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1.
Blood Press ; 33(1): 2350981, 2024 May 03.
Article En | MEDLINE | ID: mdl-38824645

OBJECTIVE: Few studies have evaluated the performance of non-drug-adjusted primary aldosteronism (PA) screening. Therefore, we aimed to examine the consistency between PA screening results with and without drug adjustment and to explore the effectiveness of screening without drug adjustment. METHODS: This prospective study included 650 consecutive patients with a high risk of incidence PA. Patients who initially screened positive underwent rescreening with drug adjustments and confirmatory tests. Regarding the remaining patients, one of every three consecutive patients underwent rescreening with drug adjustments and confirmatory tests. The changes in aldosterone and renin concentrations were compared between patients with essential hypertension (EH) and those with PA before and after drug adjustment. Sensitivity and specificity were used to assess the diagnostic performance of screening without drug adjustment, using the confirmatory test results as the reference. RESULTS: We screened 650 patients with hypertension for PA. Forty-nine patients were diagnosed with PA and 195 with EH. Regarding drugs, 519 patients were taking angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), or diuretics alone or in combination. Forty-one patients were taking beta-blockers. Ninety patients were taking beta-blockers in combination with other drugs. In patients treated with ACEIs, ARBs, CCBs, or diuretics alone, or in combination, or beta-blockers alone, PA positivity was determined using the criteria, aldosterone-to-renin ratio (ARR) >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, and negativity, using the criteria, ARR <9 pg/mL/pg/mL; the sensitivity and specificity were 94.7% and 94.5%, respectively. After drug adjustment, the sensitivity and specificity of screening were 92.1% and 89%, respectively. CONCLUSIONS: In patients not treated with beta-blockers combined with others, when ARR >38 pg/mL/pg/mL and plasma aldosterone concentration (PAC) >100 pg/mL, or, ARR <9 pg/mL/pg/mL, non-drug-adjusted screening results were identical to with drug adjustment. Non-drug-adjusted screening could reduce the chance of medication adjustment, enable patients to continue their treatments and avoiding adverse effects, is of clinical importance.


Primary aldosteronism (PA) is the most common form of endocrine hypertension. The risk of stroke, myocardial infarction, heart failure, atrial fibrillation, and deterioration of kidney function is higher in PA than in essential hypertension (EH), even with the same blood pressure (BP) levels. However, many patients remain undiagnosed because most antihypertensive drugs substantially interfere with PA screening results, which makes drug adjustment necessary. This can be a time-consuming and unsafe process, requiring 4­6 weeks, and could lead to a hypertensive crisis and other complications. Some studies have suggested that certain antihypertensive drugs can be continued during PR screening. However, few studies have evaluated the performance of non-drug-adjusted PA screening. Therefore, in this prospective study, we aimed to compare patients with hypertension and a high risk of PA before and after drug adjustment and to use confirmatory test results as a reference to explore the diagnostic or exclusion effect. We found that non-drug-adjusted screening performs similarly to drug-adjusted screening in a particular group of patients. Our findings could aid in preventing unnecessary drug adjustment for PA screening, thereby reducing the risk in these patients.


Aldosterone , Hyperaldosteronism , Humans , Hyperaldosteronism/diagnosis , Hyperaldosteronism/blood , Hyperaldosteronism/drug therapy , Female , Middle Aged , Male , Prospective Studies , Aldosterone/blood , Renin/blood , Adult , Calcium Channel Blockers/therapeutic use , Hypertension/drug therapy , Hypertension/blood , Hypertension/diagnosis , Antihypertensive Agents/therapeutic use , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Mass Screening/methods , Aged , Angiotensin Receptor Antagonists/therapeutic use
2.
Hypertens Res ; 47(6): 1719-1727, 2024 Jun.
Article En | MEDLINE | ID: mdl-38565699

Recent studies have explored the association between primary aldosteronism and cardiovascular disease incidence. The association between specific primary aldosteronism treatments and differential improvement in cardiovascular event rates is yet to be established. This study was designed to compare the relative effects of spironolactone therapy and surgical intervention on cardiovascular outcomes among primary aldosteronism patients. This retrospective observational study included 853 primary aldosteronism patients from the First Affiliated Hospital of China Medical University between 2014 and 2022. Patients who had completed abdominal computed tomography (CT) examinations with similar metabolic characteristics and 6-month follow-up analyses were included in this study. These patients were separated into a surgical treatment group (n = 33) and a spironolactone treatment group (n = 51). Demographic data, biochemical analysis results, liver/spleen (L/S) X-ray attenuation ratio, hospitalization frequency, and cardiovascular events were compared between the two groups. The spironolactone group demonstrated significantly improved metabolic characteristics compared to the surgical group, shown by lower BMI, blood pressure, total cholesterol (TC), insulin resistance index (IRI), and reduced non-alcoholic fatty liver disease prevalence. Metabolic parameters did not differ significantly within the surgical treatment group when comparing pre- and postoperative values. The incidence of cardiovascular events was lower in the spironolactone group compared to the surgery group (23/33 vs. 20/51, P < 0.001) despite higher hospitalization rates(37/31 vs. 61/53, P < 0.001). In patients with primary aldosteronism, spironolactone treatment is more effective than surgical intervention in remediating abnormal lipid and glucose metabolism while improving cardiovascular outcomes. Chinese clinical trial registry registration number: ChiCTR2300074574.


Cardiovascular Diseases , Hyperaldosteronism , Spironolactone , Humans , Hyperaldosteronism/complications , Hyperaldosteronism/drug therapy , Hyperaldosteronism/therapy , Male , Female , Middle Aged , Retrospective Studies , Adult , Cardiovascular Diseases/etiology , Spironolactone/therapeutic use , Glycolipids/metabolism , Mineralocorticoid Receptor Antagonists/therapeutic use , Treatment Outcome , Adrenalectomy , China/epidemiology
3.
Hypertension ; 81(6): 1391-1399, 2024 Jun.
Article En | MEDLINE | ID: mdl-38525605

BACKGROUND: Current guidelines and consensus documents recommend withdrawal of mineralocorticoid receptor antagonists (MRAs) before primary aldosteronism (PA) subtyping by adrenal vein sampling (AVS), but this practice can cause severe hypokalemia and uncontrolled high blood pressure. Our aim was to investigate if unilateral PA can be identified by AVS during MRA treatment. METHODS: We compared the rate of unilateral PA identification between patients with and without MRA treatment in large data sets of patients submitted to AVS while off renin-angiotensin system blockers and ß-blockers. In sensitivity analyses, the between-group differences of lateralization index values after propensity score matching and the rate of unilateral PA identification in subgroups with undetectable (≤2 mUI/L), suppressed (<8.2 mUI/L), and unsuppressed (≥8.2 mUI/L) direct renin concentration levels were also evaluated. RESULTS: Plasma aldosterone concentration, direct renin concentration, and blood pressure values were similar in non-MRA-treated (n=779) and MRA-treated (n=61) patients with PA, but the latter required more antihypertensive agents (P=0.001) and showed a higher rate of adrenal nodules (82% versus 67%; P=0.022) and adrenalectomy (72% versus 54%; P=0.01). However, they exhibited no significant differences in commonly used AVS indices and the area under the receiving operating characteristic curve of lateralization index, both under unstimulated conditions and postcosyntropin. Several sensitivity analyses confirmed these results in propensity score matching adjusted models and in patients with undetectable, or suppressed or unsuppressed renin levels. CONCLUSIONS: At doses that controlled blood pressure and potassium levels, MRAs did not preclude the identification of unilateral PA at AVS. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.


Adrenal Glands , Hyperaldosteronism , Mineralocorticoid Receptor Antagonists , Adult , Female , Humans , Male , Middle Aged , Adrenalectomy/methods , Aldosterone/blood , Blood Pressure/physiology , Blood Pressure/drug effects , Hyperaldosteronism/blood , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Hyperaldosteronism/surgery , Mineralocorticoid Receptor Antagonists/therapeutic use , Propensity Score , Renin/blood , Retrospective Studies , Treatment Outcome , Case-Control Studies
4.
Hypertens Res ; 47(6): 1707-1718, 2024 Jun.
Article En | MEDLINE | ID: mdl-38548912

Patients with primary aldosteronism have an increased risk of developing cardiovascular disease. The response to mineralocorticoid receptor antagonists varies among individuals, indicating diverse mineralocorticoid receptor activities in these patients. This study explored the factors linked to the efficacy of blood pressure reduction through mineralocorticoid receptor antagonists in patients with primary aldosteronism. We examined the relationship between the reduction in blood pressure and patient characteristics in a group of 41 patients with primary aldosteronism (24 males, mean age 55 ± 13 years, including 34 patients diagnosed with bilateral primary aldosteronism) before and after undergoing treatment with mineralocorticoid receptor antagonists. Significant reductions in office blood pressure were observed 3 and 6 months after treatment initiation. Single correlation analyses showed that the urinary chloride-to-potassium ratio displayed the strongest positive association with blood pressure reduction, surpassing plasma aldosterone concentration, plasma renin activity, and urinary sodium-to-potassium ratio, at 3 and 6 months. Multiple correlation analyses revealed a consistent and independent positive correlation between the urinary chloride-to-potassium ratio and blood pressure reduction at 3 and 6 months. The optimal threshold for the urinary chloride-to-potassium ratio with respect to its ability to lower blood pressure, was determined as 3.18. These results imply that the urinary chloride-to-potassium ratio may be independently associated with the effectiveness of blood pressure reduction facilitated by mineralocorticoid receptor antagonists. Moreover, it could potentially serve as a valuable predictor of the effectiveness of these agents and function as an indicator of endogenous mineralocorticoid receptor activity in patients with primary aldosteronism.


Aldosterone , Blood Pressure , Hyperaldosteronism , Mineralocorticoid Receptor Antagonists , Potassium , Humans , Hyperaldosteronism/drug therapy , Male , Middle Aged , Mineralocorticoid Receptor Antagonists/therapeutic use , Mineralocorticoid Receptor Antagonists/pharmacology , Female , Blood Pressure/drug effects , Aged , Potassium/blood , Potassium/urine , Adult , Aldosterone/blood , Receptors, Mineralocorticoid/metabolism , Chlorides/urine , Chlorides/blood , Renin/blood , Treatment Outcome
5.
J Am Heart Assoc ; 13(7): e030142, 2024 Apr 02.
Article En | MEDLINE | ID: mdl-38497438

Aldosterone is a steroid hormone that primarily acts through activation of the mineralocorticoid receptor (MR), a nuclear receptor responsible for downstream genomic regulation. Classically, activation of the MR in the renal tubular epithelium is responsible for sodium retention and volume expansion, raising systemic blood pressure. However, activation of the MR across a wide distribution of tissue types has been implicated in multiple adverse consequences for cardiovascular, cerebrovascular, renal, and metabolic disease, independent of blood pressure alone. Primary aldosteronism, heart failure, and chronic kidney disease are states of excessive aldosterone production and MR activity where targeting MR activation has had clinical benefits out of proportion to blood pressure lowering. The growing list of established and emerging therapies that target aldosterone and MR activation may provide new opportunities to improve clinical outcomes and enhance cardiovascular and renal health.


Drug-Related Side Effects and Adverse Reactions , Hyperaldosteronism , Hypertension , Humans , Aldosterone , Blood Pressure , Hyperaldosteronism/drug therapy , Receptors, Mineralocorticoid/metabolism , Heart , Kidney , Mineralocorticoid Receptor Antagonists/therapeutic use
6.
Arch Endocrinol Metab ; 68: e230211, 2024 Mar 15.
Article En | MEDLINE | ID: mdl-38530960

Objective: Despite its recognized importance, primary hyperaldosteronism (PHA) remains an underdiagnosed condition in clinical practice. The objective of the present study was to evaluate PHA screening practices by general practitioners and specialists in endocrinology and cardiology. Subjects and methods: This cross-sectional, observational study invited physicians to respond voluntarily to an online survey. The survey collected the respondents' sociodemographic data and answers to five hypothetical clinical cases meeting Endocrine Society criteria for PHA screening. Results: In all, 126 physicians responded to the online survey. Endocrinologists were the specialists who most often chose PHA screening, although the screening rates were overall low, ranging from 36.5% to 92.9%, depending on the case and the respondents' specialty. The survey also assessed the reasons for not choosing PHA screening, which included limited availability of tests within the public health services, interference of antihypertensive medications on hormone levels, and failure to identify the screening indication. Being an endocrinologist was an independent predictor for choosing PHA screening for the patients in Cases #1 and #5 (p = 0.001 and p = 0.002, respectively). Conclusion: Endocrinologists were the specialists who most often chose PHA screening, although the screening rates were overall low among all specialists. These findings highlight a need for continuing medical education programs addressing PHA screening and making the diagnosis of PHA more present in the daily clinical practice of physicians treating patients with hypertension.


General Practitioners , Hyperaldosteronism , Hypertension , Humans , Cross-Sectional Studies , Antihypertensive Agents , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy
7.
High Blood Press Cardiovasc Prev ; 31(1): 43-53, 2024 Jan.
Article En | MEDLINE | ID: mdl-38225508

INTRODUCTION: Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA. AIM: To compare the development of cardiovascular, renal and metabolic complications between medically treated patients with PA and those who underwent adrenalectomy, taking the renin status during MRA treatment into account. METHODS: A multicenter retrospective study (SPAIN-ALDO Register) of patients with PA treated at 35 Spanish tertiary hospitals. Patients on MRA were divided into two groups based on renin suppression (n = 90) or non-suppression (n = 70). Both groups were also compared to unilateral PA patients (n = 275) who achieved biochemical cure with adrenalectomy. RESULTS: Adrenalectomized patients were younger, had higher plasma aldosterone concentration, and lower potassium levels than MRA group. Patients on MRA had similar baseline characteristics when stratified into treatment groups with suppressed and unsuppressed renin. 97 (55.1%) of 176 patients without comorbidities at diagnosis, developed at least one comorbidity during follow-up (median 12 months vs. 12.5 months' follow-up after starting MRA and surgery, respectively). Surgery group had a lower risk of developing new cardiovascular events (HR 0.40 [95% CI 0.18-0.90]) than MRA group. Surgical treatment improved glycemic and blood pressure control, increased serum potassium levels, and required fewer antihypertensive drugs than medical treatment. However, there were no differences in the cardiometabolic profile or the incidence of new comorbidities between the groups with suppressed and unsuppressed renin levels (HR 0.95 [95% CI 0.52-1.73]). CONCLUSION: Cardiovascular, renal, and metabolic events were comparable in MRA patients with unsuppressed and suppressed renin. Effective surgical treatment of PA was associated with a decreased incidence of new cardiovascular events when compared to MRA therapy.


Cardiovascular Diseases , Hyperaldosteronism , Hypertension , Humans , Adrenalectomy , Aldosterone , Biomarkers , Cardiovascular Diseases/drug therapy , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Hyperaldosteronism/epidemiology , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Mineralocorticoid Receptor Antagonists/pharmacology , Mineralocorticoid Receptor Antagonists/therapeutic use , Potassium/metabolism , Registries , Renin/metabolism , Retrospective Studies , Spain/epidemiology
10.
Endocr Rev ; 45(1): 69-94, 2024 Jan 04.
Article En | MEDLINE | ID: mdl-37439256

Primary aldosteronism (PA) is an endocrinopathy characterized by dysregulated aldosterone production that occurs despite suppression of renin and angiotensin II, and that is non-suppressible by volume and sodium loading. The effectiveness of surgical adrenalectomy for patients with lateralizing PA is characterized by the attenuation of excess aldosterone production leading to blood pressure reduction, correction of hypokalemia, and increases in renin-biomarkers that collectively indicate a reversal of PA pathophysiology and restoration of normal physiology. Even though the vast majority of patients with PA will ultimately be treated medically rather than surgically, there is a lack of guidance on how to optimize medical therapy and on key metrics of success. Herein, we review the evidence justifying approaches to medical management of PA and biomarkers that reflect endocrine principles of restoring normal physiology. We review the current arsenal of medical therapies, including dietary sodium restriction, steroidal and nonsteroidal mineralocorticoid receptor antagonists, epithelial sodium channel inhibitors, and aldosterone synthase inhibitors. It is crucial that clinicians recognize that multimodal medical treatment for PA can be highly effective at reducing the risk for adverse cardiovascular and kidney outcomes when titrated with intention. The key biomarkers reflective of optimized medical therapy are unsurprisingly similar to the physiologic expectations following surgical adrenalectomy: control of blood pressure with the fewest number of antihypertensive agents, normalization of serum potassium without supplementation, and a rise in renin. Pragmatic approaches to achieve these objectives while mitigating adverse effects are reviewed.


Hyperaldosteronism , Hypertension , Humans , Aldosterone , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Hyperaldosteronism/surgery , Renin , Mineralocorticoid Receptor Antagonists/therapeutic use , Biomarkers
11.
Hypertens Res ; 47(1): 157-167, 2024 Jan.
Article En | MEDLINE | ID: mdl-37717115

Primary aldosteronism (PA) is typically managed with mineralocorticoid receptor antagonists (MRAs) barring adrenalectomy. The efficacy of esaxerenone, a nonsteroidal MRA, were explored in patients with PA. Various parameters such as the urinary albumin to creatinine ratio (UACR) and serum levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were evaluated in 25 PA patients before and 3 and 6 months after esaxerenone treatment. Systolic and diastolic blood pressure (BP), and the estimated glomerular filtration rate decreased after treatment, while serum levels of potassium and active renin increased. Significant reductions were observed in UACR 3 and 6 months after treatment. A significant decrease in NT-proBNP was evident at 6 months but not 3 months after treatment. Correlation analysis indicated that the reductions in BP and UACR at 3 months were independent of estimated daily salt intake. Furthermore, the effect of esaxerenone treatment on lowering UACR and NT-proBNP levels was independent of BP reduction. Responders whose systolic BP decreased 6 months after esaxerenone treatment by more than 10 mmHg compared to pretreatment had higher pretreatment NT-proBNP and similar UACR before and after treatment when compared with nonresponders. Esaxerenone improved mental, physical, and social quality of life (QOL) 6 months after treatment compared to healthy controls and increased over time. No patients discontinued treatment due to severe hyperkalemia or renal dysfunction. In conclusion, esaxerenone is a safe and effective MRA for PA treatment, offering significant benefits in terms of hypertension, albuminuria, NT-proBNP levels, and QOL improvement. Esaxerenone effectively lowers BP, UACR, and serum levels of NT-proBNP independent of dietary salt intake in mild PA patients. ARC active renin concentration, DBP diastolic blood pressure, MR mineralocorticoid receptor, MRA mineralocorticoid receptor antagonist, NT-proBNP N-terminal pro-brain natriuretic peptide, PA primary aldosteronism, QOL quality of life, SBP systolic blood pressure, SF-36 Medical Outcomes Study 36-Item Short-Form Health Survey, UACR urinary albumin to creatinine ratio.


Hyperaldosteronism , Natriuretic Peptide, Brain , Humans , Blood Pressure , Quality of Life , Renin , Creatinine , Albumins/pharmacology , Hyperaldosteronism/drug therapy , Mineralocorticoid Receptor Antagonists/therapeutic use , Mineralocorticoid Receptor Antagonists/pharmacology
12.
J Formos Med Assoc ; 123 Suppl 2: S91-S97, 2024 Mar.
Article En | MEDLINE | ID: mdl-37291044

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 ß-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.


Hyperaldosteronism , Hypertension , Humans , Antihypertensive Agents/therapeutic use , Aldosterone , Calcium Channel Blockers/therapeutic use , Renin , Hypertension/diagnosis , Hypertension/drug therapy , Adrenergic beta-Antagonists/therapeutic use , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Angiotensin Receptor Antagonists/therapeutic use
13.
Endocrine ; 84(1): 245-252, 2024 Apr.
Article En | MEDLINE | ID: mdl-38087188

OBJECTIVE: Aldosterone-producing adenoma (APA) and bilateral idiopathic hyperaldosteronism (IHA) are the most common subtypes of primary aldosteronism (PA), and the PA subtype dictates the treatment options. This study aimed to identify predictors of declined estimated glomerular filtration rate (eGFR) following each treatment in patients with APA and IHA. METHODS: We retrospectively investigated 45 patients with APA who had undergone adrenalectomy (ADX) and 37 patients with IHA who had received treatment with a mineralocorticoid receptor antagonist (MRA) to identify pre-treatment risk factors for eGFR decline during the post-treatment follow-up period. RESULTS: Patients with APA who underwent ADX exhibited higher eGFR declines than patients with IHA treated with MRA at the 6-month post-treatment evaluation point. A high preoperative plasma aldosterone concentration (PAC) in patients with APA and a high body mass index (BMI) in patients with IHA were identified as independent predictors of higher eGFR decline at 6 months post-treatment (ß=0.42 and ß=0.36, respectively). In patients with APA, the cutoff PAC to best predict a 20% decrease in eGFR following ADX, as determined by receiver operating characteristic analysis, was 524 pg/mL. In patients with IHA, the cutoff BMI to best predict a 10% decrease in eGFR following MRA administration was 25.3 kg/m2. In addition, lower preoperative flow-mediated vasodilation was associated with eGFR decline after ADX in patients with APA. CONCLUSIONS: Greater attention should be given to the above-mentioned risk factors to prevent renal impairment following each treatment in patients with both APA and IHA.


Adenoma , Hyperaldosteronism , Hypertension , Kidney Diseases , Humans , Aldosterone , Hyperaldosteronism/complications , Hyperaldosteronism/drug therapy , Hyperaldosteronism/surgery , Hypertension/complications , Retrospective Studies , Adenoma/complications , Risk Factors , Mineralocorticoid Receptor Antagonists/therapeutic use , Kidney Diseases/complications
14.
Endocrine ; 83(1): 188-195, 2024 Jan.
Article En | MEDLINE | ID: mdl-37924464

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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 ß-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). CONCLUSIONS: Not every patient receiving ß-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 ß-blockers, ACEIs, ARBs, DHP-CCBs and spironolactone when determining the ARR during the initial test.


Hyperaldosteronism , Hypertension , Humans , Antihypertensive Agents/therapeutic use , Antihypertensive Agents/pharmacology , Renin , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Retrospective Studies , Angiotensin Receptor Antagonists/therapeutic use , Hypertension/diagnosis , Hypertension/drug therapy , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Calcium Channel Blockers/therapeutic use
15.
J Clin Endocrinol Metab ; 109(3): e1280-e1289, 2024 Feb 20.
Article En | MEDLINE | ID: mdl-37946600

CONTEXT: Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, but the comparative outcomes of targeted treatment remain unclear. OBJECTIVE: To compare the clinical outcomes in patients treated for primary aldosteronism over time. METHODS: Medline and EMBASE were searched. Original studies reporting the incidence of mortality, major adverse cardiovascular outcomes (MACE), progression to chronic kidney disease, or diabetes following adrenalectomy vs medical therapy were selected. Two reviewers independently abstracted data and assessed study quality. Standard meta-analyses were conducted using random-effects models to estimate relative differences. Time to benefit meta-analyses were conducted by fitting Weibull survival curves to estimate absolute risk differences and pooled using random-effects models. RESULTS: 15 541 patients (16 studies) with PA were included. Surgery was consistently associated with an overall lower risk of death (hazard ratio [HR] 0.34, 95% CI 0.22-0.54) and MACE (HR 0.55, 95% CI 0.36-0.84) compared with medical therapy. Surgery was associated with a significantly lower risk of hospitalization for heart failure (HR 0.48 95% CI 0.34-0.70) and progression to chronic kidney disease (HR 0.62 95% CI 0.39-0.98), and nonsignificant reductions in myocardial infarction and stroke. In absolute terms, 200 patients would need to be treated with surgery instead of medical therapy to prevent 1 death after 12.3 (95% CI 3.1-48.7) months. CONCLUSION: Surgery is associated with lower all-cause mortality and MACE than medical therapy for PA. For most patients, the long-term surgical benefits outweigh the short-term perioperative risks.


Diabetes Mellitus , Hyperaldosteronism , Hypertension , Renal Insufficiency, Chronic , Humans , Time , Hyperaldosteronism/drug therapy , Hyperaldosteronism/surgery
16.
Hypertension ; 80(12): 2495-2500, 2023 Dec.
Article En | MEDLINE | ID: mdl-37800386

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?


Hyperaldosteronism , Hypertension , Humans , Spironolactone/therapeutic use , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Antihypertensive Agents/therapeutic use , Hypertension/diagnosis , Hypertension/drug therapy , Blood Pressure , Aldosterone , Renin
17.
BMC Psychiatry ; 23(1): 787, 2023 10 27.
Article En | MEDLINE | ID: mdl-37891534

BACKGROUND: Primary aldosteronism (PA) is an adrenal gland disease, that induces increased secretion of the mineralocorticoid, aldosterone, resulting in symptoms such as hypertension. This study reports a patient with agoraphobia and panic attacks, associated with PA. This patient's psychiatric symptoms improved after treatment with eplerenone, a mineralocorticoid receptor antagonist. CASE PRESENTATION: The patient was a 40-year-old female with agoraphobia, which refers to the irrational fear of situations that may cause anxiety, and panic attacks characterized by profuse sweating, palpitations, and generalized weakness. She was diagnosed with hypertension from PA. Subsequently, she received treatment with eplerenone, which improved her agoraphobia and panic attacks. CONCLUSIONS: There have been no previous reports on PA associated with agoraphobia and panic attacks that improved with pharmacotherapy. Patients with agoraphobia and panic attacks should be evaluated for PA. In patients with PA, pharmacotherapy with eplerenone should be considered.


Hyperaldosteronism , Hypertension , Panic Disorder , Humans , Female , Adult , Panic Disorder/complications , Panic Disorder/drug therapy , Agoraphobia/complications , Agoraphobia/drug therapy , Agoraphobia/diagnosis , Eplerenone/therapeutic use , Hyperaldosteronism/complications , Hyperaldosteronism/drug therapy
18.
Hypertension ; 80(12): 2601-2610, 2023 Dec.
Article En | MEDLINE | ID: mdl-37855142

BACKGROUND: Primary aldosteronism (PA) is associated with increased mortality. The extent to which this phenomenon is affected by sex, age, comorbidities at diagnosis, and different treatment modalities is largely unknown. The objective was to determine all-cause and cause-specific mortality in a population-based cohort of patients with PA and the impact of age at diagnosis, sex, comorbidities, and treatment modalities. METHODS: We used national registers to identify patients diagnosed with PA between 1997 and 2019 (n=2419) and controls (n=24 187) from the general population, matched for sex, age, and county of residence. We obtained mortality data from the Cause-of-Death Register. We used Cox regression models, adjusted for socioeconomic factors and diabetes, to estimate adjusted hazard ratios (HRs [95% CI]). RESULTS: Overall, 346 (14.3%) patients with PA and 2736 (11.3%) controls died during a median follow-up time of 8.1 years. PA was associated with increased risk from all-cause mortality (HR, 1.23 [95% CI, 1.10-1.38]), death from cardiovascular disease (HR, 1.57 [95% CI, 1.30-1.89]), and stroke (HR, 1.85 [95% CI, 1.16-2.93]). Patients with cardiovascular disease at diagnosis (HR, 1.53 [1.26-1.85]), age >56 years (HR, 1.28 [95% CI, 1.13-1.45]), patients treated with a low dose of a mineralocorticoid receptor antagonist (HR, 1.30 [95% CI, 1.02-1.66]), and untreated patients (HR, 2.51 [95% CI, 1.72-3.67]) had excess mortality. CONCLUSIONS: Mortality, mainly due to cardiovascular disease, is increased in patients with PA compared with controls from the general population, particularly in patients aged >56 years, patients with preexisting cardiovascular comorbidities, and patients receiving low dose of a mineralocorticoid receptor antagonist.


Cardiovascular Diseases , Hyperaldosteronism , Humans , Cardiovascular Diseases/epidemiology , Sweden/epidemiology , Mineralocorticoid Receptor Antagonists/therapeutic use , Risk Factors , Hyperaldosteronism/diagnosis , Hyperaldosteronism/drug therapy , Hyperaldosteronism/epidemiology
19.
Expert Opin Investig Drugs ; 32(11): 985-995, 2023.
Article En | MEDLINE | ID: mdl-37883217

INTRODUCTION: Hypertension, a global health concern, poses a significant risk for other cardiovascular diseases. While lifestyle modifications and interventions like the Dietary Approaches to Stop Hypertension (DASH) diet offer some respite, their maintenance can be challenging. Recently, the spotlight has turned toward the renin-angiotensin-aldosterone system, a crucial player in the pathophysiology of hypertension. Contrary to other drugs, Baxdrostat, an innovative aldosterone synthase inhibitor (ASI), targets aldosterone synthesis, mitigating negative systemic effects. AREAS COVERED: Baxdrostat showcases rapid absorption, high oral bioavailability, and significant selectivity for aldosterone synthase which presents a proactive approach to hypertension management by reducing aldosterone levels. Early trials have demonstrated its potential in lowering blood pressure in resistant hypertension cases. Current clinical trials are also exploring its application in primary aldosteronism and chronic kidney disease, with preliminary findings indicating its promise as a novel antihypertensive agent. This article encapsulates the current state of knowledge regarding Baxdrostat, encompassing its uses, ongoing clinical trials, and potential future clinical applications. EXPERT OPINION: Future research endeavors will play a pivotal role in unveiling the effectiveness and safety profile of this novel medication. Thus, positioning the baxdrostat as a valuable addition to the armamentarium of antihypertensive agents, especially for patients with complex, multifactorial hypertensive conditions.


Hyperaldosteronism , Hypertension , Humans , Aldosterone/pharmacology , Aldosterone/therapeutic use , Cytochrome P-450 CYP11B2/pharmacology , Hyperaldosteronism/drug therapy , Hypertension/drug therapy , Renin-Angiotensin System , Antihypertensive Agents/adverse effects , Enzyme Inhibitors/pharmacology , Mineralocorticoid Receptor Antagonists/pharmacology , Renin/pharmacology , Renin/therapeutic use , Clinical Trials, Phase II as Topic
20.
JCI Insight ; 8(20)2023 Oct 23.
Article En | MEDLINE | ID: mdl-37698934

Somatic gain-of-function mutations in the L-type calcium channel CaV1.3 (CACNA1D gene) cause adrenal aldosterone-producing adenomas and micronodules. De novo germline mutations are found in a syndrome of primary aldosteronism, seizures, and neurologic abnormalities (PASNA) as well as in autism spectrum disorder. Using CRISPR/Cas9, we here generated mice with a Cacna1d gain-of-function mutation found in both adenomas and PASNA syndrome (Cacna1dIle772Met/+). These mice show reduced body weight and increased mortality from weaning to approximately 100 days of age. Male mice do not breed, likely due to neuromotor impairment, and the offspring of female mice die perinatally, likely due to lack of maternal care. Mice generated by in vitro fertilization showed elevated intracellular calcium in the aldosterone-producing zona glomerulosa, an elevated aldosterone/renin ratio, and persistently elevated serum aldosterone on a high-salt diet as signs of primary aldosteronism. Anesthesia with ketamine and xylazine induced tonic-clonic seizures. Neurologic abnormalities included hyperlocomotion, impaired performance in the rotarod test, impaired nest building, and slight changes in social behavior. Intracellular calcium in the zona glomerulosa, aldosterone levels, and rotarod performance responded to treatment with the calcium channel blocker isradipine, with implications for the therapy of patients with aldosterone-producing lesions and with PASNA syndrome.


Adenoma , Autism Spectrum Disorder , Hyperaldosteronism , Humans , Male , Female , Mice , Animals , Aldosterone , Hyperaldosteronism/drug therapy , Hyperaldosteronism/genetics , Isradipine , Calcium , Mutation , Seizures
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