KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated with a Greater Recovery of Arterial Stiffness.

Yi-Yao Chang,Chien-Ting Pan,Chin-Chen Chang,Bo-Ching Lee,Vin-Cent Wu,Shih-Yuan Peng,Li-Yu Daisy Liu,Yen-Hung Lin,Zheng-Wei Chen,Kang-Yung Peng,Chia-Hung Chou,Cheng-Hsuan Tsai,Che-Wei Liao,Yu-Wei Chiu,Chi-Sheng Hung

doi:10.3390/cancers13174313

Abstract

Simple SummaryPrimary aldosteronism (PA) is the most common form of secondary hypertension and induces various cardiovascular injuries. Aldosterone-producing adenoma (APA) is one of the major forms of PA. The occurrence of APA is closely correlated with somatic mutations, including KCNJ5. We described here the impact of KCNJ5 somatic mutations on arterial stiffness excluding the influence of age, sex, and blood pressure status. We found KCNJ5 mutation carriers had similar arterial stiffness before surgery, but greater improvement of arterial stiffness after adrenalectomy compared with non-carriers. Hence, APA patients with KCNJ5 mutations had a greater improvement in arterial stiffness after adrenalectomy than those without mutations.Primary aldosteronism is the most common form of secondary hypertension and induces various cardiovascular injuries. In aldosterone-producing adenoma (APA), the impact of KCNJ5 somatic mutations on arterial stiffness excluding the influence of confounding factors is uncertain. We enrolled 213 APA patients who were scheduled to undergo adrenalectomy. KCNJ5 gene sequencing of APA was performed. After propensity score matching (PSM) for age, sex, body mass index, blood pressure, number of hypertensive medications, and hypertension duration, there were 66 patients in each group with and without KCNJ5 mutations. The mutation carriers had a higher aldosterone level and lower log transformed brachial–ankle pulse wave velocity (baPWV) than the non-carriers before PSM, but no difference in log baPWV after PSM. One year after adrenalectomy, the mutation carriers had greater decreases in log plasma aldosterone concentration, log aldosterone–renin activity ratio, and log baPWV than the non-carriers after PSM. Only the mutation carriers had a significant decrease in log baPWV after surgery both before and after PSM. KCNJ5 mutations were not correlated with baseline baPWV after PSM but were significantly correlated with ∆baPWV after surgery both before and after PSM. Conclusively, APA patients with KCNJ5 mutations had a greater regression in arterial stiffness after adrenalectomy than those without mutations.

Highlights

Primary aldosteronism (PA) is the most common form of secondary endocrine hypertension, which accounts for 5–15% of all cases of hypertension [1,2,3]
Of the 213 aldosterone-producing adenoma (APA) patients who received adrenalectomy, 126 (59.2%) had KCNJ5 somatic mutations. Of these 126 mutation carriers, sequencing of adenoma specimens demonstrated that 75 patients had p.Gly151Arg (c.451G > A or c.451G > C), 45 had p.Leu168Arg (c.503T > G), 3 had p.Thr158Ala (c.472A > G), and 3 had p.Glu145Gln (c.433G > C) mutations in the heterozygous state
The matched APA patients with KCNJ5 mutations had a lower rate of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II blocker (ARB) use (p = 0.037), higher aldosterone level (p = 0.012), higher aldosterone-to-renin ratio (ARR) (p = 0.017), and lower potassium level (p < 0.001) than the non-carriers (Table 1)

Summary

Introduction

Primary aldosteronism (PA) is the most common form of secondary endocrine hypertension, which accounts for 5–15% of all cases of hypertension [1,2,3]. Previous animal studies have shown that aldosterone infusion in uninephrectomized rats accompanied with a high sodium diet could cause increased arterial stiffness associated with fibronectin accumulation [4] This effect was independent of wall stress as shown by normotensive controls and reversal of vascular damage by treatment with an aldosterone antagonist [4]. In clinical studies, increased carotid–femoral pulse wave velocity (PWV), which represents increased arterial stiffness, has been noted in patients with PA compared to patients with essential hypertension (EH) after adjusting for all clinical variables including 24 h blood pressure [5] These effects on arteries have been shown to be reversed after adrenalectomy [6,7]

Methods

Results

Conclusion