Aldosterone-producing adenoma-harbouring KCNJ5 mutations is associated with lower prevalence of metabolic disorders and abdominal obesity

Chen, Kuan-Ming; Chang, Yu‐Ling; Wu, Tsu‐Juey; Lee, Bo-Ching; Chen, Po-Ting; Liu, Kao–Lang; Hong, Jia‐Sheng; Chang, Chin‐Chen; Wu, Vin‐Cent; Lin, Yen‐Hung

doi:10.1097/hjh.0000000000002948

Cited by 10 publications

(8 citation statements)

References 36 publications

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“…The mechanism of aortic calcification formation is complex and involves multifactorial vascular inflammation ( 40 ). In our prior study we investigated serum CRP levels in PA patients, and showed that KCNJ5 mutations were associated with lower levels of pro-inflammation factors ( 41 ), metabolic syndrome and abdominal obesity ( 42 ). This may explain why the patients without KCNJ5 somatic mutations had a higher burden of aortic calcified plaques despite lower blood pressure and less severe aldosteronism compared to those with KCNJ5 somatic mutations.…”

Section: Discussionmentioning

confidence: 99%

KCNJ5 Somatic Mutation Is Associated With Higher Aortic Wall Thickness and Less Calcification in Patients With Aldosterone-Producing Adenoma

et al. 2022

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ObjectivePrimary aldosteronism (PA) is the most common type of secondary hypertension, and it is associated with a higher rate of cardiovascular complications. KCNJ5 somatic mutations have recently been identified in aldosterone-producing adenoma (APA), however their influence on vascular remodeling and injury is still unclear. The aim of this study was to investigate the association between KCNJ5 somatic mutation status and vascular status.MethodsWe enrolled 179 APA patients who had undergone adrenalectomy from a prospectively maintained database, of whom 99 had KCNJ5 somatic mutations. Preoperative clinical, biochemical and imaging data of abdominal CT, including abdominal aortic calcification (AAC) score, aortic diameter and wall thickness at levels of superior (SMA) and inferior (IMA) mesenteric arteries were analyzed.ResultsAfter propensity score matching for age, sex, body mass index, triglycerides and low-density lipoprotein, there were 48 patients in each KCNJ5 (+) and KCNJ5 (-) group. Mutation carriers had a lower AAC score (217.3 ± 562.2 vs. 605.6 ± 1359.1, P=0.018), higher aortic wall thickness (SMA level: 2.2 ± 0.6 mm vs. 1.8 ± 0.6 mm, P=0.006; IMA level: 2.4 ± 0.6 mm vs. 1.8 ± 0.7 mm, P<0.001) than non-carriers. In multivariate analysis, KCNJ5 mutations were independently associated with AAC score (P=0.014) and aortic wall thickness (SMA level: P<0.001; IMA level: P=0.004). After adrenalectomy, mutation carriers had less aortic wall thickness progression than non-carriers (Δthickness SMA: -0.1 ± 0.8 mm vs. 0.9 ± 0.6 mm, P=0.024; IMA: -0.1 ± 0.6 mm vs. 0.8 ± 0.7 mm, P=0.04).ConclusionKCNJ5 mutation carriers had less calcification burden of the aorta, thickened aortic wall, and less wall thickness progression than non-carriers.

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Section: Discussionmentioning

confidence: 99%

KCNJ5 Somatic Mutation Is Associated With Higher Aortic Wall Thickness and Less Calcification in Patients With Aldosterone-Producing Adenoma

et al. 2022

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“…No differences existed between the two subtypes in terms of TC and FBG levels among non‐Asian patients with PA. We supposed the different lifestyles play an important part. In addition, KCNJ5 mutation, prevalent in APA patients of Asian ethnicity, 42 might matter. According to Chen et al., 42 IHA patients exhibited significantly higher TG levels than APA patients with KCNJ5 mutations but showed no difference compared with those without KCNJ5 mutations, which is in accordance with our results.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, KCNJ5 mutation, prevalent in APA patients of Asian ethnicity, 42 might matter. According to Chen et al., 42 IHA patients exhibited significantly higher TG levels than APA patients with KCNJ5 mutations but showed no difference compared with those without KCNJ5 mutations, which is in accordance with our results. Given the relatively small number of studies included in each subgroup, additional research should be conducted to validate it.…”

Section: Discussionmentioning

confidence: 99%

Meta‐analysis of blood parameters related to lipid and glucose metabolism between two subtypes of primary aldosteronism

Zhu

2022

J of Clinical Hypertension

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It remains unclear whether metabolic profiles differ within the subtypes of primary aldosteronism (PA). This meta‐analysis aimed to compare the blood parameters related to lipid and glucose metabolism at baseline between unilateral PA and bilateral PA. A search was performed using PubMed, Web of Science, and Sciencedirect databases, supplemented by hand‐searching of related references. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated for each parameter. Twenty‐one studies involving 4197 patients with PA were included. Compared with bilateral PA groups, unilateral PA groups demonstrated significantly lower low‐density lipoprotein cholesterol (LDL‐C, SMD: −.14 mmol/L, 95% CI: −.20, −.07), total cholesterol (TC, SMD: −.16 mmol/L, 95% CI: −.23, −.09), triglyceride (TG, SMD: −.22 mmol/L, 95% CI: −.29, −.16), fasting blood glucose (FBG, SMD: −.11 mmol/L, 95% CI: −.18, −.04), hemoglobin A1c (HbA1c, SMD: −.21%, 95% CI: −.30, −.13), and homeostasis model assessment‐insulin resistance (HOMA‐IR, SMD: −.40, 95% CI: −.58, −.23). No significant difference was found in high‐density lipoprotein cholesterol (HDL‐C) level between the two groups (SMD: .40 mmol/L, 95% CI: −.02, .11). To sum up, comparison of several blood metabolic parameters between the two subtypes suggested that the bilateral PA may associate with a higher prevalence of impaired glucose and lipid metabolism than unilateral PA; however, results should be treated with caution. Additional well‐designed studies are needed to prove the present results and better elucidate the link between metabolic abnormalities and etiologies of each PA subtype.

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“…This change may be driven by the decline of renal function after treatment of PA, which would lead to a decrease of lipoprotein lipase and hepatic triglyceride lipase and interfere with the metabolism of lipids (110). As for KCNJ5 mutation, the previous study revealed only patients with mutations had a significant increase of TG after adrenalectomy, but not in patients without mutations (103).…”

Section: Relationships Of Kcnj5 Somatic Mutations With Metabolic Diso...mentioning

confidence: 99%

“…CT is a well-established imaging tool to quantify abdominal adipose tissue, utilizing the Hounsfield Units (HU) range to measure the subcutaneous and visceral fat areas (102). Concerning the effect of KCNJ5 somatic mutations on MetS, Chen et al first reported that APA patients with KCNJ5 mutations had fewer MetS, lower triglyceride (TG) levels, waist circumference, and subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) area than those without KCNJ5 mutations even after matching for age (103). APA patients with KCNJ5 mutations also had fewer MetS and lower triglyceride levels compared to patients with BAH.…”

Section: Relationships Of Kcnj5 Somatic Mutations With Metabolic Diso...mentioning

confidence: 99%

Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism

Chang

Lee²,

Chen³

et al. 2023

Front. Endocrinol.

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BackgroundPrimary aldosteronism (PA) is the leading cause of curable endocrine hypertension, which is associated with a higher risk of cardiovascular and metabolic insults compared to essential hypertension. Aldosterone-producing adenoma (APA) is a major cause of PA, which can be treated with adrenalectomy. Somatic mutations are the main pathogenesis of aldosterone overproduction in APA, of which KCNJ5 somatic mutations are most common, especially in Asian countries. This article aimed to review the literature on the impacts of KCNJ5 somatic mutations on systemic organ damage.Evidence acquisitionPubMed literature research using keywords combination, including “aldosterone-producing adenoma,” “somatic mutations,” “KCNJ5,” “organ damage,” “cardiovascular,” “diastolic function,” “metabolic syndrome,” “autonomous cortisol secretion,” etc.ResultsAPA patients with KCNJ5 somatic mutations are generally younger, female, have higher aldosterone levels, lower potassium levels, larger tumor size, and higher hypertension cure rate after adrenalectomy. This review focuses on the cardiovascular and metabolic aspects of KCNJ5 somatic mutations in APA patients, including left ventricular remodeling and diastolic function, abdominal aortic thickness and calcification, arterial stiffness, metabolic syndrome, abdominal adipose tissue, and correlation with autonomous cortisol secretion. Furthermore, we discuss modalities to differentiate the types of mutations before surgery.ConclusionKCNJ5 somatic mutations in patients with APA had higher left ventricular mass (LVM), more impaired diastolic function, thicker aortic wall, lower incidence of metabolic syndrome, and possibly a lower incidence of concurrent autonomous cortisol secretion, but better improvement in LVM, diastolic function, arterial stiffness, and aortic wall thickness after adrenalectomy compared to patients without KCNJ5 mutations.

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Aldosterone-producing adenoma-harbouring KCNJ5 mutations is associated with lower prevalence of metabolic disorders and abdominal obesity

Cited by 10 publications

References 36 publications

KCNJ5 Somatic Mutation Is Associated With Higher Aortic Wall Thickness and Less Calcification in Patients With Aldosterone-Producing Adenoma

KCNJ5 Somatic Mutation Is Associated With Higher Aortic Wall Thickness and Less Calcification in Patients With Aldosterone-Producing Adenoma

Meta‐analysis of blood parameters related to lipid and glucose metabolism between two subtypes of primary aldosteronism

Cardiovascular and metabolic characters of KCNJ5 somatic mutations in primary aldosteronism

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