A cross-sectional study of the effects of ß-blocker therapy on the interpretation of the aldosterone/renin ratio: can dosing regimen predict effect?

CONTEXT AND AIM: Aldosterone/renin ratio (ARR) is used as the primary screening tool for primary aldosteronism. Its interpretation is often challenging because of the interference of antihypertensive medication. ß-blocker therapy suppresses renin production by inhibiting ß-adrenergic receptors in the juxtaglomerular apparatus of the kidney and consequently aldosterone secretion (to a lesser extent). Therefore, ß-blocker therapy has the potential to elevate the ARR. The aim of this study was to investigate whether or not the effect of ß-blocker therapy on the ARR could be predicted from the dosing regimen. METHODS: A prospective cross-sectional study was conducted. Participants were stratified into one of four groups (control/low/medium/high) based on the quantity of ß-blocker prescribed. ARR was calculated from renin/aldosterone, measured using two assay systems. RESULTS: Eighty-nine volunteers were recruited to our study. In the control group, zero patients had a positive ARR using plasma renin activity (PRA)/direct renin concentration (DRC). In the low, medium, and high-dose ß-blocker groups between 8-25% of patients demonstrated screen positive ARR results for primary aldosteronism using DRC and PRA. DRC was significantly lower in patients in the medium/high-dose groups and PRA significantly lower in the low/medium/high-dose groups compared with controls. ARR using DRC was significantly higher in the medium/high-dose groups and ARR using PRA was significantly higher in the low/medium/high-dose groups compared with controls. CONCLUSION: Our study suggests that ß-blocker therapy is associated with an increased risk of positive ARR screens for primary aldosteronism irrespective of the dose of ß-blocker prescribed, in patients in whom it is clinically reasonable to expect that primary aldosteronism may be present.

ß-Blocker withdrawal is preferable for accurate interpretation of the aldosterone-renin ratio in chronically treated hypertension.

OBJECTIVES: To evaluate the effects of ß-adrenoreceptor antagonists (ß-blockers) on the aldosterone-renin ratio (ARR) in the context of antihypertensive polypharmacy in chronic hypertension. To determine the optimal duration of ß-blocker withdrawal required to normalize the ARR. DESIGN: A prospective, longitudinal study design was employed investigating two groups whom either remained on or withdrew from ß-blocker therapy. METHODS: Hypertensive individuals taking ß-blockers and a combination of thiazide diuretics, α1-blockers, calcium channel antagonists and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were recruited and followed over 10-12 weeks. ß-Blockers were withdrawn at the first visit. Blood pressure (BP) was measured at each visit and blood drawn serially for measurement of plasma renin activity (PRA), direct renin concentration (DRC) and aldosterone. BP was optimized by maximizing non-renin-suppressing antihypertensives. Main outcomes were ARR, DRC, PRA and aldosterone. Plasma renin activity was calculated from angiotensin I measured using radioimmunoassay (RIA), DRC was measured using chemiluminescent immunoassay assay, and aldosterone was measured using both RIA and Chemilluminescence Assay (CIL). RESULTS: False-positive ARR for primary aldosteronism (PA) occurred in 31% of patients taking ß-blockers. ARR returned to normal following ß-blocker withdrawal resulting from an increase in the DRC and PRA without affecting aldosterone. The optimum time for ß-blocker withdrawal was 2 weeks when using DRC and 3 weeks for PRA. ß-Blocker withdrawal did not adversely affect blood pressure. CONCLUSION: Raised ARR consequent to ß-blocker therapy causes false-positive screening for PA. Where ß-blockers can be safely withdrawn, this effect is reversed within 2-3 weeks depending on whether DRC or PRA is used to calculate ARR.