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

Abstract

Context: The plasma concentrations of angiotensin-converting enzyme 2 (pACE2) has been independently associated with cardiovascular diseases.

Objective: Higher pACE2 concentrations may be found in patients with primary aldosteronism (PA) and might lead to increased cardiovascular events.

Methods: Using 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.

Results: Incident PA and essential hypertension (EH) patients had similarly elevated pACE2 (47.04 ± 22.06 vs 46.73 ± 21.06 ng/mL; P = .937). Age was negatively (β = -2.15; P = .033) and higher serum potassium level (β = 2.29; P = .024) was positively correlated with higher pACE2 in PA patients. Clinical complete hypertension remission after adrenalectomy (Primary Aldosteronism Surgery Outcome criteria) was achieved in 36 (50%) of 72 surgically treated unilateral PA (uPA) patients. At follow-up, pACE2 decreased in surgically treated patients who had (P < .001) or had no (P = .006) hypertension remission, but the pACE2 attenuation was not statistically significant in uPA (P = .085) and bilateral PA (P = .409) administered with mineralocorticoid receptor antagonist (MRA). Persistently elevated pACE2 (> 23 ng/mL) after targeted treatments was related to all-cause mortality and cardiovascular events among PA patients (hazard ratio = 8.8; P = .04); with a mean follow-up of 3.29 years. TMPRSS2 messenger RNA (mRNA) expression was higher in uPA (P = .018) and EH (P = .038) patients than in normotensive controls; it was also decreased after adrenalectomy (P < .001).

Conclusion: PA and EH patients had elevated pACE2 and higher expression of TMPRSS2 mRNA compared to those of normotensive population. Persistently elevated pACE2 (> 23 ng/mL) after targeted treatments was associated risk of mortality and incident cardiovascular events.