Screening For Primary Aldosteronism Research Articles

FRI147 A Direct-To-Patient Primary Aldosteronism Screening Program In The United States: Implementing Guidelines Nationwide

Abstract Disclosure: J.M. Brown: Consulting Fee; Self; Bayer, Inc. B. Bacare: None. Y.M. Niebuhr: None. L.C. Tsai: None. E.E. Abel: None. B. Honzel: None. A. Vaidya: Consulting Fee; Self; Corcept Therapeutics, HRA Pharmaceuticals, Mineralys. Context: Primary aldosteronism (PA) is a prevalent but grossly underrecognized contributor to the global burden of hypertension, excess cardiovascular and renal disease, and death. Though Endocrine Society guidelines recommend high risk populations who should be screened for PA, fewer than 2% of these at-risk patients are ever tested. Given the poor rates of routine screening within guideline-eligible populations, we designed and implemented a direct-to-patient virtual-based PA screening intervention. Methods: Participants with one or more guideline indications for PA screening were recruited using social media, online recruitment platforms, and online patient portals to participate in a video visit to review medical history and to arrange a local reference lab draw for plasma renin activity (PRA), aldosterone (via LC-MS/MS), and a basic metabolic panel, without adjustment of medications. Screening results were categorized as “Likely Confirmed PA”, “Possible PA”, or “Unlikely PA” based on established diagnostic frameworks. Test results, their interpretations, and possible next clinical steps (i.e., further testing, referral, empiric treatment) were communicated directly to patients and their primary care providers, with annual reminders and follow-up. Results: To date, 3220 participants from 12 states in the eastern USA had been contacted, with 2504 eligible. At the time of submission, 212 participants had completed laboratory assessment, with the remainder pending. 79 (37.3%) participants had resistant hypertension, 95 (44.8%) had hypertension with hypokalemia, 75 (35.4%) had hypertension with sleep apnea, 11 (5.2%) had hypertension with adrenal mass, and 90 (42.5%) had hypertension with a family history of early hypertension and/or stroke. Indicated PA screening had not previously been performed despite access to specialist care: 55% had an endocrinologist, cardiologist, and/or nephrologist. 27.4% of the participants had screening results consistent with either “likely confirmed PA” (7.1%) or “possible PA” (20.3%). Of those with both resistant hypertension and hypokalemia, 35.0% met criteria for “likely confirmed” or “possible” PA. A “likely confirmed” diagnosis of PA was associated with a median aldosterone-to-renin ratio of 33 ng/dL per ng/mL/h [IQR: 24, 76] and prevalent cardiometabolic comorbidities (33.3% had diabetes, 20.0% coronary artery disease, 13.3% heart failure). Conclusions: This ongoing, prospective, virtual-based, direct-to-patient PA screening program identified confirmed or possible PA in up to 27.4% of guideline-eligible participants. By reaching patients directly, rather than relying on routine clinical screening that is known to be dramatically underutilized, this study highlights the unrecognized prevalence of PA and demonstrates a novel approach to identifying this common, morbid, and treatable condition across the USA. Presentation: Friday, June 16, 2023

Screening for primary aldosteronism on and off interfering medications.

To determine whether antihypertensives will affect diagnostic accuracy of the aldosterone-to-renin ratio (ARR) to an extent that is clinically relevant. Confirmatory tests were used to confirm or exclude PA diagnosis. Area under the receiver operating characteristic curve (AUC), specificity and sensitivity of ARR performance in different conditions were calculated. 208 PA and 78 essential hypertension (EH), and 125 PA and 206 EH patients, were included in the retrospective and prospective cohort, respectively. AUC of ARR on interfering medications was comparable to ARR off interfering medications (retrospective: 0.82 vs. 0.87, p = 0.20; prospective: 0.78 vs. 0.84, p = 0.07). At a threshold of 20 pg/μIU, the sensitivity of ARR on interfering medications was lower (11.1-23.2%) while the specificity was higher (10.2-15.2%) than ARR off interfering medications. However, when the ARR threshold on interfering medications was lowered to 10 pg/μIU, both the sensitivity (retrospective: 0.91 vs. 0.90, p = 0.61; prospective: 0.86 vs. 0.82, p = 0.39) and specificity (retrospective: 0.49 vs. 0.59, p = 0.20; prospective: 0.58 vs. 0.66, p = 0.10) were comparable to the ARR threshold off interfering medications. Using ARR to screen for PA whilst taking interfering antihypertensive drugs is feasible in most cases, but the ARR threshold needs to be reduced. ClinicalTrials.gov identifier: NCT04991961.

THU591 HyperAldosteronism In Pregnancy Predicted Impacts (H.A.P.P.I.): A Retrospective Cohort Study

Abstract Disclosure: D. Oprea: None. F. Lefrançois: None. A.C. Côté: None. M. Roy-Lacroix: None. M. St-Jean: None. N. Sauvé: None. Introduction: Hypertensive disorders of pregnancy (HDP) are increasing worldwide and are associated with a high rate of maternal and fetal morbidity and mortality. Primary aldosteronism (PA) is a frequent and reversible cause of secondary hypertension in young non-pregnant women (18%) (1). Until now, no studies have detailed the prevalence, nor the outcomes associated with PA during pregnancy. Research Question: In HDP, are cases of PA associated with different impacts on maternal-fetal health compared to pregnant women without PA? Methods: This retrospective cohort study compared 252 pregnancies according to their PA status. We included pregnancies that were followed at the Centre Hospitalier Universitaire de Sherbrooke (CHUS) between 2011 and 2022, and who had had an aldosterone/renin ratio (ARR) screening for PA, in a five-year period before or after the analyzed pregnancy. Monofetal and twin pregnancies were included. Concomitant diagnoses of pheochromocytoma, hyperthyroidism or Cushing syndrome were excluded. The primary objective of this study was to describe the occurrence of HDP in women with PA. Secondary objectives were to describe maternal, fetal and neonatal outcomes and compare them according to PA status. Results: Among 252 pregnancies, 15 were diagnosed with a PA (concerning 12 women). Our preliminary analysis showed a greater prevalence of advanced maternal age (53.3% vs 24.5, p = 0.028) and Afro-American ethnicity (60.0 % vs 10.1%, p < 0.001) in the PA group, in addition to a tendency towards class I obesity (40.0% vs 13.1%, p = 0.166) in this group. There were no differences in terms of prevalence of chronic hypertension (26.7% vs 25.7 %, p = 0.936), delivery mode and overall fetal morbidity and mortality. Although not statistically significant, preeclamspia tended to be more frequent (40.0% vs 27.0%, p = 0.276) and gestational hypertension less frequent (0.0 % vs 16.0%, p = 0.092) during pregnancy in the PA group. 40.1% (vs 19.0%, p = 0.052) of PA-associated HDP were diagnosed in post-partum (including 33.4 % of preeclampsia in this group) and required intravenous hypertensive treatment (40.0% vs 23.2%, p = 0.209). Also, 13.3% of pregnancies in the PA group (vs. 3.0 %, p = 0.093) required hospitalization at the intensive care unit (ICU). All cases of PA were diagnosed within 5 years pre-conception or post-partum. Conclusion: Pregnancies with PA diagnosis within a five-year period tended to present more frequently with HDP as preeclampsia, especially in the post-partum period, and often required more intensive antihypertensive treatment and ICU hospitalization. The upcoming second prospective phase of this study will better assess the prevalence of PA in pregnant women experiencing HDP. Reference: (1) Alam S. et al., Clin Endocrinol, June 2021;94(6):895903. Presentation: Thursday, June 15, 2023

THU587 High Prevalence Of Primary Aldosteronism Diagnosis In Patients With Papillary Thyroid Cancer And Hypertension: A Cross-sectional Case-control Study

Abstract Disclosure: A.W. Maciel: None. T. Freitas: None. D.L. Danilovic: None. G.F. Fagundes: None. F. Freitas-Castro: None. L. Santana: None. A. Guimaraes: None. A. Pio-Abreu: None. J. V. Silveira: None. F. Consolim-Colombo: None. L. Bortolotto: None. M.C. Fragoso: None. A. Latronico: None. L. Drager: None. B.B. Mendonca: None. A.O. Hoff: None. M.Q. Almeida: None. Introduction: Aldosterone excess can cause oxidative stress leading to DNA damage in vitro and in vivo. Single case reports demonstrated a coincidence of primary aldosteronism (PA) with different malignancies. A higher prevalence of thyroid nodules and non-toxic multinodular goiter was described in patients with PA compared to those with essential hypertension (HT). A single study showed an association between PA and papillary thyroid cancer (PTC), but without a paired control group. Objective: To assess PA prevalence in a transversal cohort of patients with PTC and HT compared to a paired control group with HT. Methods: In this cross-sectional case-control study, PA was investigated in all patients with PTC and HT (n= 114), regardless of HT severity, under active surveillance at a cancer institute from 2019 to 2022. The control group included 228 (2:1) age-, sex- and body mass index (BMI)-matched individuals from a retrospective cohort of HT previously investigated for PA from 2011 to 2022. Serum aldosterone and plasma direct renin concentrations were measured by a chemiluminescent immunoassay. A positive PA screening was defined by aldosterone ≥10 ng/dL and aldosterone to renin ratio ≥2 ng/dL/μUI/mL. Results: Age, sex and BMI were not statistically different between PTC and control groups, respectively (age 59.8 ± 12 vs. 58.9 ± 12.3 yrs, p= 0.67; 79% vs. 81% women, p= 0.67; BMI 30.7 ± 5.8 vs. 30.8 ± 6.5 Kg/m2, p= 0.98). PA was diagnosed in 35 out of 114 PTC patients with HT. The prevalence of PA in the PTC group (30.5%, confidence interval (IC) 22.6%-40.1%) was significantly higher when compared to the paired control group with HT (11.84%, CI 8.08%-16.93%; p< 0.0001). Although PA prevalence was higher in the PTC group, only 20.2% had stage 3/resistant HT (vs. 38% in the control group, p= 0.003). The number of anti-hypertensive medications was lower in the PTC group compared to controls (2 drugs, 1 to 3 vs. 4 drugs, 3 to 5, respectively; p< 0.001). When analyzing only PA patients in both groups, frequency of stage 3/resistant HT and number of medications were lower in the PTC group (p< 0.001 and p< 0.001, respectively). Although HT was more severe in PA patients without PTC, aldosterone and renin levels were not different in PA patients from PTC and control groups, respectively (p= 0.15 and p= 0.34). Conclusion: PA prevalence was strikingly high among patients with PTC and HT, supporting the recommendation of PA screening in this patient group, regardless of HT severity. Presentation: Thursday, June 15, 2023

THU589 Positivity Rates Of Screening Criteria For Primary Aldosteronism: A Cohort Comparison Study

Abstract Disclosure: M. Marcelli: None. A. Panov: None. C. Bi: None. J.W. Funder: None. M.J. McPhaul: None. Current screening for primary aldosteronism (PA) relies on a single blood draw for plasma aldosterone concentration (PAC) and plasma renin activity (PRA) to establish an aldosterone-to-renin ratio (ARR). However, ARR cutoff levels vary between expert centers. Many studies have demonstrated that PAC may not represent a patient’s actual aldosterone status, suggesting the possible fallibility of the ARR. To investigate this possibility, we compared the positivity rates of 2 indicators of probable PA—ARR>28.9 and suppressed renin (PRA<1 ng/ml/hr)—in a cohort of 38,507 paired PAC and PRA samples. For each indicator, we also assessed positivity rates by self-reported sex (20578 [53.5%] women, 17882 [46.5%] men). Of the cohort, 1623 (4.2%) tested positive for possible PA based on an ARR of 28.9; 19551 (50.8%) tested positive for suppressed renin. Among the latter group, 2585 (6.7%) had PAC>15 ng/dL, 8465 (22%) between 5-15 ng/dL, and 8501 (22.1%) < 5 ng/dL. A recent algorithm suggested by Vaidya (1) defines the first of these groups as overtly positive screening and the second, intermediate group as positive screening, for a total positivity rate of 28.7%. Given the suppressed renin, there are probably a handful of positive PA cases, even in the 22.1 % group with PAC<5 ng/dL. A second finding was that rates of probable PA differed by sex. These differences were minor for the ARR criterion (4.3% of women vs. 4.1% of men tested positive) but major for the suppressed renin criterion with PAC>15 ng/dL (5.7% of women vs. 7.9% of men tested positive) and 5-15 ng/dL (23.6% of women vs. 20.2 of men tested positive). Florid PA was the only condition where more males than females tested positive, a finding deserving further expert consideration and study. In comparing two indicators of probable PA, the ARR criterion yielded a lower positivity rate than the suppressed renin criterion, suggesting that most PA cases may remain undetected if using AAR as a screening test.Reference: (1) JCEM 2020;105:3771 Presentation: Thursday, June 15, 2023

THU607 Improving Screening For Primary Aldosteronism Among People With Apparent Treatment Resistant Hypertension

Abstract Disclosure: K. Zekarias: None. K. Tessier: None. J. Kohlenberg: None. Introduction: The screening rate for primary aldosteronism (PA) is low among people with resistant hypertension. People with PA experience significantly more cardiovascular complications than those with primary hypertension and an equivalent degree of blood pressure control1. Therefore, identification of people with PA for early-directed therapy is crucial. Objective: We aimed to improve the screening rate for PA among people with apparent treatment resistant hypertension (aTRH), defined as blood pressure >140/90 despite the concurrent use of three antihypertensive drug classes or any person with hypertension on >4 antihypertensive medications. Methods: Using an electronic medical record (EMR) best practice alert (BPA), we implemented a quality improvement (QI) program from 9/17/2022-3/16/2023. We included adults ≥18 years of age with aTRH, who were identified using ICD codes, the last three blood pressure measurements and the antihypertensive medication list. During office visits with nephrologists, cardiologists, endocrinologists, family medicine physicians, and internists, a BPA notified providers if the person with aTRH had not been previously screened for PA with plasma aldosterone and plasma renin activity. The alert defined aTRH, suggested that screening be performed regardless of active medications, and contained an order set for plasma aldosterone, plasma renin activity, and plasma potassium. Furthermore, the BPA suggested referral to an endocrinologist if the patient fulfilled criteria for positive case detection for PA, defined as plasma renin activity < 1 ng/mL/hour and plasma aldosterone concentration (PAC) > 10 ng/dL or the plasma aldosterone to renin ratio (ARR) > 30 with PAC > 10. We compared the PA screening rate after the implementation of the BPA to the PA screening rate over the 1 year prior to the BPA implementation (9/16/2021-9/16/2022). Results: Plasma aldosterone lab orders were placed for 3.4% (179/5,261) of people with aTRH post-BPA implementation compared to 1.9% (211/10,944) pre-BPA implementation (p<0.01). Positive case detection for PA occurred in 25% (38/152) of people screened post -BPA implementation compared to 27% (47/173) pre-BPA implementation (p=0.66). People with aTRH who were younger (p<0.01) were more likely to be screened for PA pre-BPA implementation and this did not change post-implementation. Conclusion: Implementation of a QI program employing a BPA with an embedded order set in the EMR improved the screening rate for PA among adults with aTRH. Reference 1. Monticone S, D'Ascenzo F, Moretti C, Williams TA, Veglio F, Gaita F, Mulatero P. Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2018 Jan; 6 (1):41-50. Presentation: Thursday, June 15, 2023

Abstract 137: Trends In Primary Aldosteronism Screening - An Underutilized Test In Hypertension

Previous studies have shown low screening rates for primary aldosteronism (PA) in at-risk hypertensive (HTN) patients. However, the impact of recent HTN guidelines on screening has not been thoroughly evaluated. Therefore, we retrospectively reviewed adults with new diagnosis of HTN seen in outpatient clinics between 1/1/2015 and 12/31/2020. We included patients with BP ≥140/90 mmHg for 2 consecutive visits or had HTN ICD codes. Patients were categorized into Stage-2 HTN or greater (BP ≥140/90 mmHg) and apparent resistant HTN (aRHTN) defined as uncontrolled BP (≥130/80 mmHg) on 3 anti-HTN drugs including a diuretic or controlled BP on ≥4 drugs based on 2018 ACC/AHA resistant HTN guidelines. A total of 34,384 patients were included with mean age 61±14 years, 53% (18,384) women, 17% (5,693) Black individuals, with 2.5 years of median follow-up. As shown in Figure 1, the PA screening rates over time ranged 1-2% and 4-6% in Stage-2 HTN or greater (A), and aRHTN (B), respectively. Moreover, rates of PA screening index by year were not increased after the launch of the 2018 ACC/AHA guidelines, for both categories. Interestingly, the proportion of PA screening did not change during the COVID-19 pandemic despite the reduction in number of patients seen in 2020. In conclusion, the rate of PA screening has not increased in the hypertensive population even after the guidelines demonstrate the need for screening in these at-risk patients. These findings highlight the underutilization of PA screening and calls for increased awareness of the disease in at-risk populations.

Abstract P101: Clinical Risk Prediction Scores For Primary Aldosteronism

Introduction: Primary aldosteronism (PA) is a common and often underdiagnosed secondary cause of hypertension with cardiovascular, kidney, and metabolic disease rates far in excess of essential hypertension matched for blood pressure levels. Current clinical scoring algorithms could reduce patient and healthcare burdens associated with expanded PA screening but have not been extensively validated in external cohorts. Methods: We evaluated six PA scoring algorithms in two populations of patients seen in the Southern Illinois University (SIU) Hypertension clinic: all patients screened for PA where a negative screen was assumed to rule out PA without further testing (n = 592) and only screen positive patients with subsequent confirmatory testing (n = 90). Area under the receiver operating characteristic curve (AUC) was used to determine their overall performance predicting PA. Negative predictive value (NPV) was used to assess the ability to identify patients with a low probability of PA. Results: Only one score showed an acceptable ability to predict PA (AUC > 0.7). NPV was inflated in the all screen cohort compared to confirmatory testing, where known status yielded low NPV for all scores. Conclusion: Currently available scoring algorithms poorly predict those with PA under current diagnostic guidelines. Equating a negative screen with a negative confirmatory test, as was common in score development, artificially inflates the NPV of these scores. Scores show limited utility in identifying screen positives that do not need to undergo further evaluation. More accurate PA risk prediction scores are needed to guide decision-making in patients suspected of having PA.

Distribution characteristics of plasma renin concentration in patients with aldosterone-producing adenoma

Objective: To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis. Methods: In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed. Results: The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 2<PRC≤4 mU/L. PRC was not suppressed (PRC>8.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome. Conclusions: Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

How should anti-hypertensive medications be adjusted before screening for primary aldosteronism?

Anti-hypertensive medications may affect plasma renin activity and/or plasma aldosterone concentration, misleading the interpretation of the aldosterone-to-renin ratio when screening for primary aldosteronism. The Task Force of Taiwan PA recommends that, when necessary, using α-adrenergic receptor blocking agents, centrally acting α-adrenergic agonists, and/or non-dihydropyridine calcium channel blockers should be considered to control blood pressure before screening for PA. We recommend temporarily holding β-adrenergic receptor blocking agents, mineralocorticoid receptor antagonists, dihydropyridine calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and all diuretics before screening for PA. Further large-scale randomized controlled studies are required to confirm the recommendations.

A Novel Enzymatic Hydrolysis Method for Urine Aldosterone Quantification: A Case for Reassessing Clinical Cut-Offs of Primary Aldosteronism.

Primary aldosteronism (PA) is a common endocrine cause of secondary hypertension. The aldosterone/renin ratio is an important tool for PA screening, and dynamic testing in serum or urine is used to confirm the diagnosis. While LC-MS/MS is considered the gold standard for testing, there is significant interlaboratory variability between the extraction procedures, which can impact diagnostic interpretation. To help overcome this, we present a simple and accurate LC-MS/MS method for the quantification of both serum and urine aldosterone using a novel enzymatic hydrolysis procedure. Serum and urine aldosterone was extracted and measured by LC-MS/MS. Urine-conjugated aldosterone glucuronide was hydrolyzed using a genetically modified glucuronidase enzyme. The assay precision, accuracy, limit of quantification, recovery, and carryover were evaluated and the new assay cut-offs were proposed. The liquid chromatography method allowed for adequate separation of the aldosterone peak from closely eluting peaks. Significant in vitro aldosterone loss was observed during acid-catalyzed hydrolysis of urine, which was corrected with the addition of the internal standard to the urine before the hydrolysis step. Glucuronidase catalyzed hydrolysis of urine aldosterone glucuronide displays good correlation with the corrected acid-catalyzed hydrolysis. Serum aldosterone showed good agreement with reference values and the consensus range reported for external quality assessment specimens. A simple, fast, and highly accurate method for the detection of serum and urine aldosterone has been developed. The proposed novel enzymatic procedure allows for short hydrolysis time and compensates for urine aldosterone loss during the hydrolysis step.

SCREENING RATES FOR PRIMARY ALDOSTERONISM ARE UNSATISFACTORY EVEN IN HYPERTENSION EXCELLENCE CENTERS. A CALL FOR COMPULSORY SCREENING FOR ALL HYPERTENSIVE PATIENTS

Objective: The Endocrine Society guidelines recommend screening for primary aldosteronism (PA) in high risk hypertensive patients. These include patients with sustained blood pressure (BP) above 150/100 mmHg, patients with resistant hypertension (HTN), hypertensive patients with spontaneous or diuretic-induced hypokalemia, adrenal incidentaloma, sleep apnea, family history of early onset HTN or cerebrovascular accident at a young age and all hypertensive first-degree relatives of patients with PA. Even though guidelines are clear and screening is simple, compliance rates among clinicians are extremely low ranging between 0.1% to 2.7%. This results in underdiagnosis of early disease, leading to an enormous extra-burden of advanced chronic kidney disease, heart failure, atrial fibrillation, and stroke. We aimed to examine the screening rate, according to the abovementioned guidelines, at our recently recognized Hypertension Excellence Center in Assuta Ashdod University Hospital. Design and method: A retrospective cohort study. We analyzed all hypertensive patients, eligible for screening between 01/18 and 12/20. We calculated screening rates and in univariate and multivariate regression analyses, looked at parameters that influence screening. Results: Of 661 patients over 18 years of age with HTN, 218 patients (33%) met the Endocrine Society guidelines for PA screening. However only 46 of them (21.1%), were referred for screening. A multivariate regression analysis, demonstrated that advanced age and male gender were associated with lower rates of screening referral. Odds ratio for age was 0.945 for every year (95% CI 0.915-0.975). Conclusions: A 21% screening rate in a Hypertension Excellence Center, although higher than prior published studies, suggests that many cases of PA are likely missed, more often in elderly population in whom adrenal micro as well as macronodular-hyperplasia is extremely common and can be the cause of secondary HTN. We therefore advocate for PA screening at least once of all hypertensive patients, preferably before the patient is started on multiple anti-hypertensive medications. This should be done regardless of patients’ age and gender, as the absolute risk for cardiovascular events in both hypertensive and PA patients increases with rising age, and treatment with mineralocorticoid receptor antagonists can be lifesaving.

PREGNANCY-RELATED COMPLICATIONS IN PRIMARY ALDOSTERONISM: A EUROPEAN SURVEY

Objective: Hypertensive pregnancy disorders, affecting 4 - 25% of pregnancies according to countries’ income, represent a major cause of maternal and fetal morbidity and mortality. Data on pregnancy's complications in patients with primary aldosteronism (PA) are scarce, despite PA being the most frequent cause of secondary hypertension. We did an international survey to collect maternal and fetal pregnancy-related complications in a cohort of women with PA recruited from 5 Hypertension Excellence Centers in Europe. Design and method: We included consecutive women aged 18 - 45 years who were pregnant either after or &lt;1-year before diagnosis of PA and excluded those who were pregnant after unilateral adrenalectomy for PA. PA diagnosis was made in each center according to guidelines. Information on maternal and fetal issues was obtained through medical records and patients’ interviews. Results: We included 78 women aged 30 ± 6 years, 33% nulliparous, 14% with past pre-eclampsia, 53% with hypokalemia, 4% smokers, 7% with type II diabetes, 4% with chronic kidney disease. They had 97 pregnancies, of which 43 occurred &lt;1 year before PA diagnosis and 54 after a median of 18 months from PA diagnosis. All women had either chronic or new onset gestational hypertension (12%). Excluding 7 spontaneous miscarriages, pregnancy-related complications occurred during 43 out of 90 pregnancies (44%), including proteinuria in 36 (40%), pre-eclampsia in 27 (30%), placental abruption in 2 (2%) and intrauterine fetal death in 6 pregnancies (7%). There was a high rate of delivery morbidity including 30% of pre-term births occurring at a median of 34 weeks of gestational age, and 35% of cesareans sections. A total of 23 out of 84 (27%) newborns had a low birth weight (&lt;2500 g) and 22 (26%) underwent neonatal intensive care. When compared to historical control cases from a systematic review, women with PA showed similar rates of maternal complications vs women with essential chronic hypertension, but higher rates of fetal complications (Figure 1). Conclusions: Our data emphasize the importance of PA screening in young hypertensive women prior pregnancy, to ensure 1) appropriate and early treatment of PA, and 2) strict follow-up during pregnancy.

Primary Aldosteronism and Drug Resistant Hypertension: A "Chicken-Egg" Story.

Drug-resistant arterial hypertension (RH) is a major risk factor for cardiovascular disease, often due to overlooked underlying causes. Identification of such causes poses significant clinical challenges. In this setting, primary aldosteronism (PA) is a frequent cause of RH and its prevalence in RH patients is likely higher than 20%.The pathophysiological link between PA and the development and maintenance of RH involves target organ damage and the cellular and extracellular effects of aldosterone excess that promote pro-inflammatory and pro-fibrotic changes in the kidney and vasculature.The feasibility of adrenal vein sampling in PA patients with RH, and the clinical benefit achieved by adrenalectomy, further emphasize the need to implement systematic screening for this common form of secondary hypertension in the management of a high-risk population as RH patients.: We herein review the current knowledge of the factors that contribute to the RH phenotype with a focus on PA and discuss the issues regarding the screening for PA in this setting and the therapeutic approaches (surgical and medical) aimed at resolving RH caused by PA.

Screening for primary aldosteronism in primary care.

Although most patients with PA are normokalemic, hypokalemia (either spontaneous or diuretic induced) in a patient with hypertension should prompt testing for PA. About 30% of patients with hypokalemia and hypertension seen in primary care have PA,[1][1] yet less than 5% of patients with

Prevalence of primary aldosteronism in patients with concomitant hypertension and obstructive sleep apnea, baseline data of a cohort.

Obstructive sleep apnea (OSA) and primary aldosteronism (PA) often coexist in hypertension, whereas whether hypertensive patients with OSA should be screened for PA is controversial and whether gender, age, obesity and OSA severity should be considered is unexplored. We explored cross-sectionally prevalence and associated factors of PA in co-existent hypertension and OSA by considering gender, age, obesity and OSA severity. OSA was defined as AHI ≥5 events/h. PA diagnosis was defined, based on the 2016 Endocrine Society Guideline. We included 3306 patients with hypertension (2564 with OSA). PA prevalence was significantly higher in hypertensives with OSA than in those without OSA (13.2 vs 10.0%, P = 0.018). In gender-specific analysis, PA prevalence was significantly higher in hypertensive men with OSA, compared to non-OSA ones (13.8 vs 7.7%, P = 0.001). In further analysis, PA prevalence was significantly higher in hypertensive men with OSA aged <45 years (12.7 vs 7.0%), 45-59 years (16.6 vs 8.5%), and with overweight and obesity (14.1 vs 7.1%) than did their counterparts (P < 0.05). For OSA severity, men participants showed increased PA prevalence from non to moderate OSA and a decrease in the severe OSA group (7.7 vs 12.9 vs 15.1 vs 13.7%, P = 0.008). Young and middle age, moderate-severe OSA, weight, and blood pressure showed a positive independent association with PA presence in logistic regression. In conclusion, PA is prevalent in co-existent hypertension and OSA, indicating the need for PA screening. Studies are needed for women, older and lean population due to the smaller samples in this study.

Screening for Primary Aldosteronism Among Hypertensive Adults with Obstructive Sleep Apnea: A Retrospective Population-Based Study.

Hypertension plus obstructive sleep apnea (OSA) is recommended in some guidelines as an indication to screen for primary aldosteronism (PA), yet prior data has brought the validity of this recommendation into question. Given this context, it remains unknown whether this screening recommendation is being implemented into clinical practice. We conducted a population-based retrospective cohort study of all adult Ontario (Canada) residents with hypertension plus OSA from 2009 to 2020 with follow-up through 2021 utilizing provincial health administrative data. We measured the proportion of individuals who underwent PA screening via the aldosterone-to-renin ratio by year. We further examined screening rates among patients with hypertension plus OSA by the presence of concurrent hypokalemia and resistant hypertension. Clinical predictors associated with screening were assessed via Cox regression modeling. The study cohort included 53,130 adults with both hypertension and OSA, of which only 634 (1.2%) underwent PA screening. Among patients with hypertension, OSA, and hypokalemia, the proportion of eligible patients screened increased to 2.8%. Among patients ≥65 years with hypertension, OSA, and prescription of ≥4 antihypertensive medications, the proportion of eligible patients screened was 1.8%. Older age was associated with a decreased likelihood of screening while hypokalemia and subspecialty care with internal medicine, cardiology, endocrinology, or nephrology were associated with an increased likelihood of screening. No associations with screening were identified with sex, rural residence, cardiovascular disease, diabetes, or respirology subspecialty care. The population-level uptake of the guideline recommendation to screen all patients with hypertension plus OSA for PA is exceedingly low.

Laboratory medicine in arterial hypertension.

In the initial diagnostics of arterial hypertension (AH) laboratory medicine is a cornerstone, along with a blood pressure (BP) measurement and an electrocardiogram. It mainly refers to routine blood and urine tests for diagnosis and monitoring primary hypertension and its associated conditions such as asymptomatic hypertension-mediated organ damage, chronic kidney disease and hypertensive disorders of pregnancy. In addition, long term non-fatal and fatal risks for cardiovascular (CV) events in hypertension are assessed based on clinical and laboratory data. Furthermore, laboratory medicine is involved in the management of hypertension, especially in monitoring the disease progression. However, antihypertensive drugs may interfere with laboratory test results. Diuretics, especially thiazides, can affect blood and urine sodium concentrations, or angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can affect the blood biomarkers of the renin-angiotensin-aldosterone system (RAAS). It's dysfunction plays a critical role in primary aldosteronism (PA), the most common endocrine disorder in secondary hypertension, which accounts for only small proportion of AH in relative terms but substantial proportion of hypertensives in absolute terms, affecting younger population and carrying a higher risk of CV mortality and morbidity. When screening for PA, aldosterone-to-renin ratio still contributes massively to the increased incidence of the disease, despite certain limits. In conclusion, laboratory medicine is involved in the screening, diagnosis, monitoring and prognosis of hypertension. It is of great importance to understand the preanalytical and analytical factors influencing final laboratory result.

Effect of Oral Contraception on Screening Tests for Primary Aldosteronism: A 10-Year Longitudinal Study.

Primary aldosteronism (PA) and oral contraception (OC) can both cause hypertension in young women. However, the effect of OC on the screening test for PA, the aldosterone to renin ratio (ARR), is not clear. We evaluated the impact of OC on the screening test for PA. In this retrospective cohort study, we analyzed data from the female offspring (Gen2) of women enrolled in the Raine Study, a population-based birth cohort, who had blood pressure (BP) measurements, blood samples, and information about OC use at age 17 years (N = 484) and/or age 27 years (N = 486). Aldosterone concentration was significantly higher in OC users than nonusers at 17 years (median 486 pmol/L vs 347 pmol/L, P < 0.001). Renin concentration was significantly lower in OC users at both 17 years (13.4 mU/L vs 20.6 mU/L) and 27 years (9.2 mU/L vs 11.8 mU/L), hence the ARR was significantly higher in OC users compared to nonusers at both 17 years (31.5 vs 18.3) and 27 years (27.3 vs 21.1). The proportion of participants with ARR > 70 pmol/mU (current threshold for PA detection) was significantly higher in OC users at both 17 years (12.6% vs 2.1%) and 27 years (6.4% vs 0.4%); however, they had comparable BP to those with ARR < 70. OC use at any age abolished the relationship between ARR and BP that is observed in nonusers. OC can increase the ARR and cause a false positive PA screening result. Until more reliable criteria for PA screening in OC users are established, alternative contraception should be considered during screening.

ME-2: MR BLOCKERS AS THE POSSIBLE FIRST-LINE THERAPY IN HYPERTENSION

Among 43 million hypertensive patients in Japan, blood pressure levels are controlled below 140/90mmHg in only a quarter of these patients. This fact may be due to poor adherence and inadequate lifestyles as well as “clinical inertia” (“diagnostic inertia” and “treatment inertia”) of health care providers. Primary aldosteronism (PA) is the most common endocrine hypertension and often associated with resistant hypertension. Five to 10% of all people in hypertension and 20% of resistant hypertension is PA. Most importantly, PA presents with higher prevalence of cardiovascular diseases than essential hypertensive patients whose blood pressure levels are controlled to the similar levels. For the case-detection testing, high plasma aldosterone (PAC) to plasma renin activity (PRA) ratio is useful based on the clinical practice guideline of many countries. However, screening of PA is rarely done between 0.7% to 4.2% of hypertensive patients in daily clinical practice. This situation is a sad state of affairs (“diagnostic inertia”), and the screening of PA should be done at least once in all hypertensive patients. For treatment of PA, administration of a mineralocorticoid receptor blocker (MRB) is recommended in patients with bilateral PA as well as ones who do not willing to undergo surgery. It is therefore crucial to administer a MRB as a first-line therapy, although it is not included in the “first-line antihypertensives”. In addition, since the PA screening test is done quantitatively, it may be insufficient to evaluate just “non-PA” when the ratio is lower than the cut-off values. It may be rather crucial to consider the pathogenesis as “borderline aldosteronism” or “mineralocorticoid receptor (MR)-associated hypertension” when the ratio is suboptimal, because a MR antagonist would be a better choice to control hypertension under such circumstances. In diabetes mellitus and chronic kidney disease, MR may be directly overactivated by varied molecular mechanisms. In addition, under the treatment with angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEi) in patients with diabetes and chronic kidney disease, PAC is suppressed firstly, but re-elevated sometimes over baseline levels (“aldosterone breakthrough”). We therefore presume that combination treatment of a MRB with first-line antihypertensives (ARB/ACEi and calcium channel blocker) may resolve “treatment inertia” of hypertension. Considering the resolution of both “diagnostic and treatment inertia” for hypertension, it is conceivable that MRB should be included in the first-line therapy for hypertension.