The Burden, Outcomes, and Management of Patients with Aldosterone Dysregulation: A Targeted Literature Review

Aldosterone dysregulation (excess aldosterone production at the source within the adrenal glands) in the absence of primary aldosteronism is a complex physiologic driver of uncontrolled hypertension and cardiovascular and kidney outcomes. Understanding the manifestations and burden of aldosterone dysregulation is critical to optimizing treatment and improving outcomes in patients with hypertension. This review examines the prevalence, patient attributes and burden of aldosterone dysregulation, and its impact on patient outcomes.

A targeted literature review of articles published between 2013 and 2024 was conducted. A patient/population, intervention, comparison, and outcomes framework was used, with a predefined search and selection protocol. Articles focused on primary aldosteronism were excluded unless they also referenced essential hypertension. A screening tool that used methods including artificial intelligence, trained using manual (human) screening, was employed to select relevant articles, which underwent human review to confirm inclusion/exclusion.

Initial searches yielded 16,501 unique articles. Following abstract screening, 327 full-text articles were reviewed, yielding 123 relevant articles. Included studies utilized a range of aldosterone-related thresholds and measures to characterize patients with aldosterone dysregulation. Several patient attributes impact aldosterone levels, including age, race, ethnicity, sex, and body mass index. Lifestyle factors such as sodium intake also impact aldosterone, but the effect varies by race and body weight. Long-term excess aldosterone was associated with elevated blood pressure (BP), cardiovascular-kidney-metabolic diseases, and end-organ damage, leading to a greater risk of adverse clinical outcomes and mortality. Further evidence is needed to determine whether these occur independently of BP levels.

Excess aldosterone is associated with poor cardiovascular-kidney-metabolic outcomes, including increased morbidity and mortality. Aldosterone dysregulation (excess aldosterone production at the source) is an underlying driver of cardiovascular-kidney-metabolic diseases, which may not be adequately addressed by current antihypertensive therapies.