KCNJ5 Somatic Mutations in Aldosterone-Producing Adenoma Are Associated With a Worse Baseline Status and Better Recovery of Left Ventricular Remodeling and Diastolic Function

Hypertension. 2021 Jan;77(1):114-125. doi: 10.1161/HYPERTENSIONAHA.120.15679. Epub 2020 Nov 30.

Abstract

Primary aldosteronism is the most common secondary endocrine form of hypertension and causes many cardiovascular injuries. KCNJ5 somatic mutations have recently been identified in aldosterone-producing adenoma. However, their impacts on left ventricular remodeling precluding the interference of age, sex, and blood pressure are still uncertain. We enrolled 184 aldosterone-producing adenoma patients who received adrenalectomy. Clinical, biochemical, and echocardiographic data were analyzed preoperatively and 1 year postoperatively. KCNJ5 gene sequencing of aldosterone-producing adenoma was performed. After propensity score matching for age, sex, body mass index, blood pressure, hypertension duration, and number of hypertensive medications, there were 60 patients in each group with and without KCNJ5 mutations. The mutation carriers had higher left ventricular mass index (LVMI) and inappropriately excessive LVMI (ieLVMI) and lower e' than the noncarriers. After adrenalectomy, the mutation carriers had greater decreases in LVMI and ieLVMI than the noncarriers. In addition, only mutation carriers had a significant decrease in E/e' after surgery. In multivariate analysis, baseline LVMI correlated with KCNJ5 mutations, the number of hypertensive medications, and systolic blood pressure. Baseline ieLVMI correlated with KCNJ5 mutations and the number of hypertensive medications. The regression of both LVMI and ieLVMI after surgery was mainly correlated with KCNJ5 mutations and changes in systolic blood pressure. Aldosterone-producing adenoma patients with KCNJ5 mutations had higher LVMI and ieLVMI and a greater regression of LVMI and ieLVMI after adrenalectomy than those without mutations. The patients with KCNJ5 mutations also benefited from adrenalectomy with regard to left ventricular diastolic function, whereas noncarriers did not.

Keywords: adenoma; adrenalectomy; blood pressure; body mass index; propensity score.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Cortex Neoplasms / genetics*
  • Adrenal Cortex Neoplasms / physiopathology
  • Adrenal Cortex Neoplasms / surgery
  • Adrenalectomy
  • Adrenocortical Adenoma / genetics*
  • Adrenocortical Adenoma / physiopathology
  • Adrenocortical Adenoma / surgery
  • Adult
  • Aged
  • Aldosterone / biosynthesis*
  • Diastole / physiology*
  • Echocardiography
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics*
  • Humans
  • Hypertrophy, Left Ventricular / etiology
  • Male
  • Middle Aged
  • Mutation*
  • Prospective Studies
  • Ventricular Remodeling / physiology*

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • KCNJ5 protein, human
  • Aldosterone