Screening For Primary Aldosteronism Research Articles

#357 Sex differences in the aldosterone-renin system must be taken into account during screening for primary aldosteronism

Abstract Background and Aims Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Patients with PA are at higher risk for cardiovascular and renal complications than those with essential hypertension. Screening for PA is rarely considered in the assessment of a hypertensive patient, in part because of difficulties in the diagnostic process. Nevertheless, identification of PA is crucial to guide patients towards optimal management, either by mineralocorticoid receptor blockade or by unilateral adrenalectomy, with the latter offering potential cure for patients with aldosterone-producing adenomas (APAs). Numerous studies show inadequate diagnostic accuracy of the aldosterone:renin ratio (ARR) for screening for PA, particularly in females, who have higher ARR variability and lower renin compared to males. Women have a higher risk of false-positive screening results leading to unnecessary confirmatory tests. Use of oral contraception (OC) or hormone replacement therapy (HRT) may also confound the ARR. The aim of this study was to develop improved screening tools for PA, including adjustments for sex-specific differences. Method PROSALDO is a multicenter prospective cohort study designed to test new diagnostic procedures for patients with suspected PA. Medication that interfere with the renin-angiotensin-aldosterone system are withdrawn before laboratory measurements. For screening, the routine ARR is calculated along with additional probability scores based on a peripheral venous steroid hormone profile (PVSP). The latter allows for identification of potentially false-negative ARR results. After a positive screening result of the ARR and/or a high probability score based on the PVSP, PA is confirmed or excluded with a saline infusion test (SIT). PA confirmation is followed by adrenal venous sampling (AVS) to identify patients with unilateral PA. We compared aldosterone, renin and ARR levels between females and males with and without PA. Renin- and sex dependent formulas for aldosterone screening cut-offs were derived from the study population. Logistic regression and the corresponding receiver operating characteristic (ROC) curves were used to determine and compare diagnostic accuracies. Results PA was confirmed in 159 (24.5%) of 649 (328 (50.5%) females and 321 (49.5%) males). Lateralization was shown in 58 out of 117 patients who underwent AVS. In hypertensive patients without PA, ARR was higher in females vs. males (26.4 vs. 11.7 pmol/mU, P < 0.0001), mainly due to a lower renin (9.2 vs. 16.2 mU/L, P < 0.0001). Furthermore, ARRs in patients with vs. without PA showed more overlap in females compared to males. Areas under ROC curves (AUROCs) for the ARR were 0.857 (CI 95%: 0.797-0.902) vs. 0.912 (CI 95%: 0.876-0.938) for females and males respectively. Using liquid chromatography mass spectrometry measurements (LC-MS/MS) of aldosterone, an ARR cut-off of 21.75 pmol/L yielded a sensitivity of 93% with only 45% specificity in females, while for males, a specificity of 66% was obtained for a sensitivity of 97.7%. This meant for females having a higher risk of false-positive screening results (OR 2.36 (CI 95%: 1.65-3.41)), even after excluding patients on OC or HRT (OR 2.17 (CI 95%: 1.5-3.17)). We derived a renin- and sex-dependent formula for the calculation of aldosterone cut-offs, which improved diagnostic accuracy for both males and females (ΔAUROC = 0.05 and 0.045, P < 0.0001 and 0.02 respectively): for a diagnostic sensitivity of 94-95%, specificity was improved to 61% in females and 82% in males. Conclusion Lower renin in females without PA leads to higher ARRs and thus a higher risk of false-positive screening results. Higher overlap of the ARR between females with and without PA compared to their male counterparts weakens utility of the ARR for discrimination of patients with and without PA. Sex- and renin-specific aldosterone cut-offs for screening for PA offer improved diagnostic accuracy. Diagnostic accuracy remains however superior in males, which highlights the need for further optimization of diagnostic procedures specifically in women.

Is Screening for Primary Aldosteronism Always the Best Option?

Is Screening for Primary Aldosteronism Always the Best Option?

EXPLORATION OF SCREENING FOR PRIMARY ALDOSTERONISM BY IMMUNOHISTOCHEMISTRY IN PATIENTS WITH ADRENAL SURGERY IN CHINESE

Objective: Primary aldosteronism (PA) is common secondary hypertension, however, the screening rate for PA is not entirely satisfactory. This study aimed to use immunohistochemical staining for retrospective analysis of screening for PA in patients with adrenal surgery in Chinese to improve the screening rate of PA. Design and method: A total of 101 patients who were diagnosed with adrenal tumors and treated with adrenalectomy were collected. Immunohistochemical staining for anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies was performed on postoperative specimens. Analysis of staining results according to the expert consensus on the histopathology of PA. Results: Of the 101 patients included, 25 (24.75%) patients had completed secondary hypertension screening before surgery. Of the remaining 76 (75.25%) patients, immunohistochemical staining was identified in 13 patients (12.87%) with PA and 4 patients (3.96%) with autonomous secretion of cortisol. Only APM or MAPM was seen in 42 patients (41.58%). APM and MAPM were used as a potential diagnostic basis leading to PA, and functional lesions were observed in postoperative pathology in 83.17% of patients. Still, 16.83% of patients did not show clear functional histopathology on pathological staining. The overall incidence of APM and MAPM was 64.36%. Increased prevalence of APM and MAPM in patients older than or equal to 50 years old compared to patients younger than 50 years old (67.14% versus. 58.06%) and in female patients compared to males (77.78% versus. 42.11%). There without a significant difference between different ages (χ2 = 0.772, P = 0.380) but there was a significant difference between genders (χ2 = 13.149, P < 0.001). Conclusions: The screening rate of PA before adrenalectomy was less than 1/4. More than 40% of patients had pathologically confirmed APM or MAPM without systematic PA screening. Meanwhile, 16.83% of patients undergoing adrenal surgery had no clear functional histopathological manifestations. The problem of inadequate screening for PA still exists. Immunohistochemistry by anti-CYP11B1 and anti-CYP11B2 monoclonal antibodies is an important tool in the pathological diagnosis of PA and will help identify potential autonomous secretion of aldosterone and guide improved screening for PA.

Insight into the status of plasma renin and aldosterone measurement: findings from 526 clinical laboratories in China.

Accurate measurements of renin and aldosterone levels play an important role in primary aldosteronism screening, which is of great importance in the management and categorization of hypertension. The objective of this studyis to investigate the current status of plasma renin and aldosterone measurements in China, which is achieved by analyzing the results of 526 clinical laboratories nationwide for three pooled fresh plasma samples derived from more than 2,000 patients. Renin and aldosterone in three pooled plasma samples were measured four times in 526 laboratories employing various measurement systems. The inter- and intra-laboratory %CV were calculated and compared. To determine the source of the substantial inter-laboratory %CV,laboratories were categorized according to the measurement systems they are using, and both the inter- and intra-measurement-system %CV were calculated and compared. Regarding renin, the majority of laboratories use four primary commercial immunoassays. However, for aldosterone, in addition to commercial immunoassays, laboratory-developed liquid chromatography-tandem mass spectrometry (LC-MS) methods are also used by laboratories. The median values of intra-laboratory %CVs, intra-measurement-system %CVs, inter-laboratory %CVs, and inter-measurement systems %CVs varied between 1.6 and 2.6 %, 4.6 and 14.9 %, 8.3 and 25.7 %, and 10.0 and 34.4 % for renin, respectively. For aldosterone, these values ranged from 1.4 to 2.2 %, 2.5-14.7 %, 9.9-31.0 %, and 10.0-35.5 %, respectively. The precision within laboratories and measurement systems for plasma renin and aldosterone measurements is satisfactory. However, the comparability between laboratories using different measurement systems remains lacking, indicating the long way to achieve standardization and harmonization for these two analytes.

Best Practice Alert to Promote Screening for Primary Aldosteronism Among People With Apparent Treatment-Resistant Hypertension

Guidelines recommend that all people with resistant hypertension should be screened for primary aldosteronism (PA). However, less than 2% of people with resistant hypertension are screened for PA. We aimed to develop a noninterruptive Best Practice Alert (BPA) and assess if implementation of the BPA in the electronic health record improved the screening rate for PA among people with apparent treatment-resistant hypertension (aTRH). We implemented a noninterruptive BPA on 9/17/2022 at our ambulatory primary care, endocrinology, nephrology, and cardiology clinics. We assessed clinical parameters of people with aTRH before (9/17/2021-9/16/2022) and after (9/17/2022-9/16/2023) the BPA was implemented. The noninterruptive BPA embedded with an order set identified people with aTRH and recommended screening for PA if it was not previously performed. There were 10 944 and 11 463 people with aTRH who attended office visits during the 12 mo before and after the BPA implementation, respectively. There were no statistically significant differences in median age (P = .096), sex (P = .577), race (P = .753), and ethnicity (P = .472) between the pre- and post- BPA implementation groups. There was a significant increase in PA screening orders placed (227 [2.1%] versus 476 [4.2%], P < .001), and PA screening labs performed (169 [1.5%] versus 382 [3.3, P < .001) after BPA implementation. PA screening tests were positive in 26% (44/169) and 23% (88/382) of people in the pre- and post-BPA groups, respectively (P = .447). In summary, implementation of a real-time electronic health record BPA doubled the screening rate for PA among people with aTRH; however, the overall screening rate was low.

Screening for Primary Aldosteronism by Mass Spectrometry Versus Immunoassay Measurements of Aldosterone: A Prospective Within-Patient Study.

Measurements of aldosterone by mass spectrometry are more accurate and less prone to interferences than immunoassay measurements, and may produce a more accurate aldosterone:renin ratio (ARR) when screening for primary aldosteronism (PA). Differences in diagnostic performance of the ARR using mass spectrometry vs immunoassay measurements of aldosterone were examined in 710 patients screened for PA. PA was confirmed in 153 patients and excluded in 451 others. Disease classifications were not achieved in 106 patients. Areas under receiver-operating characteristic curves (AUROC) and other measures were used to compare diagnostic performance. Mass spectrometry-based measurements yielded lower plasma aldosterone concentrations than immunoassay measurements. For the ARR based on immunoassay measurements of aldosterone, AUROCs were slightly lower (P = 0.018) than those using mass spectrometry measurements (0.895 vs 0.906). The cutoff for the ARR to reach a sensitivity of 95% was 30 and 21.5 pmol/mU by respective immunoassay and mass spectrometry-based measurements, which corresponded to specificities of 57% for both. With data restricted to patients with unilateral PA, diagnostic sensitivities of 94% with specificities >81% could be achieved at cutoffs of 61 and 52 pmol/mU for respective immunoassay and mass spectrometry measurements. Mass spectrometry-based measurements of aldosterone for the ARR provide no clear diagnostic advantage over immunoassay-based measurements. Both approaches offer limited diagnostic accuracy for the ARR as a screening test. One solution is to employ the higher cutoffs to triage patients likely to have unilateral PA for further tests and possible adrenalectomy, while using the lower cutoffs to identify others for targeted medical therapy.German Clinical Trials Register ID: DRKS00017084.

Testing for Primary Hyperaldosteronism in Resistant Essential Hypertensive Patients

Background: Hypertension is a common condition that affects many people all over the world. It could be associated with several complications especially in cases of resistant hypertension. Many clinical practice guidelines recommend screening for primary aldosteronism especially in persons with resistant hypertension owing to the worse prognosis when compared with blood pressure-matched essential hypertension. Objective: The study aimed to screen for primary aldosteronism in high-risk hypertensive Egyptian patients, and to determine the challenges faced in the diagnosis. Material and methods: 50 high-risk hypertensive patients were recruited from the Outpatient Endocrinology Clinic out of 200 hypertensive patients in the period from February 2019 and April 2021. Creatinine, Glycosylated hemoglobin (HBA1c), lipid profile, potassium level, sodium level, Plasma Aldosterone Concentration (PAC), Active Renin Concentration (ARC), and aldosterone/ Renin Ratio (ARR) were assessed in all patients. Results: A series of 50 hypertensive patients screened for PA (26 females and 24 males) with a mean age of 41.88±11.91 SD. We found that 41(82%) patients were receiving antihypertensive medications and 9(18%) patients didn’t receive treatment for hypertension previously. 9(18%) patients kept on no treatment, 6(12%) patients were kept on the same anti-hypertensive medications, and 35(70%) of them were shifted to other anti-hypertensive drugs. 4 patients out of total 50 patients had a positive ARR (&gt;46), while 13(26%) patients out of total 50 hypertensive patients had low renin levels. There was a statistically significant relation between serum Aldosterone/ Renin Ratio (ARR) and serum Potassium (K) with P-value=0.001 (Figure 4), also a statistically significant relation between serum aldosterone/ renin ratio (ARR) and (systolic blood pressure, diastolic blood pressure) with P-value=0.001 was found. Conclusion: We recommend routine screening for PA in high-risk hypertensive patients that could offer targeted treatment before adverse cardiovascular consequences develop.

Development of a diagnostic model for pre-washout screening of primary aldosteronism.

Primary aldosteronism (PA) diagnosis is affected by antihypertensive drugs that are commonly taken by patients with suspected PA. In this study, we developed and validated a diagnostic model for screening PA without drug washout. We retrospectively analyzed 1095 patients diagnosed with PA or essential hypertension. Patients were randomly grouped into training and validation sets at a 7:3 ratio. Baseline characteristics, plasma aldosterone concentration (PAC), and direct renin concentration (DRC) before and after drug washout were separately recorded, and the aldosterone-to-renin ratio (ARR) was calculated. PAC and ARR were higher and direct renin concentration was lower in patients with PA than in patients with essential hypertension. Furthermore, the differences in blood potassium and sodium concentrations and hypertension grades between the two groups were significant. Using the abbreviations potassium (P), ARR (A), PAC (P), sodium (S), and hypertension grade 3 (3), the model was named PAPS3. The PAPS3 model had a maximum score of 10, with the cutoff value assigned as 5.5; it showed high sensitivity and specificity for screening PA in patients who exhibit difficulty in tolerating drug washout. PA screening remains crucial, and standard guidelines should be followed for patients to tolerate washout. The PAPS3 model offers an alternative to minimize risks and enhance diagnostic efficiency in PA for those facing washout challenges. Despite its high accuracy, further validation of this model is warranted through large-scale clinical studies.

Prevalence of primary aldosteronism in acute stroke or transient ischemic attack: a systematic review and meta-analysis.

Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension with a prevalence of 14% in patients with newly diagnosed hypertension. Patients with PA experience a higher rate of cardiovascular events including stroke when compared to those with blood pressure matched essential hypertension. This systematic review and meta-analysis summarize current evidence on the prevalence of PA in patients with acute stroke or transient ischemic attack (TIA). Two reviewers independently reviewed the literature for observational studies on the prevalence of PA in patients with acute stroke or TIA. MEDLINE and Embase were searched for studies up to December 13, 2023. Three single center studies conducted in Japan, Singapore and China were found to meet the inclusion criteria. The reported prevalence of PA in two cohort studies of adults with stroke or TIA were 3.1% and 4.0% and a third cross-sectional study in adults under 45 years old revealed a prevalence rate of 12.9%. Following a meta-analysis, the pooled prevalence of PA in adults with stroke or TIA is 5.8% [95% CI 1.6%-12.3%]. A considerable proportion of patients with stroke or TIA may have PA as the underlying cause of their hypertension. Given the increased risk of stroke associated with PA, clinicians should consider screening for PA in hypertensive patients with stroke or TIA. Further research is needed to evaluate the effect of timing and interfering medications on test results, which will inform an evidence-based approach to testing for PA following TIA or stroke. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022328644.

Performance of aldosterone-to-renin ratio before washout of antihypertensive drugs in screening of primary aldosteronism.

The aim of this study is to evaluate performance of aldosterone-to-renin ratio (ARR) before washout of antihypertensive drugs as a screening test for primary aldosteronism (PA). This retrospective analysis included consecutive patients suspected of having secondary hypertension during a period from January 2017 to May 2022 at authors' institute. For inclusion in the final analysis, ARR must be available prior to as well as after discontinuation of antihypertensives. Patients with ARR ≥2.4(ng/dL)/(μIU/mL) after washout proceeded to confirmatory tests. Diagnosis of PA was established based on positive result of the confirmatory test. Diagnostic accuracy of ARR prior to the washout in predicting PA are shown as sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). The analysis included a total of 1306 patients [median age of 50.2 (41.0-59.0) years, 64.0% male]. Confirmatory tests showed PA in 215(16.5%) patients and essential hypertension (EH) in the remaining 1091(83.5%) patients. In comparison to the second screening test, the first screening test (before washout of antihypertensives) yielded lower plasma aldosterone and higher renin, and consequently lower ARR in both the PA and EH groups. At a cutoff of 0.7(ng/dL)/(μIU/ml), ARR before washout had 96.3% sensitivity, 61.2% specificity, 0.33 PPV and 0.99 NPV. At a lower cutoff of 0.5(ng/dL)/(μIU/ml), the sensitivity, specificity, PPV and NPV are 97.7%, 52.0%, 0.29 and 0.99. ARR prior to washout of antihypertensives is a sensitive screening test for PA. Washout of antihypertensives could be omitted and further investigation for PA is not warranted if ARR was ≤ 0.7(ng/dL)/(μIU/ml) before washout.

Optimizing the aldosterone-to-renin ratio cut-off for screening primary aldosteronism based on cardiovascular risk: a collaborative study

ABSTRACT Objectives Aldosterone-to-renin ratio (ARR) based screening is the first step in the diagnosis of primary aldosteronism (PA). However, the guideline-recommended ARR cutoff covers a wide range, from the equivalent of 1.3 to 4.9 ng·dl−1/mIU∙l−1. We aimed to optimize the ARR cutoff for PA screening based on the risk of cardiovascular diseases (CVD). Methods Longitudinally, we included hypertensive participants from the Framingham Offspring Study (FOS) who attended the sixth examination cycle and followed up until 2014. At baseline (1995–1998), we used circulating concentrations of aldosterone and renin to calculate ARR (unit: ng·dl−1/mIU∙l−1) among 1,433 subjects who were free of CVD. We used spline regression to calculate the ARR threshold based on the incident CVD. We used cross-sectional data from the Chongqing Primary Aldosteronism Study (CONPASS) to explore whether the ARR cutoff selected from FOS is applicable to PA screening. Results In FOS, CVD risk increased with an increasing ARR until a peak of ARR 1.0, followed by a plateau in CVD risk (hazard ratio 1.49, 95%CI 1.19–1.86). In CONPASS, when compared to essential hypertension with ARR < 1.0, PA with ARR ≥ 1.0 carried a higher CVD risk (odds ratio 2.24, 95%CI 1.41–3.55), while essential hypertension with ARR ≥ 1.0 had an unchanged CVD risk (1.02, 0.62–1.68). Setting ARR cutoff at 2.4 ~ 4.9, 10% ~30% of PA subjects would be unrecognized although they carried a 2.45 ~ 2.58-fold higher CVD risk than essential hypertension. Conclusions The CVD risk-based optimal ARR cutoff is 1.0 ng·dl−1/mIU∙l−1 for PA screening. The current guideline-recommended ARR cutoff may miss patients with PA and high CVD risk. Clinical Trial Registration ClinicalTrials.gov (NCT03224312)

Comparison of plasma aldosterone measured by chemiluminescence immunoassay and liquid chromatography-tandem mass spectrometry in screening test for primary aldosteronism

BackgroundWhether chemiluminescence immunoassay (CLIA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) for plasma aldosterone concentration (PAC) measurement can be used interchangeably in primary aldosteronism (PA) screening is still controversial. The purpose of this study was to compare CLIA to LC-MS/MS for PAC measurement in PA screening. MethodsAll participants underwent aldosterone-to-renin ratio (ARR) testing. PA was diagnosed by captopril challenge test or saline infusion test. PAC in screening test was measured with CLIA and LC-MS/MS. Plasma direct renin concentration in screening and confirmatory test was measured with CLIA. The concordance between CLIA and LC-MS/MS for PAC measurement in PA screening was analyzed. ResultsTwenty-one healthy volunteers, 61 patients with essential hypertension (EH) and 43 PA patients were enrolled. Median PAC by CLIA was 84.7 % higher than that by LC-MS/MS in screening test (P < 0.001). A positive correlation of PAC was observed between the two assays (Pearson r coefficient 0.770, P < 0.001). When ARR was used in differentiating PA from EH, there was no difference in the area under the receiver operating characteristic curve between CLIA and LC-MS/MS for PAC measurement (0.968 vs 0.950, P = 0.249). ConclusionCLIA and LC-MS/MS for PAC measurement exhibited high and comparable efficacy in PA screening. CLIA is a reliable and feasible alternative in PA screening test.

Evaluation of a Best-Practice Advisory for Primary Aldosteronism Screening

Primary aldosteronism (PA) is a common cause of secondary hypertension and an independent risk factor for cardiovascular morbidity and mortality. Fewer than 2% to 4% of patients at risk are evaluated for PA. To develop and evaluate an electronic health record best-practice advisory (BPA) that assists with PA screening. This prospective quality improvement study was conducted at academic center outpatient clinics. Data analysis was performed between February and June 2023 and included adults with hypertension and at least 1 of the following: 4 or more current antihypertensive medications; hypokalemia; age younger than 35 years; or adrenal nodule(s). Patients previously tested for PA were excluded. A noninterruptive BPA was developed to trigger for PA screening candidates seen in outpatient setting by clinicians who treat hypertension. The BPA included an order set for PA screening and a link to results interpretation guidance. (1) The number of PA screening candidates identified by the BPA between October 1, 2021, and December 31, 2022; (2) the rates of PA screening; and (3) the BPA use patterns, stratified by physician specialty were assessed. Over 15 months, the BPA identified 14 603 unique candidates (mean [SD] age, 65.5 [16.9] years; 7300 women [49.9%]; 371 [2.5%] Asian, 2383 [16.3%] Black, and 11 225 [76.9%] White individuals) for PA screening, including 7028 (48.1%) with treatment-resistant hypertension, 6351 (43.5%) with hypokalemia, 1537 (10.5%) younger than 35 years, and 445 (3.1%) with adrenal nodule(s). In total, 2040 patients (14.0%) received orders for PA screening. Of these, 1439 patients (70.5%) completed the recommended screening within the system, and 250 (17.4%) had positive screening results. Most screening orders were placed by internists (40.0%) and family medicine physicians (28.1%). Family practitioners (80.3%) and internists (68.9%) placed most orders via the embedded order set, while specialists placed most orders (83.0%-95.4%) outside the BPA. Patients who received screening were younger and included more women and Black patients than those not screened. The likelihood of screening was higher among patients with obesity and dyslipidemia and lower in those with chronic kidney disease and established cardiovascular complications. The study results suggest that noninterruptive BPAs are potentially promising PA screening-assistance tools, particularly among primary care physicians. Combined with artificial intelligence algorithms that optimize the detection yield, refined BPAs may contribute to personalized hypertension care.

Hypertension in the emergency department: A missed opportunity to screen for primary aldosteronism?

Primary aldosteronism (PA) is a common but underdiagnosed secondary cause of hypertension. Emergency departments (EDs) often assess patients with severe hypertension or its sequelae, some of whom have underlying PA. We aimed to determine the proportion of patients presenting to the ED with hypertension who meet the Endocrine Society criteria for PA testing and the proportion who were screened. We performed a structured retrospective chart review of adults who presented to three EDs in an Australian tertiary health network between August 2019 and February 2020, with a coded presenting complaint of hypertension. Clinical parameters to determine whether the patients met the criteria for PA testing were extracted from electronic medical records. Of the 418 patients who presented to the EDs with documented elevated blood pressure (BP), 181 patients (43.3%) fulfilled PA screening criteria and nine patients (2.2%) underwent PA testing. Individuals who fulfilled screening criteria were older; had higher prevalence of Type 2 diabetes, coronary artery disease, and congestive heart failure; took more antihypertensive medications; and had lower estimated glomerular filtration rate. Individuals who were tested for PA were younger and had higher BP on presentation. Screening for PA was more frequent in patients who were referred to medical teams. As far as we are aware, our study is the first to evaluate PA testing in hypertensive patients who present to ED. More than 40% of adults presenting to the EDs with hypertension met the current criteria for testing for PA but only few were tested. These results emphasize that increased awareness of PA in the ED is needed to encourage opportunistic testing, referral, and treatment, especially in patients who present with hypertensive emergencies. Prospective studies are required to determine the feasibility and effectiveness of this.

Diagnostic Delay and Disease Burden in Primary Aldosteronism: An International Patient Survey.

Primary aldosteronism (PA) is a common but underdiagnosed cause of hypertension. Many patients experience preventable end-organ injury due to delayed or missed diagnosis but data on the experience of patients are limited. We evaluated the lived experience of PA and determines factors associated with diagnostic delay through an international anonymous online cross-sectional survey, codesigned by researchers and PA consumers. We distributed the survey through academic medical centers, Amazon Mechanical Turk, Twitter, PA patient advocacy groups, and hypertension support groups on Facebook between March 21 and June 5, 2022. Of 684 eligible respondents, 66.5% were women. Diagnostic delay (defined as ≥5 years between the diagnosis of hypertension and PA) was reported in 35.6%. Delay was more likely in women than in men (odds ratio, 1.55 [95% CI, 1.10-2.20]) and respondents with ≥3 comorbidities versus none (odds ratio, 1.77 [95% CI, 1.05-3.02]), ≥10 symptoms versus none (odds ratio, 2.73 [95% CI, 1.74-4.44]), and on ≥4 antihypertensive medications versus none (odds ratio, 18.23 [95% CI, 6.24-77.72]). Three-quarters of patients (74.4%) experienced reduced symptom burden following targeted PA treatment. Quality of life improved in 62.3% of patients, and greater improvement was associated with being a woman (odds ratio, 1.42, [95% CI, 1.02-1.97]), receiving adrenalectomy (odds ratio, 2.36 [95% CI, 1.67-3.35]), and taking fewer antihypertensive medications following diagnosis (odds ratio, 5.28 [95% CI, 3.55-7.90]). One-third of patients with PA experienced prolonged diagnostic delays. Targeted treatment led to reduced symptom burden and improved quality of life. Gender differences in diagnostic delay and symptom burden are prominent. These findings suggest that routine screening for PA at the onset of hypertension may reduce diagnostic delay and facilitate timely diagnosis.

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.

National Rates of Primary Aldosteronism Screening in Patients with CKD

National Rates of Primary Aldosteronism Screening in Patients with CKD

Development of a risk-prediction model for primary aldosteronism in veterans with hypertension

BackgroundRates of screening for primary aldosteronism in patients who meet the criteria are exceedingly low (1%–3%). To help clinicians prioritize screening in patients most likely to benefit, we developed a risk-prediction model. MethodsUsing national Veterans Health Administration data, we identified patients who met the criteria for primary aldosteronism screening between 2000 and 2019. We performed multivariable logistic regression to identify characteristics associated with positive primary aldosteronism testing before generating a risk-scoring system based on the coefficients (0< β < 0.5 = 1 pt, 0.5 ≤ β < 1 = 2 pts, 1 ≤ β < 1.5 = 3 pts) and then tested the system performance using an internal validation cohort. ResultsWe identified 502,190 patients who met primary aldosteronism screening criteria, of whom 1.6% were screened and 15% tested positive. Based on the regression model, we generated a risk-scoring system based on a total of 9 possible points in which age under 50, absence of smoking history, and resistant hypertension each scored 1 point; elevated serum sodium 2 points; and hypokalemia 3 points. Rates of positive screening increased with risk score, with 5.6% to 6.7% of those scoring 0 points testing positive; 7.9% to 9.0% 1 point; 8.6% to 10% 2 points; 13% to 14% 3 points; 21% 4 points; 22% to 38% 5 points; 27% to 38% 6 points; 42% to 49% 7 points; and 50% to 51% ≥8 points. ConclusionIn hypertensive patients who meet the criteria for primary aldosteronism screening, rates of positive screening range from 5.6% to 51%. Use of our risk-predication model incorporating these factors can identify patients most likely to benefit from testing.

Who and How Should We Screen for Primary Aldosteronism?

There are mounting data that at least 30% of hypertensives who are appropriately screened have primary aldosteronism (PA), rather than the commonly reported figure of 5% to 10%. Second, there are similar data that undertreated patients with PA have a 3-fold higher risk profile than essential hypertensives with the same blood pressure levels. Third, clinicians managing hypertension measure success as sustainable lowering of blood pressure; untreated hypertensive patients with PA are thus in double jeopardy. Finally, and crucially, fewer than 1% of patients with hypertension are ever screened-let alone investigated-for PA. Accordingly, for "Who should we screen?" the answer is simple-all patients with hypertension. For "How they should be screened?" the answer is also simple-add spironolactone 25 mg/day for 4 weeks and measure the blood pressure response. In established hypertension, a fall of <10 mm Hg means PA is unlikely; above 12 mm Hg PA, it is probable. Newly presenting hypertension is much the same-hold off on first-order antihypertensive(s) and prescribe spironolactone 25 mg/day for 4 weeks. If blood pressure falls into the normal range, continue; if it does not, prescribe a standard antihypertensive. It is likely that the above protocols-a first start, amenable to refinement-will find additional hypertensives with unilateral PA; it is probable that the overwhelming majority will have bilateral disease. What this means is that we have a major public health issue on our hands: how can this be the case?

FRI123 Development And Impact Of A Best Practice Alert For Primary Aldosteronism Screening

Abstract Disclosure: S. Charoensri: None. L. Bashaw: None. C. Dehmlow: None. T. Ellies: None. A.F. Turcu: None. Background: Primary aldosteronism (PA) is a common cause of secondary hypertension, affecting up to 25% of patients with treatment-resistant hypertension. PA amplifies the risk of cardiovascular morbidity and mortality above that of equivalent primary hypertension. Despite this, &amp;lt;3% of candidates for PA screening are ever evaluated, including in academic centers with facile access to all required resources for PA subtyping and treatment. Clinical decision support tools, such as best practice alerts (BPA), can leverage electronic medical records technology to support health care delivery improvement efforts. Intervention and Measurements: In collaboration with institutional Informational Technology services, we developed an algorithm that identifies PA screening candidates as adult patients with hypertension and one of the following criteria: ≥ 4 current antihypertensive medications; age &amp;lt; 35 years; hypokalemia (defined by potassium supplements or low serum potassium in the past year); or adrenal mass on problem list. The algorithm excluded patients who had both plasma aldosterone and renin measurements within the past 5 years. A non-disruptive BPA to suggest PA screening was constructed and set to trigger in patients meeting inclusion and exclusion criteria when evaluated in outpatient setting by clinicians who treat hypertension, including Internists, Family Practitioners, Cardiologists, Nephrologists, and Endocrinologists. An order set for PA screening and a link to results interpretation guidance were also embedded within the BPA. The BPA was first piloted between Aug-Sept 2021, and then launched on October 1st, 2021. We assessed the number of unique patients identified by the BPA between Oct 1st, 2021- Dec 14th, 2022, stratified by PA screening indications; attitude towards the BPA; and number of patients who received PA screening orders. Results: In total, the BPA identified 14,443 unique candidates for PA screening, including: 6944 patients with treatment-resistant hypertension; 6583 patients with hypertension and hypokalemia; 1527 patients with hypertension &amp;lt;35 years; and 444 with hypertension and an adrenal mass. During the same time frame, 3614 (25%) patients received orders for plasma aldosterone and renin. Patients tested were on average 57 +/-17 years old, 2000 (55.3%) were women, 2573 (71.2%) were White, 712 (19.7%) Black, and 105 (2.9%) Asian. Of new orders, 1364 (37.7%) were placed by Internists, 685 (18.9%) by Family Medicine physicians, 559 (15.5%) by Endocrinologists, 235 (6.5%) by Cardiologists, and 50 (1.4%) by Nephrologists. Family Practitioners and Internists placed most orders via the embedded BPA order set (66.6% and 46.3%, respectively), while Endocrinologists placed 98.6% of the orders outside of the BPA order set. Conclusions: Non-disruptive BPAs enhance the rates of PA screening, particularly among Internists and Family Practitioners. Presentation: Friday, June 16, 2023