https://orcid.org/0009-0005-9078-6223
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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)
Abbreviations
ARR, aldosterone-to-renin ratio; CI, confidence interval; CVD, cardiovascular disease; FOS, Framingham Offspring Study; ORs, odds ratios; PAC, plasma aldosterone concentration; PRC, plasma renin concentration; SAC, serum aldosterone concentration.
Acknowledgments
We thank the participants and staff of the Framingham Offspring Study. We thank other members of the Chongqing Primary Aldosteronism Study (CONPASS) Group: Mei Mei, MD, PhD; Suxin Luo, MD, PhD; Kangla Liao, MD; Yao Zhang, MD, PhD; Yunfeng He, MD, PhD; Yihong He, MD; Ming Xiao, PhD; and Bin Peng, PhD for suggestions of study design and revision.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Author contributions
Conception and design: J.B.H., Q.F.L., S.M.Y. Analysis and interpretation of the data: J.B.H., R.L.L, X.J.C., Q.L.Z., and W.J.L. Drafting of the article: C.X.H., J.Y., F.F.W. and H.S. Critical revision of the article for important intellectual content: L.Q.M., Y.S., and Y.W. Obtaining of funding: J. H., Q.L., L.Q.M., and S.M.Y. Administrative, technical, or logistic support: Q. C., Z.W., Z. F., and Y. S. Collection and assembly of data: Z.H.W., Q.F.C., Y.S., Y.W. and L.Q.M.
Data availability statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Ethics approval and consent to participate
Framingham Offspring Study (FOS) was approved by the institutional review board of Boston University Medical Center and conducted in accordance with the declaration of Helsinki. All the participants in FOS provided written informed consent. Chongqing Primary Aldosteronism Study (CONPASS) was approved by the ethical committee of Chongqing Medical University (No: 201411) and conducted in accordance with the declaration of Helsinki. All the participants in CONPASS provided written informed consent.