Sex-Specific Association of Primary Aldosteronism With Visceral Adiposity

Yu Hatano; Nagisa Sawayama; Hiroshi Miyashita; Tomoyuki Kurashina; Kenta Okada; Manabu Takahashi; Masatoshi Matsumoto; Satoshi Hoshide; Takahiro Sasaki; Shuichi Nagashima; Ken Ebihara; Harushi Mori; Kazuomi Kario; Shun Ishibashi


J Endo Soc. 2022;6(8) 

In This Article

Abstract and Introduction


Context: The association between primary aldosteronism and obesity, especially its sex difference, remains unknown.

Objective: To assess the association for each subtype of primary aldosteronism with obesity parameters including visceral adipose tissue and differences between sexes.

Methods: In this case-control study, 4 normotensive controls were selected for each case with primary aldosteronism. Multivariable conditional logistic regression models were used to estimate the association between each type of primary aldosteronism and obesity indicators. We used a random forest to identify which visceral or subcutaneous tissue areas had a closer association with disease status.

Results: The study subjects included 42 aldosterone-producing adenoma cases (22 women) and 68 idiopathic hyperaldosteronism cases (42 women). In multivariable conditional logistic regressions, aldosterone-producing adenoma was significantly associated with body mass index only in men (odds ratio [OR] [95% CI)], 4.62 [1.98–10.80] per 2.89 kg/m2) but not in women (OR [95% CI], 1.09 [0.69–1.72] per 3.93 kg/m2) compared with the matched controls, whereas idiopathic hyperaldosteronism was associated with body mass index in both men (OR [95% CI], 3.96 [2.03–7.73] per 3.75 kg/m2) and women (OR [95% CI], 2.65 [1.77–3.96] per 3.85 kg/m2) compared with the matched controls. In random forests, visceral adipose tissue areas were the better predictor of both aldosterone-producing adenoma and idiopathic hyperaldosteronism than subcutaneous adipose tissue.

Conclusions: Aldosterone-producing adenoma cases were obese among men, but not among women. Idiopathic hyperaldosteronism cases were obese among both men and women. Visceral adipose tissue may contribute to the pathophysiology of primary aldosteronism.


Primary aldosteronism (PA) is the most frequent form of secondary hypertension, with a prevalence of 5% to 15% in all hypertensive patients.[1,2] The 2 predominant causes of PA are aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA).[3,4] Patients with PA have a higher prevalence of cardiovascular events and mortality than patients with essential hypertension.[4–7] Primary aldosteronism is a major public health issue given the increase in its prevalence.[8] There is therefore a pressing unmet need to identify the mechanisms of PA to drive preventative initiatives and improve health outcomes.

Although the increase in its prevalence is most likely a reflection of active screening and surveillance of at-risk patients, other environmental factors such as the substantial increase in the prevalence of obesity could be related to its development.[9,10] A prior study suggested that the prevalence of obesity was significantly higher in patients with IHA than in patients with essential hypertension.[11] However, other studies found no significant association between PA and obesity.[12–14] These studies used subjects with essential hypertension, which is also significantly associated with obesity, as controls. This could mask the association between PA and obesity.[15] Therefore, it is necessary to compare PA cases with normotensive controls who have standard obesity parameters to determine whether PA is associated with obesity.

Ohno et al suggested that patients with IHA were more obese than those with APA.[11] In addition, a difference between sexes has been reported; body mass index (BMI) was significantly higher in IHA patients compared with APA among women, but not among men.[16] However, it remains uncertain whether the association between each subtype of PA and obesity differ by sex compared with non-PA cases. Elucidating the sex-specific association may clarify the underlying mechanisms of PA.

Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are different in their patterns of molecular properties and their roles in the regulation of whole-body metabolism.[17–20] Abdominal VAT is considered to be the more pathogenic fat depot because of stronger associations with most cardiometabolic risk factors compared with SAT.[21,22] A prior study reported a positive association of plasma aldosterone (PAC) with visceral fat area among IHA cases.[23] However, this is limited only among PA cases; it did not include any control groups. To the best of our knowledge, there have been no previous studies comparing the distribution of adipose tissue between PA cases and control groups. We hypothesized that VAT area had a closer association with each subtype of PA than SAT area because patients with PA have a high prevalence of cardiovascular events.[4–7] However, conventional generalized linear model may not be appropriate because of multicollinearity between BMI, VAT, and SAT areas. Thus, we used a random forest, a machine learning algorithm, which can minimize the effect of multicollinearity.[24]

Using a dataset of PA patients and health checkup participants whose adipose tissue areas were measured by computed tomography (CT), we assessed (1) whether obesity parameters, including VAT area, were associated with each type of PA; (2) whether the associations differed by sex; and (3) which of the VAT and SAT areas had a closer association with each type of PA.