Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study

Abstract

ABSTRACT Objectives Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl−1/mIU∙l−1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD). Methods Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995–1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl−1/mIU∙l−1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening. Results In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19–1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41–3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62–1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension. Conclusions The CVD risk-based optimal ARR cutoff is 1.0 ng·dl−1/mIU∙l−1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk. Clinical Trial Registration ClinicalTrials.gov (NCT03224312)