Ethnic differences in plasma aldosterone concentration and regulatory mechanisms of aldosterone: protocol for a systematic review and meta-analysis

INTRODUCTION: Black ethnic cohorts, when compared with white cohorts, have disproportionately higher rates of essential hypertension and related complications. Ethnic differences in the renin-angiotensin-aldosterone system have been identified in black ethnic cohorts displaying a low-renin, salt-sensitive phenotype in comparison to white individuals. Studies have highlighted lower levels of aldosterone in black cohorts compared with white cohorts. However, when renin is considered, in the form of the aldosterone-renin ratio (ARR), the ARR is higher in black cohorts. The Framingham study highlighted that people in the upper quartile for baseline aldosterone were more likely to have a higher blood pressure and develop hypertension at 4 year follow-up. Therefore, the inappropriately suppressed aldosterone may be contributing to the ethnic differences in hypertension prevalence and prognosis. METHODS AND ANALYSIS: Four databases will be searched (MEDLINE, Embase, Scopus and Cochrane Library) to identify eligible studies from database creation to August 2025. Two investigators will independently review the search results and document reasons for full-text exclusions. The main outcomes are to assess if there are ethnic differences in baseline aldosterone, baseline plasma renin activity (PRA) and ARR. We will also look at ethnic differences in regulatory mechanisms of aldosterone, such as serum potassium and 24 hour urinary electrolytes, that may explain the potential differences in aldosterone and ARR in black and white ethnic cohorts. Studies looking at normotensive and hypertensive individuals will be included. Studies in paediatric populations (<18 years) will be excluded. We will include studies without language restriction. Risk of bias assessment will be completed with a modified Newcastle-Ottawa scale. Subgroup analysis and sensitivity analyses will be completed to verify the accuracy of the study results and the consistency of the inferences. ETHICS AND DISSEMINATION: As this review will involve analysis of previously published data, ethical approval is not required. The results will be submitted to a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD420251025642.