Synergistic effect of albuminuria on atherosclerosis in patients with primary aldosteronism

Ting-Wei Kao; Che-Wei Liao; Cheng-Hsuan Tsai; Yi-Yao Chang; Chien-Ting Pan; Chin-Chen Chang; Bo-Ching Lee; Wei-Chieh Huang; Kuo-How Huang; Ching-Chu Lu; Tai-Shuan Lai; Chieh-Kai Chan; Jeff S Chueh; Vin-Cent Wu; Chi-Sheng Hung; Zheng-Wei Chen; Yen-Hung Lin

doi:10.1177/20406223231210114

Synergistic effect of albuminuria on atherosclerosis in patients with primary aldosteronism

Ther Adv Chronic Dis. 2023 Nov 9:14:20406223231210114. doi: 10.1177/20406223231210114. eCollection 2023.

Authors

Ting-Wei Kao¹, Che-Wei Liao^{1

2}, Cheng-Hsuan Tsai¹, Yi-Yao Chang^{3

4}, Chien-Ting Pan^{5

6}, Chin-Chen Chang⁷, Bo-Ching Lee⁷, Wei-Chieh Huang⁸, Kuo-How Huang⁹, Ching-Chu Lu¹⁰, Tai-Shuan Lai¹, Chieh-Kai Chan¹¹, Jeff S Chueh, Vin-Cent Wu¹, Chi-Sheng Hung¹, Zheng-Wei Chen¹², Yen-Hung Lin¹

Affiliations

¹ Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
² Department of Medicine, National University Cancer Center, Taipei, Taiwan.
³ Department of Cardiovascular Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan.
⁴ Graduate Institute of Medicine, Yuan Ze University, Taoyuan City, Taiwan.
⁵ Department of Internal Medicine, National University Hospital and National University College of Medicine, Taipei, Taiwan.
⁶ Department of Internal Medicine, National University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.
⁷ Department of Medical Imaging, National University Hospital and National University College of Medicine, Taipei, Taiwan.
⁸ Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
⁹ Department of Urology, National University Hospital and National University College of Medicine, Taipei, Taiwan.
¹⁰ Department of Nuclear Medicine, National University Hospital, Taipei, Taiwan.
¹¹ Department of Internal Medicine, National University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan.
¹² Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, No. 579, Sec. 2, Yun-Lin Rd., Douliu City, Yun-Lin County 640203.

Abstract

Background: Primary aldosteronism (PA) has been associated with atherosclerosis beyond the extent of essential hypertension, but the impact of albuminuria remains unknown.

Objective: To investigate the effect of concomitant albuminuria on arterial stiffness in PA.

Design: Prospective cohort study.

Methods: A prospective cohort study was conducted to evaluate the association of albuminuria (>30 mg/g in morning spot urine) with arterial stiffness, as measured non-invasively by pulse wave velocity (PWV) in patients with PA. Propensity score matching (PSM) with age, sex, diabetes, systolic and diastolic blood pressure, creatinine, potassium, number of antihypertensive medications, and hypertension history was used to balance baseline characteristics. The effects of albuminuria on PWV before and 1 year after treatment were analyzed.

Results: A total of 840 patients with PA were enrolled, of whom 243 had concomitant albuminuria. After PSM, there were no significant differences in baseline demographic parameters except alpha-blocker and spironolactone use. PWV was greater in the presence of albuminuria (p = 0.012) and positively correlated with urine albumin-creatinine ratio. Multivariable regression analysis identified albuminuria, age, body weight, systolic blood pressure, and calcium channel blocker use as independent predictors of PWV. As for treatment response, only PA patients with albuminuria showed significant improvements in PWV after PSM (p = 0.001). The magnitude of improvement in PWV increased with urine albumin-creatinine ratio and reached plateau when it exceeded 100 mg/g according to restricted cubic spline analysis.

Conclusion: Concomitant albuminuria in PA was associated with greater arterial stiffness and more substantial improvement after targeted treatment. Both the baseline and the improved extent of PWV increased in correlation with rising urine albumin-creatinine ratio levels, reaching a plateau when the urine albumin-creatinine ratio surpassed 100 mg/g.

Keywords: albuminuria; atherosclerosis; primary aldosteronism; pulse wave velocity.

Plain language summary

Albuminuria and primary aldosteronism synergistically induce atherosclerosis Albuminuria is a common comorbidity in patients with primary aldosteronism (PA), and both has been established to potentiate atherosclerosis. However, the interaction in between remained enigmatic. In this study, we accessed the synergistic vascular impact in a prospectively enrolled cohort. Arterial rigidity was assessed non-invasively by brachial–ankle pulse wave velocity. Concomitant albuminuria in patients with PA was associated with pronouncedly greater arterial stiffness and was further demonstrated as an independent predictor for atherosclerosis. In addition, PA-targeted treatment effectively reversed arterial stiffness, especially in individuals with concomitant albuminuria. The beneficial effect of PA-targeted treatment on PWV increased with rising urine albumin–creatinine ratio levels, eventually plateauing when the UACR surpassed 100 mg/g.