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https://www.readbyqxmd.com/read/29332570/proprotein-convertase-subtilisin-kexin-type-9-inhibition-in-cardiovascular-prevention
#1
Ali Ali, Pierluigi Costanzo, Angela Hoye
Elevated levels of Low Density Lipoprotein cholesterol (LDL-C) are directly associated with increased risk for atherosclerotic cardiovascular and cerebrovascular events. Statins have been used to control serum LDL-C and this has translated into reduction in cardiovascular and cerebrovascular events. However, despite high dose statin therapy, LDL-C control may remain inadequate in some patients, particularly those with familial hypercholesterolemia. A new therapeutic approach has emerged in recent years with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors...
January 10, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29321358/genetic-variants-influencing-lipid-levels-and-risk-of-dyslipidemia-in-chinese-population
#2
Huaichao Luo, Xueping Zhang, Ping Shuai, Yuanying Miao, Zimeng Ye, Ying Lin
Recently, several human genetic and genomewide association studies (GWAS) have discovered many genetic loci that are associated with the concentration of the blood lipids. To confirm the reported loci in Chinese population, we conducted a crosssection study to analyse the association of 25 reported SNPs, genotyped by the ABI SNaPshot method, with the blood levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) in 1900 individuals by multivariate analysis...
December 2017: Journal of Genetics
https://www.readbyqxmd.com/read/29315397/cost-effectiveness-with-pcsk9-inhibitors-a-matter-of-costs
#3
Heinz Drexel
No abstract text is available yet for this article.
January 1, 2018: European Heart Journal. Cardiovascular Pharmacotherapy
https://www.readbyqxmd.com/read/29313544/dietary-supplementation-of-defatted-kenaf-hibiscus-cannabinus-l-seed-meal-and-its-phenolics-saponins-rich-extract-effectively-attenuates-diet-induced-hypercholesterolemia-in-rats
#4
Kim Wei Chan, Maznah Ismail, Norhaizan Mohd Esa, Mustapha Umar Imam, Der Jiun Ooi, Nicholas M H Khong
Kenaf is one of the important commercial fiber crops worldwide and defatted kenaf seed meal (DKSM) is a secondary by-product from the kenaf industry. Thus, efforts to turn this low-cost agricultural waste into value-added functional food ingredients will definitely bring advantageous impacts to the community health, environment and economy. The present study was aimed to investigate the cardioprotective properties of DKSM and its phenolics-saponins rich extract (PSRE) in diet-induced hypercholesterolemic rat model...
January 9, 2018: Food & Function
https://www.readbyqxmd.com/read/29310364/high-circulating-proprotein-convertase-subtilisin-kexin-type-9-concentration-associates-with-cardiovascular-risk-a-meta-analysis-of-cohort-studies
#5
Chengfeng Qiu, Quan Zhou, Xiaohui Li, Zhen Zhang, Pingyu Zeng, Zeng Cao, Bingjie Pan, Xiaogang Li, Alex F Chen
Whether the baseline circulating proprotein convertase subtilisin/Kexin type 9 (PCSK9) concentration associates with cardiovascular risk remains uncertain. This study aimed to investigate the predictive value of circulating PCSK9 in cardiovascular risk prediction.Relevant studies were searched through the MEDLINE, EMBASE, and Cochrane Library databases. The relative risk (RR) and 95% confidence interval (CI) were pooled to evaluate the association between the circulating PCSK9 concentration and cardiovascular risk...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29306457/cost-effectiveness-of-pcsk9-inhibition-in-addition-to-standard-lipid-lowering-therapy-in-patients-at-high-risk-for-vascular-disease
#6
Manon C Stam-Slob, Yolanda van der Graaf, Anthonius de Boer, Jacoba P Greving, Frank L J Visseren
BACKGROUND: As proprotein convertase subtilisin-kexin type 9 (PCSK9) monoclonal antibodies are entering the market, we assessed the cost-effectiveness of PCSK9 inhibition added to standard lipid-lowering therapy in patient groups at high risk for major adverse cardiovascular events (MACE). METHODS: A lifetime Markov Model was designed to estimate healthcare costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) for PCSK9 inhibition added to standard therapy in patients with Familial Hypercholesterolemia (FH), patients with vascular disease at high MACE recurrence risk, and patients with vascular disease with diabetes mellitus...
February 15, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29305812/proprotein-convertase-subtilisin-kexin-type-9-pcsk9-inhibitors-and-cardiovascular-risk-does-a-further-analysis-of-the-fourier-trial-suggest-changes-in-the-target-of-lipid-lowering-therapy
#7
EDITORIAL
Nazzareno Cervelli, Giuliano Tocci, Claudio Ferri
No abstract text is available yet for this article.
January 5, 2018: High Blood Pressure & Cardiovascular Prevention: the Official Journal of the Italian Society of Hypertension
https://www.readbyqxmd.com/read/29299849/lipid-management-in-chronic-kidney-disease-systematic-review-of-pcsk9-targeting
#8
REVIEW
BinBin Zheng-Lin, Alberto Ortiz
Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD) and CKD is considered a coronary artery disease risk equivalent. So far, statins have been the mainstay of primary and secondary prevention of cardiovascular disease in the general population. However, their benefit on outcomes is limited and controversial in CKD patients and new therapeutic approaches to reduce cardiovascular risk are needed. Monoclonal antibodies targeting proprotein convertase subtilisin/kexin 9 (PCSK9) reduce low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) in high-risk populations and cardiovascular events in secondary prevention...
January 3, 2018: Drugs
https://www.readbyqxmd.com/read/29296222/effect-of-cilostazol-on-plasma-levels-of-proprotein-convertase-subtilisin-kexin-type-9
#9
I-Chih Chen, Wei-Kung Tseng, Yi-Heng Li, Shih-Ya Tseng, Ping-Yen Liu, Ting-Hsing Chao
The protein complex proprotein convertase subtilisin/kexin type 9 (PCSK9) serves as an important target for the prevention and treatment of atherosclerosis and lipid homeostasis. This study investigated the effect of cilostazol on plasma PCSK9 concentrations. We performed a post hoc analysis of two prospective, double-blind, randomized controlled trials including 115 patients of whom 61 received cilostazol 200 mg/day and 54 received placebo for 12 weeks. Linear regression analysis was performed to determine the associations between several parameters and changes in PCSK9 levels...
December 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/29284604/homozygous-familial-hypercholesterolemia-patients-with-identical-mutations-variably-express-the-ldlr-low-density-lipoprotein-receptor-implications-for-the-efficacy-of-evolocumab
#10
Aurélie Thedrez, Dirk J Blom, Stéphane Ramin-Mangata, Valentin Blanchard, Mikaël Croyal, Kevin Chemello, Brice Nativel, Matthieu Pichelin, Bertrand Cariou, Steeve Bourane, Lihua Tang, Michel Farnier, Frederick J Raal, Gilles Lambert
OBJECTIVE: Evolocumab, a PCSK9 (proprotein convertase subtilisin kexin type 9)-neutralizing antibody, lowers low-density lipoprotein cholesterol (LDL-C) in homozygous familial hypercholesterolemic (HoFH) patients with reduced LDLR (low-density lipoprotein receptor) function. However, their individual responses are highly variable, even among carriers of identical LDLR genetic defects. We aimed to elucidate why HoFH patients variably respond to PCSK9 inhibition. APPROACH AND RESULTS: Lymphocytes were isolated from 22 HoFH patients enrolled in the TAUSSIG trial...
December 28, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29283060/effects-of-high-intensity-statin-therapy-in-the-treatment-of-diabetic-dyslipidemia-in-patients-with-coronary-artery-disease
#11
Marija Vavlukis, Sasko Kedev
BACKGROUND: Diabetic dyslipidemia has specifics that differ from dyslipidemia in patients without diabetes, which contributes to accelerated atherosclerosis equally as dysglycemia. The aim of this study was to deduce the interdependence of diabetic dyslipidemia and cardiovascular diseases (CVD), therapeutic strategies and the risk of diabetes development with statin therapy. METHOD: We conducted a literature review of English articles through PubMed, PubMed Central and Cochrane, on the role of diabetic dyslipidemia in atherosclerosis, the antilipemic treatment with statins, and the role of statin therapy in newly developed diabetes, by using key words: atherosclerosis, diabetes mellitus, diabetic dyslipidemia, CVD, statins, nicotinic acid, fibrates, PCSK9 inhibitors...
December 27, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29281604/results-of-the-glagov-trial
#12
REVIEW
Steven E Nissen, Stephen J Nicholls
Statins therapy reduces atheroma in proportion to the reduction of low-density lipoprotein cholesterol (LDL-C). Proprotein convertase subtilisin--kexin type 9 (PCSK9) inhibitors are a new class of injectable human monoclonal antibodies shown to lower LDL-C when added to statin therapy. In a randomized, double-blind, placebo-controlled study, 968 patients with symptomatic coronary artery disease were treated with statins alone or combined with the PCSK9 inhibitor, evolocumab, and assessed for change in percent, total volume, and regression of coronary atheroma...
December 2017: Cleveland Clinic Journal of Medicine
https://www.readbyqxmd.com/read/29273581/mortality-differences-associated-with-treatment-responses-in-cantos-and-fourier-insights-and-implications
#13
Paul M Ridker
Similarities and differences in two contemporary post-randomization on-treatment analyses from the FOURIER and CANTOS trials may provide insight into what factors drive reductions in cardiovascular mortality and all-cause mortality among atherosclerosis patients already treated with high intensity statins. In the first paper, the FOURIER investigators elegantly demonstrate that lower is better for low-density lipoprotein cholesterol (LDLC) after adjunctive therapy with the PCSK9 inhibitor evolocumab1 For the FOURIER primary endpoint (a composite of myocardial infarction, stroke, coronary revascularization, unstable angina, or cardiovascular death), there was a highly significant monotonic relationship between sequentially lower achieved LDLC concentrations and lower cardiovascular risk, extending even to those with on-treatment LDLC below 20 mg/dL...
December 22, 2017: Circulation
https://www.readbyqxmd.com/read/29261184/analysis-of-publicly-available-ldlr-apob-and-pcsk9-variants-associated-with-familial-hypercholesterolemia-application-of-acmg-guidelines-and-implications-for-familial-hypercholesterolemia-diagnosis
#14
Joana Rita Chora, Ana Margarida Medeiros, Ana Catarina Alves, Mafalda Bourbon
PurposeFamilial hypercholesterolemia (FH) is an autosomal disorder of lipid metabolism presenting with increased cardiovascular risk. Although more than 1,700 variants have been associated with FH, the great majority have not been functionally proved to affect the low-density lipoprotein receptor cycle. We aimed to classify all described variants associated with FH and to establish the proportion of variants that lack evidence to support their pathogenicity.MethodsWe followed American College of Medical Genetics and Genomics (ACMG) guidelines for the classification, and collected information from a variety of databases and individual reports...
October 26, 2017: Genetics in Medicine: Official Journal of the American College of Medical Genetics
https://www.readbyqxmd.com/read/29260404/new-treatment-options-for-lipid-lowering-therapy-in-subjects-with-type-2-diabetes
#15
Roberto Scicali, Antonino Di Pino, Viviana Ferrara, Francesca Urbano, Salvatore Piro, Agata Maria Rabuazzo, Francesco Purrello
Dyslipidemias represent a variety of quantitative and/or qualitative lipoprotein abnormalities. According to etiology, we distinguish primary dyslipidemias with strictly genetic background and secondary ones with their origin in other disease or pathological states. Diabetic dyslipidemia is a type of secondary dyslipidemia and plays an important role in determining the cardiovascular risk of subjects with type 2 diabetes. In these patients, insulin resistance is responsible for overproduction and secretion of atherogenic very low density lipoprotein...
December 19, 2017: Acta Diabetologica
https://www.readbyqxmd.com/read/29259136/stepwise-processing-analyses-of-the-single-turnover-pcsk9-protease-reveal-its-substrate-sequence-specificity-and-link-clinical-genotype-to-lipid-phenotype
#16
John S Chorba, Adri M Galvan, Kevan M Shokat
Proprotein convertase subtilisin/kexin type 9 (PCSK9) downregulates the low-density lipoprotein (LDL) receptor (LDL-R), elevating LDL cholesterol (LDL-C) and accelerating atherosclerotic heart disease, making it a promising cardiovascular drug target. To achieve its maximal effect on the LDL-R, PCSK9 requires auto-proteolysis. After cleavage, PCSK9 retains its prodomain in the active site as a self-inhibitor. Unlike other proprotein convertases, however, this retention is permanent, inhibiting any further protease activity for the remainder of its life cycle...
December 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29245109/autosomal-recessive-hypercholesterolemia-in-spain
#17
Rosa María Sánchez-Hernández, Pablo Prieto-Matos, Fernando Civeira, Eduardo Esteve Lafuente, Manuel Frías Vargas, José T Real, Fernando Goñi Goicoechea, Francisco J Fuentes, Miguel Pocovi, Mauro Boronat, Ana María Wägner, Luis Masana
BACKGROUND AND AIMS: Autosomal recessive hypercholesterolemia (ARH) is a very rare disease, caused by mutations in LDL protein receptor adaptor 1 (LDLRAP1). It is characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and increased risk of premature cardiovascular disease. We aimed to characterize ARH in Spain. METHODS: Data were collected from the Dyslipidemia Registry of the Spanish Atherosclerosis Society. A literature search was performed up to June 2017, and all diagnostic genetic studies for familial hypercholesterolemia of Spain were reviewed...
December 6, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29242844/effects-of-increased-body-weight-and-short-term-weight-loss-on-serum-pcsk9-levels-a-prospective-pilot-study
#18
Theodosios D Filippatos, Evangelos Liberopoulos, Maria Georgoula, Constantinos C Tellis, Alexandros D Tselepis, Moses Elisaf
Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with low-density lipoprotein (LDL) catabolism, but its serum concentration is not uniformly associated with cardiovascular disease in clinical studies. Obesity is linked with increased cardiovascular risk, but the effect of increased body weight and short-term weight loss on serum PCSK9 levels is not well studied. Material and methods: The aim of this prospective pilot study was to assess differences in serum PCSK9 levels (determined with a quantitative sandwich enzyme immunoassay) between otherwise healthy drug-naïve obese subjects and healthy individuals with normal body weight...
2017: Archives of Medical Sciences. Atherosclerotic Diseases
https://www.readbyqxmd.com/read/29241886/pcsk9-inhibitors-show-value-for-patients-and-the-us-health-care-system
#19
Wei-Han Cheng, Étienne Gaudette, Dana P Goldman
BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the US Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. OBJECTIVES: To estimate the long-term health and economic value of PCSK9 inhibitors for Americans (51 years and older). METHODS: We conducted simulations using the Future Elderly Model, an established dynamic microsimulation model to project the lifetime outcomes for the US population aged 51 years and older...
December 2017: Value in Health: the Journal of the International Society for Pharmacoeconomics and Outcomes Research
https://www.readbyqxmd.com/read/29236976/-highest-risk-highest-benefit-strategy-a-pragmatic-cost-effective-approach-to-targeting-use-of-pcsk9-inhibitor-therapies
#20
Lieven Annemans, Chris J Packard, Andrew Briggs, Kausik K Ray
No abstract text is available yet for this article.
December 11, 2017: European Heart Journal
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