Circulating Plasma Concentrations of ACE2 in Primary Aldosteronism and Cardiovascular Outcomes

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 (beta = -2.15; P = .033) and higher serum potassium level (beta = 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.

Automated summary

Elevated pACE2 concentrations and increased expression of TMPRSS2 mRNA are observed in patients with primary aldosteronism (PA) and essential hypertension (EH). After hypertension remission following adrenalectomy, pACE2 levels decrease. Persistently elevated pACE2 is associated with increased risk of mortality and cardiovascular events.