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https://www.readbyqxmd.com/read/28555526/statin-intolerance-in-heterozygous-familial-hypercolesterolemia-with-cardiovascular-disease-after-pcsk-9-antibodies-what-else
#1
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/28500517/role-of-non-statins-ldl-c-thresholds-and-special-population-considerations-a-look-at-the-updated-2016-acc-consensus-committee-recommendations
#2
REVIEW
Bhavin B Adhyaru, Terry A Jacobson
PURPOSE OF REVIEW: The 2013 ACC/AHA Cholesterol guidelines was a major paradigm shift in the management and treatment of dyslipidemia. The new guidelines outlined "statin benefit groups," highlighted weighing the benefit versus risks of statin therapy ("net benefit"), and discussed the importance of shared decision making between patients and providers in primary prevention. While there was widespread agreement on the main groups benefiting from statin therapy, there was significant controversy regarding LDL-C goals and thresholds, the role of non-statin therapy, and the use of statins in specific populations...
June 2017: Current Atherosclerosis Reports
https://www.readbyqxmd.com/read/28471246/why-published-studies-of-the-cost-effectiveness-of-pcsk-9-inhibitors-yielded-such-markedly-different-results
#3
Peter P Toth, Warren Stevens, Jacquelyn W Chou
No abstract text is available yet for this article.
July 2017: Journal of Medical Economics
https://www.readbyqxmd.com/read/28456517/proprotein-convertase-inhibition-paralyzing-the-cell-s-master-switches
#4
Andres J Klein-Szanto, Daniel E Bassi
Proprotein convertases are serine proteases responsible for the cleavage and subsequent activation of protein substrates, many of them relevant for the development of an ample variety of diseases. Seven of the PCs, including furin and PACE4, recognize and hydrolyze the C-terminal end of the general sequence RXRR/KXR, whereas PCSK-9 recognizes a series of non-basic amino acids. In some systems, PC-mediated substrate activation results in the development of pathological processes, such as cancer, endocrinopathies, and cardiovascular and infectious diseases...
April 27, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28412198/potential-role-of-lycopene-in-targeting-proprotein-convertase-subtilisin-kexin-type-9-to-combat-hypercholesterolemia
#5
Sahir Sultan Alvi, Irfan A Ansari, Imran Khan, Johar Iqbal, M Salman Khan
Proprotein convertase subtilisin/kexin type 9 (PCSK-9) is a serine protease of the proprotien convertase (PC) family that has profound effects on plasma low density lipoprotein cholesterol (LDL-C) levels, the major risk factor for coronary heart disease (CHD), through its ability to mediate LDL receptor (LDL-R) protein degradation and reduced recycling to the surface of hepatocytes. Thus, the current study was premeditated not only to evaluate the role of lycopene in targeting the inhibition of PCSK-9 via modulation of genes involved in cholesterol homeostasis in HFD rats but also to examine a correlation between HFD induced inflammatory cascades and subsequent regulation of PCSK-9 expression...
April 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28289523/pcsk9-inhibitors-a-new-era-of-lipid-lowering-therapy
#6
REVIEW
Rahul Chaudhary, Jalaj Garg, Neeraj Shah, Andrew Sumner
Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia...
February 26, 2017: World Journal of Cardiology
https://www.readbyqxmd.com/read/28032426/lipoprotein-a-in-postmenopausal-women-assessment-of-cardiovascular-risk-and-therapeutic-options
#7
REVIEW
Panagiotis Anagnostis, Spyridon Karras, Irene Lambrinoudaki, John C Stevenson, Dimitrios G Goulis
INTRODUCTION: Lipoprotein(a) [Lp(a)], a low-density lipoprotein (LDL)-like particle, has been independently associated with increased cardiovascular disease (CVD) risk in various populations, such as postmenopausal women. The purpose of this narrative review is to present current data on the role of Lp(a) in augmenting CVD risk in postmenopausal women and focus on the available therapeutic strategies. METHODS: PubMed was searched for English language publications until November 2015 under the following terms: "therapy" OR "treatment" AND ["lipoprotein (a)" OR "Lp(a)"] AND ("postmenopausal women" OR "menopausal women" OR "menopause")...
December 2016: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/27771416/candidate-gene-analysis-of-the-fibrinogen-phenotype-reveals-the-importance-of-polygenic-co-regulation
#8
H Toinét Cronjé, Cornelie Nienaber-Rousseau, Lizelle Zandberg, Tinashe Chikowore, Zelda de Lange, Tertia van Zyl, Marlien Pieters
Fibrinogen and its functional aspects have been linked to cardiovascular disease. There is vast discrepancy between the heritability of fibrinogen concentrations observed in twin studies and the heritability uncovered by genome wide association studies. We postulate that some of the missing heritability might be explained by the pleiotropic and polygenic co-regulation of fibrinogen through multiple targeted genes, apart from the fibrinogen genes themselves. To this end we investigated single nucleotide polymorphisms (SNPs) in genes coding for phenotypes associated with total and γ' fibrinogen concentrations and clot properties...
July 2017: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/27747489/current-consensus-and-controversies-in-guidelines-for-lipid-and-hypertension-management-in-diabetes
#9
Om P Ganda, Joanna Mitri
Despite major advances, many patients with diabetes are currently achieving suboptimal control of lipids and blood pressure. The new cholesterol guidelines by the ACC/AHA have reignited the emphasis on more intensive treatment with statins in the population at high risk of CVD, including those with diabetes. While these guidelines do not include specific lipid goals, several other guidelines have retained previously defined risk-based LDL-C and non-HDL-C goals. More recent data indicate potential benefits in CVD outcomes with non-statin therapy added to statin therapy...
November 2016: Current Cardiology Reports
https://www.readbyqxmd.com/read/27662822/the-anti-adipogenic-effect-of-peripheral-blood-mononuclear-cells-is-absent-with-pcsk9-loss-of-function-variants
#10
AnneMarie Gagnon, Teik C Ooi, Marion Cousins, Colette Favreau, Kathy Henry, Anne Landry, Alexander Sorisky
OBJECTIVE: To determine the effect of (1) an oral fat load and (2) pro-protein convertase subtilisin/kexin type (PCSK) 9 loss-of-function (LOF) variant status on the ability of peripheral blood mononuclear cells (PBMC) to inhibit human adipogenesis. METHODS: PBMC from subjects with one or more PCSK9 LOF variants versus non-variant controls were compared in the fasting state and after an oral fat load. RESULTS: Fasting triglyceride (TG) levels were lower in the LOF variant versus non-variant group but rose to the same level after the oral fat load...
September 24, 2016: Obesity
https://www.readbyqxmd.com/read/27424187/evaluation-of-a-new-genetic-epidemiology-resource-the-intermountain-genealogy-registry
#11
Stacey Knight, Arthur T Maness, Sue M Dintelman, Benjamin D Horne
BACKGROUND: Many landmark genetic breakthroughs, including the recent discovery of PCSK-9 inhibitor drugs, were accomplished with substantial contributions from evaluation of pedigrees. Finding and ascertaining high-value pedigrees is not trivial and requires considerable time and cost. Here, we describe the creation of the Intermountain Genealogy Registry for use in studying the genetics of cardiovascular and other diseases. METHODS: Using publicly available pedigree records and probabilistic linkage techniques, we created a genealogy of ≈23 million records that we linked to 3...
July 16, 2016: Human Heredity
https://www.readbyqxmd.com/read/27096698/the-new-face-of-hyperlipidemia-management-proprotein-convertase-subtilisin-kexin-inhibitors-pcsk-9-and-their-emergent-role-as-an-alternative-to-statin-therapy
#12
REVIEW
Lillian Smith, Juan Mosley, Jarah Yates, Luke Caswell
This review analyzes Proprotein Convertase Subtilisin/Kexin 9 inhibitors (PCSK-9), a new medication class that has arisen in the last year to combat hypercholesterolemia. They are targeted towards patients who are unable to achieve acceptable low density lipoprotein (LDL) levels despite maximum statin therapy, as well as those who are unable to tolerate maximum statin therapy due to side effects such as myopathy or myalgia. Two of these medications have been released in the last year: alirocumab (Praluent) and evolocumab (Repatha)...
2016: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/26976708/xanthohumol-improves-dysfunctional-glucose-and-lipid-metabolism-in-diet-induced-obese-c57bl-6j-mice
#13
Cristobal L Miranda, Valerie D Elias, Joshua J Hay, Jaewoo Choi, Ralph L Reed, Jan F Stevens
Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals. The mice were fed a high-fat diet (60% kcal as fat) supplemented with XN at dose levels of 0, 30, or 60 mg/kg body weight/day, for 12 weeks. Dietary XN caused a dose-dependent decrease in body weight gain...
June 1, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/26652782/-pcsk9-inhibition-as-the-new-hope-for-patients-with-familial-hypercholesterolemia-statin-intolerance-and-eventually-for-those-at-the-highest-cardiovascular-risk-focused-on-alirocumab-praluent%C3%A2
#14
REVIEW
Richard Češka
At the present time there are novel hypolipidemics registered globally (alirocumab was the first drug of this group in the world registered by an American drug agency FDA) and in Europe, which in many ways differ from the medicines administered until now. They are bringing another advancement in the treatment of disorders of lipid metabolism and in preventive cardiology. Alirocumab is a fully human monoclonal antibody to PCSK-9 enzyme (proprotein convertase subtilisin kexin-9). PCSK-9 enzyme plays an important role in the metabolism of LDL-cholesterol through affecting the breakdown and eventually the amount and activity of LDL-receptors...
November 2015: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/26547456/predicting-the-overuse-of-pcsk-9-inhibitors
#15
Rene Rodriguez-Gutierrez, Nilay D Shah, Victor M Montori
No abstract text is available yet for this article.
November 10, 2015: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/26545013/atherosclerosis-stabilization-with-pcsk-9-inhibition-an-evolving-concept-for-cardiovascular-prevention
#16
Jennifer G Robinson, Donald D Heistad, Keith A A Fox
Monoclonal antibodies (mAbs) to proprotein convertase subtilisin/kexin type 9 (PCSK-9) can further lower LDL-C by ≥60% in statin-treated patients. Preliminary data suggest they may reduce cardiovascular (CVD) events. Ongoing PCSK-9 mAb cardiovascular outcomes trials could provide the opportunity to determine whether a "legacy effect" similar to that observed for statins will occur over the post-trial observation period. We hypothesize these trials could demonstrate that (1) very aggressive LDL-C lowering with PCSK-9 mAbs added to background statin therapy will induce extensive atherosclerosis stabilization and regression in the large majority of treated patients, and (2) continued maintenance therapy with high intensity statin therapy (with or without ezetimibe) should then inhibit new plaque formation, with a long-term prevention of CVD events...
December 2015: Atherosclerosis
https://www.readbyqxmd.com/read/26492546/emerging-innovative-therapeutic-approaches-targeting-pcsk9-to-lower-lipids
#17
REVIEW
G P S Shantha, J G Robinson
Statins are established therapies for cardiovascular disease prevention and ezetimibe has recently been shown to modestly reduce cardiovascular events when added to background statin therapy. Yet here remains a clear unmet need for additional therapies aimed at lowering low density lipoprotein cholesterol (LDL-C) to further reduce cardiovascular risk. Multiple strategies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition have emerged as effective modalities for LDL-C lowering. PCSK9 monoclonal antibodies are the farthest along in clinical development and alirocumab and evolocumab were approved for clinical use by regulatory agencies in 2015...
January 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/26432726/ldl-cholesterol-statins-and-pcsk-9-inhibitors
#18
REVIEW
Sanjiv Gupta
Reduction of low density lipoprotein cholesterol (LDLc) is of vital importance for the prevention of atherosclerotic cardiovascular disease (ASCVD). Statin is the most effective therapy today to lower LDLc by inhibiting HMG-CoA-reductase. However despite intensive statin therapy, there remains a residual risk of recurrent myocardial infarction in about 20-30% cases. Moreover a few patients develop statin intolerance. For severe hypercholesterolemia, statins alone or in combination of ezetimibe, niacin and fenofibrate have been advocated...
September 2015: Indian Heart Journal
https://www.readbyqxmd.com/read/26398165/proprotein-convertase-subtilisin-kexin-type-9-inhibition-the-dream-of-translational-medicine
#19
LETTER
Chakradhara Rao S Uppugunduri, Melvin George
No abstract text is available yet for this article.
February 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/26363575/-importance-of-dyslipidaemia-in-cardiovascular-disease-a-point-of-view
#20
Juan F Ascaso, Rafael Carmena
The authors present their view on the prevention of cardiovascular diseases, accepting the European ESC/EAS guidelines. They consider that the aim of the lipid control, based on LDL-C goals, is essential for the prevention and treatment of cardiovascular diseases. In subjects with metabolic syndrome (mainly, abdominal obesity, pre-diabetes and diabetes), the primary objective should be apoB or Non-HDL-C, which are better associated with cardiovascular risk. The treatment must be lifestyle changes and control of other risk factors...
November 2015: Clínica e Investigación en Arteriosclerosis
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