Screening Tool For Primary Aldosteronism Research Articles

Poor Performance of Angiotensin II Enzyme-Linked Immuno-Sorbent Assays in Mostly Hypertensive Cohort Routinely Screened for Primary Aldosteronism.

Primary aldosteronism (PA) is the most common, but broadly underdiagnosed, form of hormonal hypertension. To improve screening procedures, current biochemical approaches aim to determine newly appreciated angiotensin II (Ang II) and calculate the aldosterone-to-angiotensin II ratio (AA2R). Thus, the aim of this study was to assess the diagnostic performance of these screening tests in comparison to the aldosterone-to-direct renin ratio (ADRR), which is routinely used. Cheap and available ELISA was used for Ang II measurement. To our knowledge, this is the first study of this laboratory method’s usage in PA. The study cohort included 20 PA patients and 80 controls. Ang II concentrations were comparable between PA and non-PA patients (773.5 vs. 873.2 pg/mL, p = 0.23, respectively). The AA2R was statistically significantly higher in PA group when compared with non-PA (0.024 vs. 0.012 ng/dL/pg/mL, p < 0.001). However, the diagnostic performance of the AA2R was significantly worse than that of the ADRR (AUROC 0.754 vs. 0.939, p < 0.01). The sensitivity and specificity of the AA2R were 70% and 76.2%, respectively. Thus, the AA2R was not effective as a screening tool for PA. Our data provide important arguments in the discussion on the unsatisfactory accuracy of renin–angiotensin system evaluation by recently repeatedly used ELISA tests.

Aldosterone-to-renin ratio is related to arterial stiffness when the screening criteria of primary aldosteronism are not met

Aldosterone-to-renin ratio (ARR) is a screening tool for primary aldosteronism (PA), but the significance of ARR when the PA criteria are not met remains largely unknown. In this cross-sectional study we investigated the association of ARR with haemodynamic variables in 545 normotensive and never-medicated hypertensive subjects (267 men, 278 women, age range 19–72 years) without suspicion of PA. Supine haemodynamic data was recorded using whole-body impedance cardiography and radial tonometric pulse wave analysis. In sex-adjusted quartiles of ARR, determined as serum aldosterone to plasma renin activity ratio, the mean values were 282, 504, 744 and 1467 pmol/µg of angiotensin I/h, respectively. The only difference in haemodynamic variables between the ARR quartiles was higher pulse wave velocity (PWV) in the highest quartile versus other quartiles (p = 0.004), while no differences in blood pressure (BP), heart rate, wave reflections, cardiac output or systemic vascular resistance were observed between the quartiles. In linear regression analysis with stepwise elimination, ARR was an independent explanatory factor for PWV (β = 0.146, p < 0.001, R2 of the model 0.634). In conclusion, ARR was directly and independently associated with large arterial stiffness in individuals without clinical suspicion of PA. Therefore, ARR could serve as a clinical marker of cardiovascular risk.Trial registration: ClinicalTrails.gov: NCT01742702.

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

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. β-blocker therapy suppresses renin production by inhibiting β-adrenergic receptors in the juxtaglomerular apparatus of the kidney and consequently aldosterone secretion (to a lesser extent). Therefore, β-blocker therapy has the potential to elevate the ARR. The aim of this study was to investigate whether or not the effect of β-blocker therapy on the ARR could be predicted from the dosing regimen. A prospective cross-sectional study was conducted. Participants were stratified into one of four groups (control/low/medium/high) based on the quantity of β-blocker prescribed. ARR was calculated from renin/aldosterone, measured using two assay systems. 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 β-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. Our study suggests that β-blocker therapy is associated with an increased risk of positive ARR screens for primary aldosteronism irrespective of the dose of β-blocker prescribed, in patients in whom it is clinically reasonable to expect that primary aldosteronism may be present.

Aldosterone to renin ratio is associated with 24 hour ambulatory blood pressure in essential hypertensives: the Styrian Hypertension study

Purpose: The aldosterone to renin ratio (ARR) is a screening tool for primary aldosteronism (PA). Accumulating evidence suggests that ARR may be significantly associated with blood pressure (BP) even below the threshold for PA. We therefore aimed to evaluate the relationship between the ARR and 24 hour ambulatory BP monitoring measurements (ABPM). Methods: We recruited essential hypertensive patients derived from the outpatient clinic at the department of internal medicine of the local medical university hospital. ABPM measurements were obtained every 15min during the day (06:00-24:00 o'clock) and every 30 min during the night (00:00–06:00). Plasma aldosterone and plasma renin concentrations were measured by means of a RadioImmunoAssay (RIA). Results: We examined 172 hypertensive patients (age: 59.6±11.3years; 51.2% females) with a mean systolic/diastolic 24-hour ABPM value of 129/77mmHg. In linear regression analyses adjusted for age, sex, 24-hour urinary sodium and body mass index, ARR was significantly associated with night-time systolic (beta coefficient:0.19; p=0.017) and diastolic ABPM (beta coefficient:0.28; p<0.001). In subgroup analyses of patients with ARR below the cut-off for positive PA screening (ARR<3.7 - ng/dl divided by μU/mL) ARR remained significantly associated with diastolic ABPM (beta coefficient:0.26; p=0.001) and by trend with systolic ABPM (beta coefficient:0.15; p=0.056). These associations remained materially unchanged when additionally adjusted for other possible confounders, e.g. antihypertensive medications, HbA1c or NT-proBNP. Conclusions: In patients with essential hypertension and even in those patients not suggestive for PA, we found a strong relationship between ARR and diastolic night-time BP. In view of the strong relationship between diastolic night-time BP and risk of cardiovascular events further studies are needed to evaluate cardio-protective effects of mineralocorticoid blockade in hypertensive patients without PA.

Assay Characteristics Influence the Aldosterone to Renin Ratio as a Screening Tool for Primary Aldosteronism: Results of the German Conn's Registry

Primary aldosteronism (PA) is the most frequent cause of secondary arterial hypertension. The aldosterone to renin ratio (ARR) is the gold standard for screening, but variability between biochemical methods used remains of concern. The aim of the study was to analyze center-specific features of biochemical diagnostic strategies prior to the 2008 consensus within the German Conn's Registry. The study was designed as a retrospective study in 5 tertiary care hospitals. Patients analyzed for PA between 1990 and 2006 were studied. Characteristics of the assays used to determine ARR during establishing the diagnosis of PA were analyzed in the retrospective part of the German Conn's Registry. Eighty-six out of 484 documented ARR values had to be excluded from further evaluations because the laboratory or the assays were unknown. In the remaining 398 patients ARR was determined using 10 different assay combinations in the centers (aldosterone plus plasma renin activity or concentration). Considerable differences were seen between the mean concentrations for aldosterone (p<0.0001), renin concentration (p<0.001), and renin activity (p=0.009) for the different assays. The differences between the absolute concentrations measured by the different assays also had significant impact upon the resulting mean ratios. If published cutoff values are applied, the use of different commercial assays to determine the ARR in clinical routine results in major differences in positive screening rates. This heterogeneity affects sensitivity and specificity of screening for PA. Our data emphasize the importance of standardized screening procedures, which must include standardization of biochemical methods.

Assessment of serum sodium to urinary sodium divided by (serum potassium)² to urinary potassium as a screening tool for primary aldosteronism

The SUSPPUP ratio [(serum sodium/urinary sodium)/(serum potassium²/urinary potassium)] has been proposed as a marker to screen for primary aldosteronism (PA). The original study found an area under the receiver operating characteristic (ROC) curve of 0·90 to detect PA; the sensitivity was 89% and specificity 86% for a ratio over 5·3 L mmol⁻¹. Patients attending a hypertension unit between 2001 and 2006 and for who renin and aldosterone measurements and concomitant serum and urinary biochemistry data were available were included if diagnosed with PA (n = 449) or essential hypertension (n = 2209). We compared the diagnostic value of the SUSPPUP ratio and of serum potassium in the whole population, in patients without interfering drugs and in patients with lateralized PA. The area under the ROC curve was significantly worse for the SUSPPUP ratio than for serum potassium in all groups: 0·72 vs. 0·76 in the whole population; 0·73 vs. 0·78 without interfering drugs; 0·76 vs. 0·82 for patients with lateralized PA. In the whole population, sensitivity was 71% for a SUSPPUP ratio ≥ 5·3 L mmol⁻¹ and serum potassium < 3·7 mmol L⁻¹, but specificity of the SUSPPUP ratio was significantly worse (61% vs. 69%). Using low serum potassium and/or high SUSPPUP ratio increased the sensitivity to 87% but decreased the specificity to 47%. The SUSPPUP ratio was outperformed by serum potassium as a screening tool for PA in this large validation sample. Its value as an adjunct to serum potassium is questionable because of the low specificity of their combination.

Aldosterone to Renin Ratio – A Reliable Screening Tool for Primary Aldosteronism?

Primary aldosteronism (PA) is defined as inappropriately high and (relatively or absolutely) autonomous aldosterone secretion, which is not adequately suppressible by sodium loading. Recent evidence shows that the PA prevalence ranges from 3 to 32%. This high prevalence of PA is suggested to be the result of both more intense screening for PA and improvement of laboratory procedures. Inappropriate high aldosterone secretion is paralleled by severe target organ damage, underlining the importance for the identification of PA at an early stage. The aldosterone to renin ratio (ARR), which reflects aldosterone hypersecretion in regard to its principal trophin renin, is currently considered the most reliable tool for PA screening. Accumulating evidence, however, points to a considerable intra-individual variation of this ratio, emphasizing the importance of standardized screening procedures. In particular, laboratory methods, posture, antihypertensive medication, and dietary salt intake are significant effectors of ARR variation. Furthermore, differentiation between low-renin essential hypertension and PA is difficult and probably arbitrary. It is the purpose of the present review to issue the reliability of the ARR as a screening tool for PA. This review also provides an overview about the physiology of the renin-angiotensin-aldosterone system, highlights current laboratory methods for aldosterone and renin determination, and addresses potential influence factors on the ARR.

Resistant hypertension: who and how to evaluate

Resistant hypertension is found in an important and rapidly growing subset of the hypertensive population, and data characterizing this group of patients are limited. The purpose of this review is to present the latest evidence on resistant hypertension, its risk factors, patient characteristics, and approach to diagnosis. We focus on important associations between resistant hypertension and primary aldosteronism and with obstructive sleep apnea. Resistant hypertension comprises 20-35% of the general hypertensive population. It is important to ascertain that a patient has true resistant hypertension and not merely uncontrolled hypertension. Twenty-four-hour ambulatory blood pressure monitoring can reliably rule out a white-coat effect and may have prognostic significance in patients with resistant hypertension. Patients should be screened for secondary causes of hypertension. Primary aldosteronism is common among patients with resistant hypertension, as is obstructive sleep apnea. A plasma aldosterone to renin ratio is a useful screening tool for primary aldosteronism. Aldosterone has been found to accelerate the increase in left ventricular mass in patients with hypertension. Patients with resistant hypertension comprise a unique subset, with risk factors and associations that are distinct or pronounced compared with the general hypertensive population. It is important to bear these associations in mind when dealing with patients with true resistant hypertension.

Salivary aldosterone to cortisol ratio: Potential screening tool for primary aldosteronism

Increased incidence of primary aldosteronism in the hypertensive population has renewed interest in the role of mineralocorticoids in cardiovascular diseases. Therefore, a simple non-invasive screening tool to detect hypersecretion of aldosterone would be useful. We have previously established and validated a highly sensitive immunoassay for the detection aldosterone in saliva. Given that autonomous hypersecretion of aldosterone should be largely independent from pituitary stimulation, we speculate that the combined analysis of salivary aldosterone (SA) and salivary cortisol (SC) might improve discrimination between normals and Conn's patients (CP). Thus, we analyzed concentrations of SA by our in-house assay and SC by a commercial assay in order to determine the ratio between the two hormones. 14 subjects with confirmed Conn's and 17 healthy volunteers (HV) participated in the study. Daytime saliva samples were collected by Salivettes (Sarstedt, Nümbrecht) between 7am and 11am. Furthermore, in a subgroup (12 CP, 8 HV) an ACTH stimulation test was performed to investigate the influence of pituitary stimulation on the ratio. Un-stimulated SA was 112.7±58.7pg/ml in CP and 65.0±24.4 in HV. The aldosterone to cortisol ratio (ACR) (±SD) was 0.107±0.087 in CP compared to 0.065±0.065 in HV (p<0.001). Post-ACTH stimulation test however, ACR decreased in both groups, 0.014±0.010 and 0.014±0.013 respectively, due to the greatly increased levels of SC compared to the less pronounced increase in SA. This influence of the pituitary ACTH stimulus also can affect the ratio throughout the day. Preliminary data in 8 CP showed that the ACR is higher in the evening compared to daytime due to lower variation in aldosterone values together with decreasing cortisol. 8am values yielded 0.055±0.034 compared to a 0.423±0.565 12pm ACR. So far, our data has shown that at baseline a ratio higher than 0.1 is suggestive of Conn's syndrome. We propose the possibility of using this ratio, elevated in CP compared to controls, as a tool in the diagnosis of primary aldosteronism.

High prevalence of primary aldosteronism using postcaptopril plasma aldosterone to renin ratio as a screening test among Italian hypertensives

The prevalence of primary aldosteronism (PA) was assessed in a specialized hypertension center. Baseline and postcaptopril (50 mg orally) aldosterone to plasma renin activity ratio (A/R) as a screening tool were preliminarily tested in a sample including 22 patients with histories of PA and 53 patients with low-renin essential hypertension (EH). Sensitivity and specificity of A/R ≥35 were 95.4% and 28.3% at baseline, compared with 100% and 67.9% after captopril. Using postcaptopril A/R ≥35 and confirmation by acute saline loading, a PA prevalence of 6.3% was found among 1046 consecutive hypertensive patients with normal renal function. Of those 66 PA patients, 16 (24.2%) had a unilateral adenoma, whereas 50 (75.8%) had idiopathic hyperaldosteronism. At presentation, 45.4% of the PA and 16.3% of EH patients were treated with two or more antihypertensive drugs (χ 2 = 33.117, P < .0001). However, among untreated patients ( n = 553), the prevalence of mild-to-moderate hypertension (ie, <180/110 mm Hg) was not different between patients with PA and those with EH (70.6% v 76.7%, χ 2 = 0.086, P = .770). Serum potassium ≥3.6 mEq/L was found in 60.6% of PA patients. In conclusion, we observed the following: 1) postcaptopril compared with baseline A/R is a better screening tool for PA; 2) PA is relatively frequent among hypertensive individuals; 3) PA is not necessarily associated with severe hypertension; and 4) hypokalemia is an insensitive screening criterion for PA.