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CLINICAL STATEMENTS AND GUIDELINES

September 16, 2025 Circulation. 2025;152:e114–e218. DOI: 10.1161/CIR.0000000000001356 e138

for sodium and volume status, is relatively autonomous of the major regulators of aldosterone secretion (angio­ tensin II and potassium), and cannot be completely sup­ pressed with sodium loading.4,5 The increased production of aldosterone induces intravascular volume expansion, suppressed plasma renin activity, sodium retention, in­ creased potassium excretion, hypertension, and cardio­ vascular and kidney damage.4–7 Although the increased potassium excretion, if prolonged and severe, may cause hypokalemia, hypokalemia is absent in the majority of cases in whom normokalemia has a low negative predic­ tive value for the diagnosis of primary aldosteronism.8,9 In two-thirds of patients with primary aldosteronism, excess aldosterone is caused by bilateral adrenal hyperplasia. In about one-third of patients with primary aldosteronism, excess aldosterone is due to increased unilateral aldo­ sterone production (aldosterone-producing adenoma, less commonly unilateral adrenal hyperplasia, or, rarely, adrenal carcinoma).4,10 Primary aldosteronism is a com­ mon cause of secondary hypertension (occurring in 5% to 10% of patients with hypertension and 20% of patients with resistant hypertension), and targeted treat­ ment is associated with improved kidney and cardiovas­ cular outcomes.3,11–13 Nonetheless, rates of screening for primary aldosteronism in appropriate patients are excep­ tionally low (1% to 2%).14–17

Recommendation-Specific Supportive Text

1 Patients with primary aldosteronism are at greater

risk for target organ damage than those with pri­ mary hypertension due to the toxic tissue effects of aldosterone even when adjusted for degree of hypertension. Meta-analyses of studies that matched patients with primary aldosteronism to those with pri­ mary hypertension showed that primary aldosteron­ ism carries a 2.0-fold increased risk of HF, 2.8-fold increased risk of stroke, 1.7-fold increased risk of coronary artery disease, 4.0-fold increased risk of AF, and increased kidney damage compared with primary hypertension.6,7 Because the deleterious effects of aldosterone overproduction may be blocked with uni­ lateral laparoscopic adrenalectomy or treatment with MRA (eg, spironolactone or eplerenone), patients with hypertension at increased risk of primary aldosteron­ ism are very likely to benefit from screening.4 These include patients with hypertension and adrenal “inci­ dentaloma,” an incidentally discovered adrenal lesion on computed tomography or magnetic resonance imaging performed for other purposes. Additionally, patients with resistant hypertension (regardless of whether hypokalemia is present), hypertension with hypokalemia (either spontaneous or diuretic-induced), and hypertension with OSA have a relatively high prevalence of primary aldosteronism (∼20%-35%).3,4 Patients with hypertension and a history of earlyonset hypertension and/or cerebrovascular accident at a young age may have primary aldosteronism due to glucocorticoid-remediable aldosteronism (familial hyperaldosteronism type-1) and therefore also war­ rant screening.4 However, the rate of screening for primary aldosteronism in guideline-recommended individuals is <2% in the United States.14,16,17

2 Growing evidence supports that primary aldoste­

ronism occurs across the full breadth of hyperten­ sion severity, with higher prevalence of primary aldosteronism as the severity of hypertension increases.3,10 The prevalence of primary aldoste­ ronism is approximately 5% to 10% among indi­ viduals with stage 1 hypertension and 11% to 22% among individuals with stage 2 hypertension, which varies depending on the modality of testing and testing thresholds used to diagnose primary aldosteronism.3,10 The prevalence of primary aldo­ steronism may be similar among individuals with stage 2 hypertension and those with resistant hypertension.3 Studies from Australia and Japan suggest that broader screening for primary aldo­ steronism in individuals with hypertension is costeffective.18,19 Nonetheless, the potential burden of additional testing outside of patients with resistant hypertension to confirm the diagnosis of primary aldosteronism and to determine optimal therapy may be taken into consideration prior to screening. 3.	 The combined interpretation of the plasma aldoste­

rone concentration, renin activity, and aldosterone to renin activity ratio is currently the most accurate and reliable means of screening for primary aldo­ steronism.2,3,20 Patients with primary aldosteronism typically have suppressed renin activity (<1 ng/ mL/h). Most data support that the plasma aldoste­ rone concentration should be at least 10 ng/dL to interpret the test as positive, but additional evalu­ ation may be indicated if the renin activity is sup­ pressed.3,4 The most commonly used cutoff value for the aldosterone to renin activity ratio is 30 when plasma aldosterone concentration is reported in nanograms per deciliter (ng/dL) and plasma renin activity in nanograms per milliliter per hour (ng/ mL/h), although some data support alternative thresholds (20 or 40).2–4,20 Patients should have unrestricted salt intake, serum potassium in the normal range (to avoid false-negative testing), and ideally, MRA (eg, spironolactone or eplerenone) withdrawn for at least 4 weeks before testing.4

4 Low screening rates may be due to several barriers

to screening, such as older guidance to withdraw antihypertensive medications that may affect renin and aldosterone levels, which has since been dis­ puted by growing evidence in support of screen­ ing despite treatment with these medications. Specifically, beta blockers (BBs) and central-alpha agonists can suppress both renin and aldosterone4;

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