Common Cause Of Hypertension Research Articles

'Essential' arterial hypertension: time for a paradigm change.

The exclusion of causes of hypertension is not systematically exploited in clinical practice. Therefore, essential hypertension is consistently presented as the most prevalent 'cause'. The paradox of a condition with unknown causes being described as a common cause of hypertension translates into a diagnosis of essential hypertension in most patients, which precludes the detection of a curable cause of hypertension. The aim of this review is to investigate how the notion of essential hypertension has developed and whether scientific evidence still support the notion of its high prevalence by examining the most recent studies. These studies provided solid scientific evidence that, when systematically sought for, secondary hypertension is quite common and that secondary hypertension is highly prevalent. The increased awareness should lead to a systematic search for, with the goal of curing or achieving a better control of high blood pressure, and ultimately improving patients' quality of life.

CARDIOVASCULAR OUTCOMES IMPROVE IN CHILDREN WITH RENOVASCULAR HYPERTENSION FOLLOWING ENDOVASCULAR AND SURGICAL INTERVENTIONS

Objective: Renovascular hypertension (RVH) is a common cause of hypertension in children. It is caused by renal artery stenosis reducing the blood supply to the renal parenchyma and activating the renin-angiotensin-aldosterone axis, often leading to cardiac remodelling. This is a longitudinal observational study that aims to describe the occurrence of hypertensive changes and their severity and also any improvement in cardiac remodelling after successful endovascular and/or surgical intervention in children with RVH. Design and method: All patients with RVH referred to our centre, who had received at least one endovascular intervention, were included. Data was collected by retrospective database review over a 22-year period. We assessed oscillometric blood pressure as well as eight echocardiographic parameters pre- and post-intervention: intraventricular septal diameter (IVSD), posterior wall diameter (PWD), left ventricular internal diastolic diameter (LVIDD), fractional shortening (FS), Relative Wall Thickness (RWT), Left Ventricular Mass (LVM) and Left Ventricular Ejection Fraction (LVEF). Results: 152 patients met inclusion criteria and had on average two endovascular interventions. Six children presented in frank heart failure. 54.4% achieved normal blood pressure (BP) control after intervention. Average z-scores improved in IVSD, PWD and FS; LVMI and RWT also improved. PWD saw the greatest reduction in mean difference in children with an abnormal (z-score reduction of 0.25, p<0.001) and severely abnormal (z-score reduction of 0.23, p<0.001) z-scores between pre- and post-intervention echocardiograms. 45.9% of children had a reduction in prescribed antihypertensive medications. Conclusions: Our study reports improvement in cardiac outcomes after either endovascular or surgical intervention. This is evidenced on BP control and echocardiogram changes in which almost half achieved normalisation in systolic BP readings and reduction in the number of children with abnormal echocardiographic parameters.

Prolonged Hypokalemia and Delayed Diagnosis of Primary Aldosteronism: Clinical Course and Risk Factors.

Primary aldosteronism (PA) is a common cause of hypertension (HT). However, diagnosis is often delayed, leading to poorer clinical outcomes. Hypokalemia with HT is characteristic of PA, and is an indication for screening. We evaluated if patients with PA had prolonged hypokalemia before diagnosis, the subsequent biochemical/clinical control, and factors associated with delayed diagnosis. Our study included all PA patients with hypokalemia diagnosed between 2001 and 2022. Delayed diagnosis was defined as duration of hypokalemia of more than 1 year from first occurrence to first evaluation by a PA specialist. Patients were reassessed post adrenalectomy using the Primary Aldosteronism Surgery Outcomes criteria. We performed multivariable analysis to assess for factors associated with delayed diagnosis. Among 240 patients with PA who presented with hypokalemia, 122 (51%) patients had delayed diagnosis, with prolonged hypokalemia of median duration 4.5 years (range, 2.4-7.5 years). Patients with delayed diagnosis were older, had longer duration of HT, higher pill burden, lower renal function, and more prevalent cardiovascular disease. Factors associated with delayed diagnosis included older age, presence of hyperlipidemia, and less severe hypokalemia (serum potassium >3.0 mmol/L). Compared to patients with early diagnosis, a lower proportion of those with delayed diagnosis underwent adrenal vein sampling (73% vs 58%) (P < .05). Sixty of 118 (50.8%) nondelayed, and 39 of 122 (32.0%) patients with delayed diagnosis, underwent surgery. Despite manifestation of hypokalemia, many patients with PA fail to be promptly screened. Greater emphasis in HT guidelines, and efforts to improve awareness of PA among primary care physicians, are urgently needed.

B-192 An LC-MS/MS Method using the Xevo TQ Absolute Mass Spectrometer for the Combined Analysis of Aldosterone and Plasma Renin Activity in Plasma for Clinical Research

Abstract Background Primary aldosteronism (PA) is a common cause of hypertension, whereby uncontrollable amounts of aldosterone are produced by a benign tumour or hyperplasia of the adrenal glands. Excess aldosterone results in significant sodium reabsorption in the kidneys, increasing water retention and blood volume, thereby causing hypertension. The renin-angiotensin-aldosterone system (RAAS) regulates the production of aldosterone and in this system, renin and aldosterone should move in synchronicity with each other throughout the day. Therefore, these two components are used to assess the status of the RAAS, particularly in the evaluation of new therapies in clinical research studies. Historically, the assessments of aldosterone and plasma renin activity (PRA) have been performed using separate methods using immunoassay or more recently liquid chromatography - tandem mass spectrometry (LC-MS/MS) platforms. One of the benefits of using LC-MS/MS for clinical research is the ability to measure multiple analytes across the proteome and metabolome using the same system and even in the same analysis to provide more information in less time and save costs. Here we evaluate a single LC-MS/MS method for the combined measurement of plasma aldosterone and renin activity for clinical research purposes. Methods Aldosterone certified reference material (Merck, UK) and Angiotensin I (Cambridge BioScience, UK) were used to create calibrators in 2% Bovine Serum Albumin (BSA) in Phosphate Buffered Saline (PBS). In-house QC material prepared in both 2% BSA in PBS and K2EDTA plasma (BioIVT, UK), were used to evaluate method precision. Plasma samples were analyzed using the newly developed method and the quantified results were compared to separate independent LC-MS/MS methods for aldosterone and plasma renin activity. Plasma samples were treated with generation buffer (Sodium acetate, EDTA, acetic acid, SBTI and PMSF) and mixed for three hours at 37 °C. Samples were precipitated, diluted and centrifuged prior to SPE. Sample supernatant was transferred to a Waters Oasis™ µElution 96 Well Plate, followed by a wash and elution. Using an ACQUITY™ UPLC™ I-Class System, samples were injected onto a Waters XBridge™ C8, 2.5 µm, 2.1 × 50 mm Column using a water/methanol/ammonium fluoride gradient elution profile and quantified with a Waters Xevo™ TQ Absolute Mass Spectrometer. Results The method demonstrated no significant carryover or matrix effects and was shown to be linear from 10 - 2500 pg/mL for aldosterone and 0.1–25 ng/mL/h for PRA. Analytical sensitivity investigations indicate the analytical sensitivity of this method would allow precise quantification (&amp;lt;20%) at 10 pg/mL and 0.1 ng/mL/h, for aldosterone and PRA, respectively. Coefficients of variation (CV) for total precision and repeatability on 5 analytical runs for low, mid and high QCs were all &amp;lt;10% (n = 25) for aldosterone and PRA. Comparison with samples previously analyzed by an independent LC-MS/MS method demonstrated good agreement for aldosterone and PRA. Conclusions We have successfully quantified aldosterone and renin activity in plasma in a single method using an SPE protocol with LC-MS/MS analysis, for clinical research purposes. The method demonstrates excellent linearity and precision, with minimal matrix effects. For Research Use Only. Not for Use in Diagnostic Procedures.

Primary hyperaldosteronism is associated with increased mortality and morbidity in patients with hypertension and diabetes.

Primary hyperaldosteronism (PA) is a common cause of hypertension. It is more prevalent in patients with diabetes. We assessed the cardiovascular impact of PA in patients with established hypertension and diabetes. Data from the National Inpatient Sample (2008-2016) was used to identify adults with PA with hypertension and diabetes comorbidities and then compared to non-PA patients. The primary outcome was in-hospital death. Secondary outcomes included ischemic stroke, hemorrhagic stroke, acute renal failure, atrial fibrillation, and acute heart failure. A total of 48,434,503 patients with hypertension and diabetes were included in the analysis, of whom 12,850 (0.03%) were diagnosed with primary hyperaldosteronism (PA). Compared to patients with hypertension and diabetes but no PA, those with PA were more likely to be younger [63(13) vs. 67 (14), male (57.1% vs. 48.3%), and African-Americans (32% vs. 18.5%) (p<0.001 for all). PA was associated with a higher risk of mortality (adjusted OR 1.076 [1.076-1.077]), ischemic stroke [adjusted OR 1.049 (1.049-1.05)], hemorrhagic stroke [adjusted OR 1.05 (1.05-1.051)], acute renal failure [adjusted OR 1.058 (1.058-1.058)], acute heart failure [OR 1.104 (1.104-1.104)], and atrial fibrillation [adjusted OR 1.034 (1.033-1.034)]. As expected, older age and underlying cardiovascular disease were the strongest predictors of mortality. However, the female gender conferred protection [OR 0.889 (0.886-0.892]. Primary hyperaldosteronism in patients with hypertension and diabetes is associated with increased mortality and morbidity.

11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma is a common cause of hypertension. This can be cured, or greatly improved, by adrenal surgery. However, the invasive nature of the standard pre-surgical investigation contributes to fewer than 1% of patients with PA being offered the chance of a cure. The primary objective of our prospective study of 143 patients with PA (NCT02945904) was to compare the accuracy of a non-invasive test, [11C]metomidate positron emission tomography computed tomography (MTO) scanning, with adrenal vein sampling (AVS) in predicting the biochemical remission of PA and the resolution of hypertension after surgery. A total of 128 patients reached 6- to 9-month follow-up, with 78 (61%) treated surgically and 50 (39%) managed medically. Of the 78 patients receiving surgery, 77 achieved one or more PA surgical outcome criterion for success. The accuracies of MTO at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7 and 65.4%. For AVS, the accuracies were 63.6 and 61.5%. MTO was not significantly superior, but the differences of 9.1% (95% confidence interval = −6.5 to 24.1%) and 3.8% (95% confidence interval = −11.9 to 9.4) lay within the pre-specified −17% margin for non-inferiority (P = 0.00055 and P = 0.0077, respectively). Of 24 serious adverse events, none was considered related to either investigation and 22 were fully resolved. MTO enables non-invasive diagnosis of unilateral PA.

S-38-7: CONTINUOUS NON-MUTAGENIC DNA DAMAGE IN PODOCYTES ACTIVATES PATHOGENIC MEMORY T CELLS THROUGH ALTERED DNA METHYLATION

Objective: Chronic kidney disease (CKD) is a common cause of hypertension and a complication of uncontrolled hypertension. Recent epigenome-wide studies suggested the association of altered DNA methylation in blood cells with kidney function. However, the mechanism and pathological significance has remained to be adequately elucidated. Design and method: To investigate the significance of DNA double-strand breaks (DSBs) in podocytes, we generated podocyte-specific I-PpoI-expressing mice (podocin-Cre ROSA26-STOP- I-PpoI, referred as I-PpoI-mice). I-PpoI is a homing endonuclease which causes non-mutagenic DSBs. Results: I-PpoI-mice showed severe albuminuria at 6 weeks of age and developed nephrotic syndrome. The mice died because of renal failure around 24 weeks of age following rapid deterioration of renal function. MeDIP-seq analysis using isolated podocytes revealed that 5219 DMRs were identified, and 5212 hypermethylated DMRs were detected in I-PpoI mice. No significant correlation between DNA methylation levels and the distance from I-PpoI cutting sites was observed. Single-cell RNA seq analysis using renal cortex revealed a marked expansion of immune cells, especially CD8+ T cells exhibited a KLRG1low IL-7Rhigh memory precursor effector cell phenotype, with high expression of NKG2D receptors in I-PpoI-mice. The expression of murine NKG2D ligands, which are upregulated by DNA damages, increased in I-PpoI-mice podocytes. In addition, the expression of human NKG2D ligands, MICB, in glomeruli was upregulated in patients with various kidney diseases including hypertensive nephropathy. Whole T cell depletion prevented exacerbation of albuminuria and attenuated glomerulosclerosis and fibrosis in I-PpoI mice, and similar results was obtained by NKG2D blocking. Me-DIP seq analysis using peripheral blood cells, which revealed hypermethylated DMRs in I-PpoI mice were enriched in binding sites for the STAT1 transcription factor. I-PpoI-mice showed a significant increase in CD44high memory/activated phenotype cells of peripheral CD8+ T cell populations, which was similar phenotype of STAT1 knockout mice. The chimeric WT mice with bone marrow (BM) cells of I-PpoI-mice exhibited an increase in albuminuria temporarily, whereas the chimeric I-PpoI-mice with BM cells of WT mice prevented renal fibrosis and renal death. Conclusions: Continuous non-mutagenic DSBs altered DNA methylation regardless of the distance from the primary DSB sites podocytes. Podocyte DNA DSBs also altered methylome of blood cells, including CD8+ T cells, leading sustained changes in immune microenvironment of the kidney and also BM. These results suggest the altered immune microenvironment in the kidney may be a therapeutic target preventing exacerbating glomerulosclerosis and renal fibrosis following podocyte DNA damage in CKD.

The complex genetic basis of fibromuscular dysplasia, a systemic arteriopathy associated with multiple forms of cardiovascular disease.

Artery stenosis is a common cause of hypertension and stroke and can be due to atherosclerosis accumulation in the majority of cases and in a small fraction of patients to arterial fibromuscular dysplasia (FMD). Artery stenosis due to atherosclerosis is widely studied with known risk factors (e.g. increasing age, male gender, and dyslipidemia) to influence its etiology, including genetic factors. However, the causes of noninflammatory and nonatherosclerotic stenosis in FMD are less understood. FMD occurs predominantly in early middle-age women, a fraction of the population where cardiovascular risk is different and understudied. FMD arteriopathies are often diagnosed in the context of hypertension and stroke and co-occur mainly with spontaneous coronary artery dissection, an atypical cause of acute myocardial infarction. In this review, we provide a comprehensive overview of the recent advances in the understanding of molecular origins of FMD. Data were obtained from genetic studies using complementary methodological approaches applied to familial, syndromic, and sporadic forms of this intriguing arteriopathy. Rare variation analyses point toward mechanisms related to impaired prostacyclin signaling and defaults in fibrillar collagens. The study of common variation, mainly through a recent genome-wide association study, describes a shared genetic link with blood pressure, in addition to point at potential risk genes involved in actin cytoskeleton and intracellular calcium homeostasis supporting impaired vascular contraction as a key mechanism. We conclude this review with future strategies and approaches needed to fully understand the genetic and molecular mechanisms related to FMD.

Primary aldosteronism - a multidimensional syndrome.

Primary aldosteronism is a common cause of hypertension and is a risk factor for cardiovascular and renal morbidity and mortality, via mechanisms mediated by both hypertension and direct insults to target organs. Despite its high prevalence and associated complications, primary aldosteronism remains largely under-recognized, with less than 2% of people in at-risk populations ever tested. Fundamental progress made over the past decade has transformed our understanding of the pathogenesis of primary aldosteronism and of its clinical phenotypes. The dichotomous paradigm of primary aldosteronism diagnosis and subtyping is being redefined into a multidimensional spectrum of disease, which spans subclinical stages to florid primary aldosteronism, and from single-focal or multifocal to diffuse aldosterone-producing areas, which can affect one or both adrenal glands. This Review discusses how redefining the primary aldosteronism syndrome as a multidimensional spectrum will affect the approach to the diagnosis and subtyping of primary aldosteronism.

Pheochromocytoma in pregnancy - a rare but dangerous diagnosis.

Pheochromocytoma is a rare cause of hypertension in pregnancy. Unrecognized, it carries a great risk for both mother and the foetus. The main reason for missing the diagnosis is the misconception that any hypertension occurring in pregnancy is gestational hypertension or pre (eclampsia). As many as 90% of patients report one or more pheochromocytoma-related symptoms antenatally, but the diagnosis is made in 75% of patients, meaning that 3 out of 10 patients are diagnosed after childbirth or post-mortem. The symptoms are similar to other more common causes of hypertension in pregnancy, which presents a major diagnostic challenge. The diagnosis is based on determination of metanephrines in plasma or 24-hour urine. Magnetic resonance imaging (MRI) and ultrasound (US) are used to localize the tumour. If the diagnosis is made before the 24th week of pregnancy, laparoscopic removal of the tumour in the second trimester is recommended. If diagnosed later, the tumour could be removed during or after delivery. Preoperative preparation with alpha blockers is required to stabilize blood pressure. The decision on the mode of delivery depends on several factors, so an experienced multidisciplinary team is needed to minimize maternal and foetal mortality.

PROFILE OF HYPERTENSION IN CHILDREN AGED 3 TO 12 YEARS: EXPERIENCE FROM A TERTIARY CARE HOSPITAL IN NORTH EAST INDIA

Objective: To study the prole of hypertensive children admitted in a tertiary care hospital in the age group of 3 to 12 years. Method: It is a Prospective type Study done over 1 year from June 2019 to May 2020 in the Department of Pediatrics, Silchar Medical College and Hospital (SMCH), a tertiary care Hospital in Assam,India. One twenty six children in the age group of 3 to 12 years meeting the inclusion criteria were admitted with hypertension. Results: During the study period a total of 3214 patients were admitted in the Pediatric Department of Silchar Medical College and Hospital. Out of which 126 patients were found to be hypertensive (3.9%). The number of males were 81(65%) and females 45(56%). The most common affected group was school going children age group (6 to 12 years). 37(29.3%) cases presented with hypertensive emergency. 22(17%) cases presented with congestive cardiac failure and 15(11.9%) cases hypertensive encephalopathy. Renal Cause of hypertension was the leading cause of admission and glomerulonephritis was the leading renal cause (80%). The mortality was 4.7% (6 out of 126 patients) and was due to complication of Glomerulonephritis. Conclusion: Hypertension is a common cause of hospitalization in children. Renal or renovascular etiology of hypertension is the most common cause of hypertension.

Long-term effect of continuous positive airway pressure therapy on blood pressure in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) is a common cause of hypertension. Previous studies have demonstrated beneficial short-term effects of continuous positive airway pressure (CPAP) therapy on blood pressure. However, long-term antihypertensive effects of CPAP have not been properly verified. This study examined the longitudinal effect of CPAP therapy adherence on blood pressure among OSA patients. All patients diagnosed with OSA and undergoing subsequent CPAP therapy at a Kanagawa-area sleep clinic were clinically followed for 24 months to examine CPAP adherence, as well as longitudinal changes in blood pressure and body weight because it may become a confound factor for changes in blood pressure. The hours of CPAP usage were collected over the course of 30 nights prior to each follow-up visit (1st, 3rd, 6th, 12th, and 24th month). The relationship between CPAP adherence and blood pressure was analyzed using mixed-effect logistic regression models. A total of 918 OSA patients were enrolled in the study. We found a significant reduction in diastolic blood pressure among patients with good CPAP adherence during the 24-month follow-up period (β = − 0.13, p = 0.03), when compared to the group with poor CPAP adherence. No significant association was found between CPAP adherence and weight loss (β = − 0.02, p = 0.59). Long-term, good CPAP therapy adherence was associated with lower diastolic blood pressure without significant weight loss.

Sir George Johnson FRCP (1818-96), high blood pressure and the continuing altercation about its origins.

What is the topic of this review? The review takes a historical approach to examining where in the body it might be possible to identify the most common cause, or causes, of long-term hypertension. It gathers evidence from histology, human and animal physiology, and computational modelling. The burden of decades of controversy is noted. What advances does it highlight? The review highlights the distinctive pathology of the afferent renal circulation and what its consequences are for the widespread view that essential hypertension is caused by elevated peripheral vascular resistance. The widely promulgated notion that long-term elevation in mean arterial blood pressure (MAP) can be caused by raised peripheral vascular resistance remains a subject of vigorous debate. According to the 1967 mathematical model of Guyton and Coleman, such a causal relationship is impossible, kidney function being the determining factor. We explore this altercation starting with Sir George Johnson's 19th-century renal vascular histological observations in patients with Bright's disease. We note the striking physiological measurements in hypertensives by Gómez and Bolomey in the 1950s, moving on to the mathematical modelling of the circulation from the 1960s up to the ∼100-parameter computer models of the present day. Confusion has been generated by the fact that peripheral resistance is raised in hypertension in close proportion to MAP whilst cardiac output often stays normal, an apparent autoregulation, the mechanism of which is poorly understood. All models allowing for the circulation to be an open system show that isolated changes in peripheral resistance cannot lead to long-term hypertension, but models fail so frequently to account for results from experiments such as salt loading that their credibility with regard to this key finding is compromised. Laboratory animal models of adrenergic renal actions resonate with a contemporary emphasis on the sympathetic nerve supply to the kidney as contributing to the characteristically markedly elevated renal afferent resistance that appears to be the most common cause of hypertension. Remarkably, there remains no account of the way in which the fixed structural changes in vessels observed by Johnson relate to this sympathetic overactivity, which can itself be modified by drugs in the medium term. In this account, we seek to locate the crime scene and identify a smoking gun.

RNF34 ablation promotes cerebrovascular remodeling and hypertension by increasing NADPH-derived ROS generation

Cerebrovascular remodeling is the most common cause of hypertension and stroke. Ubiquitin E3 ligase RING finger protein 34 (RNF34) is suggested to be associated with the development of multiple neurological diseases. However, the importance of RNF34 in cerebrovascular remodeling and hypertension is poorly understood. Herein, we used mice with a global RNF34 knockout as well as RNF34 floxed mice to delete RNF34 in endothelial cells and smooth muscle cells (SMCs). Our results showed that global RNF34 knockout mice substantially promoted angiotensin II (AngII)-induced middle cerebral artery (MCA) remodeling, hypertension, and neurological dysfunction. Endothelial cell RNF34 did not regulate the development of hypertension. Rather, SMC RNF34 expression is a critical regulator of hypertension and MCA remodeling. Loss of RNF34 enhanced AngII-induced mouse brain vascular SMCs (MBVSMCs) proliferation, migration and invasion. Furthermore, MCA and MBVSMCs from SMC RNF34-deficient mice showed increased superoxide anion and reactive oxygen species (ROS) generation as well as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, but exhibited no marked effect on mitochondria-derived ROS. Knockout of RNF34 promoted p22phox expression, leading to increased binding of p22phox/p47phox and p22phox/NOX2, and eventually NADPH oxidase complex formation. Immunoprecipitation assay identified that RNF34 interacted with p22phox. RNF34 deletion increased p22phox protein stability by inhibiting ubiquitin-mediated degradation. Blockade of NADPH oxidase activity or knockdown of p22phox significantly abolished the effects of RNF34 deletion on cerebrovascular remodeling and hypertension. Collectively, our study demonstrates that SMC RNF34 deficiency promotes cerebrovascular SMC hyperplasia and remodeling by increased NADPH-derived ROS generation via reducing p22phox ubiquitin-dependent degradation.

Preeclampsia for the Nephrologist: Current Understanding in Diagnosis, Management, and Long-term Outcomes.

Preeclampsia is a multisystem progressive disorder of pregnancy that can be potentially catastrophic for the mother and the fetus. It involves complex perturbations of the kidney and systemic physiology, along with long-term effects on vascular and kidney health. Thus, the nephrologist plays a key role in the peripartum and long-term management of preeclampsia. Recent translational research has improved our understanding of its pathophysiology, and there is hope for novel therapies. In this review, we discuss the evolution of diagnostic criteria and dilemmas in the diagnosis of hypertensive disorders in pregnancy. We summarize the advances in the pathogenesis and prediction of preeclampsia. We describe the management and prevention of preeclampsia focusing specially on the forthcoming strategies from the nephrologist's perspective. We address the evidence regarding long-term outcomes for the mother and the child. We end with exploring areas warranting future research.

What Is the Most Common Cause of Secondary Hypertension?: An Interdisciplinary Discussion

Traditional statements in medical textbooks pointed that 90 to 95% of cases of hypertension is essential or primary. However, secondary hypertension seems to be common in those patients with resistant forms of hypertension. Appropriate investigation and treatment may have prognostic impact but frequently hypertension remission did not occur raising concerns about the real meaning of secondary hypertension. Here, we provided an interdisciplinary and critical discussion comprising an endocrinologist, a nephrologist, and a cardiologist with expertise in resistant hypertension. We reviewed the literature approaching each one of the recognizable cause of hypertension. Recent studies pointed that the most common causes of secondary hypertension are those who overall responses to their treatments do not promote hypertension remission including obstructive sleep apnea (OSA), chronic kidney disease, renovascular hypertension and primary aldosteronism. The authors raised concerns regarding the lack of inclusion of obesity by several societies as a formal cause of hypertension considering not only the biologic plausibility but also the huge impact of weight loss therapies such as bariatric surgery on hypertension remission. In contrast, there is no discussion that a very rare condition-namely pheochromocytoma-is the most "typical" cause of hypertension by promoting hypertension remission in the majority of patients after surgical procedure. Hypertension is a complex condition with multiple environmental and genetics interactions. In clinical practice, it is challenging to prove causality in hypertension. Common conditions largely acceptable as causes of hypertension (OSA, chronic kidney disease, renovascular hypertension, and primary aldosteronism) frequently occur in a setting of an established hypertension background and therefore do not promote hypertension remission in a significant proportion of patients. If obesity becomes largely accepted by several societies as a secondary form of hypertension, this pandemic condition will be certainly the most common cause of hypertension.

0653 Positive Effects of Long Term Continuous Positive Airway Pressure Therapy on Blood Pressure in Obstructive Sleep Apnea Patients

Abstract Introduction Obstructive sleep apnea (OSA) is one of the common causes of hypertension. Therefore, we examine the longitudinal effect of continuous positive airway pressure (CPAP) therapy and its adherence on blood pressure among OSA patients. Methods One thousand two hundred ninety-three (male 1,130, female 163) patients, who were diagnosed with OSA and underwent CPAP therapy were investigated for longitudinal changes (24 months observation period) in the levels of blood pressure and body weight. The longitudinal analyses were performed by mixed effect model. Multiple Imputation with Chained Equations was also used to impute missing data. Good CPAP adherence is defined as more than 70% of the time using CPAP more than 4hours at all the measuring. Poor CPAP adherence is defined as less than 70% of the time using CPAP more than 4hours at all the measuring time points. Results The patient group with good CPAP adherences), compared to poor CPAP adherence, showed significant diastolic blood pressure reduction in 24 months follow-up period (β=-0.13, p=0.03) despite a lack of significant weight loss (β=-0.02, p=0.59). However, no significant associations were found between systolic blood pressure and CPAP adherence (β=-0.14, p=0.11). Conclusion CPAP therapy was found to have a longitudinal effect on diastolic blood pressure despite a lack of significant weight loss. Support

Surgical approach to patients with primary aldosteronism.

Primary hyperaldosteronism (PA) is one of the most common causes of hypertension that is amenable to surgical cure. Once a patient has a biochemical diagnosis of PA, workup should proceed with tumor lateralization to determine whether the patient has unilateral or bilateral disease. Tumor lateralization can be done with noninvasive imaging such as a CT or MRI. However, in older patients or in patients with non-lateralizing imaging, arteriovenous sampling (AVS) should be considered. If the patient has confirmed unilateral disease, options for surgical intervention include laparoscopic or, less commonly, open. Laparoscopic adrenalectomy for PA has been shown to be a safe and effective procedure that is associated with less morbidity compared to open adrenalectomy. Patients can either undergo a laparoscopic transabdominal adrenalectomy via a lateral (most common) or anterior approach or a retroperitoneoscopic adrenalectomy via a posterior approach. The majority of patients have complete biochemical success, defined as normalization of plasma aldosterone, renin and potassium levels and appropriate suppression with stimulation tests. Less than half of patients have complete clinical success, defined as normotensive with no antihypertensive medications. However, the majority of patients who do not have complete clinical success will have some improvement in their blood pressure and/or are able to decrease the number of antihypertensive medications that they require.

Chemogenetic activation of adrenocortical Gq signaling causes hyperaldosteronism and disrupts functional zonation.

The mineralocorticoid aldosterone is produced in the adrenal zona glomerulosa (ZG) under the control of the renin-angiotensin II (AngII) system. Primary aldosteronism (PA) results from renin-independent production of aldosterone and is a common cause of hypertension. PA is caused by dysregulated localization of the enzyme aldosterone synthase (Cyp11b2), which is normally restricted to the ZG. Cyp11b2 transcription and aldosterone production are predominantly regulated by AngII activation of the Gq signaling pathway. Here, we report the generation of transgenic mice with Gq-coupled designer receptors exclusively activated by designer drugs (DREADDs) specifically in the adrenal cortex. We show that adrenal-wide ligand activation of Gq DREADD receptors triggered disorganization of adrenal functional zonation, with induction of Cyp11b2 in glucocorticoid-producing zona fasciculata cells. This result was consistent with increased renin-independent aldosterone production and hypertension. All parameters were reversible following termination of DREADD-mediated Gq signaling. These findings demonstrate that Gq signaling is sufficient for adrenocortical aldosterone production and implicate this pathway in the determination of zone-specific steroid production within the adrenal cortex. This transgenic mouse also provides an inducible and reversible model of hyperaldosteronism to investigate PA therapeutics and the mechanisms leading to the damaging effects of aldosterone on the cardiovascular system.

Primary Aldosteronism: Cardiovascular Outcomes Pre- and Post-treatment.

Primary aldosteronism (PA) is a common form of hypertension characterized by autonomous aldosterone secretion from one or both adrenal glands. The purpose of this review is to synthesize recent research findings regarding cardiovascular disease risk in PA both pre- and post-targeted therapy. Previously considered a rare disease, recent prevalence studies demonstrate that PA is actually a very common, yet vastly under-diagnosed, etiology of hypertension. Prior to targeted therapy, PA is associated with substantially higher rates of cardiovascular disease compared with essential hypertension. Surgical adrenalectomy is highly effective in curing or improving hypertension as well as mitigating cardiovascular disease risk in patients with unilateral PA. For the remainder of PA patients, MR antagonists are recommended; however, several recent studies have brought into question their effectiveness in improving cardiovascular outcomes. PA is a common cause of hypertension that leads to disproportionately high rates of cardiovascular disease. Future studies are needed to enhance the clinical approach to both identification and treatment of patients with PA to optimize long-term cardiovascular outcomes.