Benefits Of Mineralocorticoid Receptor Antagonists Research Articles

Efficacy and safety of eplerenone treatment for patients with diabetic nephropathy: A meta-analysis.

Diabetic nephropathy (DN), which is correlated with an increased risk of cardiovascular disease, significantly elevates the morbidity and mortality of patients with diabetes. Recently, the benefits of mineralocorticoid receptor antagonists in chronic kidney disease (CKD), such as their anti-inflammatory and anti-fibrotic properties, have been discovered. Thus, the present meta-analysis aimed to systematically assess the efficacy and safety of eplerenone treatment in patients with DN. Six electronic databases—PubMed, The Cochrane Library, Embase, Web of Science, CNKI (China National Knowledge Infrastructure), and CBM(Chinese BioMedical Literature Database)—were searched to retrieve randomized controlled trials that assessed eplerenone treatment in patients with DN and were published up to July 31, 2021. Eight randomized controlled trials involving 838 patients were included. Between the eplerenone treatment groups and controls, significant differences were identified in 24-h urine protein levels (mean difference [MD], −19.63 [95% CI, −23.73 to −15.53], P < 0.00001), microalbuminuria (MD, -7.75 [95% CI, -9.75 to -5.75], P < 0.00001), urinary albumin-creatinine ratio (MD, -48.29 [95% CI, -64.45 to -32.14], P < 0.00001), systolic blood pressure (SBP) (MD, -2.49 [95% CI, -4.48 to -0.50], P = 0.01), serum potassium levels (MD, 0.19 [95% CI, 0.13 to 0.24], P < 0.00001), and levels of the renal fibrosis indicator laminin (MD, -8.84 [95% CI, -11.93 to -5.75], P < 0.00001). However, for the effect of estimated glomerular filtration rate (MD, 1.74 [95% CI, -0.87 to 4.35], P = 0.19) and diastolic blood pressure (MD, -0.51 [95% CI, -1.58 to 0.57], P = 0.36), the differences between the two groups were not significant. In addition, no noticeable difference was identified in the adverse events of hyperkalemia and cough between them. These findings suggest that eplerenone exerts beneficial effects on DN by significantly reducing urinary albumin or protein excretion, SBP, and laminin levels, without increasing the incidence of hyperkalemia and other adverse events.

Aldosterone Blockade in Acute Myocardial Infarction: A Systematic Review and Meta-Analysis.

Background A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists (MRA) in acute myocardial infarction (AMI) patients is lacking. Objective To summarize the evidence on the efficacy and safety of MRA in patients admitted for AMI. Methods Articles were identified through PubMed, Embase, Cochrane Library, Ovid (Medline1946-2021), and ClinicalTrials.gov databases from their inception to December 31, 2020. Results 15 articles with a total of 11,861 patients were included. MRA reduced the risk of all-cause mortality by 16% (relative ratio (RR): 0.84; 95% confidence interval (CI) (0.76, 0.94); P = 0.002) and the incidence of cardiovascular adverse events by 12% (RR: 0.88, 95% CI (0.83, 0.93), P < 0.00001) in post-AMI patients, and further analysis demonstrated that early administration of MRA within 7 days after AMI resulted in a greater reduction in all-cause mortality (RR: 0.72, 95% CI (0.61, 0.85), P < 0.0001). Subgroup analyses showed that post-STEMI patients without left ventricular systolic dysfunction (LVSD) treated with MRA had a 36% reduction in all-cause mortality (RR: 0.64, 95% CI (0.46, 0.89), P = 0.007) and a 22% reduction in cardiovascular adverse events (RR: 0.78, 95% CI (0.67, 0.91), P = 0.002). Meanwhile, post-STEMI patients without LVSD treated with MRA get significant improvements in left ventricular ejection fraction (mean difference (MD): 2.69, 95% CI (2.44, 2.93), P < 0.00001), left ventricular end-systolic index (MD: -4.52 ml/m2, 95% CI (-8.21, -0.83), P = 0.02), and left ventricular end-diastolic diameter (MD: -0.11 cm, 95% CI (-0.22, 0.00), P = 0.05). The corresponding RR were 1.72 (95% CI (1.43, 2.07), P < 0.00001) for considered common adverse events (hyperkalemia, gynecomastia, and renal dysfunction). Conclusions Our findings suggest that MRA treatment reduces all-cause mortality and cardiovascular adverse events in post-AMI patients, which is more significant in patients after STEMI without LVSD. In addition, MRA treatment may exert beneficial effects on the reversal of cardiac remodeling in patients after STEMI without LVSD.

Comparison between Spironolactone and Eplerenone on LV Systolic Function in Patients with Chronic Heart Failure

Background:Chronic heart failure (CHF) is the most common and prognostically unfavorable outcome of many diseases of the cardiovascular system. Clinical trials have demonstrated mortality and morbidity benefits of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure. These studies have used either eplerenone or spironolactone as the MRA. Eplerenone is a selective aldosterone antagonist expected to have a lower incidence of hormonal side effects than spironolactone. The present study is designed to compare these two drugs in chronic heart failure patients as no head to head trial between these two drugs is found regarding improvement of systolic function, tolerability and safety. The aim of this study is to compare the effects of eplerenone and spironolactone on LV systolic function in patients with chronic heart failure in a single center.&#x0D; Methods:It was a randomized clinical trial single blind study. A total of 224 cases of chronic heart failure with reduced ejection fraction and NYHA class III or IV were selected by random sampling, from July 2017 to June 2018. Each patient was randomly allocated into either of the two arms, and was continued receiving treatment with either spironolactone (Arm-I) or eplerenone(Arm-II). Each patient was evaluated clinically, biochemically and echocardiographically at the beginning of treatment (baseline) at 1 month and at the end of 6th month. Echocardiography was performed to find out change in left ventricular systolic function.&#x0D; Result: After 6 months of treatment, ejection fraction was found higher in the eplerenonearm (40.3 ± 6.5 versus 38.3 ± 4.6%; P &lt; 0.05). Ejection fraction (EF) changes were 6.2% in eplerenone group and 4.1% in spironolactonearm. A significant reduction in left ventricular end-systolic volume (21.9±2.5 in group I versus 14.9±5.7 in group II; P &lt; 0.05) and left ventricular systolic diameter (48.7±4.0 in arm I versus 45.2±4.9 in arm II; P&lt;0.05) occurred after 6 months of treatment. But no significant differences were observed in left ventricular end-diastolic volume (187.8±37.4 versus 184.5±33.9; P=0.101) and left ventricular diastolic diameter (60.1±4.5 versus 61.0±4.9; P=0.0818) between arms. Assessment of blood pressure six months after treatment shows, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were improved in both arms but difference between two arms were statistically non-significant (p&gt;0.05).&#x0D; Conclusion: In this study, the improvement in systolic function was more in eplerenone arm, which also had fewer adverse side effects when compared to spironolactone arm. So, it can be concluded that eplerenone can be advised in patient with chronic heart failure in addition to other drugs that are used to treat heart failure.&#x0D; University Heart Journal Vol. 16, No. 2, Jul 2020; 65-70

Emerging therapeutic strategies for transplantation-induced acute kidney injury: protecting the organelles and the vascular bed

ABSTRACTIntroduction: Renal ischemia-reperfusion injury (IRI) is a significant clinical challenge faced by clinicians in a broad variety of clinical settings such as perioperative and intensive care. Renal IRI induced acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and health-care costs.Areas covered: This paper focuses on the pathophysiology of transplantation-related AKI and recent findings on cellular stress responses at the intersection of 1. The Unfolded protein response; 2. Mitochondrial dysfunction; 3. The benefits of mineralocorticoid receptor antagonists. Lastly, perspectives are offered to the readers.Expert opinion: Renal IRI is caused by a sudden and temporary impairment of blood flow to the organ.Defining the underlying cellular cascades involved in IRI will assist us in the identification of novel interventional targets to attenuate IRI with the potential to improve transplantation outcomes. Targeting mitochondrial function and cellular bioenergetics upstream of cellular damage may offer several advantages compared to targeting downstream inflammatory and fibrosis processes.An improved understanding of the cellular pathophysiological mechanisms leading to kidney injury will hopefully offer improved targeted therapies to prevent and treat the injury in the future.

Impact of mineralocorticoid receptor antagonists on the risk of sudden cardiac death in patients with heart failure and left-ventricular systolic dysfunction: an individual patient-level meta-analysis of three randomized-controlled trials

Sudden cardiac death (SCD) is an important cause of death in patients with left-ventricular systolic dysfunction (LVSD). Mineralocorticoid receptor antagonists (MRAs) may attenuate this risk. We aimed to assess the impact of MRAs on SCD in patients with LVSD. A fixed-effect meta-analysis at individual patient-level was performed using 11,032 patients recruited in three placebo-controlled randomized trials: Randomized Aldactone Evaluation Study (RALES), Eplerenone Post Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS), and Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS-HF). Treatment effect was determined using a Cox proportional hazards model stratified by study. Patients receiving MRAs were at lower risk of SCD compared with placebo-treated patients after a mean follow-up of 18months (HR 0.77, 95% CI 0.66-0.89). This effect was consistent across trials and did not change substantially after adjustment for 14 baseline co-variates. Moreover, the benefits of MRAs were consistent across study subgroups, except for a greater effect in those < 65years old and those using beta-blockers. Using stratified analyses, we also found a consistent effect in relevant subsets of patient defined by heart failure cause, NYHA class or LVEF ≤ 35%. MRAs reduce the risk for SCD by 23% in patients with heart failure and LVSD. In these patients, the use of MRAs, on top of other evidence-based medications, should be optimized. It might be useful to re-assess the benefit of implantable cardiac defibrillator (ICD) placement, as ICD treatment effect was evaluated in trials enrolling patients not receiving MRAs.

Clinical impact of mineralocorticoid receptor antagonists treatment after acute coronary syndrome in the real world: A propensity score matching analysis.

Recent studies suggest that the benefit of mineralocorticoid receptor antagonists in the acute coronary syndrome setting is controversial. The aim of this study was to examine the current long-term prognostic benefit of mineralocorticoid receptor antagonists in patients with acute coronary syndrome. We conducted a retrospective cohort study of 8318 consecutive acute coronary syndrome patients. Baseline patient characteristics were examined and a follow-up period was established for registry of death, major cardiovascular adverse events and heart failure re-hospitalization. We performed a propensity-matching analysis to draw up two groups of patients paired according to whether or not they had been treated with mineralocorticoid receptor antagonists. The prognostic value of mineralocorticoid receptor antagonists to predict events during follow-up was analysed using Cox regression. Among the study participants, only 524 patients (6.3%) were discharged on mineralocorticoid receptor antagonists. Patients on mineralocorticoid receptor antagonists had a different clinical and pharmacological profile. These differences disappeared after the propensity score analysis. The median follow-up was 40.7 months. After the propensity score analysis, the cardiovascular mortality and heart failure readmission rates were similar between patients who were discharged on mineralocorticoid receptor antagonists and those whose not. The use of mineralocorticoid receptor antagonists was only associated with a reduction in major cardiovascular adverse events (hazard ratio=0.83, 95% confidence interval 0.69-0.97, p=0.001). Our results do not corroborate the long-term benefit of mineralocorticoid receptor antagonists to improve survival after acute coronary syndrome in a large cohort of patients with heart failure or reduced left ventricular ejection fraction and diabetes. Their prescription was associated with a significantly lower incidence of major cardiovascular adverse events during the long-term follow-up without effect on heart failure development.

Mineralocorticoid Receptor Antagonists in Muscular Dystrophy Mice During Aging and Exercise.

Mineralocorticoid receptor antagonists added to angiotensin converting enzyme inhibitors have shown preclinical efficacy for both skeletal and cardiac muscle outcomes in young sedentary dystrophin-deficient mdx mice also haploinsufficient for utrophin, a Duchenne muscular dystrophy (DMD) model. The mdx genotypic DMD model has mild pathology, making non-curative therapeutic effects difficult to distinguish at baseline. Since the cardiac benefit of mineralocorticoid receptor antagonists has been translated to DMD patients, it is important to optimize potential advantages for skeletal muscle by further defining efficacy parameters. We aimed to test whether therapeutic effects of mineralocorticoid receptor antagonists added to angiotensin converting enzyme inhibitors are detectable using three different reported methods of exacerbating the mdx phenotype. We tested treatment with lisinopril and the mineralocorticoid receptor antagonist spironolactone in: 10 week-old exercised, 1 year-old sedentary, and 5 month-old isoproterenol treated mdx mice and performed comprehensive functional and histological measurements. None of the protocols to exacerbate mdx phenotypes resulted in dramatically enhanced pathology and no significant benefit was observed with treatment. Since endogenous mineralocorticoid aldosterone production from immune cells in dystrophic muscle may explain antagonist efficacy, it is likely that these drugs work optimally during the narrow window of peak inflammation in mdx mice. Exercised and aged mdx mice do not display prolific damage and inflammation, likely explaining the absence of continued efficacy of these drugs. Since inflammation is more prevalent in DMD patients, the therapeutic window for mineralocorticoid receptor antagonists in patients may be longer.

Mineralocorticoid Antagonists in ESRD: An Overview of Clinical Trial Evidence.

Add-on therapy with the Mineralocorticoid-Receptor-Antagonists (MRAs) spironolactone and eplerenone was shown to enhance the cardioprotective action of angiotensinconverting- enzyme-inhibitors (ACEIs), angiotensin-receptor-blockers (ARBs) and/or β-blockers in nondialysis patients with congestive heart failure (CHF) and reduced left ventricular (LV) ejection fraction. The risk/benefit ratio of MRAs in dialysis patients is less well defined, owing to concerns that their cardioprotective actions may be counteracted by excess risk of hyperkalemia. We performed a systematic literature search of MEDLINE/PubMed database (inception to September 15, 2016) to identify randomized controlled studies evaluating the effects of spironolactone and eplerenone on surrogate cardiovascular risk factors and clinical outcomes in patients receiving hemodialysis or peritoneal dialysis. A growing body of evidence derived from small randomized studies suggests that MRA therapy improves a number of surrogate cardiovascular risk factors (i.e. blood pressure, LV mass index, LV ejection fraction, carotid intima-media-thickness) in long-term dialysis patients. Two larger studies evaluating "hard" cardiovascular endpoints showed that these cardioprotective actions of MRAs are translated into a clinically relevant (up to 60%) reduction in the risk of all-cause and cardiovascular mortality. On the other hand, MRA use was shown to be accompanied by a parallel increase in the risk of hyperkalemia and gynecomastia. Small, hypothesis-generating randomized trials support a cardioprotective role of MRA therapy in patients receiving hemodialysis or peritoneal dialysis. These promising results call for larger, properly-designed studies aiming to fully elucidate the potential harms and benefits of MRAs in this high-risk population. In anticipation of the results of ongoing outcome trials, the wide use of MRAs in dialysis patients should be avoided.

P3436Use and benefit of mineralocorticoid receptor antagonists in elderly patients with left ventricular systolic dysfunction and chronic kidney disease

P3436Use and benefit of mineralocorticoid receptor antagonists in elderly patients with left ventricular systolic dysfunction and chronic kidney disease

Does aspirin detract from the benefits of mineralocorticoid receptor antagonists in patients with heart failure and a reduced left ventricular ejection fraction? Probably!

Does aspirin detract from the benefits of mineralocorticoid receptor antagonists in patients with heart failure and a reduced left ventricular ejection fraction? Probably!

Aldosterone in vascular and metabolic dysfunction

This review will highlight recent developments in mineralocorticoid receptor research which impact aldosterone-associated vascular and cardiometabolic dysfunction. The mineralocorticoid receptor is also expressed in vascular smooth muscle and vascular endothelium, and contributes to vascular function and remodeling. Adipocyte-derived leptin stimulates aldosterone secretion, which may explain the observed link between obesity and hyperaldosteronism. Adipocyte mineralocorticoid receptor overexpression produces systemic changes consistent with metabolic syndrome. Ongoing studies with novel nonsteroidal mineralocorticoid receptor antagonists may provide a novel treatment for diabetic nephropathy and heart failure in patients with chronic kidney disease, with reduced risk of hyperkalemia. Ongoing research continues to demonstrate novel roles of the vascular and adipocyte mineralocorticoid receptor function, which may explain the beneficial metabolic and vascular benefits of mineralocorticoid receptor antagonists.

Selection of a mineralocorticoid receptor antagonist for patients with hypertension or heart failure

Clinical trials have demonstrated morbidity and mortality benefits of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure. These studies have used either spironolactone or eplerenone as the MRA. It is generally believed that these two agents have the same effects, and the data from studies using one drug could be extrapolated for the other. National and international guidelines do not generally discriminate between spironolactone and eplerenone, but strongly recommend using an MRA for patients with heart failure due to LV systolic dysfunction and post-infarct LV systolic dysfunction. There are no major clinical trials directly comparing the efficacy of these two drugs. This article aims to compare the pharmacokinetics and pharmacodynamics of spironolactone and eplerenone, and to analyse the available data for their cardiovascular indications and adverse effects. We have also addressed the role of special circumstances including co-morbidities, concomitant drug therapy, cost, and licensing restrictions in choosing an appropriate MRA for a particular patient, thus combining an evidence-based approach with personalized medicine.

Importance of the time of initiation of mineralocorticoid receptor antagonists on risk of mortality in patients with heart failure

Several studies have definitively shown the benefit of mineralocorticoid receptor antagonists (MRAs) in patients with heart failure (HF). However, very few prior studies examined the relationship between the timing of initiation of MRAs and prognosis. In addition, on this topic, there is no information regarding the specific population of patients suffering a first episode of decompensated congestive HF. We studied a homogenous cohort of patients discharged alive from our hospital after a first episode of decompensated congestive HF, in order to clarify the association between time of aldosterone receptor antagonist (ARA) initiation (within the first 90 days after hospital discharge) and mortality. Our population was composed of a series of consecutive patients. All-cause mortality was compared between patients who initiated MRAs at discharge (early group) and those who initiated MRAs one month later and up to 90 days after discharge (delayed group). We used prescription time distribution matching to control for survival difference between groups. The early and delayed groups consisted of 365 and 320 patients, respectively. During the one-year follow-up, a significant difference in mortality was demonstrated between groups. Adjusted hazard ratios (HRs) for early versus delayed initiation were 1.72 (95% confidence interval (CI) 0.96 to 2.84) at six months, and 1.93 (95% CI 1.18 to 3.14) at one year. Delay of MRA initiation up to 30 to 90 days after discharge implies a significant increase in mortality compared with MRA initiation at discharge, after a first episode of decompensate congestive HF.

MINERALOCORTICOID RECEPTOR ANTAGONISTS IN DIABETIC PATIENTS HOSPITALIZED WITH HEART FAILURE: INSIGHTS FROM THE EVEREST TRIAL

Despite benefits of mineralocorticoid receptor antagonists (MRAs) in heart failure with reduced ejection fraction (HFrEF), concerns for adverse events in patients (pts) with diabetes (DM) limit use. The characteristics and outcomes of DM pts receiving MRAs are not well characterized. We analyzed 1,

Impact of Mineralocorticoid Receptor Antagonists on Changes in Cardiac Structure and Function of Left Ventricular Dysfunction

Background— A comprehensive evaluation of the benefits of mineralocorticoid receptor antagonists on cardiac remodeling is lacking. We aimed to evaluate the impact of mineralocorticoid receptor antagonists on changes in cardiac structure and function of left ventricular dysfunction. Methods and Results— Articles were identified by online searches in PubMed, EMBASE, Cochrane, and ClinicalTrials.gov databases before June 2012, by hand searches of reviews and relevant journals, and by contact with the authors. Qualified articles were restricted to randomized controlled trials. There were, respectively, 12, 4, and 3 qualified trials that randomized 572, 647, and 407 patients to spironolactone, canrenoate, and eplerenone, and 531, 655, and 395 patients to placebo or active treatment, respectively. Overall, under mineralocorticoid receptor antagonist treatment there was improvement in left ventricular ejection fraction (weighted mean difference, 2.97; 95% confidence interval [95% CI], 2.26–3.67; P &lt;0.0005), left ventricular end-systolic and end-diastolic volume index (weighted mean difference, −5.64; 95% CI, −7.94 to −3.34; P &lt;0.0005 and weighted mean difference, −7.46; 95% CI, −11.63 to −3.3; P &lt;0.0005), serum amino-terminal peptide of procollagen type-III (weighted mean difference, −1.12; 95% CI, −1.49 to −0.74; P &lt;0.0005), B-type natriuretic peptide (weighted mean difference, −67.06; 95% CI, −91.24 to −42.88; P &lt;0.0005), peak velocities of early mitral inflow (E; weighted mean difference, −9.57; 95% CI, −12.98 to −6.17; P &lt;0.0005), and E wave deceleration time (weighted mean difference, 7.08; 95% CI, 4.07–10.09; P &lt;0.0005). There was low probability of heterogeneity and publication bias. Conclusions— Our findings demonstrate that mineralocorticoid receptor antagonist treatment may exert beneficial effects on the reversal of cardiac remodeling and improvement of left ventricular function.

Mineralocorticoid Receptor Antagonists and Mortality in Heart Failure With Concurrent Atrial Fibrillation

Aldosterone is the major mineralocorticoid in the human body and is produced in the zona glomerulosa of the cortex in the adrenal glands, and its secretion is stimulated by angiotensin II, adrenocorticotrophic hormone, catecholamines, and local potassium levels. Its levels in plasma are elevated 4-fold in heart failure (HF).1 Through a variety of mechanisms, aldosterone is believed to play a role in the pathogenesis and progression of left ventricular dysfunction.2 The mineralocorticoid receptor antagonists (MRAs) spironolactone and eplerenone have consistently demonstrated a 20% reduction in mortality and 21% reduction in sudden death, which has been counterbalanced by a 6% to 12% risk of hyperkalemia (potassium >6.0 mEq/L) depending on the baseline estimated glomerular filtration rate.3,4,5 Article see p 586 In this issue of Circulation: Heart Failure , O’Meara and colleagues report on a retrospective analysis from …

Role of mineralocorticoid receptor in insulin resistance

Recent data suggest that mineralocorticoid receptor activation can affect insulin resistance independent of its effects on blood pressure. This review discusses new evidence linking mineralocorticoid receptor to insulin resistance and the underlying mechanisms of these effects. Observational studies have shown mineralocorticoid activity to be associated with insulin resistance irrespective of race, blood pressure or body weight. Increased mineralocorticoid activity may be the common link between obesity, hypertension, dyslipidemia and insulin resistance, features that make up the metabolic syndrome. Treatment of primary aldosteronism is associated with a decrease in insulin resistance and provides one of the most convincing evidences in favor of the contribution of mineralocorticoid receptor to insulin resistance. Dietary salt restriction, which increases aldosterone levels, is also associated with an increase in insulin resistance. Potential mechanisms by which mineralocorticoid receptor may contribute to insulin resistance include a decreased transcription of the insulin receptor gene, increased degradation of insulin receptor substrates, interference with insulin signaling mechanisms, decreased adiponectin production and increased oxidative stress and inflammation. Advantages of mineralocorticoid receptor antagonists on insulin resistance have been demonstrated in animal models. There may be a benefit of mineralocorticoid receptor antagonists in human insulin resistance states, but more clinical research is needed to explore these possibilities.

Is There an Unrecognized Epidemic of Primary Aldosteronism? (Pro)

My answer is “no.” Although primary aldosteronism (PA) is likely more common than most experts believed in the 1960–1990 interval, it is not nearly as common as Dr Calhoun and other investigators report from 1990 until now. As many younger clinicians may not remember, this same issue arose soon after Dr Jerome Conn characterized this disease in 1955.1 Reporting on the prevalence of PA in his highly referred population of likely suspects, Dr Conn and coworkers’ estimates were as high as 20%.2 Subsequently, studies on unreferred patients supported a prevalence of <1%.3 The lower estimate was commonly accepted until Gordan and colleagues started screening for PA with the plasma aldosterone:renin ratio (ARR) first described in 19764 and expanded by Hiramatsu et al in 1981.5 In 1993, Gordon et al6 reported an elevated ARR in 20% of 199 patients, with 8.5% having an abnormal saline suppression test and 2.5% proven to have an aldosterone-producing adenoma. Since then, numerous series have been reported (Table). As seen in Table 1, the prevalence of an elevated ARR has varied from 5.5% to 39.0%. Part of the wide variation rises from the use of varying thresholds; more of the variation rises from inclusion of various types of patients. The latter point must be recognized, because most patients in these series were referred to specialized centers, just as Dr Conn’s high numbers were largely derived from a referred population. View this table: Prevalence of Autonomous Hyperaldosteronism and APAs in Patients Tested by ARR Two recently published series epitomize the vagaries of most series listed in the Table. The first is a study of 1125 recently diagnosed subjects with hypertension referred to 14 specialized hypertension clinics throughout Italy.27 Plasma renin activity and plasma aldosterone were measured at baseline and again 60 …