Long-Term Follow-Up of Patients With High Aldosterone-to-Renin Ratio but Negative Confirmatory Test for Primary Aldosteronism

Objective: About 10% of patients with hypertension has elevated aldosterone-to-renin ratio and 50-70% of them have a negative confirmatory test for primary aldosteronism (PA). However, the appropriate follow-up of these patients is currently unknown. We investigated the incidence of PA in patients with previous negative confirmatory testing for PA, with a follow-up comprised between 2 and 8 years. Design and method: A total of 184 patients with a previously positive screening test for PA followed by a negative confirmatory test were enrolled in two hypertension centres: Torino and München. We repeated the screening test for PA and, if positive, the confirmatory test: either seated saline infusion test or captopril challenge test. Results: About 20% of patients had confirmed PA diagnosis after a mean follow-up of 5 years: 16% in Torino and 24% in München. When subtype diagnosis was offered systematically, 31% of patients displayed a unilateral form of PA. Patients with new onset of PA showed higher systolic blood pressure (142±17 versus 133±12 mmHg, P=0.005), diastolic blood pressure (89±8 versus 85±9 mmHg, P=0.007) and a higher rate of cardiac organ damage (60.9% versus 35.8%, P=0.031) than patients without PA, despite similar implementation of anti-hypertensive therapy. A mild progression of autonomous aldosterone secretion was present even in patients without confirmed PA, with increase of aldosterone post-saline infusion test (3.3 [2.3-4.3] versus 4.5 [3.5-5.4] ng/dL; P<0.001), but with relatively stable blood pressure levels. Among patients without PA, aldosterone post-saline infusion test at follow-up was positively associated with the follow-up time (β 0.262 [0.005; 0.520]; P=0.046). Conclusions: One fifth of patients with a negative confirmatory test for PA develop overt PA over time. A clinical follow-up of patients with a negative confirmatory test is advisable, along with the repetition of PA investigation, especially in patients with worsening of blood pressure control.