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https://www.readbyqxmd.com/read/29036960/-two-cases-report-of-primary-aldosteronism-with-positive-cardiac-troponin
#1
L J Yang, H Wang, Y D Zhang
No abstract text is available yet for this article.
October 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
https://www.readbyqxmd.com/read/29035537/discovery-of-a-novel-piperidine-based-inhibitor-of-cholesteryl-ester-transfer-protein-cetp-that-retains-activity-in-hypertriglyceridemic-plasma
#2
Ken Yamada, Margaret Brousseau, Wataru Honma, Akiko Iimura, Hidetomo Imase, Yuki Iwaki, Toshio Kawanami, Daniel LaSala, Guiqing Liang, Hironobu Mitani, Kazuhiko Nonomura, Osamu Ohmori, Meihui Pan, Dean F Rigel, Ichiro Umemura, Kayo Yasoshima, Guoming Zhu, Muneto Mogi
Herein we describe the discovery and characterization of a novel, piperidine-based inhibitor of cholesteryl ester transfer protein (CETP) with a core structure distinct from other reported CETP inhibitors. A versatile synthesis starting from 4-methoxypyridine enabled an efficient exploration of the SAR, giving a lead molecule with potent CETP inhibition in human plasma. The subsequent optimization focused on improvement of pharmacokinetics and mitigation of off-target liabilities, such as CYP inhibition, whose improvement correlated with increased lipophilic efficiency...
October 16, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29034356/renal-denervation-reduces-pulmonary%C3%A2-vascular-remodeling-and-right-ventricular-diastolic-stiffness-in-experimental-pulmonary-hypertension
#3
Denielli da Silva Gonçalves Bos, Chris Happé, Ingrid Schalij, Wioletta Pijacka, Julian F R Paton, Christophe Guignabert, Ly Tu, Raphaël Thuillet, Harm-Jan Bogaard, Albert C van Rossum, Anton Vonk-Noordegraaf, Frances S de Man, M Louis Handoko
Neurohormonal overactivation plays an important role in pulmonary hypertension (PH). In this context, renal denervation, which aims to inhibit the neurohormonal systems, may be a promising adjunct therapy in PH. In this proof-of-concept study, we have demonstrated in 2 experimental models of PH that renal denervation delayed disease progression, reduced pulmonary vascular remodeling, lowered right ventricular afterload, and decreased right ventricular diastolic stiffness, most likely by suppression of the renin-angiotensin-aldosterone system...
February 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/29034304/validated-low-volume-aldosterone-immunoassay-tailored-to-gclp-compliant-investigations-in-small-sample-volumes
#4
J Schaefer, B B Burckhardt, J Tins, A Bartel, S Laeer
INTRODUCTION: Heart failure is well investigated in adults, but data in children is lacking. To overcome this shortage of reliable data, appropriate bioanalytical assays are required. OBJECTIVES: Development and validation of a bioanalytical assay for the determination of aldosterone concentrations in small sample volumes applicable to clinical studies under Good Clinical Laboratory Practice. METHODS: An immunoassay was developed based on a commercially available enzyme-linked immunosorbent assay and validated according to current bioanalytical guidelines of the EMA and FDA...
December 2017: Pract Lab Med
https://www.readbyqxmd.com/read/29034264/reducing-cardiac-fibrosis-na-k-atpase-signaling-complex-as-a-novel-target
#5
X Fan, J Xie, J Tian
Cardiac fibrosis is a common pathological process in cardiac disease and may lead to heart failure. It can also cause sudden death even in those without cardiac symptoms. Tissue fibrosis can be categorized into two categories: replacement fibrosis (also called reparative fibrosis) and reactive fibrosis. In replacement fibrosis, infiltration of inflammatory cells and accumulation of Extracellular Matrix (ECM) proteins are the initial steps in forming scarlike fibrotic tissue after acute cardiac injury and cardiac cell necrosis...
2017: Cardiovascular Pharmacology: Open Access
https://www.readbyqxmd.com/read/29034087/spironolactone-in-cardiovascular-disease-an-expanding-universe
#6
REVIEW
John W Funder
Spironolactone has been marketed for over half a century as a 'potassium-sparing diuretic', used primarily in patients with ascites. With the realization that primary aldosteronism is the most common (5-13%) form of secondary hypertension, it has become widely used as a mineralocorticoid receptor antagonist. More recently, in the wake of the RALES trial, spironolactone in addition to standard therapy has been shown to be very beneficial in heart failure with a reduced ejection fraction. Despite the failure of the TOPCAT trial, spironolactone is being increasingly used in diastolic heart failure (i...
2017: F1000Research
https://www.readbyqxmd.com/read/29032132/prognostic-importance-of-temporal-changes-in-resting-heart-rate-in-heart-failure-and-preserved-ejection-fraction-from-the-topcat-study
#7
Ali Vazir, Brian Claggett, Bertram Pitt, Inder Anand, Nancy Sweitzer, James Fang, Jerome Fleg, Jean Rouleau, Sanjiv Shah, Marc A Pfeffer, Scott D Solomon
OBJECTIVES: The aim of this study was to examine the relationship between baseline heart rate (HR), change in HR from a preceding visit, and time-updated HR with subsequent outcomes in patients with heart failure with preserved ejection fraction (HFpEF) in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial. BACKGROUND: Higher resting HR and increase in HR over time in patients with heart failure are associated with adverse outcomes...
October 4, 2017: JACC. Heart Failure
https://www.readbyqxmd.com/read/29031359/treatment-of-abnormalities-of-potassium-homeostasis-in-ckd
#8
REVIEW
Biff F Palmer, Deborah J Clegg
Hyperkalemia, defined as serum potassium concentrations greater than 5.0 to 5.5 mEq/L, is a frequent occurrence in clinical practice because of the increasing incidence and prevalence of CKD. Patients at risk for this disorder are commonly treated with drugs that interfere in the renin-angiotensin-aldosterone system, thereby enhancing the occurrence and prevalence of this disorder. Discontinuation of these drugs because of the development of hyperkalemia deprives these patients the renal-protective and cardiovascular benefits this class of pharmacology has been shown to provide...
September 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29031358/hyperkalemia-and-hypokalemia-in-ckd-prevalence-risk-factors-and-clinical-outcomes
#9
REVIEW
Sarah Gilligan, Kalani L Raphael
Abnormalities of serum potassium are common in patients with CKD. Although hyperkalemia is a well-recognized complication of CKD, the prevalence rates of hyperkalemia (14%-20%) and hypokalemia (12%-18%) are similar. CKD severity, use of medications such as renin-angiotensin-aldosterone system inhibitors and diuretics, and dietary potassium intake are major determinants of serum potassium concentration in CKD. Demographic factors, acid-base status, blood glucose, and other comorbidities contribute as well. Both hyperkalemia and hypokalemia are associated with similarly increased risks of death, cardiovascular disease, and hospitalization...
September 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29031357/regulation-of-potassium-homeostasis-in-ckd
#10
REVIEW
Thomas D DuBose
Disturbances of potassium homeostasis can cause either hyperkalemia or hypokalemia and result in serious consequences. Although the consequences of acute and chronic hyperkalemia and treatment of these conditions in CKD have been widely appreciated by nephrologists, more recent information has focused attention on the consequences of chronic hypokalemia. Several recent studies have documented a "U-shaped" relationship between the serum [K(+)] and higher mortality in several clinical studies. The causes of dyskalemias are placed into the unique perspective of patients with CKD and its evolution with progression of CKD to later stages and focuses on the pathophysiology of these disorders...
September 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/29030398/on-the-effect-of-hyperaldosteronism-inducing-mutations-in-na-k-pumps
#11
Dylan J Meyer, Craig Gatto, Pablo Artigas
Primary aldosteronism, a condition in which too much aldosterone is produced and that leads to hypertension, is often initiated by an aldosterone-producing adenoma within the zona glomerulosa of the adrenal cortex. Somatic mutations of ATP1A1, encoding the Na/K pump α1 subunit, have been found in these adenomas. It has been proposed that a passive inward current transported by several of these mutant pumps is a "gain-of-function" activity that produces membrane depolarization and concomitant increases in aldosterone production...
October 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/29030153/potassium-homeostasis-in-health-and-disease-a-scientific-workshop-cosponsored-by-the-national-kidney-foundation-and-the-american-society-of-hypertension
#12
Csaba P Kovesdy, Lawrence J Appel, Morgan E Grams, Lisa Gutekunst, Peter A McCullough, Biff F Palmer, Bertram Pitt, Dominic A Sica, Raymond R Townsend
While much emphasis, and some controversy, centers on recommendations for sodium intake, there has been considerably less interest in recommendations for dietary potassium intake, in both the general population and patients with medical conditions, particularly acute and chronic kidney disease. Physiology literature and cohort studies have noted that the relative balance in sodium and potassium intakes is an important determinant of many of the sodium-related outcomes. A noteworthy characteristic of potassium in clinical medicine is the extreme concern shared by many practitioners when confronted by a patient with hyperkalemia...
October 6, 2017: Journal of the American Society of Hypertension: JASH
https://www.readbyqxmd.com/read/29029808/potassium-homeostasis-in-health-and-disease-a-scientific-workshop-cosponsored-by-the-national-kidney-foundation-and-the-american-society-of-hypertension
#13
Csaba P Kovesdy, Lawrence J Appel, Morgan E Grams, Lisa Gutekunst, Peter A McCullough, Biff F Palmer, Bertram Pitt, Dominic A Sica, Raymond R Townsend
While much emphasis, and some controversy, centers on recommendations for sodium intake, there has been considerably less interest in recommendations for dietary potassium intake, in both the general population and patients with medical conditions, particularly acute and chronic kidney disease. Physiology literature and cohort studies have noted that the relative balance in sodium and potassium intakes is an important determinant of many of the sodium-related outcomes. A noteworthy characteristic of potassium in clinical medicine is the extreme concern shared by many practitioners when confronted by a patient with hyperkalemia...
September 29, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/29022080/urinary-potassium-to-urinary-potassium-plus-sodium-ratio-can-accurately-identify-hypovolemia-in-nephrotic-syndrome-a-provisional-study
#14
Werner Keenswijk, Mohamad Ikram Ilias, Ann Raes, Raymond Donckerwolcke, Johan Vande Walle
There is evidence pointing to a decrease of the glomerular filtration rate (GFR) in a subgroup of nephrotic children, likely secondary to hypovolemia. The aim of this study is to validate the use of urinary potassium to the sum of potassium plus sodium ratio (UK/UK+UNa) as an indicator of hypovolemia in nephrotic syndrome, enabling detection of those patients who will benefit from albumin infusion. We prospectively studied 44 nephrotic children and compared different parameters to a control group (36 children)...
October 11, 2017: European Journal of Pediatrics
https://www.readbyqxmd.com/read/29021385/aldosterone-is-essential-for-angiotensin-ii-induced-upregulation-of-pendrin
#15
Daigoro Hirohama, Nobuhiro Ayuzawa, Kohei Ueda, Mitsuhiro Nishimoto, Wakako Kawarazaki, Atsushi Watanabe, Tatsuo Shimosawa, Takeshi Marumo, Shigeru Shibata, Toshiro Fujita
The renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, increasing levels of the Cl(-)/HCO3(-) exchanger pendrin in β-intercalated cells and the Na(+)-Cl(-) cotransporter (NCC) in distal convoluted tubules. However, the independent roles of AngII and aldosterone in regulating these levels remain unclear. In C57BL/6J mice receiving a low-salt diet or AngII infusion, we evaluated the membrane protein abundance of pendrin and NCC; assessed the phosphorylation of the mineralocorticoid receptor, which selectively inhibits aldosterone binding in intercalated cells; and measured BP by radiotelemetry in pendrin-knockout and wild-type mice...
October 11, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29021336/pooled-analysis-of-multiple-crossover-trials-to-optimize-individual-therapy-response-to-renin-angiotensin-aldosterone-system-intervention
#16
Sergei I Petrykiv, Gozewijn Dirk Laverman, Frederik Persson, Liffert Vogt, Peter Rossing, Martin H de Borst, Ronald T Gansevoort, Dick de Zeeuw, Hiddo J L Heerspink
BACKGROUND AND OBJECTIVES: In the treatment of CKD, individual patients show a wide variation in their response to many drugs, including renin-angiotensin-aldosterone system inhibitors (RAASi). To investigate whether therapy resistance to RAASi can be overcome by uptitrating the dose of drug, changing the mode of intervention (with drugs from similar or different classes), or lowering dietary sodium intake, we meta-analyzed individual responses to different modes of interventions. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Randomized crossover trials were analyzed to assess correlation of individual responses to RAASi and nonsteroidal anti-inflammatory drugs (NSAIDs; n=395 patients)...
October 11, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/29021272/combined-salt-and-caloric-restrictions-potential-adverse-outcomes
#17
Tsuyoshi Homma, Mika Homma, Yuefei Huang, Korapat Mayurasakorn, Nurul Mahamad Rodi, Anis Amalina Abdul Hamid, Shelley Hurwitz, Tham Yao, Gail K Adler, Luminita H Pojoga, Gordon H Williams, Jose R Romero
BACKGROUND: We hypothesized that caloric restriction (CR) and salt restriction (ResS) would have similar effects on reducing cardiovascular risk markers and that combining CR and ResS would be synergistic in modulating these markers. METHODS AND RESULTS: To test our hypothesis, rats were randomized into 2 groups: ad libitum liberal salt diet (ad libitum/high-sodium, 1.6% sodium) or ResS diet (ad libitum/ResS, 0.03% sodium). CR was initiated in half of the rats in each group by reducing caloric intake to 60% while maintaining sodium intake constant (CR/high-sodium, 2...
October 11, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29019079/pharmacotherapy-choice-is-associated-with-2-year-mortality-for-patients-with-heart-failure-and-reduced-ejection-fraction
#18
Nancy M Albert, Dana A Drzayich Antol, Richard W DeClue, Adrianne Waldman Casebeer, Yong Li, Stephen Stemkowski, Chun-Lan Chang
INTRODUCTION: Factors associated with mortality for patients with heart failure and reduced ejection fraction (HFrEF) are known; however, the association between initial pharmacotherapy (IPT) and mortality is unclear in real-world settings. METHODS: Using a retrospective design and claims database, 14,359 Medicare patients with HFrEF from August 2010 to July 2015 were identified. Index date was first HF claim. IPT was mono- or combo-angiotensin-converting enzyme inhibitor (ACEI), angiotensin II receptor blocker (ARB), beta-blocker (BB), hydralazine-nitrate (HN), and aldosterone antagonist (AA) within 1 year post-index...
October 10, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/29018938/heart-failure-with-preserved-ejection-fraction-current-management-and-future-strategies-expert-opinion-on-the-behalf-of-the-nucleus-of-the-heart-failure-working-group-of-the-german-society-of-cardiology-dkg
#19
REVIEW
Carsten Tschöpe, Christoph Birner, Michael Böhm, Oliver Bruder, Stefan Frantz, Andreas Luchner, Lars Maier, Stefan Störk, Behrouz Kherad, Ulrich Laufs
About 50% of all patients suffering from heart failure (HF) exhibit a reduced ejection fraction (EF ≤ 40%), termed HFrEF. The others may be classified into HF with midrange EF (HFmrEF 40-50%) or preserved ejection fraction (HFpEF, EF ≥ 50%). Presentation and pathophysiology of HFpEF is heterogeneous and its management remains a challenge since evidence of therapeutic benefits on outcome is scarce. Up to now, there are no therapies improving survival in patients with HFpEF. Thus, the treatment targets symptom relief, quality of life and reduction of cardiac decompensations by controlling fluid retention and managing risk factors and comorbidities...
October 10, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/29017166/the-role-of-the-mineralocorticoid-receptor-in-inflammation-focus-on-kidney-and-vasculature
#20
Zachary Belden, Jeffrey A Deiuliis, Mirela Dobre, Sanjay Rajagopalan
BACKGROUND: The remarkable success of clinical trials in mineralocorticoid receptor (MR) inhibition in heart failure has driven research on the physiological and pathological role(s) of nonepithelial MR expression. MR is widely expressed in the cardiovascular system and is a major determinant of endothelial function, smooth muscle tone, vascular remodeling, fibrosis, and blood pressure. An important new dimension is the appreciation of the role MR plays in immune cells and target organ damage in the heart, kidney and vasculature, and in the development of insulin resistance...
October 10, 2017: American Journal of Nephrology
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