血浆醛固酮/肾素活性比值——一个敏感的原发性醛固酮增多症的筛查指标

血浆醛固酮／肾素活性比值（ARR）是一个敏感的原发性醛固酮增多症（PA）的筛查指标，ARR的应用使高血压人群中PA的检出率明显增加。但目前ARR仍是一个非标准化的筛选方法，不同研究所采用的ARR切点差别很大，故应对ARR进行更深入和系统的研究，以提高ARR筛查方法的准确性。     

醛固酮/肾素比值在原发性醛固酮增多症筛查中的临床价值

目的 回顾分析瑞金医院内分泌科近5年怀疑原发性醛固酮增多症患者的资料,用受试者工作特征( receiver operating characteristic,ROC)曲线下面积评估醛固酮/肾素比值(aldosterone to renin ratio,ARR)在诊断原发性醛固酮增多症(原醛症)中的临床价值.方法 收集瑞金医院内分泌科2006年1月至2010年8月行卧位及立位ARR测定的590例怀疑原发性醛固酮增多症入院患者的临床资料,其中确诊为原醛症的患者357例,确诊为原发性高血压的患者233例.分析瑞金医院内分泌科2010年9月至2011年4月行随机及立位ARR测定的100例怀疑原醛症患者的临床资料,其中确诊为原醛症的患者29例,确诊为原发性高血压的患者71例.综合分析卧位、立位及随机ARR ROC曲线,以确定合适的切点用于诊断原发性醛固酮增多症.结果 2006年1月至2010年8月行卧位及立位ARR测定的590例患者卧位ARRROC曲线下面积为0.838(0.805～0.867),立位ARR ROC曲线下面积为0.873(0.843 ～0.899),两曲线下面积比较有显著差异(P＜0.01).2010年9月至2011年4月行立位及随机ARR测定的100例患者立位及随机ARR ROC曲线下面积分别为0.962(0.928 ～0.995)及0.944(0.893 ～0.994),两者比较无显著差异(P＞0.05).立位ARR切点为400(pg· ml-1)/(ng·ml-1·h-1)时,诊断原醛症患者的敏感性为91.9％,特异性为64.2％.结论 立位ARR比卧位ARR更适应作为原醛症的筛查指标,随机ARR与立位ARR在原醛症诊断中具有相似的临床价值.本研究认为,在严格控制患者药物、体位、检测时间条件下,ARR切点400( pg·ml-1)/(ng·ml-1·h-1)是原醛症筛查试验比较合适的切点.     

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 (χ² = 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%, χ² = 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.     

Low plasma renin activity and high aldosterone/renin ratio are associated with untreated isolated systolic hypertension

Abstract Objective. Isolated systolic hypertension (ISH) is generally encountered in elderly patients and there are scarce data regarding the renin-angiotensin-aldosterone system (RAAS) activity in patients with ISH. We aimed to determine the plasma renin activity (PRA), plasma aldosterone levels (PAL) and aldosterone/PRA ratio (PAL/PRA) in patients (age >50 years) with ISH and to compare these values with patients with essential hypertension (EH) as well as subjects with normal blood pressure values (control) who have similar age and cardiovascular risk profile. Methods. Consecutively, 42 untreated ISH patients, 30 patients with EH and 29 normal subjects were included in the study. Parameters were presented as median (interquartile range). Results. There were no significant differences regarding age, gender and other cardiovascular risk factors among groups. As expected, systolic, diastolic blood pressure and pulse pressure values were significantly different among groups. Besides, PRA values were found to be significantly lower in patients with ISH (0.4 [0.2-1.1] ng/ml/h) compared with the EH (0.95 [0.5-2.6] ng/ml/h, p =0.024) and control (1.3 [0.7-2.1] ng/ml/h, p =0.001) groups. Although, PAL were similar among groups, PAL/PRA ratio was significantly higher in ISH group (134.1 [73-224]) compared with those with EH (42.2 [35-84], p <0.001) and the control group (53.3 [30-106], p =0.001). No significant difference was present with respect to PAL/PRA ratio between EH and control groups. Conclusions. Our findings suggested that in patients with ISH, despite lower PRA levels, PAL/PRA ratio is significantly higher compared with the patients with EH and subjects with normal blood pressure. Since higher PAL/PRA levels is an indicator of relative aldosterone excess, medications blocking RAAS activity including aldosterone antagonists may have useful cardiovascular consequences in addition to their antihypertensive effects in ISH.     

Performance of the basal aldosterone to renin ratio and of the renin stimulation test by furosemide and upright posture in screening for aldosterone-producing adenoma in low renin hypertensives

An aldosterone-producing adenoma causes surgically correctable hypertension. Screening tests should be assessed for their accuracy and ability to detect aldosterone-producing adenoma in an appropriate population. This study aims to validate the accuracy and efficacy of the basal plasma aldosterone concentration (picomoles per liter) to PRA (nanograms per liter/sec) ratio and of combined stimulation of PRA by the furosemide and upright posture test in screening for aldosterone-producing adenoma in hypertensives with PRA less than 0.28 ng/liter.sec (1 ng/ml.h). Thirty-five aldosterone-producing adenoma and 79 nonaldosterone-producing adenoma patients were retrospectively selected from among 159 patients examined with the furosemide and upright posture test between 1989 and 1999. Selection criteria were based on blood pressure, PRA, and plasma aldosterone concentration. Diagnosis was based on surgical outcome, computed tomography scans with adrenal scintigraphy, or venous sampling. The accuracy and efficacy of basal (aldosterone/PRA ratio) and dynamic (postfurosemide and upright posture PRA) screening tests were assessed based on test sensitivity, specificity, likelihood ratio, and receiver operating characteristics. At a cut-off value of 3,200, the aldosterone/PRA ratio had a high sensitivity of 1.0 and a low specificity of 0.61. The importance was strengthened by using a multilevel likelihood ratio, i.e. positive (aldosterone/PRA ratio >10,000), negative (aldosterone/PRA ratio <3,200), and neutral (intermediate aldosterone/PRA ratio) levels. Patients with a positive level had a likelihood ratio of 7.1 and were likely to have an aldosterone-producing adenoma. The aldosterone/PRA ratio enclosed a larger area under the receiver operating characteristics curve (0.905) than did postfurosemide and upright posture PRA (0.826). In conclusion, the plasma aldosterone concentration to PRA ratio is an effective screening and diagnostic test when a triple level likelihood ratio is applied. The furosemide and upright posture test did not raise the posttest probability over that obtained using the aldosterone/PRA ratio.     

Determination of the aldosterone/renin ratio in 269 patients with adrenal incidentaloma.

To determine the prevalence of primary aldosteronism among patients with incidentally discovered adrenal adenomas ('incidentalomas') plasma concentrations of aldosterone (PA) and plasma renin activity (PRA) were determined in 269 patients (100 normotensives, 169 hypertensives) newly referred incidentaloma patients. Among the 100 normotensives a PA [ng/dl]/PRA [ng/ml.h]-ratio (A/R-R) >50 and a concomitant elevation of PA (>15 pg/ml) was initially seen in two cases but further investigations excluded the presence of primary aldosteronism in both patients suggesting a prevalence of primary aldosteronism of <1% among normotensive patients with adrenal incidentaloma. Among the 169 hypertensive incidentaloma patients 14 presented with both, an elevated PA [>15 pg/ml] and an A/R-R >50. Primary aldosteronism was confirmed in 6 of this cases resulting in a prevalence of primary aldosteronism among hypertensive incidentaloma patients of 4%. Although obtained in patients with a supposedly high pre-test probability of primary aldosteronism this percentage--while in keeping with the older literature--is surprisingly low given the recently reported large(r) prevalence of primary aldosteronism among hypertensives in general.     

Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism

Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. Antihypertensive therapy can interfere with the interpretation of this parameter, but a correct washout period can be potentially harmful. We have investigated the effects of therapy with atenolol, amlodipine, doxazosin, fosinopril, and irbesartan on the ARR in a group of 230 patients with suspected primary aldosteronism. The percent change from control of ARR in patients taking amlodipine was -17%+/-32; atenolol, 62%+/-82; doxazosin, -5%+/-26; fosinopril, -30%+/-24; and irbesartan, -43%+/-27. The ARR change induced by atenolol was significantly higher compared with that induced by all other drugs (P<0.0001), and the ARR change induced by irbesartan was significantly lower than that induced by doxazosin (P<0.0001). One of 55 patients from the group taking amlodipine (1.8%) and 4/17 of the patients taking irbesartan (23.5%) gave a false-negative ARR (<50). None of the patients of the groups taking fosinopril, doxazosin, and atenolol displayed a false-negative ARR. Doxazosin and fosinopril can be used in hypertensive patients who need to undergo aldosterone and PRA measurement for the diagnosis of primary aldosteronism; amlodipine gave a very small percentage of false-negative diagnoses. beta-Blockers also do not interfere with the diagnosis of primary aldosteronism, but they can be responsible for an increased rate of false-positive ARRs. The high rate of false-negative diagnoses in patients undergoing irbesartan treatment requires confirmation in a higher number of patients.     

Detection of primary aldosteronism by the 6-hour integrated aldosterone/renin ratio

An outpatient diagnostic procedure measuring the 6-hour integrated plasma concentration of aldosterone and plasma renin activity was used to detect primary aldosteronism in 12 patients with low renin hypertension, including six with mild hypertension and normal urinary excretion and spot plasma levels of aldosterone. The ratio of integrated plasma concentration of aldosterone to plasma renin activity in the 12 patients (mean, 339; range, 116-700; p less than 0.0001) did not overlap with that measured in 105 normotensive controls (mean, 27.8; range, 5-97) or in 87 subjects with essential hypertension (mean, 29.2; range, 4-67). Eight patients had surgically proven adenomas (3 of which measured less than 5 mm) with normalization of blood pressure following adrenalectomy. The four remaining patients had bilateral hyperplasia. The 6-hour integrated plasma concentration of aldosterone to plasma renin activity ratio was found to be a useful new outpatient diagnostic tool for evaluation of primary hyperaldosteronism.     

原发性醛固酮增多症筛查中血浆醛固酮/肾素活性比值的影响因素

血浆醛固酮水平/肾索活性比值(ARR)是筛查原发性醛固酮增多症的实用指标.由于影响肾素和醛同酮分泌的因素众多,ARR切点值变异范围较大,至今仍然是一个缺乏标准化的指标.本文综述这些因素,旨在临床上提高ARR的诊断效力.     

Effect of age on aldosterone/renin ratio (ARR) and comparison of screening accuracy of ARR plus elevated serum aldosterone concentration for primary aldosteronism screening in different age groups

The serum aldosterone concentration (SAC)/plasma renin activity (PRA) ratio (ARR) is considered a useful screening test in the differential diagnosis of essential hypertension (EH) and primary aldosteronism (PA). The purpose of this study is to investigate the effect of age on ARR and compare the screening accuracy of ARR plus elevated SAC for PA screening in different age groups. Thirty-nine patients with PA, 274 patients with EH, and 153 healthy volunteers were recruited. Blood was sampled for SAC and PRA measuring under keeping upright posture for 1 h. Levels of SAC, PRA, and ARR were compared at different ages range for the respective three groups of subjects. The screening accuracy of ARR plus elevated SAC was compared in different age groups and PA patients served as the same positive subjects. In the EH group, logarithmically transformed ARR (Log-ARR) increased with advancing age and reached its peak in the ≥ 60 years group; in the normotensives group, Log-ARR reached its peak in the 40-49 years group and slightly declined with advancing age. In the PA group, Log-ARR was not age dependent. Screening accuracy increased when combined index of ARR and SAC was used in the ≥ 40 years group but not in the <40 years group. Although the number of EH patients with elevated ARR increased with advancing age, but the screening accuracy and cutoff values of ARR were not affected by age. Using the combined index of ARR and SAC increased the screening accuracy for the patients older than 40 years, but not necessary for the patients younger than 40 years.     

Optimal use and interpretation of the aldosterone renin ratio to detect aldosterone excess in hypertension

With the introduction of the aldosterone/renin ratio as a screening test, the detection rate of primary aldosteronism has increased considerably. Nevertheless, no consensus has so far been reached regarding the cutoff points, operating characteristics or indeed even the reference values for reporting the aldosterone/renin ratio using plasma active renin (ng/l or mU/l) measured by immunoradiometric assay. We review the characteristics of this ratio in normal individuals, essential hypertension and primary hyperaldosteronism in an attempt to reach an agreement regarding its optimum use and interpretation - both using the renin activity or concentration. It seems that the optimal cutoff for patients with primary aldosteronism is above 30 ng/dl per mug/l/h or 800 pmol/l per mug/l/h or 130 pmol/ng or 80 pmol/mU. We explore enhancing measures such as captopril loading or use with a plasma aldosterone cutoff as well as pitfalls with the test such as confounding medications or the need for confirmatory testing. For the latter, demonstration of autonomous aldosterone production via salt loading is widely used, but may not be most advantageous and may even be contraindicated in patients with severe hypertension. The renin stimulation test may be an alternative being safe, well tolerated, and cost effective.     

Prevalence of primary aldosteronism among unselected hypertensive patients: a prospective study based on the use of an aldosterone/renin ratio above 25 as a screening test.

Primary aldosteronism (PA) has been considered a rare cause of hypertension. The introduction of the aldosterone/renin ratio (ARR) as a screening test has led to an increase in the detection rate. The aim of this study was to evaluate the prevalence of PA among unselected hypertensive patients by using an ARR >25 as a screening test. We studied 3,000 consecutive unselected hypertensive patients. Blood samples for the determination of plasma renin activity (PRA), aldosterone (ALD) and electrolytes were drawn in the morning, and patients with an ARR >25 underwent intravenous saline infusion as a confirmatory test. Adrenal CT and a dexamethasone suppression test were performed in patients with confirmed PA. Patients with a positive dexamethasone test underwent genetic testing for glucocorticoid-remediable aldosteronism (GRA). Out of 3,000 hypertensives, 684 (22.8%) showed an ARR >25 and 177 of them (5.9% of the whole population) had a positive saline loading test. Only 44 of them (24.8%) were hypokalemic. CT was performed in all the patients with confirmed PA and 53 of them (29.9%) had a solitary adrenal macroadenoma, 112 (63.3%) had bilateral adrenal enlargement and 12 (6.8%) had normal appearing adrenal glands. Of 177 patients given dexamethasone to identify GRA, 8 (4.5%) showed aldosterone suppression but only one (0.1%) tested positive for the chimeric gene. In conclusion, our findings indicate that standardized application of an ARR >25 to unselected hypertensive patients, followed by i.v. saline loading as a confirmatory test, can result in the detection of a large number of patients with PA (5.9% of the studied population), most of whom are normokalemic. Bilateral adrenal hypertrophy represents the more common form of PA.     

The aldosterone to renin ratio in the evaluation of patients with incidentally detected adrenal masses

Incidentally discovered adrenal masses are diagnosed with increasing frequency, especially among patients with hypertension. Thus, a reliable screening test for primary hyperaldosteronism (PA) is essential to avoid unnecessary diagnostic procedures to this population. The aim of the present study is the evaluation of aldosterone to renin ratio (ARR), using plasma renin concentration, in the diagnostic algorithm of patients with adrenal incidentaloma. A total of 123 individuals were studied: 17 patients with proven PA (age 55.5 ± 1.4 years), 27 patients with nonfunctioning adrenal incidentaloma (age 60.3 ± 1.8 years, 14 hypertensives and 13 normotensives) and 79 control subjects (age 58.7 ± 1.4 years, 27 hypertensives and 52 normotensives). A receiver operating characteristic (ROC) analysis disclosed that an ARR ≥32 combines a sensitivity of 100% with a specificity of 96.2% for the diagnosis of PA. No difference in ΑRR between hypertensive and normotensive individuals harbouring an adrenal incidentaloma and hypertensive and normotensive controls was found. Patients with adrenal incidentalomas with subtle glucocorticoid hypersecretion demonstrated similar ARR compared to patients with normal cortisol secretion. In conclusion, ARR is reliable for the exclusion of PA in patients with adrenal incidentalomas. Furthermore, subtle aldosterone hypersecretion, as indicated by increased ARR, in patients with adrenal incidentalomas is not associated with the presence of hypertension or subtle glucocorticoid hypersecretion.     

血浆醛固酮/肾素活性比值在诊断原发性醛固酮增多症患者的价值

目的采用血浆醛固酮/肾素活性比值(ARR)在高血压患者中筛选原发性醛固酮增多症(原醛)病例,治疗和随访患者、分析其临床特点,从而探讨原醛的临床特点和 ARR 在原醛诊断中的价值。方法收集门诊和住院的高血压患者902例(其中3级高血压609例),空腹采血并用放射免疫方法测定血浆肾素和醛固酮水平及血生化指标,计算 ARR。对比值大于25(ng/dl 比ng·ml~(-1)·h~(-1))的126例疑诊为原醛的病例进行肾上腺薄层 CT 扫描,分析其临床特点、用抗醛固酮药物治疗并进行随访。结果原醛在高血压人群中占14%(126/902),肾上腺 CT 见54例单侧或双侧增生和25例腺瘤;原醛合并低血钾占39%(49/126);25例患者接受外科治疗,有效率100%,其中48%(12/25)能达到治愈;用螺内酯治疗有效率为89%(48/54),单药控制率为24%(13/54)。结论中国人原醛占高血压10%以上,ARR 应作为高血压尤其是重度和难治性高血压患者的常规检查,ARR 在原醛诊断中有重要意义,可以提高原醛的诊断率。     

Aldosterone and aldosterone: renin ratio associations with insulin resistance and blood pressure in African Americans

African Americans have more hypertension and hypertension-related morbidity than whites. Aldosterone, in presence of a high salt intake, contributes to hypertension and tissue injury. Inappropriately elevated aldosterone levels could explain this racial disparity. Our study was conducted to determine if aldosterone is associated with elevated blood pressure (BP) or insulin resistance, independent of obesity. A study was conducted on 483 young adult African Americans without cardiovascular or renal disease. Measurements included anthropometrics, BP, lipids, glucose, insulin, aldosterone, and renin. Urine sodium and potassium estimated sodium intake. The cohort was stratified by tertiles of aldosterone and tertiles of aldosterone/renin ratio (ARR). Average urine sodium/potassium ratio was >3.0 in all groups. Insulin resistance, estimated by homeostasis model, was lowest in the low aldosterone group (geometric mean 1.5 [0.6, 2.2]) compared with the high aldosterone group (1.7 [0.9, 2.7], P < .01). Adjusted analyses detected a significant association of aldosterone with insulin resistance, independent of other variables. BP was significantly higher in the high ARR group compared with low and mid ARR groups (P < .01). The significant association of ARR with BP with high dietary sodium suggests that insufficiently suppressed aldosterone may contribute to BP sensitivity to sodium in African Americans.     

Effect of postural changes on aldosterone to plasma renin ratio in patients with suspected secondary hypertension

AimsTo study the influence of postural changes on aldosterone to renin ratio (ARR) in patients with suspected secondary hypertension and to evaluate the sensitivity and specificity of the recommended seated ARR compared to supine and upright ARR for primary aldosteronism screening.MethodsFifty-three hypertensive patients were prospectively hospitalized for secondary hypertension exploration (age: 51 ± 12, 66% males). After withdrawal of drugs interfering with renin angiotensin system, plasma aldosterone and direct renin concentration were measured in the morning, at bed after an overnight supine position, then out of bed after 1 hour of upright position and finally 2 hours later after 15 minutes of seating. Minimal renin value was set at 5 μUI/mL.ResultsReferring to ARR cut-off of 23 pg/μUI, the sensitivity of seated ARR was 57.1% and specificity was 92.3%. The negative and positive predictive values were 95.1% and 45.2% respectively. Compared to these results, a cut-off of 19 improved sensitivity to 85.7% with a specificity of 89.7%. Negative and positive predictive values were 98.3% and 41.1% respectively. Seated ARR mean value was lower than supine and upright ARR mean values, due to an overall increase in renin at seating compared to the supine position by factor 1.9 while aldosterone just slightly increased by factor 1.2. Seated ARR correlated to supine and upright ARR: correlation coefficients (r) 0.90 and 0.93 respectively (P < 0.001).ConclusionsCurrent recommended measurement of ARR in the seating position is fairly correlated to supine and upright ARR. A suggested cut-off value of 19 instead of 23 pg/μUI increased the discriminating power of this test.