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Purpose: To investigate patients with primary aldosteronism (PA) and the prevalence of normal-tension glaucoma (NTG)., Design: Cross-sectional study., Methods: Newly diagnosed PA patients were evaluated in this cross-sectional study, with ophthalmic examinations such as intraocular pressure measurements by a Goldmann applanation tonometer, central corneal thickness, slit-lamp biomicroscopic examination, gonioscopy, ophthalmoscopy, fundus photography, visual field test with a Humphrey Field Analyzer 24-2 SITA Standard program, and optical coherence tomography of the peripapillary retinal nerve fiber layer, performed in each of the subjects. Optic disc appearance, perimetric results, optical coherence tomography results, and other ocular findings were all used for determining the glaucoma diagnosis. The primary outcome was shown the prevalence of NTG in patients with PA., Results: NTG prevalence in the 212 PA patients was 11.8% (95% confidence interval [CI], 4.7%-20.7%). As compared to the hypertensive patients without PA, the hypertensive patients with PA exhibited a significantly increased NTG prevalence (odds ratio; 4.019, 95% CI, 1.223-13.205; P = .022). Increased NTG prevalence was associated with age, ranging from 8.8% (95% CI, 2.1%-15.6%) for those aged 40 to 49 years, to 37.5% (95% CI, 13.8%-61.2%) for those aged 70 years and older. In 72 hypertensive patients without PA, who were used as the controls, NTG prevalence was 5.2%, with a 95% CI ranging from 0.5% to 14.4%., Conclusions: There was an 11.8% prevalence of NTG in PA patients, with these patients at an elevated risk of NTG, which was not mediated by blood pressure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Observational studies have reported associations between primary aldosteronism (PA) and cardiovascular outcomes, including coronary artery diseases (CAD), congestive heart failure (CHF), and stroke. However, establishing causality remains a challenge due to the lack of randomized controlled trial data on this topic. We thus aimed to investigate the causal relationship between PA and the risk of developing CAD, CHF, and stroke., Methods and Results: Cross-ancestry meta-analysis of genome-wide association studies combining East Asian and European ancestry (1560 PA cases and 742 139 controls) was conducted to identify single-nucleotide variants that are associated with PA. Then, using the identified genetic variants as instrumental variables, we conducted the 2-sample Mendelian randomization analysis to investigate the causal relationship between PA and incident CAD, CHF, and stroke among both East Asian and European ancestry. Summary association results were extracted from large genome-wide association studies consortia. Our cross-ancestry meta-analysis of East Asian and European populations identified 7 genetic loci significantly associated with the risk of PA, for which the genes nearest to the lead variants were CASZ1 , WNT2B , HOTTIP , LSP1 , TBX3 , RXFP2 , and NDP . Among the East Asian population, the pooled odds ratio estimates using these 7 genetic instruments of PA were 1.07 (95% CI, 1.03-1.11) for CAD, 1.10 (95% CI, 1.01-1.20) for CHF, and 1.13 (95% CI, 1.09-1.18) for stroke. The results were consistent among the European population., Conclusions: Our 2-sample Mendelian randomization study revealed that PA had increased risks of CAD, CHF, and stroke. These findings highlight that early and active screening of PA is critical to prevent future cardiovascular events.

Aldosterone secretion in primary aldosteronism (PA) is often regulated by adrenocorticotropic hormone (ACTH) in addition to its autonomous secretion. However, the clinical characteristics and risk of cardiovascular and cerebrovascular (CCV) events in PA patients with aldosterone responsiveness to ACTH stimulation remain unclear. This study aimed to investigate the prevalence of CCV events in PA patients with high aldosterone responsiveness to ACTH stimulation. A retrospective cross-sectional study was conducted as part of the Japan Primary Aldosteronism Study/Japan Rare Intractable Adrenal Disease project. PA patients with adrenal venous sampling (AVS) between January 2006 and March 2019 were enrolled. The ACTH-stimulated plasma aldosterone concentration (PAC) of the inferior vena cava during AVS was used to evaluate aldosterone responsiveness to ACTH. We analyzed the relationship between responsiveness and previous CCV events. Logistic regression analysis demonstrated that the ΔPAC (the difference between the PAC measurements before and after ACTH stimulation) significantly increased the odds of previous CCV events in PA patients after adjusting for classical CCV event risk factors, baseline PAC and duration of hypertension (relative PAC: odds ratio [OR], 2.896; 95% confidence interval [CI], 0.989-8.482; ΔPAC: OR, 2.344; 95% CI, 1.149-4.780; ACTH-stimulated PAC: OR, 2.098; 95% CI, 0.694-6.339). This study clearly demonstrated that aldosterone responsiveness to ACTH is closely related to previous CCV events. The responsiveness of the PAC to ACTH could be useful in predicting CCV event risk.Registration Number in UMIN-CTR is UMIN000032525.

Competing Interests: The authors declare no conflict of interest.