Circulating Plasma Concentrations of ACE2 in Primary Aldosteronism and Cardiovascular Outcomes

• Published in: The journal of clinical endocrinology and metabolism 2022-12, Vol.107 (12), p.3242-3251
• Main Authors: Wu, Vin-Cent, Hu, Ya-Hui, Chang, Chin-Chen, Chan, Chieh-Kai, Lai, Tai-Shuan, Lin, Yen-Hung, Wang, Shuo-Meng, Lu, Ching-Chu, Liu, Yu-Chun, Tsai, Yao-Chou, Chueh, Jeff S
• Format: Article
• Language: English
• Subjects: ACE inhibitors; Aldosterone; Chronic kidney failure; Clinical; Corticosteroids; Enzymes; Gene expression; Heart failure; Hyperaldosteronism; Hypertension; Messenger RNA; Thrombin
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgac539

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 met alloprotease 17 (ADAM17) were assessed in peripheral blood mononuclear cells. Results: Incident PA and essential hypertension (EH) patients had similarly elevated pACE2 (47.04[+ or -] 22.06 vs 46.73 [+ or -]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. Key Words: angiotensin-converting enzyme 2 (ACE2), aldosterone, hyperaldosteronism, primary aldosteronism, COVID-19 Abbreviations: ACEi, ACE inhibitor; ACE2, angiotensin-converting enzyme 2; ADAM17, met alloprotease 17; Af, atrial fibrillation; APA, aldosterone-producing adenoma; ARR, aldosterone-renin ratio; biPA, bilateral PA; BP, blood pressure; CHF, congestive heart failure; CKD, chronic kidney disease; CVD, cardiovascular diseases; EH, essential hypertension; FC, fold change; GEO, Gene Expression Omnib