Cause Of Secondary Hypertension Research Articles

OR02-03 Twenty-four-hour Tissue Microdialysis Of Aldosterone And Metabolites In Primary Aldosteronism

Abstract Disclosure: M.A. Grytaas: None. P. Methlie: None. I. Marinelli: None. E. Zavala: None. M. Øksnes: None. T. Upton: None. K. Simunkova: None. D.A. Vassiliadi: None. K. Løvås: None. S. Bensing: None. I. Botusan: None. K. Berinder: None. G.M. Russell: None. G. Ueland: None. O. Kampe: None. S. Tsagarakis: None. S.L. Lightman: None. E.S. Husebye: None. Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension but is grossly underdiagnosed. Early detection, accurate discrimination between unilateral and bilateral PA and appropriate treatment are vital to prevent cardiovascular and renal complications. The current workup however is a cumbersome, multistep process that may not detect dynamic aldosterone variability or nocturnal hypersecretion. Furthermore, subtype determination with adrenal venous sampling is invasive and technically challenging. Novel dynamic 24-hour steroid profiling may represent a major step forward in the diagnostics and subtyping of PA. Aim: To assess 24-hour rhythmicity of aldosterone and metabolites in PA, and to develop a novel dynamic diagnostic tool to discriminate PA from healthy subjects (HS), using tissue microdialysis. Material and methods: Twenty-minute frequency microdialysis fractions were collected over 24 hours from 64 ambulatory patients with PA (26 bilateral, 24 unilateral, 14 with undetermined subtype) using the U-Rhythm sampler followed by multiplex hormone assay liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixteen patients subsequently treated with adrenalectomy for unilateral PA had additional postoperative samplings. Microdialysis samplings from 214 HS were used as controls. We calculated statistical distributions of dynamic biomarkers of abnormality, and developed a machine learning classifier that discriminates PA from HS. Results: Although there were large interindividual variations, PA patients did show a disturbed circadian rhythmicity of aldosterone compared with HS, including some with multiple very high ultradian spikes. Unilateral PA had higher aldosterone spikes and more disturbed rhythmicity compared with bilateral PA. A profound reduction of aldosterone levels and normalisation of rhythmicity was seen post adrenalectomy. Applying a Random Forest classifier in a subgroup of 20 PA patients, 82% specificity and 85% sensibility were achieved to discriminate PA from HS. Our analysis also suggests 18-hydroxycortisol as the most discriminative dynamic biomarker. Conclusions: We demonstrate for the first time circadian and ultradian rhythms of aldosterone in a large cohort of PA compared with HS. Based on our preliminary results, dynamic 24-hour samplings may provide a novel method for diagnosing and subtyping PA, and assess biochemical cure after adrenalectomy. Presentation: Thursday, June 15, 2023

FRI139 Identification Of Robust Aldosterone-Producing Adenomas-related Genes Using Adrenal Genome-wide Transcriptome Analysis

Abstract Disclosure: S. Lee: None. T. Lee: None. G. Yoo: None. J. Lim: None. Primary aldosteronism (PA), the most common cause of secondary hypertension, is caused by aldosterone overproduction in one or two adrenal glands. It carries a higher risk of cardiovascular disease and mortality compared to essential hypertension. In an effort to identify the underlying molecular mechanisms regarding aldosterone secretion and cell proliferation in aldosterone-producing adenomas (APA), genome-wide transcriptome analyses have been conducted; however, there are still some limitations that need to be addressed since a relatively small number of samples were analyzed at a single center in most studies. In this study, we performed integrative and systematic analysis using adrenal transcriptome datasets to verify candidate genes robustly associated with APA and obtain more generalized signatures involved in the pathophysiology of PA. Three mRNA datasets for adrenal tissues (GSE8514, GSE60042, and GSE64957) were obtained from the Gene Expression Omnibus Database. For the first two datasets, normal adrenal samples from patients with renal cell carcinoma and adrenal tissue samples adjacent to APA were included as controls, respectively. In GSE64957, zona glomerulosa (ZG) and zona fasciculata (ZF) samples were analyzed separately in the current study (GSE64957ZG and GSE64957ZF). Differentially expressed gene (DEG) investigation and comparative analysis were conducted using the limma method. The selection criteria for APA-related genes were as follows: those that are significantly dysregulated in more than three of the four datasets and show a consistent trend of up- or down-regulation in four datasets. 5,375 genes were present in all transcriptome datasets; for the GSE64957ZG, 57 DEGs were identified in the APA group, among which 14, 7, and 37 genes were also dysregulated in the APA group of GSE64957ZF, GSE8514, and GSE60042, respectively. All comparisons among four lists of DEGs exhibited significant enrichment results. The highest degree of overlap was shown in the DEG pair of GSE64957ZG-GSE60042. As a result, approximately 20 genes (12 upregulated and 12 downregulated DEGs), including CYP11B2, PCP4, and ATP2A3, were selected as the final APA-related genes. This study demonstrated several candidate genes that are strongly relevant to APA by examining whole genome disease-related signatures. Besides CYP11B2, it seems that alteration in PCP4 and ATP2A3 genes would be much more involved in the pathogenesis of PA, which warrants further investigation along with validation for the role of the remaining genes. Presentation: Friday, June 16, 2023

FRI125 Recurrence Of Primary Aldosteronism Long-Term After Adrenalectomy For Aldosterone-Producing Adenoma With KCNJ5 Gene Mutation: A Two-Cases Report

Abstract Disclosure: K. Aiga: None. M. Kometani: None. D. Aono: None. S. Karashima: None. T. Yoneda: None. Primary aldosteronism (PA) is a major cause of secondary hypertension. PA is known to have higher prevalence of cerebral or cardiovascular complications, indicating the importance of early detection and treatment for PA. PA is caused by autonomous secretion of aldosterone in the adrenal glands. PA is characterized by high plasma aldosterone concentration, low plasma renin activity and hypokalemia. PA is classified into unilateral PA (aldosterone-producing adenoma [APA] or unilateral hyperplasia) and bilateral PA (bilateral adrenal hyperplasia). PA with aldosterone excess in bilateral adrenal glands is defined as bilateral PA. On the other hand, PA with aldosterone excess in unilateral adrenal gland is defined as unilateral PA. Strategies for PA treatment depends on the subtype of PA. Medication by mineralocorticoid receptor antagonists is a common treatment for bilateral PA. Adrenalectomy is the most efficient treatment for unilateral PA. In general, patients tend to maintain normal serum potassium level and blood pressure after adrenalectomy, and recurrence of PA is extremely rare. Recently, mutation in the gene named KCNJ5 was found to derive APA. Herein, we report two cases of PA recurrence more than 10 years after surgical treatment for APA. Somatic mutation in KCNJ5 was detected in the first occurrence of PA in both cases. First case, a 52-year-old woman was examined for hypertension 22 years after total adrenalectomy of the right adrenal gland. Recurrent PA was diagnosed based on high aldosterone-renin-ratio (ARR), identification of left adrenal gland tumor by computed tomography (CT), and a confirmatory test. Second case, a 65-year-old man was examined for hypertension 17 years after total adrenalectomy of the left adrenal gland. He had maintained his blood pressure using medication since the onset of hypertension 4 years after the surgery. A year later, a high ARR was observed. PA recurrence was determined by a right adrenal gland tumor noted on CT and a confirmatory test. Tissues of the adrenal gland were obtained from adrenalectomy in both cases. Histopathological analysis revealed presence of one adenoma in the first case, while two adenomas were confirmed in the second case. Somatic mutation in KCNJ5 gene was detected in both cases. To date, there are no specific guidelines established for the management of recurrent PA. Early detection is crucial for the prevention of severe cardiovascular diseases. Long-term follow-up is recommended after the treatment of PA. Presentation: Friday, June 16, 2023

Key to the Treatment of Primary Aldosteronism in Secondary Hypertension: Subtype Diagnosis.

Primary aldosteronism (PA) is a leading global cause of secondary hypertension. Subtyping diagnosis of PA is the key to surgery, but accurate classification of PA is crucial but challenging in clinical diagnosis and treatment. The purpose of this review is to provide a summary of current literature and propose subtyping diagnosis flow chart to help us classify PA quickly and accurately. Early diagnosis and accurate typing are essential for the timely treatment and appropriate management of PA. For most patients, adrenal venous sampling (AVS) is the central choice for typing diagnosis, but AVS is invasive and difficult to promote effectively. CT can help identify unilateral typical adenomas in select patients to avoid AVS. New radionuclide imaging has shown value in the diagnosis and classification of PA, which distinguishes adrenocortical hyperplasia from adenoma and can replace AVS in some patients. Accurately diagnosing unilateral PA is crucial for determining the appropriate treatment strategy for PA. The simple flow chart of PA subtyping diagnosis based on the current literature needs to be verified and evaluated by follow-up researches.

Evaluation of Blood Pressure in Children Treated with Ceftriaxone: A Case-Control Study

Background: In children, high blood pressure can develop into hypertension and its consequences during puberty and adulthood. High blood pressure in children is often secondary to other causes, including renal diseases. Nephrolithiasis is one of the causes of secondary hypertension. The extensive use of cephalosporins in hospitals, particularly ceftriaxone, can result in nephrolithiasis. Therefore, the purpose of this study was to assess the relationship between ceftriaxone treatment and elevated blood pressure in children. Method: The research was conducted as a case-control study over an 18-month period from 2018 to 2019. In this study, blood pressure was measured in 111 children aged 3-13 years who were hospitalized at Amir Kabir Hospital in Arak and received ceftriaxone for at least 48 hours. As a control group, 111 children who did not receive ceftriaxone had their blood pressure measured. The blood pressure levels and percentiles of children in the two groups were then compared. Result: In the case and control groups, the mean age was 5.1±1.61 and 6.04±2.4 years, and the mean height was 109.17±10.71 and 114.86±12.95 cm, respectively. A slightly higher mean systolic blood pressure percentile was observed in the case group (65.59±18.17) than in the control group (65.28±14.51) (P=0.112), and the mean diastolic blood pressure percentile was also slightly higher in the case group (58.89±18.88) than in the control group (54.85±19.28) (P=0.317). The difference in diastolic blood pressure was greater than in systolic blood pressure. However, these detected differences were slight and not statistically significant. Conclusion: This study showed no association between blood pressure levels and ceftriaxone treatment in children older than three years who received the medicine for at least 48 hours. However, additional research is suggested, focusing on the effects of the medicine at higher doses and over a longer period of time following administration.

Characterizing Hypertension Specialist Care in Canada: A National Survey

BackgroundThe hypertension specialist often receives referrals of patients with young-onset, severe, difficult-to-control hypertension, patients with hypertensive emergencies, and patients with secondary causes of hypertension. Specialist hypertension care compliments primary care for these complex patients and contributes to an overall hypertension control strategy. The objective of this study was to characterize hypertension centres and the practice patterns of Canadian hypertension specialists. MethodsAdult hypertension specialists across Canada were surveyed to describe hypertension centres and specialist practice in Canada, including the following: the patient population managed by hypertension specialists; details on how care is provided; practice pattern variations; and differences in access to specialized hypertension resources across the country. ResultsThe survey response rate was 73.5% from 25 hypertension centres. Most respondents were nephrologists and general internal medicine specialists. Hypertension centres saw between 50 and 2500 patients yearly. A mean of 17% (± 15%) of patients were referred from the emergency department and a mean of 52% (± 24%) were referred from primary care. Most centres had access to specialized testing (adrenal vein sampling, level 1 sleep studies, autonomic testing) and advanced therapies for resistant hypertension (renal denervation). Considerable heterogeneity was present in the target blood pressure in young people with low cardiovascular risk and in the diagnostic algorithms for investigating secondary causes of hypertension. ConclusionsThese results summarize the current state of hypertension specialist care and highlight opportunities for further collaboration among hypertension specialists, including standardization of the approach to specialist care for patients with hypertension.

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.

Impact of Hemodialysis Time Prolongation on Blood Pressure Control

Abstract Introduction Hypertension prevalence among ESRD patients range from 76% to 90%. Sodium & volume overload is among the main mechanisms. Increasing the duration of dialysis time, either by longer session hours or increased sessions, aiming at reducing the dry weight to achieve euvolemia, may be beneficial for individuals who failed to achieve target BP or ideal volume status during standard HD prescription hours. We aim to study the effect of increasing hemodialysis session time on blood pressure control. Methods This observational study was conducted on 50 adult clinically stable hypertensive prevalent HD patients on thrice weekly maintenance HD. Patients with secondary causes of hypertension and Patients with decompensated medical conditions were excluded from our study. Patients were divided into 2 groups: (A) 25 patients who received longer session hemodialysis session (4.5 hour) and (B) 25 patients HD who received the usual 4 hours session. Revision of antihypertensive medications& dosages, dry weight was reassessed regularly, and they were instructed to restrict their salt intake as much as possible aiming at BP < 140/90 mmHg. they were followed up for a period of 6 months assess changes of pre-dialysis blood pressure to monitor response. Results Patients in both groups were age matched, with male sex predominance (64%in groupA&56% in groupB). Patients in both groups underwent their HD sessions mostly through AVF (68% and 92% for group A and B respectively). Ultrafiltration volume declined significantly with longer HD sessions compared to conventional sessions (pvalue <0.001 vs 0.523). Longer HD session time session was associated with highly significant decline in mean SBP, (p-value <0.001). Longer HD session time session was associated with highly statistically significant decline in mean DBP, (p-value <0.001). The decline in mean perdialysis SBP & DBP was -17.27 &-9 mmHg, respectively and the rate of decline of postdialysis SBP & DBP was -6.45 & -12.38 mmHg, respectively at 6th month compared to values in 1st month of follow up period. Conclusion Longer HD session duration is associated with better improvement in UF volume, mean SBP&DBP, pre-dialysis SBP&DBP and post-dialysis SBP&DBP as well.

Simple standing test without furosemide is useful in the diagnosis of primary aldosteronism

Primary aldosteronism (PA) is a well-known cause of secondary hypertension. We have long performed the simple standing test in patients with PA. On the other hand, there are few reports on the usefulness of the simple standing test in PA. This study is a single-center, retrospective, observational study. A total of 173 patients with hypertension or adrenal tumor admitted to Kawasaki Medical School were included. Eighty patients who met the exclusion criteria were excluded, and 31 patients without PA (non-PA), 26 patients with unilateral PA, and 36 patients with bilateral PA were included in the study. The simple standing test was performed after 120 min of standing or sitting followed, and the aldosterone/renin ratio (ARR) and percentage of increase plasma aldosterone concentration (%increase of PAC) was calculated. The mean ARR in the simple standing test in unilateral PA (1143 (528–2200)) and bilateral PA subjects (521 (374–765)) were significantly higher compared to non-PA subjects (152 (102–240)) (p < 0.0001, p = 0.0013, respectively). The percentage increase of PAC after standing loading was significantly lower in unilateral PA subjects (110 (96–140)) compared to non-PA subjects (187 (155–244)) (p = 0.0003), with no difference between non-PA and bilateral PA subjects (p = 0.99). The cutoff value of the ARR in the simple standing test for diagnosis of PA in this study was 364 (AUC = 0.948, sensitivity = 83.8%, specificity = 93.5%, false positive rate = 3.7%, false negative rate = 25.6%, p < 0.001), which was not inferior to the diagnostic performance of the captopril loading test. The diagnostic performance of the simple standing test for PA was not inferior to that of the captopril loading test. The percentage increase of PAC in unilateral PA subjects was significantly lower compared to bilateral PA subjects. These results demonstrate the usefulness of the simple standing test, which can be performed simultaneously with general screening tests of PA.

Pheochromocytoma “the great masquerader” presenting as hypertensive retinopathy: A case report

At first glance, the ophthalmologist might seem to be invading a medical territory, not in their domain, when they write of Pheochromocytoma, but this is not true. Pheochromocytoma is an uncommon tumor that develops in chromaffin cells of the paraganglia or adrenal medulla which can give rise to malignant hypertension (systolic &amp;#62;200 mg Hg &amp; diastolic &amp;#62;140). Pheochromocytoma-induced hypertension may present with many physical symptoms and signs, although sometimes the ocular features are the only clues that are present. Clinical suspicion of secondary hypertension should always be considered when fundus examination shows hypertensive retinopathy changes in a younger age group (18 years in our case). The patient, in our case, developed hypertensive retinopathy with macular star development due to Pheochromocytoma. It stresses the significance of a thorough search for a secondary cause of hypertension in young patients.

Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks.

Primary aldosteronism (PA) is the most common cause of secondary hypertension and is associated with increased morbidity and mortality when compared with blood pressure-matched cases of primary hypertension. Current limitations in patient care stem from delayed recognition of the condition, limited access to key diagnostic procedures, and lack of a definitive therapy option for nonsurgical candidates. However, several recent advances have the potential to address these barriers to optimal care. From a diagnostic perspective, machine-learning algorithms have shown promise in the prediction of PA subtypes, while the development of noninvasive alternatives to adrenal vein sampling (including molecular positron emission tomography imaging) has made accurate localization of functioning adrenal nodules possible. In parallel, more selective approaches to targeting the causative aldosterone-producing adrenal adenoma/nodule (APA/APN) have emerged with the advent of partial adrenalectomy or precision ablation. Additionally, the development of novel pharmacological agents may help to mitigate off-target effects of aldosterone and improve clinical efficacy and outcomes. Here, we consider how each of these innovations might change our approach to the patient with PA, to allow more tailored investigation and treatment plans, with corresponding improvement in clinical outcomes and resource utilization, for this highly prevalent disorder.

Predictive model for persistent hypertension after surgical intervention of primary aldosteronism

Primary aldosteronism (PA) is one of the most common causes of secondary hypertension and is potentially curable. However, a large number of patients still undergo persistent hypertension (PHT) after unilateral adrenal surgery. This research retrospectively studied the factors associated with this clinical difficulty and established a prediction model for the postoperative PHT; Methods: 353 patients from 2014 to 2021 with PA undergoing unilateral adrenal surgery were enrolled in this study. Clinical and biochemical characteristics were reviewed and the associating factors were examined using univariate and multivariate analysis. A nomogram-based prediction model was established correspondingly; results: 46.2% (163/190) of patients had post-surgical PHT. Multivariate analysis suggested that BMI ≥ 25, diabetes, duration of hypertension, male gender, and ARR were independent predictors of PHT after surgery. The prediction model based on the nomogram showed good discrimination ability (the C index of the training group and the validation group were 0.783 and 0.769, respectively), and the calibration curves and the Hosmer–Lemeshow test were good as well. Clinical usefulness was quantified using the decision curve analysis; This nomogram is an integration of the clinical and biochemical data of patients before surgery, and is a reliable tool with high accuracy for predicting the postoperative PHT in patients with PA.

The Value of Targeting CXCR4 With 68Ga-Pentixafor PET/CT for Subtyping Primary Aldosteronism.

Primary aldosteronism (PA) is one of the leading causes of secondary hypertension, and its diagnostic subtyping consistently presents a clinical challenge. This study aimed to investigate the potential of 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) in PA classification and its applicability in guiding the development of clinical treatment plans by increasing the sample size. We prospectively enrolled 120 patients with either PA or nonfunctional adenoma (NFA) for analysis. All patients underwent 68Ga-Pentixafor PET/CT. Of these, 11 patients underwent adrenal venous sampling (AVS), 77 underwent adrenalectomy, 76 received pathological diagnoses, and 71 underwent immunohistochemical detection of aldosterone synthase (CYP11B2). Immunohistochemistry for C-X-C chemokine receptor 4 (CXCR4) was performed in 62 cases. Follow-up was conducted for all patients. Among the 120 patients, 66 were diagnosed with aldosterone-producing adenoma (APA), 33 with idiopathic hyperaldosteronism (IHA), and 21 with NFA. For APA patients, the sensitivity, specificity, and accuracy of visual analysis using 68Ga-Pentixafor PET/CT were 92.40%, 94.40%, and 93.33%, respectively. Furthermore, for APA patients with a nodule greater than 1 cm in diameter, when the maximum standard uptake value was 7.3 or greater, the specificity was 100%; and for APA patients with a nodule less than 1 cm in diameter, 68Ga-Pentixafor PET/CT also exhibited high sensitivity. AVS was successfully performed in 5 patients. Among the 5 patients, the concordance rate between the AVS and 68Ga-Pentixafor PET/CT for PA subtyping was 60%. In the 77 patients who underwent adrenalectomy, 61 PET/CT scans displayed positive lesions, all of which benefited from the surgery. Additionally, the concordance rate between 68Ga-Pentixafor PET/CT imaging and CYP11B2 was 81.69%. 68Ga-Pentixafor PET/CT is a reliable and noninvasive functional imaging technique that demonstrates high accuracy in classifying PA and provides valuable guidance for clinical treatment decision-making.

The Impact of Obesity on the Resolution of Hypertension Following Adrenalectomy for Primary Hyperaldosteronism

BackgroundThis study aims to determine the impact of patient obesity on the resolution of hypertension and pill burden post-adrenalectomy for PA. Primary hyperaldosteronism (PA) is the most common cause of secondary hypertension that may be remedied with surgery (unilateral adrenalectomy). Obesity may independently cause hypertension through several mechanisms including activation of the renin–angiotensin–aldosterone pathway. The influence of obesity on the efficacy of adrenalectomy in PA has not been established.MethodsThis is a retrospective analysis of prospectively collected data on patients undergoing adrenalectomy for PA at a single, tertiary-care surgical centre from January 2015 to December 2020. Electronic health records of patients were screened to collect relevant data. The primary outcomes of the study include post-operative blood pressure, the reduction in the number of anti-hypertensive medications and potassium supplementation burden post-adrenalectomy.ResultsFifty-three patients were included in the final analysis. There was a significant reduction in the blood pressure and the number of anti-hypertensive medications in all patients after adrenalectomy (p < 0.001). Of the 34 patients (64.2%) with pre-operative hypokalaemia, all became normokalaemic and were able to stop supplementation. However obese patients required more anti-hypertensive medications to achieve an acceptable blood pressure than overweight or normal BMI patients (p < 0.01). Multivariate logistic regression analysis showed that male gender and BMI were independent predictors of resolution of hypertension (p <0.01).ConclusionUnilateral adrenalectomy improves the management of hypertension and hypokalaemia when present in patients with PA. However, obesity has an independent deleterious impact on improvement in blood pressure post-adrenalectomy for PA.

Advances in the molecular imaging of primary aldosteronism.

Primary aldosteronism (PA) is the most common cause of secondary hypertension. It predisposes to adverse outcomes such as nephrotoxicity and cardiovascular damage, which are mediated by direct harm from hypertension to the target organs. Accurate subtype diagnosis and localization are crucial elements in choosing the type of treatment for PA in clinical practice since the dominant side of aldosterone secretion in PA affects subsequent treatment options. The gold standard for diagnosing PA subtypes, adrenal venous sampling (AVS), requires specialized expertise, the invasive nature of the procedure and high costs, all of which delay the effective treatment of PA. Nuclide molecular imaging is non-invasive and has wider applications in the diagnosis and treatment of PA. This review aims to provide a summary of the application of radionuclide imaging in the diagnosis, treatment management and prognostic assessment of PA.

Rapidly reversible acute neurological, renal, and cardiac impairment during malignant hypertension

BackgroundMalignant hypertension is a model of the rapid changes that a high afterload and renin-angiotensin levels can induce on target organs such as the heart. We present a case of a young man affected by malignant hypertension with multi-organ involvement who showed quick remission after adequate antihypertensive treatment.Case summaryA 41-year-old jazz pianist with a family history of coronary artery disease presented to the emergency department for asthenia and epigastric pain, associated with right eye visual impairment. No neurological symptoms. An echocardiogram showed left ventricular hypertrophy with severe impairment of ejection fraction (22%) due to global hypokinesia. There was renal insufficiency (creatinine 2.51 mg/dl, eGFR 34 ml/min, HS Troponin T 127 pg/dl, NT pro-BNP 22,672 pg/ml, CRP 32 mg/L, sodium 129 mEq/L with normal kaliemia. The following day, anterior T wave inversion was observed in the electrocardiogram. At a cardiac magnetic resonance. Concentric hypertrophy of the left ventricle was observed with normal myocardial T1 mapping values (1100 ± 38 ms), ruling out Fabry’s disease. There was no obvious myocardial edema at T2 weighted. The viral panel for acute myocarditis resulted in negative. After the exclusion of all possible secondary causes, malignant essential hypertension was the final diagnosis, and additional tests confirmed multi-organ damage. An ophthalmological examination demonstrated hypertensive retinopathy with hemorrhages, cottony exudates, and macular lipid exudation, especially in the right eye. A brain MRI showed small areolas of T2 hyperintensity in the white matter of both cerebral hemispheres, suggestive of chronic microangiopathy, and left nuclear micro lacunar ischemia.The patient was treated with full-dose calcium channel blockers (amlodipine 10 mg), beta-blockers (bisoprolol 10 mg), alpha2 agonists (slow-release clonidine patch), selective a1 blocker (doxazosine 16 mg), and furosemide 50 mg. After the exclusion of renal stenosis and improvement of renal function, Ramipril was added up to a final dose of 10 mg daily. In parallel with the achievement of a satisfactory blood pressure control, visual impairment disappeared with a reduction of retinal ischemic exudates and hemorrhages at the ophthalmological follow-up assessment.At the time of discharge, an echocardiographic re-evaluation confirmed concentric hypertrophy of the left ventricle with markedly reduced wall thicknesses, with a partial recovery in left ventricular ejection function (EF 44%).Six months after discharge, the patient is in good general condition under optimal medical therapy (without furosemide) with normalized blood pressure values (130–140/80 mmHg). At 6 months from discharge, creatinine was only mildly increased (1.5 mg/dl, eGFR 59.5 ml/min) and NT-pro BNP nearly normalized (452 pg/ml).DiscussionMalignant hypertension is a cardiovascular emergency and requires immediate and careful intervention to lower blood pressure and reduce organ injury. It is an exclusion diagnosis that can be advanced once the causes of secondary hypertension have been excluded. Remission of organ injury is possible and might be rapid under adequate antihypertensive treatment, but patients require a close follow-up.

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.

ARTERIAL HYPERTENSION DOES NOT SLEEP

Objective: Sleep apnea is a secondary cause of hypertension and is suggested by non-dipper profile at ambulatory blood pressure monitoring (ABPM). The prevalence is estimated between 30-50% in hypertensive patients. Design and method: A 60 year-old man with cardiovascular risk factors (hypertension, diabetes, dislipidemia, obesity, transient ischemic attack) presented to the outpatient clinic with high values of self-monitoring blood pressure despide multiple lowering blood pressure therapy. On physical examination his body mass index was 39.6 kg/m2, neck circumference 50 cm. The ECG was in sinus rhythm with hypertrophic phenotype confirmed by echocardiogram, which also showed left ventricle preserved ejection fraction, grade III diastolic dysfunction, mildly enlarged left atrium. Laboratory tests exluded endocrinologic and renal causes. Despite lifestyle changes and a good adherence to multiple associated antihypertensive treatment, ABPM revealed a non-dipper profile (dipping index 4.86%) (figure 1). The patient underwent the polygraphy test which showed the apnea-hypopnea index (AHI) of 10.6, which led to a diagnosis of mild sleep apnea, the t90% of 57 pointed out severe hypoxia and high pulse variances 104 (figure 1). The further Holter monitoring revealed episodes of atrial flutter and atrial fibrillation. Results: After 3 months of continuous positive airways pressure (CPAP) therapy, on top of the same antihypertensive drugs and anticoagulation, led to optimal blood pressure values and normal ABPM profile (figure 2). The polygraphy parameters AHI, t90% and pulse variances normalised too. (figure 1) Conclusions: Obstructive sleep apnea is a prevalent secondary cause of hypertension and atrial arythmias, still greatly underdiagnosed. It is associated with abdominal obesity, large neck, snoring, daytime fatigue and a decrease in the quality of life. Polygraphy is a feasible method for diagnose sleep apnea and monitoring the treatment. CPAP treatment abolishes apnea, normalises blood oxigenation thereby prevents arterial pressure surges, restoring the nocturnal ‘dipping’ pattern and normal sinus rythm.

CASE REPORT OF A RARE CAUSE OF SECONDARY HYPERTENSION ILLUSTRATING THE IMPORTANCE OF CARDIO-OBSTETRICS PRECONCEPTION COUNSELING

Objective: Our objective is to illustrate the value of preconception management of rare case of secondary hypertension namely Middle Aortic Coarctation (MAC), which is characterized by a constriction of the upper abdominal aorta. During pregnancy, MAC can lead to feto-maternal unfavorable hemodynamic balance (Fig.1). On the one hand, elevation of the arterial blood pressure (BP) of the upper part of the body increases the maternal cardiovascular risk i.e. stroke or aortic dissection. On the other hand, hypo-perfusion of the lower part of the body reduces uterine perfusion, increases fetal risk of preeclampsia, placental insufficiency or fetal growth restriction. Design and method: Here, we report the case of a 30-year-old woman with severe hypertension and plans to become pregnant. She previously underwent percutaneous transluminal angioplasty (PTA) and aortic stenting and presented with elevated BP in both arms (right 177/117 mmHg, left 180/121 mmHg) and decreased ABI bilaterally (Tab. 1). A computed tomography angiography of the aorta was performed showing an aortic stent in a supraceliac position with 79% in-stent stenosis. She underwent a new PTA with in-stent re-stenting (Fig. 2). Results: Post PCA, the four extremities BP measurements showed a reduction of her BP values and a normalization of the ABI bilaterally (Table 1). 24h-ABPM confirmed the BP reduction (mean 24h- systolic BP of 135 mmHg, diastolic BP of 101 mmHg), but still remaining-elevated. Therefore, we started an antihypertensive treatment with a successful BP control (125/82 mmHg). Conclusions: The management of MAC in already pregnant women can be particularly challenging. Indeed, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers are contraindicated. Furthermore, PTA during pregnancy expose the fetus to radiation and reports for CoA angioplasty and stenting during pregnancy are very limited. Herby, we decided on an interventional rather than conservative approach. This case illustrates the importance of preconception screening and treatment of chronic hypertension in women with plans to become pregnant. It highlights the fact that secondary causes of hypertension do not have to be overlooked in this population.

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.