Aldosterone To Active Renin Ratio Research Articles

Practical recommendations for antihypertensive therapy during the primary aldosteronism screening test.

The aldosterone-to-renin activity ratio (ARR) is recommended as a screening test for primary aldosteronism (PA). The use of antihypertensive medication is one of the most important factors to take into account when interpreting the ARR. The goal of this study was to compare the effect of various antihypertensive drug classes on biochemical testing and provide practical recommendations for antihypertensive medication regimens in patients suspected of having PA. We retrospectively investigated 4218 hypertensive patients who underwent PA detection between January 2020 and February 2023. Finally, 25 patients with essential hypertension (EH) and 39 with PA were involved. The enrolled EH patients were selected from EH patients with at least two screening tests with interfering medication changes for at least 4 weeks. A total of 2/18 (11.1%) EH patients had opposite screening results after angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitors (ACEIs), dihydropyridine-calcium channel blockers (DHP-CCBs) and diuretics were withdrawn. A total of 3/3 (100%) of the patients were initially screened as positive but had results that tested negative after β-blockers withdrawal. A total of 3/39 (7.7%) PA patients were misdiagnosed with EH with drug effects. Only plasma renin activity was markedly reduced after antihypertensive medication washout (P = 0.0173). Not every patient receiving β-blockers, ACEIs, ARBs and DHP-CCBs with negative reports needed withdrawal or switching antihypertensive drugs. We recommend that patients be left on a regimen that includes β-blockers, ACEIs, ARBs, DHP-CCBs and spironolactone when determining the ARR during the initial test.

Diagnostic Accuracy of the Aldosterone-to-Active Renin Ratio for Detecting Primary Aldosteronism.

ContextThe aldosterone–to–active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but prospective study data on its sensitivity and specificity are sparse.ObjectiveTo investigate the diagnostic accuracy of the AARR for detecting PA.DesignProspective diagnostic accuracy study.SettingThis study was conducted from February 2009 to August 2015 at the outpatient clinic of the Department of Endocrinology and Diabetology of the Medical University of Graz, Austria.ParticipantsFour hundred patients with arterial hypertension who were referred to a tertiary care center for screening for endocrine hypertension.InterventionParticipants had a determination of the AARR (index test) and a second AARR determination followed by a saline infusion test (SIT) after 2 to 6 weeks. PA was diagnosed in individuals with any AARR ≥3.7 ng/dL/µU/mL [including a plasma aldosterone concentration (PAC) of ≥9 ng/dL] who had a PAC ≥10 ng/dL after the SIT. We did not substantially alter antihypertensive drug intake.Main Outcome MeasuresPrimary outcome was the receiver-operating characteristic (ROC) curve of the AARR in diagnosing PA.ResultsA total of 382 participants were eligible for analyses; PA was diagnosed in 18 (4.7%) patients. The area under the ROC curve of the AARR in detecting PA was 0.973 (95% CI, 0.956 to 0.990). Sensitivity and specificity for a positive AARR in diagnosing PA were 100% (95% CI, 81.5% to 100.0%) and 89.6% (95% CI, 86.0% to 92.5%), respectively.ConclusionsThe AARR has good diagnostic accuracy for detecting PA.

The correlation between the carotid artery plaque and the change of aldosterone level related indexes during captopril challenge test

To investigate the correlation between the carotid artery plaque and the change of plasma aldosterone level related indexes during captopril challenge test. The patients with hypertension were enrolled as research objects and the captopril challenge test were carried out when they were hospitalized to screen the cause of hypertension. There were intact carotid artery duplex ultrasonography diagnostic data in them (83 cases). They were divided into the plaque group(57 cases) with carotid artery plaque and no plaque group( 26 cases) without carotid artery plaque according to the carotid artery duplex ultrasonography diagnostic data. The correlation between the carotid artery plaque and the changes of aldosterone concentration, renin activity and aldosterone to renin activity ratio(ARR) in two groups were analyzed. The detection rate of carotid artery plaque was 68.67%. Compare with no plaque group, the patients in plaque group were elder and the level of apolipoprotein A1,(APOA1) was lower (all P＜0.05). The ARR difference value before and after captopril challenge test was lower ( P＜0.05).The aldosterone difference value and the renin activity difference value before and after captopril challenge test were higher in plaque group (all P＜0.05).The aldosterone difference value and the renin activity difference value were positive in plaque group and were negative in no plaque group. The difference value of the ARR was negative in plaque group and was positive in no plaque group. Logistic regression analysis showed that the age, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence after excluding gender difference and other factors. The detection rate of carotid artery plaque was high among hospitalized patients with hypertension, the difference value of ARR and the aldosterone before and after captopril challenge test could be associated independently with carotid artery plaque occurrence.

Aldosterone-to-Renin Ratio Is Associated With Reduced 24-Hour Heart Rate Variability and QTc Prolongation in Hypertensive Patients.

Aldosterone is considered to exert direct effects on the myocardium and the sympathetic nervous system. Both QT time and heart rate (HR) variability (HRV) are considered to be markers of arrhythmic risk and autonomous dysregulation. In this study, we investigated the associations between aldosterone, QT time, and HRV in patients with arterial hypertension.We recruited 477 hypertensive patients (age: 60.2 ± 10.2 years; 52.3% females) with a mean systolic/diastolic 24-hour ambulatory blood pressure monitoring (ABPM) value of 128 ± 12.8/77.1 ± 9.2 mmHg and with a median of 2 (IQR: 1–3) antihypertensive agents. Patients were recruited from the outpatient clinic at the Department of Internal Medicine of the Medical University of Graz, Austria. Blood samples, 24-hour HRV derived from 24-hour blood pressure monitoring (ABPM) and ECG's were obtained. Plasma aldosterone and plasma renin concentrations were measured by means of a radioimmunoassay. Twenty-four-hour urine specimens were collected in parallel with ABPM.Mean QTc was 423.3 ± 42.0 milliseconds for males and 434.7 ± 38.3 milliseconds for females. Mean 24H-HR and 24H-HRV was 71.9 ± 9.8 and 10.0 ± 3.6 bpm, respectively. In linear regression analyses adjusted for age, sex, body mass index, ABPM, and current medication, aldosterone to active renin ratio (AARR) was significantly associated with the QTc interval, a marker for cardiac repolarization abnormalities (mean = 426 ± 42.4 milliseconds; β-coefficient = 0.121; P = 0.03) as well as with the 24-hour heart rate variability a surrogate for autonomic dysfunction (median = 9.67 [IQR = 7.38–12.22 bpm]; β-coefficient = −0.133; P = 0.01).In hypertensive patients, AARR is significantly related to QTc prolongation as well as HRV. Further studies investigating the effects of mineralocorticoid receptor blocker and aldosterone synthase inhibitors on QTc and HRV are warranted.

Abstract 431: A Novel Score System for Primary Aldosteronism Screening, PUK2 score: Combination of Urine pH and Serum Uric Acid and K+ Levels

Background: Hypokalemia is not a sensitive marker of primary aldosteronism (PA) , and method for screening PA by routine clinical parameters has not yet been established. Objective: We examined whether serum uric acid (UA) or urine pH alone, or their combination with serum K+ level is usable for PA screening . Design and Setting: Cross-sectional analyses were retrospectively performed on consecutive patients who visited a single general hospital from April 2012 to September 2013. Participants: Entry criteria were age <75 years old, hypertension and presence of data on serum aldosterone (ng/dL) and renin activity (ng/mL/hr). Exclusion criteria were use of aldosterone blockers, ACE inhibitors, angiotensin receptor antagonists, diuretics, beta-adrenergic blockers, steroids or UA-lowering drugs and diagnosis of secondary hypertensions other than PA. Main Outcome Measures: Diagnosis of PA was made in accordance with the guideline of Japanese Society of Hypertension: patients with aldosterone-to-renin activity ratio (ARR) > 20 and one or more positive results in captopril challenge test, furosemide-upright test, saline infusion test and/or ACTH stimulation test. Results: We enrolled 103 patients (PA = 29, essential hypertension [eHT] = 74). PA has lower serum K+ (3.5±0.32 vs 3.8±0.23 mEq/L, p<0.001, mean ± S.D.), higher urine pH (6.6±0.83 vs 6.1±0.62, p<0.001) and lower UA (5.6±1.6 vs 6.5±1.2 mg/dL, p=0.004) compared with those in eHT. Urine pH≧ 7.0 and UA < 6.0 mg/dL were selected as optimum cutoffs for diagnosis of PA by ROC curve analysis. Multivariable logistic regression analysis indicated that high urine pH, low UA and hypokalemia (K < 3.5 mEq/L) were independently associated with PA. Using the cutoff values, we developed a score system, PUK2 score, which is derived from the sum of point values of PA predictor; 1 point was assigned to low UA and to high urine pH and 2 points were assigned to hypokalemia. The prevalence of PA in the patients with PUK2 score of 0, 1, 2 and 3~ was 5.0%, 31%, 37%, and 83%,respectively. Furthermore, the likelihood ratio in patients with PUK2 score of 0 was 0.13 (95%CI: 0.034-0.52). Conclusions: PUK2 score is easy to use and useful for screening PA in hypertensive patients.

Marinobufagenin in essential hypertension and primary aldosteronism: a cardiotonic steroid with clinical and diagnostic implications

Background: The cardiotonic steroid marinobufagenin (MBG) is increasingly suggested to be responsible for some of the cardiovascular injury that has been previously attributed to aldosterone. We examined the clinical correlates of circulating MBG concentrations in hypertensive patients and tested the hypothesis that MBG serves as a reliable diagnostic tool for detecting primary aldosteronism (PA).Methods: Plasma MBG concentrations (mean: 0.51 ± 0.25 nmol/l) were measured in the morning fasting samples in 20 patients with PA and 20 essential hypertensive (EH) controls matched for age, sex, body mass index, renal function, urinary sodium and intake of antihypertensive medication (mean age: 51.6 years; 52.2% women).Results: Overall, plasma MBG was directly correlated with plasma aldosterone, aldosterone to active renin ratio (AARR), diastolic blood pressure, mean carotid intima-media thickness, serum sodium, urinary protein to creatinine ratio and inversely with serum potassium levels. Plasma MBG levels were significantly higher in patients with PA compared to EH (mean: 0.68 ± 0.12 versus 0.35 ± 0.24 nmol/l; p < 0.001). ROC analysis yielded a greater AUC for plasma MBG compared to the AARR, PAC and serum potassium levels for detecting PA. Youden's Index analyses yielded the optimal plasma MBG cut-off score for diagnosing PA at > 0.49 nmol/l with specificity and sensitivity values of 0.85 and 0.95, respectively, which were higher than those at the optimum AARR cut-off at > 3.32 ng/dl/µU/ml.Conclusions: In a well-characterized cohort, values of plasma MBG were significantly related to clinical correlates of cardiovascular and renal disease. Plasma MBG emerged as a valuable alternative to the AARR for screening of PA.

Aldosterone to Active Renin Ratio Is Associated With Nocturnal Blood Pressure in Obese and Treated Hypertensive Patients: The Styrian Hypertension Study

High aldosterone levels are considered to play a key role in arterial hypertension. Data on the relationship between the aldosterone to active renin ratio (AARR), a quantity of aldosterone excess, and ambulatory blood pressure (BP) monitoring (ABPM) during the night are, however, sparse. Hypertensive patients were recruited from local outpatient clinics who underwent 24-hour urine collection and in parallel ABPM. Plasma aldosterone and renin concentrations were measured by radioimmunoassay. A total of 211 patients (age, 60.2±10.2years; 51.9% female) with a mean systolic/diastolic ABPM value of 128.7±12.8/77.1±9.2mmHg were evaluated. In backwards linear regression analyses adjusted for age, sex, body mass index, smoking, glomerular filtration rate, hemoglobin A1c , N-terminal prohormone of brain natriuretic peptide, urinary sodium/potassium ratio, and ongoing antihypertensive medication, AARR was significantly associated with nocturnal systolic (ß-coefficient: 0.177; P=.017) and diastolic BP (ß-coefficient: 0.162; P=.027). In patients with arterial hypertension, a significant association between AARR and nighttime BP even after adjustment for a broad panel of confounders was found.

Aldosterone to Active Renin Ratio as Screening Test for Primary Aldosteronism: Reproducibility and Influence of Orthostasis and Salt Loading

Measurement of the aldosterone to active renin ratio (AARR) is the recommended screening test for primary aldosteronism (PA), but several sampling conditions impact on the AARR. We aimed to evaluate the reproducibility and the influence of orthostasis and salt loading on the AARR. The Graz Endocrine Causes of Hypertension (GECOH) study is a diagnostic accuracy study among hypertensive patients at a tertiary care centre in Graz, Austria. With a median interval of 4 weeks we determined the AARR under standardized sampling conditions twice in the sitting position, after 1h in the supine position, and after a salt infusion test (SIT). We identified 9 patients with PA and 151 patients with essential hypertension (EH). The Pearson correlation coefficient between both AARR measurements in the sitting position was 0.79 (p<0.001). In EH, recumbency was associated with a significant decrease of aldosterone and, to a lesser extent, of renin, thus lowering the AARR as compared to the sitting position (p<0.001 for all). In PA, recumbency had only minor effects, but it increased the rate of false negative AARR. SIT suppressed the AARR and its components in EH, whereas in PA only renin was slightly decreased. AARR has a good intra-individual reproducibility and decreases during recumbency. These results suggest that a single AARR determination in the sitting position is a reliable screening tool for PA.

Long-term re-evaluation of primary aldosteronism after medical treatment reveals high proportion of normal mineralocorticoid secretion

In most cases of primary aldosteronism (PA), An adrenal aldosterone-secreting tumor cannot be reasonably proven, so these patients undergo medical treatment. Controversial data exist about the evolution of PA after medical therapy: long-term treatment with mineralocorticoid antagonists has been reported to normalize aldosterone levels but other authors failed to find remission of mineralocorticoid hypersecretion. Thus, we planned to retest aldosterone secretion in patients with medically treated PA diagnosed at least 3 years before. Retrospective, cross-sectional study. The same workup for PA as at diagnosis (basal aldosterone to renin activity ratio (ARR) and aldosterone suppression test) was performed after stopping interfering drugs and low-salt diet, in 34 subjects with PA diagnosed between 3 and 15 years earlier, by case finding from subgroups of hypertensive patients at high risk for PA. Criteria for persistence of PA were the same as at diagnosis (ARR (pg/ml per ng per ml per h) >400, aldosterone >150 pg/ml basally, and >100 pg/ml after saline infusion) or less restrictive. PA was not confirmed in 26 (76%) of the patients and also not in 20 (59%) using the least restrictive criteria suggested by international guidelines. Unconfirmed PA was positively associated with female sex, higher potassium levels, longer duration of hypertension, and follow-up, but not with adrenal mass, aldosterone levels at diagnosis, and treatment with mineralocorticoid antagonists. This study suggests that mineralocorticoid hyperfunction in patients with PA after medical treatment may decline spontaneously. Higher potassium concentration and duration of treatment seem to increase the probability of this event.

Characteristics of 330 cases with primary aldosteronism

Objective: To analyze the clinical characteristics of PA patients. Methods: 330 cases of PA from January 2006 to March 2010 in the Hypertension Department of the People's Hospital of Xinjiang Uygur autonomous region were recruited in the retrospective study. The characteristics of blood pressure and serum potassium were analyzed. Results: The common symptoms of patients with PA were hypertension (100%), headache (36.67%), dizziness (33.94%), palpitation (4.85%), and limb fatigue (4.24%). The prevalence of 1, 2 and 3 stage hypertension in these subjects was 3.64%, 20.91% and 75.45%, respectively. Of all PA patients, 89.09% were young adults and 81.82% were overweight and obese. There were more male patients with PA in the overweight and obese groups compared with that of normal weight groups (χ2=22.82, P<0.001). The incidence of hypokalemia was 32.12%. The concentration of serum potassium was not associated with the course (r=−0.084, P>0.05). Logistic regression showed that the concentration of plasma aldosterone was the independent risk factors of hypokalemia in PA patients (beta=0.067, P<0.001). The aldosterone-to-renin activity ratio (ARR) was >20 in 94.24% of the patients with PA. Conclusions: The incidence of PA patients with hypokalemia is low. It is important to screen PA in moderate to severe hypertension of young adults with or without hypokalemia, in particular for males who are overweight and obese. ARR>20 is a practical index for screening PA, which will help to reduce the rate of missed diagnosis of PA.

Graz Endocrine Causes of Hypertension (GECOH) study: a diagnostic accuracy study of aldosterone to active renin ratio in screening for primary aldosteronism

BackgroundPrimary aldosteronism (PA) affects approximately 5 to 10% of all patients with arterial hypertension and is associated with an excess rate of cardiovascular complications that can be significantly reduced by a targeted treatment. There exists a general consensus that the aldosterone to renin ratio should be used as a screening tool but valid data about the accuracy of the aldosterone to renin ratio in screening for PA are sparse. In the Graz endocrine causes of hypertension (GECOH) study we aim to prospectively evaluate diagnostic procedures for PA.Methods and designIn this single center, diagnostic accuracy study we will enrol 400 patients that are routinely referred to our tertiary care center for screening for endocrine hypertension. We will determine the aldosterone to active renin ratio (AARR) as a screening test. In addition, all study participants will have a second determination of the AARR and will undergo a saline infusion test (SIT) as a confirmatory test. PA will be diagnosed in patients with at least one AARR of ≥ 5.7 ng/dL/ng/L (including an aldosterone concentration of ≥ 9 ng/dL) who have an aldosterone level of ≥ 10 ng/dL after the saline infusion test. As a primary outcome we will calculate the receiver operating characteristic curve of the AARR in diagnosing PA. Secondary outcomes include the test characteristics of the saline infusion test involving a comparison with 24 hours urine aldosterone levels and the accuracy of the aldosterone to renin activity ratio in diagnosing PA. In addition we will evaluate whether the use of beta-blockers significantly alters the accuracy of the AARR and we will validate our laboratory methods for aldosterone and renin.ConclusionScreening for PA with subsequent targeted treatment is of great potential benefit for hypertensive patients. In the GECOH study we will evaluate a standardised procedure for screening and diagnosing of this disease.

Primary Hyperaldosteronism in the Hypertensive Disease

Primary aldosteronism (PA) is one of the potentially curable forms of hypertension. The hypertension is secondary to aldosterone action in the kidney, reabsorbing sodium and water that increases the intravascular volume and blood pressure. PA was previously believed to account for less than 1% of hypertensive patients when hypokalemia is used as screening method. However, recent studies using the plasma aldosterone to renin activity ratio (ARR) as screening test have demonstrated a high prevalence of PA in hypertensive populations. This prevalence vary depending on the severity of hypertensive disease being higher in stages 2 (8.55%) and 3 (13.5%) of the disease. Only a small proportion of PA patients (between 9 and 37%) are hypokalemic. The diagnosis of PA is advocated to confirm the autonomy of aldosterone secretion from the renin-angiotensin system and to differentiate the clinical subtypes of the disease. The most common subtypes of PA are idiopathic aldosteronism and aldosterone-producing adenoma. Other causes are glucocorticoid-remediable aldosteronism, unilateral or primary adrenal hyperplasia and adrenal carcinoma. This article reviews the new data about prevalence, diagnosis criteria and describes the clinical, biochemical and genetic characteristics of the different subtypes of the disease. Keywords: Primary aldosteronism, mineralocorticoids, hypertension

Plasma aldosterone to renin ratio predicts treatment response in primary aldosteronism: Is volume loading needed?

Volume loading is considered the golden standard of the confirmatory tests in the diagnostics of primary aldosteronism (PA). However, it is time‐consuming, and it is unclear to what extent it improves the diagnostics of PA in comparison to simple screening tests. To study this question, the diagnostics with and without oral sodium loading (OSL) were evaluated by receiver operating characteristic curves analyses in 77 consecutive OSL patients. The final diagnosis was essential hypertension in 39 cases and PA in 38 cases, determined by review of the patient records, biochemical tests, imaging findings, and the response to therapy with spironolactone and/or operation. Plasma aldosterone‐to‐renin‐activity ratio (ARR) and daily urinary aldosterone had a good diagnostic ability that did not significantly improve by accomplishing OSL. Cut‐off values with optimal sensitivity and specificity were ≥1050 pmol/l per ng/ml/h for upright ARR, and ≥45 nmol/day for daily urinary aldosterone. To conclude, carefully conducted outpatient tests are sufficient for the diagnostics of PA, when the diagnosis is justified by the positive response to treatment. However, volume loading serves as an additional diagnostic tool in the most problematic cases, improving slightly the discriminative ability of urinary aldosterone determination.

Aldosterone to Renin ratio in a primary care setting: the Bussolengo study.

The aim of the study was to evaluate the prevalence of hypertension associated with an elevated aldosterone to renin activity ratio (ARR) in a sample of adults aged 35-74 yr, randomly selected from the population register of the Bussolengo Health District (northern Italy) and representative of the total population of the district. Subjects (n = 1462) were randomly selected from the population register and examined by their general practitioners. Complete data for 1348 individuals were available for final statistical analysis. Apart from verapamil or alpha-blockers, no hypotensive drugs were allowed during the 4 wk before assay. Direct active renin and aldosterone were measured in the plasma of hypertensive patients after 2 h in the upright posture. Of 412 identified hypertensive patients, 287 subjects agreed to give blood (70% response rate). An aldosterone to active renin ratio (AARR) of 32 pg/ml was taken as the cut-off value, equivalent to an ARR of 50 ng/dl/ng/ml.h. An elevated AARR was observed in 32.4% of the hypertensive patients, with increased prevalence in females and in people aged 55 yr or older. As an elevated AARR is frequent in the general hypertensive population, screening should not be limited to the patients referred to specialist units.