The Spectrum of Subclinical Primary Aldosteronism and Incident Hypertension: A Cohort Study

Presentation Number: OR10-5
Date of Presentation: April 3rd, 2017

Jenifer Michelle Brown*1, Cassianne Robinson-Cohen2, Matthew Allison3, Rene Baudrand4, Joachim Ix3, Bryan Kestenbaum5, Ian de Boer2 and Anand Vaidya6
1Brigham and Women's Hospital, Harvard Medical School, MA, 2University of Washington, Seattle, WA, 3University of California, San Diego, 4Pontificia Univ, Santiago, Chile, 5University of Washington, 6Brigham and Women's Hospital, Harvard Medical School, Boston, MA


Context: Primary aldosteronism is characterized by “renin-independent aldosteronism” and excessive mineralocorticoid receptor (MR) activity that causes hypertension. Recent evidence of autonomous aldosterone-producing cell clusters in morphologically normal adrenal glands suggests a histopathological basis for more subtle or even subclinical renin-independent aldosteronism.

Objective: To test the hypothesis that there is a clinically relevant continuum of renin-independent aldosteronism with inappropriate MR activation among normotensives that increases the risk for incident hypertension.

Methods: We examined a prospective cohort of 850 untreated normotensive participants in the Multi-Ethnic Study of Atherosclerosis with measurements of serum aldosterone and plasma renin activity (PRA). Subjects were stratified by physiologic PRA phenotypes “renin-independent”: PRA ≤0.50 ng/mL/h; “indeterminate”: PRA 0.51-0.99 ng/mL/h; and “renin-dependent”: PRA ≥1.0 ng/mL/h). Prospective analyses investigated whether aldosterone levels, in the context of renin phenotype, independently associated with incident hypertension events in multivariable discrete Cox proportional hazards models. Cross-sectional analyses investigated biomarkers of MR activity: the association between aldosterone and serum potassium and urinary fractional excretion of potassium using adjusted linear regression.

Results: Participants with a PRA ≤0.50 ng/mL/h represented 46% of the cohort. The incident rate of hypertension was highest among the renin-independent phenotype (85 vs 53 vs 54 cases per 1,000 person-years of follow-up). Further, among these participants, higher aldosterone levels were independently associated with a higher risk for incident hypertension (adjusted HR=1.38 [1.09, 1.75] per 5 ng/dL of aldosterone); whereas no such association was observed among indeterminate or renin-dependent phenotypes (HR=1.19 [0.95, 1.50] and HR=1.06 [0.86, 1.32] per 5 ng/dL of aldosterone). Higher aldosterone, in the context of a PRA ≤0.50 ng/dL/h, was significantly associated with lower serum potassium within the normal range (adjusted β= -0.044 mEq/L per 5 ng/dL of aldosterone, P = 0.004) and higher urinary fractional excretion of potassium (adjusted β=0.844 percent per 5 ng/dL of aldosterone, P=0.0007). Again, no such relationship was seen in indeterminate or renin-dependent PRA phenotypes.

Conclusions and Clinical Relevance: Among normotensives with a suppressed PRA, higher aldosterone concentrations were associated with an increased risk for incident hypertension and corresponding evidence for higher MR activation. These findings indicate a prevalent and clinically relevant spectrum of “subclinical” renin-independent aldosteronism in normotension.


Nothing to Disclose: JMB, CR, MA, RB, JI, BK, ID, AV