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https://www.readbyqxmd.com/read/28340366/effect-of-ezetimibe-on-low-and-high-density-lipoprotein-subclasses-in-sitosterolemia
#1
Rgia A Othman, Semone B Myrie, David Mymin, Jean-Baptiste Roullet, Robert D Steiner, Peter J H Jones
BACKGROUND AND AIMS: Sitosterolemia displays high plasma total sterols [high plant sterols (PS) + normal to high total cholesterol (TC)] with normal to moderately elevated low-density lipoprotein (LDL) levels. High LDL, intermediate-density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, low high-density lipoprotein (HDL), and increased non-HDL and the ratios of TC and triglycerides (TG) to HDL can increase the risk for atherosclerosis. Ezetimibe (EZE) can reduce plasma PS and TC levels in sitosterolemia, but its effect on lipoprotein subclasses has not been previously reported...
March 10, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28334528/why-prodrugs-and-propesticides-succeed
#2
John E Casida
What are the advantages of bioactivation in optimizing drugs and pesticides? Why are there so many prodrugs and propesticides? These questions are examined here by considering compounds selected on the basis of economic value or market success. The 100 major drugs and 90 major pesticides are divided into ones acting directly and those definitely or possibly requiring bioactivation. Established or candidate prodrugs accounted for 19% of the total drug sales with corresponding values of 20, 37 and 17% for proinsecticides, proherbicides and profungicides...
March 23, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/28328244/-adherence-to-statins-in-patients-with-myocardial-infarction-in-hungary
#3
János Tomcsányi
INTRODUCTION: Statin therapy has proven to be one cornerstone for prevention and treatment of cardiovascular disease, but the clinical application is suboptimal. Adherence to statin therapy in Hungary in primary prevention is very low, but not known in patients with myocardial infarction. AIM: This study was designed to determine the statin and ezetimib adherence after myocardial infarction in respect of total mortality. METHOD: A retrospective study was carried out based on the National Health Insurance database between 2013-2015...
March 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28325524/current-status-of-lipid-management-in-acute-coronary-syndrome
#4
REVIEW
Koichiro Fujisue, Kenichi Tsujita
The development of coronary revascularization has dramatically improved early cardiovascular outcomes in patients with acute coronary syndrome (ACS). However, patients who have experienced myocardial infarction (MI) are at high risk of recurrence of cardiovascular events compared with those who are healthy or have stable coronary artery disease. Acute coronary events induce further inflammatory responses and plaque vulnerability in either a coronary culprit or whole vessels. The majority of data have supported the importance of coronary risk management to prevent secondary events...
March 18, 2017: Journal of Cardiology
https://www.readbyqxmd.com/read/28322747/quantitation-of-the-rates-of-hepatic-and-intestinal-cholesterol-synthesis-in-lysosomal-acid-lipase-deficient-mice-before-and-during-treatment-with-ezetimibe
#5
Jen-Chieh Chuang, Adam M Lopez, Stephen D Turley
Esterified cholesterol (EC) and triglycerides, contained within lipoproteins taken up by cells, are hydrolysed by lysosomal acid lipase (LAL) in the late endosomal/lysosomal (E/L) compartment. The resulting unesterified cholesterol (UC) is transported via Niemann-Pick type C2 and C1 into the cytosolic compartment where it enters a putative pool of metabolically active cholesterol that is utilized in accordance with cellular needs. Loss-of-function mutations in LIPA, the gene encoding LAL, result in dramatic increases in tissue concentrations of EC, a hallmark feature of Wolman Disease and Cholesteryl Ester Storage Disease (CESD)...
March 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28321334/the-interpretation-of-cholesterol-balance-derived-synthesis-data-and-surrogate-noncholesterol-plasma-markers-for-cholesterol-synthesis-under-lipid-lowering-therapies
#6
REVIEW
Frans Stellaard, Dieter Lütjohann
The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin...
2017: Cholesterol
https://www.readbyqxmd.com/read/28316281/are-potentially-clinically-meaningful-benefits-misinterpreted-in-cardiovascular-randomized-trials-a-systematic-examination-of-statistical-significance-clinical-significance-and-authors-conclusions
#7
G Michael Allan, Caitlin R Finley, James McCormack, Vivek Kumar, Simon Kwong, Emelie Braschi, Christina Korownyk, Michael R Kolber, Adriennne J Lindblad, Oksana Babenko, Scott Garrison
BACKGROUND: While journals and reporting guidelines recommend the presentation of confidence intervals, many authors adhere strictly to statistically significant testing. Our objective was to determine what proportions of not statistically significant (NSS) cardiovascular trials include potentially clinically meaningful effects in primary outcomes and if these are associated with authors' conclusions. METHODS: Cardiovascular studies published in six high-impact journals between 1 January 2010 and 31 December 2014 were identified via PubMed...
March 20, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28315682/n-terminal-domain-of-the-cholesterol-transporter-niemann-pick-c1-like-1-npc1l1-is-essential-for-%C3%AE-tocopherol-transport
#8
Jun Kamishikiryo, Misaki Haraguchi, Shunsuke Nakashima, Yuka Tasaka, Hiroe Narahara, Narumi Sugihara, Tetsuya Nakamura, Tetsuo Morita
Both cholesterol and α-tocopherol are essential lipophilic nutrients for humans and animals. Although cholesterol in excess causes severe problems such as coronary heart disease, it is a necessary component of cell membranes and is the precursor for the biosynthesis of steroid hormones and bile acids. Niemann-Pick C1-like 1 (NPC1L1) is a cholesterol transporter that is highly expressed in the small intestine and liver in humans and plays an important role in cholesterol homeostasis. Cholesterol promotes NPC1L1 endocytosis, which is an early step in cholesterol uptake...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28302290/statin-intolerance-and-risk-of-coronary-heart-events-and-all-cause-mortality-following-myocardial-infarction
#9
Maria-Corina Serban, Lisandro D Colantonio, Angelika D Manthripragada, Keri L Monda, Vera A Bittner, Maciej Banach, Ligong Chen, Lei Huang, Ricardo Dent, Shia T Kent, Paul Muntner, Robert S Rosenson
BACKGROUND: Many patients report adverse reactions to, and may not tolerate, statin therapy. These patients may be at increased risk for coronary heart disease (CHD) events and mortality. OBJECTIVES: This study evaluated the risk for recurrent myocardial infarction (MI), CHD events, and all-cause mortality in Medicare beneficiaries with statin intolerance and in those with high adherence to statin therapy. METHODS: We studied 105,329 Medicare beneficiaries who began a moderate- or high-intensity statin dosage after hospitalization for MI between 2007 and 2013...
March 21, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28298250/use-of-lipid-lowering-drugs-in-patients-at-very-high-risk-of-cardiovascular-events-an-analysis-on-nearly-3-000-000-italian-subjects-of-the-arno-observatory
#10
Aldo P Maggioni, Silvia Calabria, Elisa Rossi, Nello Martini
AIM: To assess clinical characteristics, use of resources and costs of patients at very high risk (VHR) of cardiovascular (CV) events. Further, to assess how VHR patients are treated with statins (rate of prescription, dosages, adherence). METHODS AND RESULTS: A record linkage analysis was carried out of patient demographics, drug prescriptions, hospital discharge, specialty procedures from the ARNO Observatory, including 2,989,512 subjects of Local Health Units well representing the whole Italian country...
February 28, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28294373/rationale-and-design-of-reduce-it-reduction-of-cardiovascular-events-with-icosapent-ethyl-intervention-trial
#11
Deepak L Bhatt, Ph Gabriel Steg, Eliot A Brinton, Terry A Jacobson, Michael Miller, Jean-Claude Tardif, Steven B Ketchum, Ralph T Doyle, Sabina A Murphy, Paresh N Soni, Rene A Braeckman, Rebecca A Juliano, Christie M Ballantyne
Residual cardiovascular risk persists despite statins, yet outcome studies of lipid-targeted therapies beyond low-density lipoprotein cholesterol (LDL-C) have not demonstrated added benefit. Triglyceride elevation is an independent risk factor for cardiovascular events. High-dose eicosapentaenoic acid (EPA) reduces triglyceride-rich lipoproteins without raising LDL-C. Omega-3s have postulated pleiotropic cardioprotective benefits beyond triglyceride-lowering. To date, no large, multinational, randomized clinical trial has proved that lowering triglycerides on top of statin therapy improves cardiovascular outcomes...
March 15, 2017: Clinical Cardiology
https://www.readbyqxmd.com/read/28291866/long-term-safety-and-efficacy-of-achieving-very-low-levels-of-low-density-lipoprotein-cholesterol-a-prespecified-analysis-of-the-improve-it-trial
#12
Robert P Giugliano, Stephen D Wiviott, Michael A Blazing, Gaetano M De Ferrari, Jeong-Gun Park, Sabina A Murphy, Jennifer A White, Andrew M Tershakovec, Christopher P Cannon, Eugene Braunwald
Importance: In the Improved Reduction of Outcomes: Vytorin Efficacy International Trial, intensive low-density lipoprotein cholesterol (LDL-C)-reducing therapy with ezetimibe/simvastatin compared with simvastatin alone was associated with a significant reduction in cardiovascular events in 18 144 patients after acute coronary syndrome. The safety of very low LDL-C levels over the long-term is unknown. Objective: To assess the safety and clinical efficacy of achieving a very low (<30 mg/dL) level of LDL-C at 1 month using data from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial...
March 14, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28291622/a-randomized-controlled-comparison-of-different-intensive-lipid-lowering-therapies-in-chinese-patients-with-non-st-elevation-acute-coronary-syndrome-nste-acs-ezetimibe-and-rosuvastatin-versus-high-dose-rosuvastatin
#13
Dan Ran, Hui-Juan Nie, Yu-Lin Gao, Song-Bai Deng, Jian-Lin Du, Ya-Jie Liu, Xiao-Dong Jing, Qiang She
BACKGROUND: Statin combined with ezetimibe demonstrates significant benefit in lowering low density lipid cholesterol (LDL-C) and cardiovascular events abroad, but whether intermediate intensity statins combined with ezetimibe is superior to high-intensity statin monotherapy in Chinese people is unknown. METHODS: A total of 125 patients were randomly assigned to a intermediate intensity rosuvastatin group (rosuvastatin 10mg/d, n=42), high-dose rosuvastatin group (rosuvastatin 20mg/d, n=41) or combination therapy group (ezetimibe 10mg/d and rosuvastatin 10mg/d, n=42) with a 12-week follow-up...
February 23, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28285379/evolocumab-for-treating-primary-hypercholesterolaemia-and-mixed-dyslipidaemia-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#14
Christopher Carroll, Paul Tappenden, Rachid Rafia, Jean Hamilton, Duncan Chambers, Mark Clowes, Paul Durrington, Nadeem Qureshi, Anthony S Wierzbicki
As part of its single technology appraisal (STA) process, the UK National Institute for Health and Care Excellence (NICE) invited the manufacturer of evolocumab (Amgen) to submit evidence on the clinical and cost effectiveness of evolocumab. The appraisal assessed evolocumab as monotherapy or in combination with a statin with or without ezetimibe, or in combination with ezetimibe (without statin therapy), in adult patients with primary hypercholesterolaemia (which includes mixed dyslipidaemia), for whom statins do not provide optimal control of their low-density lipoprotein cholesterol (LDL-C) levels and/or for whom statins are contraindicated or not tolerated...
March 11, 2017: PharmacoEconomics
https://www.readbyqxmd.com/read/28279967/ezetimibe-increases-endogenous-cholesterol-excretion-in-humans
#15
Xiaobo Lin, Susan B Racette, Lina Ma, Michael Wallendorf, Richard E Ostlund
OBJECTIVE: Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. APPROACH AND RESULTS: In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo...
March 9, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28276256/lipid-lowering-treatment-modifications-among-patients-with-hyperlipidemia-and-a-prior-cardiovascular-event-a-us-retrospective-cohort-study
#16
Rajeshwari S Punekar, Kathleen M Fox, Carly J Paoli, Akshara Richhariya, Mark J Cziraky, Shravanthi R Gandra, Peter P Toth
BACKGROUND: Numerous studies demonstrate that, even with use of statins, many patients are unable to meet their LDL-C goals. This study examined modifications to statin and/or ezetimibe therapy among patients with hyperlipidemia and prior history of cardiovascular (CV) events in a US commercially insured population. METHODS: Adults (age ≥18 years) initiating statins and/or ezetimibe between 1 January 2007 and 31 December 2008 were identified from HealthCore Integrated Research Database...
March 9, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28262189/hypercholesterolemia-as-a-risk-factor-for-cardiovascular-disease-current-controversial-therapeutic-management
#17
REVIEW
Arturo Zárate, Leticia Manuel-Apolinar, Renata Saucedo, Marcelino Hernández-Valencia, Lourdes Basurto
Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane; however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite the recognition of historical events for 200 years starting with Chevreul naming "cholesterine"; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor (r-LDL), as well as the emergence of different drugs such as fibrates, statins and cetrapibs during this decade promising to increase HDL, and the most recent, ezetimibe and anti-PCSK9 to inhibit the degradation of r-LDL, morbidity has not been reduced in cardiovascular disease...
October 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28259659/bean-peptides-have-higher-in-silico-binding-affinities-than-ezetimibe-for-the-n-terminal-domain-of-cholesterol-receptor-niemann-pick-c1-like-1
#18
Luis M Real Hernandez, Elvira Gonzalez de Mejia
Niemann-Pick C1 like-1 (NPC1L1) mediates cholesterol absorption at the apical membrane of enterocytes through a yet unknown mechanism. Bean, pea, and lentil proteins are naturally hydrolyzed during digestion to produce peptides. The potential for pulse peptides to have high binding affinities for NPC1L1 has not been determined. In this study , in silico binding affinities and interactions were determined between the N-terminal domain of NPC1L1 and 14 pulse peptides (5≥ amino acids) derived through pepsin-pancreatin digestion...
March 1, 2017: Peptides
https://www.readbyqxmd.com/read/28257594/ezetimibe-for-the-treatment-of-nonalcoholic-fatty-liver-disease-a-meta-analysis
#19
Yukiomi Nakade, Kenta Murotani, Tadahisa Inoue, Yuji Kobayashi, Takaya Yamamoto, Norimitsu Ishii, Tomohiko Ohashi, Kiyoaki Ito, Yoshitaka Fukuzawa, Masashi Yoneda
AIM: Several studies on the efficacy of ezetimibe, a potent inhibitor of cholesterol absorption, in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) have been conducted; however, the results are inconsistent. We conducted a meta-analysis to evaluate the efficacy of ezetimibe in treating NAFLD and NASH. METHODS: Pubmed, Medline, and Cochrane Library Full Text Database were searched until June 2016. The main inclusion criteria included original studies investigating the use of ezetimibe for the treatment of NAFLD and NASH...
March 3, 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/28245873/effect-of-two-lipid-lowering-strategies-on-high-density-lipoprotein-function-and-some-hdl-related-proteins-a-randomized-clinical-trial
#20
Chan Joo Lee, Seungbum Choi, Dong Huey Cheon, Kyeong Yeon Kim, Eun Jeong Cheon, Soo-Jin Ann, Hye-Min Noh, Sungha Park, Seok-Min Kang, Donghoon Choi, Ji Eun Lee, Sang-Hak Lee
BACKGROUND: The influence of lipid-lowering therapy on high-density lipoprotein (HDL) is incompletely understood. We compared the effect of two lipid-lowering strategies on HDL functions and identified some HDL-related proteins. METHODS: Thirty two patients were initially screened and HDLs of 21 patients were finally analyzed. Patients were randomized to receive atorvastatin 20 mg (n = 11) or atorvastatin 5 mg/ezetimibe 10 mg combination (n = 10) for 8 weeks...
February 28, 2017: Lipids in Health and Disease
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