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https://www.readbyqxmd.com/read/28644091/prevention-of-cardiovascular-disease-in-patients-with-familial-hypercholesterolaemia-the-role-of-pcsk9-inhibitors
#1
Ivan Pećin, Merel L Hartgers, G Kees Hovingh, Ricardo Dent, Željko Reiner
Familial hypercholesterolaemia is an autosomal dominant inherited disorder characterised by elevated low-density lipoprotein cholesterol levels and consequently an increased risk of atherosclerotic cardiovascular disease (ASCVD). Familial hypercholesterolaemia is relatively common, but is often underdiagnosed and undertreated. Cardiologists are likely to encounter many individuals with familial hypercholesterolaemia; however, patients presenting with premature ASCVD are rarely screened for familial hypercholesterolaemia and fasting lipid levels are infrequently documented...
January 1, 2017: European Journal of Preventive Cardiology
https://www.readbyqxmd.com/read/28643240/pcsk9-inhibitors-treating-the-right-patients-in-daily-practice
#2
REVIEW
Peta King, Stephen J Nicholls
PURPOSE OF REVIEW: Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9) have emerged as a novel approach to low-density lipoprotein cholesterol (LDL-C) lowering. The potential role of PCSK9 inhibitors in clinical practice will be reviewed. RECENT FINDINGS: Clinical trials have demonstrated that PCSK9 inhibitors produce robust LDL-C lowering when administered either as monotherapy or in combination with statins. This provides the opportunity to achieve effective lipid lowering in familial hypercholesterolemia, patients with either established atherosclerotic cardiovascular disease or high risk primary prevention and an important opportunity to treat patients with statin intolerance...
August 2017: Current Cardiology Reports
https://www.readbyqxmd.com/read/28639183/proprotein-convertase-subtilisin-kexin-type-9-pcsk9-and-its-inhibitors-a-review-of-physiology-biology-and-clinical-data
#3
REVIEW
Ashwin Durairaj, Alberto Sabates, Jonathan Nieves, Brian Moraes, Seth Baum
Atherosclerotic cardiovascular disease (ASCVD) remains the number one killer in the western world. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and ezetimibe has been shown to reduce the risk of cardiovascular events. Now, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mabs) are available for high-risk individuals with ASCVD or familial hypercholesterolemia on maximally tolerated statin therapy but requiring greater LDL-C reduction. PCSK9 mab outcome trial results from the Further Cardiovascular Outcomes Research with PCSK9 Inhibitions in Subjects with Elevated Risk (FOURIER) study, which was presented at the American College of Cardiology in March 2017, which demonstrated a decrease of 15% in primary and 20% secondary end points over a 2-year period [1••]...
August 2017: Current Treatment Options in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28637178/the-at04a-vaccine-against-proprotein-convertase-subtilisin-kexin-type-9-reduces-total-cholesterol-vascular-inflammation-and-atherosclerosis-in-apoe-3leiden-cetp-mice
#4
Christine Landlinger, Marianne G Pouwer, Claudia Juno, José W A van der Hoorn, Elsbet J Pieterman, J Wouter Jukema, Guenther Staffler, Hans M G Princen, Gergana Galabova
Aims: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a promising therapeutic target for the treatment of hypercholesterolaemia and atherosclerosis. PCSK9 binds to the low density lipoprotein receptor and enhances its degradation, which leads to the reduced clearance of low density lipoprotein cholesterol (LDLc) and a higher risk of atherosclerosis. In this study, the AT04A anti-PCSK9 vaccine was evaluated for its therapeutic potential in ameliorating or even preventing coronary heart disease in the atherogenic APOE*3Leiden...
June 19, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28636184/pharmacokinetics-pharmacodynamics-of-bococizumab-a-monoclonal-antibody-to-pcsk9-after-single-subcutaneous-injection-at-3-sites-nct-02043301
#5
Ellen Q Wang, Anna Plotka, Joanne Salageanu, Catherine Sattler, Carla Yunis
AIM: To characterize the single-dose pharmacokinetics (PK) and pharmacodynamics (PD) of bococizumab, a monoclonal antibody inhibiting proprotein convertase subtilisin/kexin type 9 (PCSK9), administered subcutaneously (s.c.) to the abdomen, thigh, or upper arm (NCT02043301). METHODS: Seventy-five adults with low-density lipoprotein cholesterol (LDL-C) ≥130 mg/dL and not on background lipid-lowering therapy were randomized (1:1:1) to a single 150-mg s.c. dose of bococizumab administered to the abdomen, thigh, or upper arm...
June 21, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28633452/threshold-effects-of-circulating-angiopoietin-like-3-levels-on-plasma-lipoproteins
#6
Sergio Fazio, Jessica Minnier, Michael D Shapiro, Sotirios Tsimikas, Patrizia Tarugi, Maurizio R Averna, Marcello Arca, Hagai Tavori
Context: Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function (LOF) gene mutations causes familial combined hypobetalipoproteinemia (FHBL) type 2 in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low LDL phenotype in carriers of ANGPTL3 mutations is unexplained. Objective: To determine whether a reduction below a critical threshold in plasma ANGPTL3 levels is a determinant of lipoprotein metabolism in FHBL2, and to study the whether PCSK9 is involved in determining low LDL levels in this condition...
June 19, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28630269/coverage-and-cardioprotective-benefits-of-pcsk9-take-center-stage-at-the-american-college-of-cardiology-meeting
#7
Bridget M Kuehn
No abstract text is available yet for this article.
June 20, 2017: Circulation
https://www.readbyqxmd.com/read/28623954/efficacy-and-safety-of-alirocumab-in-patients-with-hypercholesterolemia-not-adequately-controlled-with-non-statin-lipid-lowering-therapy-or-the-lowest-strength-of-statin-odyssey-nippon-study-design-and-rationale
#8
Tamio Teramoto, Akira Kondo, Arihiro Kiyosue, Mariko Harada-Shiba, Yasushi Ishigaki, Kimimasa Tobita, Yumiko Kawabata, Asuka Ozaki, Marie T Baccara-Dinet, Masataka Sata
BACKGROUND: Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). METHODS: The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone)...
June 17, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28623742/effect-of-intensive-ldl-cholesterol-lowering-with-pcsk9-monoclonal-antibodies-on-tendon-xanthoma-regression-in-familial-hypercholesterolemia
#9
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/28623549/elevated-circulating-pcsk9-concentrations-predict-subclinical-atherosclerotic-changes-in-low-risk-obese-and-non-obese-patients
#10
Štefan Tóth, Ján Fedačko, Tímea Pekárová, Zdenka Hertelyová, Matan Katz, Adil Mughees, Jozef Kuzma, Peter Štefanič, Ivan Kopolovets, Daniel Pella
INTRODUCTION: Many studies have highlighted the important role of PCSK9 in the development of cardiometabolic changes and its possible function as a biomarker of myocardial infarction or ischemic heart disease. This study aimed to determine the relationship between circulating PCSK9 levels and subclinical vascular changes in the group of low risk patients without manifest cardiovascular diseases. METHODS: In this study, 120 healthy patients, free of manifest cardiovascular diseases, diabetes mellitus, and without lipid-lowering therapy, were divided into three groups based on BMI: normal weight (N = 50), overweight (N = 30), and obese (N = 40)...
June 16, 2017: Cardiology and Therapy
https://www.readbyqxmd.com/read/28619117/the-elevation-of-plasma-concentrations-of-apob-48-containing-lipoproteins-in-familial-hypercholesterolemia-is-independent-of-pcsk9-levels
#11
Jean-Philippe Drouin-Chartier, Jean-Charles Hogue, André J Tremblay, Jean Bergeron, Benoît Lamarche, Patrick Couture
BACKGROUND: Previous studies have reported high plasma concentrations of both intestinal apolipoprotein (apo) B-48-containing lipoproteins and PCSK9 in subjects with familial hypercholesterolemia (FH). However, the extent to which LDL receptor deficiency and PCSK9 levels influence plasma apoB-48 concentrations in humans remains to be fully characterized. The objective of the study was to assess the independent association between FH, PCSK9 concentrations and plasma apoB-48 levels in a large cohort of genetically defined FH heterozygotes (HeFH) and homozygotes (HoFH)...
June 15, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28618994/role-of-anti-pcsk9-antibodies-in-the-treatment-of-patients-with-statin-intolerance
#12
Julia Schreml, Ioanna Gouni-Berthold
Statin intolerance is usually defined as the inability of a patient to tolerate statin-treatment due to muscle-related complaints. While randomised trials show that these complaints occure with similar frequency in patients receiving placebo, namely in up to ~5% of the subjects, data from registries as well as clinical experience indicate a much higher frequency of up to ~30%. The lack of standard definition or of a diagnostic marker of statin intolerance confounds the problem. The diagnosis remains subjective based on the symptoms the patient reports...
June 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28618915/coronary-artery-disease-risk-stratification-and-patient-selection-for-more-aggressive-secondary-prevention
#13
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
#14
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/28617192/emerging-biologic-therapies-for-hypercholesterolaemia
#15
Giacomo Pucci, Arrigo F Cicero, Claudio Borghi, Giuseppe Schillaci
LDL-cholesterol (LDL-C) is one of the most well-established risk factors for CV disease. Indeed, therapies that decrease LDL-C are proven to effectively reduce the risk of atherosclerotic CV disease. Monoclonal antibodies (mAbs) that target proprotein convertase subtilisin/kexin type 9 (PCSK9) have recently gained traction as a promising therapeutic strategy. Areas covered: In this review, the authors discuss the effectiveness of mAbs against PCSK9 in lowering low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid fractions...
June 15, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28616272/the-effects-of-additional-ezetimibe-treatment-to-baseline-rosuvastatin-on-circulating-pcsk9-among-patients-with-stable-angina
#16
Jian Zhang, Mingzhi Long, Yichao Yu
BACKGROUND: Blood lipid management is one of the effective strategies for coronary heart disease, and statins are the first-line lipid-lowering drugs. Low density lipoprotein cholesterol (LDL-C) drop brings about cardioprotective effects. Proprotein convertase subtilisin kexin type 9 (PCSK9) is known to increase LDL-C, thus hazarding LDL-C reduction-induced benefits. To date, how PCSK9 responds to various lipid-lowering strategies has not been fully clarified. METHODS: This study involves patients with stable angina and aims to explore and clarify the short-term impacts of rosuvastatin and ezetimibe, alone or in combination, on circulating PCSK9...
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28611099/cell-based-bioluminescent-assay-for-monitoring-the-interaction-between-pcsk9-and-the-ldl-receptor
#17
Sarah J Duellman, Thomas Machleidt, James J Cali, Jolanta Vidugiriene
Monitoring the expression of cell-surface receptors, their interaction with extracellular ligands, and their fate upon ligand binding is important for understanding receptor function and developing new therapies. We describe a cell-based method that utilizes bioluminescent protein complementation technology to interrogate binding of a cellular receptor with its extracellular protein ligand, specifically LDLR and PCSK9. Purified, full-length tagged PCSK9 is added to assay wells containing cells that stably express LDLR with an extracellular complementary tag...
June 13, 2017: Journal of Lipid Research
https://www.readbyqxmd.com/read/28607329/influence-of-long-term-physical-activity-on-pcsk9-hdl-ldl-c-and-lp-a-a-prospective-observational-trial
#18
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/28607103/dynamin-related-protein-1-inhibition-attenuates-cardiovascular-calcification-in-the-presence-of-oxidative-stress
#19
Maximillian Rogers, Natalia Maldonado-Martinez, Joshua D Hutcheson, Claudia Goettsch, Shinji Goto, Iwao Yamada, Tyler Faits, Hiromi Sesaki, Masanori Aikawa, Elena Aikawa
Rationale: Mitochondrial changes occur during cell differentiation and cardiovascular disease. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. We hypothesized that DRP1 plays a role in cardiovascular calcification, a process involving cell differentiation and a major clinical problem with high unmet needs. Objective: To examine the effects of osteogenic promoting conditions on DRP1, and whether DRP1 inhibition alters the development of cardiovascular calcification. Methods and Results: DRP1 was enriched in calcified regions of human carotid arteries, examined by immunohistochemistry...
June 12, 2017: Circulation Research
https://www.readbyqxmd.com/read/28606094/what-is-the-impact-of-pcsk9-rs505151-and-rs11591147-polymorphisms-on-serum-lipids-level-and-cardiovascular-risk-a-meta-analysis
#20
Chengfeng Qiu, Pingyu Zeng, Xiaohui Li, Zhen Zhang, Bingjie Pan, Zhou Y F Peng, Yapei Li, Yeshuo Ma, Yiping Leng, Ruifang Chen
BACKGROUND: PCSK9 rs505151 and rs11591147 polymorphisms are identified as gain- and loss-of-function mutations, respectively. The effects of these polymorphisms on serum lipid levels and cardiovascular risk remain to be elucidated. METHODS: In this meta-analysis, we explored the association of PCSK9 rs505151 and rs11591147 polymorphisms with serum lipid levels and cardiovascular risk by calculating the standardized mean difference (SMD) and odds ratios (OR) with 95% confidence intervals (CI)...
June 12, 2017: Lipids in Health and Disease
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