary Aldosteronism and Cardiovascular Outcomes.

Abstract

ContextThe plasma concentrations of angiotensin-converting enzyme 2 ([pACE2) has been independently associated with cardiovascular diseases.ObjectiveHigher [pACE2] concentrations could be found in patients with primary aldosteronism (PA) and might lead to increased cardiovascular events.MethodsUsing an inception observational cohort, we examined [pACE2] among 168 incident patients with PA. The expression of ACE2, serine protease 2 (TMPRSS2), and metalloprotease 17 (ADAM17) were assessed in peripheral blood mononuclear cells (PBMCs).ResultsIncident PA and EH patients had similarly elevated [pACE2] (47.04 ± 22.06 vs. 46.73 ± 21.06 ng/ml, p= 0.937). Age was negatively (β, -2.15, p= 0.033) and higher serum potassium level (β, 2.29, p= 0.024) was positively correlated with higher [pACE2] in PA patients. Clinical complete hypertension-remission after adrenalectomy (PASO criteria) was achieved in 36 (50%) of the 72 surgically-treated uPA patients. At follow-up, the [pACE2] decreased in surgically-treated patients who had (p< 0.001) or had no (p= 0.006) hypertension-remission, but the [pACE2] attenuation was not significant in uPA (p= 0.085) and biPA (p= 0.409) administered with minerocorticoid receptor antagonist (MRA). Persistently elevated [pACE2] (> 23ng/ml) after targeted treatments was related to all-cause mortality and cardiovascular events among PA patients (HR, 8.8, p = 0.04); with a mean followed up of 3.29 years. TMPRSS2 mRNA expression was higher in uPA (p= 0.018) and EH (p= 0.038) patients than that in normotensive controls; it was also decreased after adrenalectomy (p< 0.001).ConclusionsPA and EH patients had elevated [pACE2] and higher expression of TMPRSS2 mRNA compared to those of normotensive population. Persistently elevated [pACE2] (> 23ng/ml) after targeted treatments was associated the risk of mortality and incident cardiovascular events.