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Circulation

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https://www.readbyqxmd.com/read/28446517/a-novel-%C3%AE-calcitonin-gene-related-peptide-analogue-protects-against-end-organ-damage-in-experimental-hypertension-cardiac-hypertrophy-and-heart-failure
#1
Aisah A Aubdool, Pratish Thakore, Fulye Argunhan, Sarah-Jane Smillie, Moritz Schnelle, Salil Srivastava, Khadija M Alawi, Elena Wilde, Jennifer Mitchell, Keith Farrell-Dillon, Daniel A Richards, Giuseppe Maltese, Richard C Siow, Manasi Nandi, James E Clark, Ajay M Shah, Anette Sams, Susan D Brain
Background -Research into the therapeutic potential of α-calcitonin gene-related peptide (α-CGRP) has been limited due to its peptide nature and short half-life. Here, we evaluate whether a novel potent and long lasting (t½ ≥ 7h) acylated α-CGRP analogue (αAnalogue) could alleviate and reverse cardiovascular disease in two distinct murine models of hypertension and heart failure in vivoMethods -The ability of the αAnalogue to act selectively via the CGRP pathway was shown in skin using a CGRP receptor antagonist...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28446516/access-to-non-statin-lipid-lowering-therapies-in-patients-at-high-risk-of-atherosclerotic-cardiovascular-disease
#2
Joshua W Knowles, William B Howard, Lala Karayan, Seth J Baum, Katherine A Wilemon, Christie M Ballantyne, Kelly D Myers
High-intensity statins are recommended for all patients with familial hypercholesterolemia (FH) and non-statin lipid lowering therapies (LLTs) are indicated when there is an inadequate response to statins(1, 2) In the pre-PCSK9 inhibitor (PCSK9i) era only about 40% of FH patients achieved an LDL-C level <100.(3) Partly based on the need for additional therapeutic options in high-risk FH patients, PCSK9 inhibitors were approved for treatment of heterozygous and homozygous FH in 2015. Nevertheless, emerging anecdotal data suggest that access to non-statin LLTs has been a challenge for FH patients though this has not been systematically evaluated...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28446515/role-of-biomarkers-for-the-prevention-assessment-and-management-of-heart-failure-a-scientific-statement-from-the-american-heart-association
#3
REVIEW
Sheryl L Chow, Alan S Maisel, Inder Anand, Biykem Bozkurt, Rudolf A de Boer, G Michael Felker, Gregg C Fonarow, Barry Greenberg, James L Januzzi, Michael S Kiernan, Peter P Liu, Thomas J Wang, Clyde W Yancy, Michael R Zile
BACKGROUND AND PURPOSE: Natriuretic peptides have led the way as a diagnostic and prognostic tool for the diagnosis and management of heart failure (HF). More recent evidence suggests that natriuretic peptides along with the next generation of biomarkers may provide added value to medical management, which could potentially lower risk of mortality and readmissions. The purpose of this scientific statement is to summarize the existing literature and to provide guidance for the utility of currently available biomarkers...
April 26, 2017: Circulation
https://www.readbyqxmd.com/read/28442482/a-bag3-coding-variant-in-mice-determines-susceptibility-to-ischemic-limb-muscle-myopathy-by-directing-autophagy
#4
Joseph M McClung, Timothy J McCord, Terence E Ryan, Cameron A Schmidt, Thomas D Green, Kevin W Southerland, Jessica L Reinardy, Sarah B Mueller, Talaignair N Venkatraman, Christopher D Lascola, Sehoon Keum, Douglas A Marchuk, Espen E Spangenburg, Ayotunde O Dokun, Brian H Annex, Christopher D Kontos
Background -Critical limb ischemia (CLI) is a manifestation of peripheral artery disease (PAD) that carries significant mortality and morbidity risk in humans, although its genetic determinants remain largely unknown. We previously discovered two overlapping quantitative trait loci (QTL) in mice, Lsq-1 and Civq-1, that affected limb muscle survival and stroke volume following femoral artery or middle cerebral artery ligation, respectively. Here we report that a Bag3 variant (Ile81Met) segregates with tissue protection from hindlimb ischemia (HLI)...
April 25, 2017: Circulation
https://www.readbyqxmd.com/read/28432149/cd73-on-t-cells-orchestrates-cardiac-wound-healing-after-myocardial-infarction-by-purinergic-metabolic-reprogramming
#5
Nadine Borg, Christina Alter, Nicole Görldt, Christoph Jacoby, Zhaoping Ding, Bodo Steckel, Christine Quast, Florian Bönner, Daniela Friebe, Sebastian Temme, Ulrich Flögel, Jürgen Schrader
Background -T-cells are required for proper healing after myocardial infarction. The mechanism of their beneficial action, however, is unknown. The pro-inflammatory "danger signal" adenosine triphosphate (ATP), released from damaged cells, is degraded by the ectonucleotidases CD39 and CD73 to the anti-inflammatory mediator adenosine. Here, we investigate the contribution of CD73-derived adenosine produced by T-cells to cardiac remodeling after ischemia/reperfusion and define its mechanism of action. Methods -Myocardial ischemia (50 min /reperfusion) was induced in global CD73(-/-) and CD4-CD73(-/-) mice...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28432148/systolic-blood-pressure-trajectory-frailty-and-all-cause-mortality-over-80-years-of-age-cohort-study-using-electronic-health-records
#6
Rathi Ravindrarajah, Nisha C Hazra, Shota Hamada, Judith Charlton, Stephen H D Jackson, Alex Dregan, Martin C Gulliford
Background -Clinical trials show benefit from lowering systolic blood pressure in people aged ≥80 years but non-randomised epidemiological studies suggest lower systolic blood pressure may be associated with higher mortality. This study aimed to evaluate associations of SBP with all-cause mortality by frailty category over 80 years of age and to evaluate SBP trajectories before death. Methods -A population-based cohort study was conducted using electronic health records of 144,403 participants aged 80 and older registered with family practices in the United Kingdom from 2001 to 2014...
April 21, 2017: Circulation
https://www.readbyqxmd.com/read/28428231/thresholds-for-ambulatory-blood-pressure-among-african-americans-in-the-jackson-heart-study
#7
Joseph E Ravenell, Daichi Shimbo, John N Booth, Daniel F Sarpong, Charles Agyemang, Danielle L Beatty Moody, Marwah Abdalla, Tanya M Spruill, Amanda J Shallcross, Adam P Bress, Paul Muntner, Gbenga Ogedegbe
Background -Ambulatory blood pressure (BP) monitoring (ABPM) is the reference standard for out-of-clinic BP measurement. Thresholds for identifying ambulatory hypertension (daytime systolic BP [SBP]/diastolic BP [DBP] ≥ 135/85 mmHg, 24-hour SBP/DBP ≥ 130/80 mmHg, and nighttime SBP/DBP ≥ 120/70 mmHg) have been derived from European, Asian and South American populations. We determined BP thresholds for ambulatory hypertension in a US population-based sample of African Americans. Methods -We analyzed data from the Jackson Heart Study (JHS), a population-based cohort study comprised exclusively of African-American adults (n=5,306)...
April 20, 2017: Circulation
https://www.readbyqxmd.com/read/28424224/novel-strategies-to-reduce-femoropopliteal-restenosis-low-dose-paclitaxel-coated-balloons-and-paclitaxel-coated-balloons-plus-stenting
#8
Andrew M Goldsweig, Herbert D Aronow
Peripheral artery disease (PAD) affects more than 200 million individuals worldwide, and those with exertional leg discomfort, rest pain, and tissue or limb loss have significantly impaired functional status and quality of life. Despite their lower associated risk of repeat revascularization, open surgical procedures have been largely supplanted by endovascular intervention for symptomatic PAD given the lower associated morbidity and mortality. Although standalone plain-old percutaneous transluminal angioplasty (PTA) was previously the standard endovascular strategy for these patients, high procedural failure and restenosis rates led to the development of new therapeutic technologies...
April 19, 2017: Circulation
https://www.readbyqxmd.com/read/28424223/low-dose-paclitaxel-coated-versus-uncoated-percutaneous-transluminal-balloon-angioplasty-for-femoropopliteal-peripheral-artery-disease-1-year-results-of-the-illumenate-european-randomized-clinical-trial
#9
Henrik Schroeder, Martin Werner, Dirk-Roelfs Meyer, Peter Reimer, Karsten Krüger, Michael R Jaff, Marianne Brodmann
Background -Numerous studies have reported favorable outcomes using drug-coated balloons (DCBs) for treatment of symptomatic peripheral artery disease (PAD) of the superficial femoral and popliteal arteries. However, the treatment effect compared to an uncoated balloon has differed greatly amongst the randomized trials with better outcomes observed with higher-dose DCBs. This European trial was designed to assess the safety and effectiveness of a next-generation low dose (2 µg/mm(2) surface dose of paclitaxel) DCB...
April 19, 2017: Circulation
https://www.readbyqxmd.com/read/28424222/randomized-comparison-of-paclitaxel-eluting-balloon-angioplasty-plus-stenting-versus-standard-balloon-angioplasty-plus-stenting-versus-directional-atherectomy-for-symptomatic-femoral-artery-disease-isar-stath
#10
Ilka Ott, Salvatore Cassese, Philipp Groha, Birgit Steppich, Martin Hadamitzky, Tareq Ibrahim, Sebastian Kufner, Karl Dewitz, Regina V Hiendlmayer, Karl-Ludwig Laugwitz, Heribert Schunkert, Adnan Kastrati, Massimiliano Fusaro
Background -Atherosclerosis in the superficial femoral artery (SFA) is common in patients suffering from peripheral artery disease. Paclitaxel-eluting balloon (PEB) angioplasty, stenting and directional atherectomy (DA) have provided new options for the treatment of SFA disease, however the comparative efficacy remains uncertain. Methods -One hundred and fifty five patients with symptomatic peripheral artery disease with de novo SFA stenotic or occlusive lesions were randomized to treatment with plain balloon angioplasty (BA) followed by PEB angioplasty and stenting (n=48), BA followed by stenting (n=52) or directional DA with distal protection and bailout stenting (n=55)...
April 19, 2017: Circulation
https://www.readbyqxmd.com/read/28424221/association-between-fetal-congenital-heart-defects-and-maternal-risk-of-hypertensive-disorders-of-pregnancy-in-the-same-pregnancy-and-across-pregnancies
#11
Heather A Boyd, Saima Basit, Ida Behrens, Elisabeth Leirgul, Henning Bundgaard, Jan Wohlfahrt, Mads Melbye, Nina Øyen
Background -Pregnant women carrying fetuses with heart defects and women with hypertensive disorders of pregnancy both often exhibit angiogenic imbalances, suggesting that the same mechanisms are involved in the etiology of the former and the pathophysiology of the latter. We conducted a register-based cohort study to determine whether offspring congenital heart defects are associated with an increased risk of hypertensive disorders of pregnancy, and whether the mechanisms driving any association are primarily maternal or fetal...
April 19, 2017: Circulation
https://www.readbyqxmd.com/read/28411247/exosomal-microrna-transfer-into-macrophages-mediates-cellular-postconditioning
#12
Geoffrey de Couto, Romain Gallet, Linda Cambier, Ervin Jaghatspanyan, Nupur Makkar, James Frederick Dawkins, Benjamin P Berman, Eduardo Marbán
BACKGROUND: Cardiosphere-derived cells (CDCs) confer cardioprotection in acute myocardial infarction (MI) via distinctive macrophage (MΦ) polarization. Here we demonstrate that CDC-secreted exosomes (CDCexo) recapitulate the cardioprotective effects of CDC therapy known as cellular postconditioning. METHODS: Rats and pigs underwent MI induced by ischemia-reperfusion prior to intracoronary infusion of CDCexo, inert fibroblast exosomes (Fbexo; control), or vehicle. Two days later, infarct size was quantified...
April 14, 2017: Circulation
https://www.readbyqxmd.com/read/28389572/prognostic-value-of-noninvasive-cardiovascular-testing-in-patients-with-stable-chest-pain-insights-from-the-promise-trial
#13
Udo Hoffmann, Maros Ferencik, James E Udelson, Michael H Picard, Quynh A Truong, Manesh R Patel, Megan Huang, Michael J Pencina, Daniel B Mark, John F Heitner, Christopher B Fordyce, Patricia A Pellikka, Jean-Claude Tardif, Matthew J Budoff, George Nahhas, Benjamin J Chow, Andrzej S Kosinski, Kerry L Lee, Pamela S Douglas
Background -Optimal management of patients with stable chest pain relies on the prognostic information provided by noninvasive cardiovascular testing, but there are limited data from randomized trials comparing anatomic with functional testing. Methods -In the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial, patients with stable chest pain and intermediate pre-test probability for obstructive coronary artery disease (CAD) were randomized to functional testing (exercise electrocardiography, nuclear stress, or stress echocardiography) or coronary computed tomography angiography (CTA)...
April 7, 2017: Circulation
https://www.readbyqxmd.com/read/28385949/primary-prevention-with-statin-therapy-in-the-elderly-new-meta-analyses-from-the-contemporary-jupiter-and-hope-3-randomized-trials
#14
Paul M Ridker, Eva Lonn, Nina P Paynter, Robert Glynn, Salim Yusuf
The use of statin therapy for secondary prevention is established in all age groups (1). However, in primary prevention, current cardiovascular guidelines in the United States and Canada describe the role for statin therapy in the elderly as uncertain.
April 6, 2017: Circulation
https://www.readbyqxmd.com/read/28385948/hemocompatibility-related-outcomes-in-the-momentum-3-trial-at-6-months-a-randomized-controlled-study-of-a-fully-magnetically-levitated-pump-in-advanced-heart-failure
#15
Nir Uriel, Paolo C Colombo, Joseph C Cleveland, James W Long, Christopher Salerno, Daniel J Goldstein, Chetan B Patel, Gregory A Ewald, Antone J Tatooles, Scott C Silvestry, Ranjit John, Christiano Caldeira, Valluvan Jeevanandam, Andrew J Boyle, Kartik S Sundareswaran, Poornima Sood, Mandeep R Mehra
BACKGROUND : The HeartMate 3 (HM3) Left Ventricular Assist System (LVAS) (Abbott) is a centrifugal, fully magnetically levitated, continuous-flow blood pump engineered to enhance hemocompatibility and reduce shear stress on blood components. The MOMENTUM 3 trial (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) compares the HM3 LVAS with the HeartMate II (HMII) LVAS (Abbott) in advanced heart failure refractory to medical management, irrespective of therapeutic intention (bridge to transplant versus destination therapy)...
April 6, 2017: Circulation
https://www.readbyqxmd.com/read/28381471/sox17-regulates-conversion-of-human-fibroblasts-into-endothelial-cells-and-erythroblasts-via-de-differentiation-into-cd34-progenitor-cells
#16
Lianghui Zhang, Ankit Jambusaria, Zhigang Hong, Glenn Marsboom, Peter T Toth, Brittney-Shea Herbert, Asrar B Malik, Jalees Rehman
Background -The mechanisms underlying the de-differentiation and lineage conversion of adult human fibroblasts into functional endothelial cells have not yet been fully defined. Furthermore, it is not known whether fibroblast de-differentiation recapitulates the generation of multipotent progenitors during embryonic development which give rise to endothelial and hematopoietic cell lineages. Here we established the role of the developmental transcription factor SOX17 in regulating the bi-lineage conversion of fibroblasts via the generation of intermediate progenitors...
April 5, 2017: Circulation
https://www.readbyqxmd.com/read/28381470/evidence-supporting-the-existence-of-a-distinct-obese-phenotype-of-heart-failure-with-preserved-ejection-fraction
#17
Masaru Obokata, Yogesh N V Reddy, Sorin V Pislaru, Vojtech Melenovsky, Barry A Borlaug
Background -Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous syndrome. Phenotyping patients into pathophysiologically homogenous groups may enable better targeting of treatment. Obesity is common in HFpEF and has many cardiovascular effects, suggesting it may be a viable candidate for phenotyping. We compared cardiovascular structure, function, and reserve capacity in subjects with obese HFpEF, non-obese HFpEF, and controls. Methods -Subjects with obese HFpEF (BMI≥35kg/m(2), n=99), non-obese HFpEF (BMI<30kg/m(2), n=96), and non-obese controls free of HF (n=71) underwent detailed clinical assessment, echocardiography and invasive hemodynamic exercise testing...
April 5, 2017: Circulation
https://www.readbyqxmd.com/read/28377486/p2x7-deficiency-blocks-lesional-inflammasome-activity-and-ameliorates-atherosclerosis-in-mice
#18
Peter Stachon, Adrian Heidenreich, Julian Merz, Ingo Hilgendorf, Dennis Wolf, Florian Willecke, Sunaina von Garlen, Philipp Albrecht, Carmen Härdtner, Nicolas Ehrat, Natalie Hoppe, Jochen Reinöhl, Constantin von Zur Mühlen, Christoph Bode, Marco Idzko, Andreas Zirlik
Background -Extracellular ATP binds as a danger signal to purinergic receptor P2X7, promotes inflammasome assembly, and IL-1β expression. We hypothesized a functional role of the signal axis ATP - P2X7 in inflammasome activation and the chronic inflammation driving atherosclerosis. Methods -P2X7-competent and -deficient macrophages were isolated and stimulated with LPS, ATP, or both. To assess whether P2X7 may have a role in atherosclerosis, P2X7 expression was analyzed in aortic arches from LDLR(-/-) mice consuming high cholesterol diet (HCD) or chow diet...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28377485/ischemic-cerebroprotection-conferred-by-myeloid-lineage-restricted-or-global-cd39-transgene-expression
#19
Amy E Baek, Nadia R Sutton, Danica Petrovic-Djergovic, Hui Liao, Jessica Ray, Joan Park, Yogendra Kanthi, David J Pinsky
Background -Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic (TG) mouse expressing human CD39 (hCD39)...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28360032/a-multimodality-strategy-for-cardiovascular-risk-assessment-performance-in-two-population-based-cohorts
#20
James A de Lemos, Colby R Ayers, Benjamin D Levine, Christopher R deFilippi, Thomas J Wang, W Gregory Hundley, Jarett D Berry, Stephen L Seliger, Darren K McGuire, Pamela Ouyang, Mark H Drazner, Matthew J Budoff, Philip Greenland, Christie M Ballantyne, Amit Khera
Background -Current strategies for cardiovascular disease (CVD) risk assessment among adults without known CVD are limited by suboptimal performance and a narrow focus on only atherosclerotic CVD (ASCVD). We hypothesized that a strategy combining promising biomarkers across multiple different testing modalities would improve global and atherosclerotic CVD risk assessment among individuals without known CVD. Methods -We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA, n=6621) and Dallas Heart Study (DHS, n=2202) who were free from CVD and underwent measurement of left ventricular hypertrophy by electrocardiogram (ECG-LVH), coronary artery calcium (CAC), N-terminal pro B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity C-reactive protein (hs-CRP)...
March 30, 2017: Circulation
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