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https://www.readbyqxmd.com/read/28623742/effect-of-intensive-ldl-cholesterol-lowering-with-pcsk9-monoclonal-antibodies-on-tendon-xanthoma-regression-in-familial-hypercholesterolemia
#1
Ana M Bea, Sofia Perez-Calahorra, Victoria Marco-Benedi, Itziar Lamiquiz-Moneo, Estibaliz Jarauta, Rocio Mateo-Gallego, Fernando Civeira
BACKGROUND AND AIMS: The effect of LDLc lowering with PCSK9 antibodies on tendon xanthomas (TX) is unknown. METHODS: TX was measured in 24 heterozygous familial hypercholesterolemia (HeFH) cases and in 24 HeFH controls with or without PCSK9 inhibitors for at least one year. RESULTS: Exposure to PCSK9 inhibitors in cases was 2.96 ± 1.33 years. LDLc decreased 80.8 ± 7.66% in cases and 56.9 ± 11.1% in controls. There was a decrease in maximum (-5...
June 8, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28618915/coronary-artery-disease-risk-stratification-and-patient-selection-for-more-aggressive-secondary-prevention
#2
François Schiele, Fiona Ecarnot, Romain Chopard
In patients with stable coronary artery disease, clinical outcomes are predominantly characterized by the consequences of atherosclerosis on the myocardium, but also by complications of atherosclerosis, notably recurrent acute coronary syndrome or stroke. Secondary prevention therapy is therefore key in this patient population. Intensification of secondary prevention therapy is possible, at the price of a therapeutic risk or a high cost, therefore justifying careful selection of patients with a high residual risk and low therapeutic risk...
June 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28618905/effective-low-density-lipoprotein-lowering-therapy-implementation-in-clinical-practice
#3
David Sinning, Ulf Landmesser
Although age-adjusted mortality of coronary heart disease has been successfully reduced over recent years, coronary heart disease still represents a leading cause of death and morbidity, in particular in patients at very high cardiovascular risk. Dyslipidaemia plays a major and causal role in the development and clinical progression of coronary heart disease. At present, low-density lipoprotein cholesterol represents the primary target of lipid-directed therapies for the prevention of cardiovascular disease and events...
June 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28607329/influence-of-long-term-physical-activity-on-pcsk9-hdl-ldl-c-and-lp-a-a-prospective-observational-trial
#4
Michael Sponder, Ioana-Alexandra Campean, Daniel Dalos, Michael Emich, Monika Fritzer-Szekeres, Brigitte Litschauer, Jutta Bergler-Klein, Senta Graf, Jeanette Strametz-Juranek
INTRODUCTION    Since PCSK9 (proprotein convertase subtilisin/kexin type 9)-inhibitors were brought to market, the interest in PCSK9 metabolism has increased dramatically.  OBJECTIVES    This study investigates prospectively the influence of long-term physical activity on PCSK9, high and low-density lipoprotein cholesterol (HDL-C/LDL-C) and lipoprotein a [Lp(a)]. PATIENTS AND METHODS    109 subjects were recruited and instructed to increase their sport pensum by 75 minutes/week of vigorous or 150 minutes/week of moderate intensity endurance training (or a mixture) within the calculated training pulse for 8 months...
June 9, 2017: Polish Archives of Internal Medicine
https://www.readbyqxmd.com/read/28577571/genetic-determinants-of-inherited-susceptibility-to-hypercholesterolemia-a-comprehensive-literature-review
#5
REVIEW
C S Paththinige, N D Sirisena, Vhw Dissanayake
Hypercholesterolemia is a strong determinant of mortality and morbidity associated with cardiovascular diseases and a major contributor to the global disease burden. Mutations in four genes (LDLR, APOB, PCSK9 and LDLRAP1) account for the majority of cases with familial hypercholesterolemia. However, a substantial proportion of adults with hypercholesterolemia do not have a mutation in any of these four genes. This indicates the probability of having other genes with a causative or contributory role in the pathogenesis of hypercholesterolemia and suggests a polygenic inheritance of this condition...
June 2, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28574577/pcsk9-and-infection-a-potentially-useful-or-dangerous-association
#6
REVIEW
Farzad Kahdemi, Amir Abbas Momtazi-Borojeni, Željko Reiner, Maciej Banach, Khalid Al Rasadi, Amirhossein Sahebkar
Elevated plasma low-density lipoprotein-cholesterol (LDL-C) concentration is the most important risk factor for atherosclerotic cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a ubiquitously expressed serine proteinase which plays a key role in cholesterol metabolism, but has been found to be implicated in some other lipid-independent physiological processes. In this review, the role of PCSK9 was evaluated not only concerning lipid metabolism but also hepatitis C virus (HCV) infection, bacterial infections/sepsis and septic shock...
June 2, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28566931/is-there-an-ideal-low-density-lipoprotein-cholesterol-level-confusion-regarding-lipid-guidelines-low-density-lipoprotein-cholesterol-targets-and-medical-management
#7
REVIEW
Thomas F Whayne
There are multiple guidelines for managing patients with high-risk cardiovascular disease, and unfortunately for the practicing clinician, these guidelines are quite variable. Some are fairly specific whereas others are not, resulting in a great deal of confusion regarding whether management of low-density lipoprotein cholesterol (LDL-C) should be tailored only, targeted only, or managed by a combination of both. In the management of cardiovascular disease, favorable cardiovascular outcomes can be obtained by simply lowering the LDL-C in the absence of any other medications...
June 2017: International Journal of Angiology: Official Publication of the International College of Angiology, Inc
https://www.readbyqxmd.com/read/28565798/pcsk9-regulates-apoptosis-in-human-lung-adenocarcinoma-a549-cells-via-endoplasmic-reticulum-stress-and-mitochondrial-signaling-pathways
#8
Xiaohui Xu, Yushang Cui, Lei Cao, Ye Zhang, Yan Yin, Xue Hu
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a member of the subtilisin family of PCs that encodes a neural apoptosis-regulated convertase 1. However, the precise role of PCSK9 in lung cancer cell apoptosis has remained elusive. In the present study, A549 human lung adenocarcinoma cells were transfected with PCSK9 small interfering (si)RNA to investigate the underlying mechanisms of apoptosis. The results indicated that PCSK9 siRNA exhibited anti-tumor activity by inducing apoptosis as determined by a Cell Counting Kit-8 and Hoechst staining analysis...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28557865/the-emerging-role-of-proprotein-convertase-subtilisin-kexin-type-9-inhibition-in-secondary-prevention-from-clinical-trials-to-real-world-experience
#9
Amritanshu S Pandey, Harpreet S Bajaj, Vinay Garg, Avinash Pandey, Subodh Verma
PURPOSE OF REVIEW: The recent advent of a highly efficacious class of low-density lipoprotein cholesterol (LDL-C) lowering agents, the proprotein convertase subtilisin/kexin type-9 (PCSK9) inhibitors, has transformed dyslipidaemia management in patients with cardiovascular disease as well as those with familial hypercholesterolemia. RECENT FINDINGS: Recent positive results of the landmark Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk cardiovascular outcome trial with evolocumab as an add-on to statin therapy demonstrate further reduction of cardiovascular events...
May 26, 2017: Current Opinion in Cardiology
https://www.readbyqxmd.com/read/28555526/statin-intolerance-in-heterozygous-familial-hypercolesterolemia-with-cardiovascular-disease-after-pcsk-9-antibodies-what-else
#10
Francesco Sbrana, Beatrice Dal Pino, Federico Bigazzi, Andrea Ripoli, Claudio Passino, Alessandra Gabutti, Emilio M Pasanisi, Christina Petersen, Alessandro Valleggi, Giancarlo Todiere, Andrea Barison, Alberto Giannoni, Luca Panchetti, Francesco Becherini, Mascia Pianelli, Roberta Luciani, Tiziana Sampietro
Background Familial hypercholesterolemia is the elective clinical condition that deserves the maximal personalisation in lipid-lowering therapy, especially in the presence of statin intolerance. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors represent a promising approach to lower low-density lipoprotein (LDL) cholesterol. Methods We enrolled 18 patients (mean age 62 ± 8 years, 72% men) affected by heterozygous familial hypercholesterolemia and cardiovascular disease, with a history of statin intolerance assigned to PCSK9 inhibitors...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28554582/geranylgeraniol-prevents-the-simvastatin-induced-pcsk9-expression-role-of-the-small-g-protein-rac1
#11
Nicola Ferri, Silvia Marchianò, Maria Giovanna Lupo, Annalisa Trenti, Giuseppe Biondo, Paola Castaldello, Alberto Corsini
Statins are known to increase the plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) through the activation of the sterol responsive element binding protein (SREBP) pathway due to the inhibition of cholesterol biosynthesis. In the present study, we explore a possible role of the prenylated proteins on the statin-mediated PCSK9 induction in Caco-2 cells. Simvastatin (40μM) induced both PCSK9 mRNA (10.7±3.2 fold) and protein (2.2±0.3 fold), after 24h incubation. The induction of PCSK9 mRNA was partially, but significantly, prevented by the co-incubation with mevalonate (MVA), farnesol (FOH) and geranylgeraniol (GGOH), while a complete prevention was observed on secreted PCSK9, evaluated by ELISA assay...
May 26, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28550993/barriers-to-pcsk9-inhibitor-prescriptions-for-patients-with-high-cardiovascular-risk-results-of-a-healthcare-provider-survey-conducted-by-the-national-lipid-association
#12
Jerome D Cohen, Mark J Cziraky, Terry A Jacobson, Kevin C Maki, Dean G Karalis
BACKGROUND: Statin therapy is recommended for reducing atherosclerotic cardiovascular disease (ASCVD) risk. Significant risk can remain because of insufficient clinical response or statin intolerance. Proprotein convertase subtilisin/kexin type-9 (PCSK9) therapy lowers low-density lipoprotein cholesterol and has recently been shown to lower ASCVD events. OBJECTIVE: The aim of the study was to assess the barriers and challenges experienced with the access and approval reimbursement process for PCSK9 inhibitor prescriptions...
May 23, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28549755/cholesterol-and-stroke-roll-of-pcsk9-inhibitors
#13
L Castilla-Guerra, M C Fernández-Moreno, M A Rico-Corral
INTRODUCTION: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the modulation of plasma levels of low density lipoprotein cholesterol (LDLC). PCSK9 binds to the LDL receptor (LDLR), disrupts its endocytic recycling itinerary and directs it to lysosomal degradation. Activation of PCSK9 can thus decrease the expression of LDLR in the liver and inhibit LDL uptake, which leads to hypercholesterolaemia. DEVELOPMENT: Currently we now know that different polymorphisms of PCSK9 are associated with the occurrence of ischaemic stroke...
May 23, 2017: Neurología: Publicación Oficial de la Sociedad Española de Neurología
https://www.readbyqxmd.com/read/28545518/design-and-rationale-of-the-odyssey-dm-dyslipidemia-trial-lipid-lowering-efficacy-and-safety-of-alirocumab-in-individuals-with-type-2-diabetes-and-mixed-dyslipidaemia-at-high-cardiovascular-risk
#14
Dirk Müller-Wieland, Lawrence A Leiter, Bertrand Cariou, Alexia Letierce, Helen M Colhoun, Stefano Del Prato, Robert R Henry, Francisco J Tinahones, Lisa Aurand, Jaman Maroni, Kausik K Ray, Maja Bujas-Bobanovic
BACKGROUND: Type 2 diabetes mellitus (T2DM) is often associated with mixed dyslipidaemia, where non-high-density lipoprotein cholesterol (non-HDL-C) levels may more closely align with cardiovascular risk than low-density lipoprotein cholesterol (LDL-C). We describe the design and rationale of the ODYSSEY DM-DYSLIPIDEMIA study that assesses the efficacy and safety of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, versus lipid-lowering usual care in individuals with T2DM and mixed dyslipidaemia at high cardiovascular risk with non-HDL-C inadequately controlled despite maximally tolerated statin therapy...
May 25, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28537000/advances-in-clinical-cardiology-2016-a-summary-of-the-key-clinical-trials
#15
REVIEW
Alastair Gray, Conor McQuillan, Ian B A Menown
INTRODUCTION: The findings of many new cardiology clinical trials over the last year have been published or presented at major international meetings. This paper aims to describe and place in context a summary of the key clinical trials in cardiology presented between January and December 2016. METHODS: The authors reviewed clinical trials presented at major cardiology conferences during 2016 including the American College of Cardiology (ACC), European Association for Percutaneous Cardiovascular Interventions (EuroPCR), European Society of Cardiology (ESC), European Association for the Study of Diabetes (EASD), Transcatheter Cardiovascular Therapeutics (TCT), and the American Heart Association (AHA)...
May 23, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28532784/update-on-the-use-of-pcsk9-inhibitors-in-adults-recommendations-from-an-expert-panel-of-the-national-lipid-association
#16
Carl E Orringer, Terry A Jacobson, Joseph J Saseen, Alan S Brown, Antonio M Gotto, Joyce L Ross, James A Underberg
An Expert Panel convened by the National Lipid Association was charged with updating the recommendations on the use of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibody therapy that were provided by the 2015 National Lipid Association Recommendations for the Patient-Centered Management of Dyslipidemia: Part 2. Recent studies have demonstrated the efficacy of these agents in reducing low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol and have confirmed their excellent safety profile...
May 19, 2017: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/28531826/how-many-familial-hypercholesterolemia-patients-are-eligible-for-pcsk9-inhibition
#17
Luis Masana, Nuria Plana, Sofia Pérez-Calahorra, Daiana Ibarretxe, Itziar Lamiquiz-Moneo, Juan Pedro-Botet, Manuel Suárez-Tembra, Pedro Valdivielso, Emilio Ortega, Fernando Civeira
BACKGROUND AND AIMS: Familial hypercholesterolemia (FH) is a high cardiovascular risk condition. Less than 20% of patients achieve the LDL targets. Although PCSK9 inhibitors improve control and reduce cardiovascular events, official recommendations for their use are restrictive. We aim to assess the number of FH patients suitable for PCSK9 inhibition according to the European guidelines. METHODS: A total of 2685 FH patients, with a minimum follow-up of 6 months, included in the Dyslipidemia Registry of the Spanish Arteriosclerosis Society, were sorted according to the intensity of their lipid-lowering therapy (LLT) and LDL cholesterol levels achieved...
July 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28529918/advances-in-dyslipidemia-management-for-prevention-of-atherosclerosis-pcsk9-monoclonal-antibody-therapy-and-beyond
#18
REVIEW
Nathan D Wong, Paul D Rosenblit, Robert S Greenfield
In 2003, select families with familial hypercholesterolemia were first identified to have gain-of-function mutations for proprotein convertase subtilisin kexin type 9 (PCSK9) followed, in 2006, by the identification of those with lifelong low levels of LDL-C and lowered atherosclerotic cardiovascular disease (ASCVD) risk who had loss-of-function PCSK9 mutations. These discoveries led to the rapid development of PSCK9-targeted monoclonal antibody (PCSK9 mAb) therapies and, in 2015, 2 'fully-humanized' PCSK9 mAbs (alirocumab and evolocumab) were marketed in the United States, Europe, and other countries...
April 2017: Cardiovascular Diagnosis and Therapy
https://www.readbyqxmd.com/read/28527325/dyslipidemia-management-update
#19
REVIEW
Yingzi Chang, Jacques Robidoux
Association of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) is well established. Reducing low-density lipoprotein-cholesterol (LDL-C) and raising high-density lipoprotein-cholesterol (HDL-C) have been the therapeutic targets to reduce the risk of ASCVD. Cholesterol-lowering medications have been used to provide both primary and secondary prevention of ASCVD for many years by reducing the absorption and reabsorption, promoting excretion, or decreasing the synthesis of cholesterol. Within the past five years, several new classes of cholesterol-lowering drugs have been tested and approved for patients with hypercholesterolemia that are not well controlled by conventional therapy (ezetimibe, bile-acid sequestrants, and statins)...
April 2017: Current Opinion in Pharmacology
https://www.readbyqxmd.com/read/28509674/evidence-for-more-intensive-cholesterol-lowering
#20
Handrean Soran, See Kwok, Safwaan Adam, Jan Hoong Ho, Paul N Durrington
PURPOSE OF REVIEW: In randomized clinical trials, reduction in cardiovascular disease (CVD) risk with cholesterol-lowering drugs correlates with the LDL cholesterol decrease. However, because the majority have investigated a fixed statin dose, current guidelines disagree about the use of statin dose titration or non-statin adjunctive cholesterol-lowering drugs. RECENT FINDINGS: We conducted a meta-analysis of all randomized controlled trials with CVD end-points, comparing two intensities of lipid-lowering regimens within the same population, using varying statins doses and/or potency, ezetimibe or PCSK9 inhibitors and compared the observed number of patients needed to be treated for 10 years to prevent one CVD event (NNT) with NNT predicted from trials of predominantly single-dose statin...
May 15, 2017: Current Opinion in Lipidology
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