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https://www.readbyqxmd.com/read/28445176/novel-lipid-modifying-drugs-to-lower-ldl-cholesterol
#1
Arjen J Cupido, Laurens F Reeskamp, John J P Kastelein
PURPOSE OF REVIEW: Statins have long been the cornerstone for the prevention of cardiovascular disease (CVD). However, because of perceived adverse effects and insufficient efficacy in certain groups of patients, considerable interest exists in the search for alternatives to lower LDL-cholesterol (LDL-C), and the recent approvals of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors underlines the success of this quest. Here, we give an updated overview on the most recent developments in the area of LDL-C lowering agents...
April 25, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28444148/risk-of-acute-myocardial-infarction-among-hcv-and-hcv-men-at-various-lipid-levels-results-from-erchives
#2
Adeel A Butt, Peng Yan, Kara W Chew, Judith Currier, Kathleen Corey, Raymond T Chung, Ashfaq Shuaib, Abdul-Badi Abou-Samra, Javed Butler, Matthew S Freiberg
Background: Risk of AMI among HCV+ versus HCV- persons with similar lipid levels is unknown. We determined incident AMI rates among HCV+ and HCV- men among various lipid strata. Methods: We created a propensity score matched (PSM) cohort, and a low cardiovascular disease (CVD) risk cohort. Primary outcome was incident AMI rates by HCV status in each lipid strata using National Cholesterol Program guidelines for lipid strata. Results: We identified 85,863 HCV+ and HCV- men in the PSM population...
April 24, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28442125/relation-of-risk-factors-and-abdominal-aortic-calcium-to-progression-of-coronary-artery-calcium-from-the-framingham-heart-study
#3
Oyere K Onuma, Karol Pencina, Saadia Qazi, Joseph M Massaro, Ralph B D'Agostino, Michael L Chuang, Caroline S Fox, Udo Hoffmann, Christopher J O'Donnell
Coronary artery calcium (CAC) and abdominal aortic calcium (AAC) on multidetector computed tomography (MDCT) permit assessment of the presence and burden of coronary and systemic atherosclerosis. Risk factors for progression of CAC and AAC and the association of AAC with CAC progression have not been well characterized in a community-dwelling cohort. We studied 1,959 asymptomatic participants from the Framingham Heart Study who underwent serial MDCT scans with a median interval of 6.1 years. Primary outcomes were (a) the incidence of CAC and AAC (CAC >0 and AAC >0 with baseline CAC = 0 and AAC = 0) and (b) absolute progression of CAC (CAC > baseline CAC and AAC > baseline AAC)...
May 15, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28437620/american-association-of-clinical-endocrinologists-and-american-college-of-endocrinology-guidelines-for-management-of-dyslipidemia-and-prevention-of-cardiovascular-disease
#4
Paul S Jellinger, Yehuda Handelsman, Paul D Rosenblit, Zachary T Bloomgarden, Vivian A Fonseca, Alan J Garber, George Grunberger, Chris K Guerin, David S H Bell, Jeffrey I Mechanick, Rachel Pessah-Pollack, Kathleen Wyne, Donald Smith, Eliot A Brinton, Sergio Fazio, Michael Davidson
OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs). METHODS: Recommendations are based on diligent reviews of the clinical evidence with transparent incorporation of subjective factors, according to established AACE/ACE guidelines for guidelines protocols...
April 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28434930/enhancing-targeted-antibiotic-therapy-via-ph-responsive-solid-lipid-nanoparticles-from-an-acid-cleavable-lipid
#5
Rahul S Kalhapure, Dhiraj R Sikwal, Sanjeev Rambharose, Chunderika Mocktar, Sanil Singh, Linda Bester, Jung Kwon Oh, Jwala Renukuntla, Thirumala Govender
An acid cleavable lipid (SA-3 M) was synthesized and used to develop pH-responsive solid lipid nanoparticles (SLNs) to deliver vancomycin base (VM-FB) to acidic infection sites. The size, polydispersity index and zeta potential of VM-FB_SA-3 M_SLNs were 132.9±9.1nm, 0.159±0.01 and -26±4.4mV respectively, with 57.80±1.1% encapsulation efficiency. VM-FB release was significantly faster at pH6.5 than pH7.4. In vitro antibacterial activity against methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA) revealed that SLNs had enhanced activity at pH6...
April 18, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/28434482/how-to-implement-clinical-guidelines-to-optimise-familial-hypercholesterolaemia-diagnosis-and-treatment
#6
Michel Farnier, Fernando Civeira, Olivier Descamps
BACKGROUND AND AIMS: Familial hypercholesterolaemia (FH) is a genetic disorder associated with significantly elevated plasma low-density lipoprotein cholesterol (LDL-C) and premature coronary heart disease (CHD). Optimal management of FH relies on early identification and treatment with statins alone or in combination with other lipid-lowering therapies. A lack of awareness of FH and its manifestations among primary care physicians and specialists has led to many individuals being misdiagnosed in the early stages of the disease, further increasing the risk of CHD and requiring much more intensive lipid-lowering strategies...
April 2017: Atherosclerosis. Supplements
https://www.readbyqxmd.com/read/28433209/practical-recommendations-for-the-management-of-cardiovascular-risk-associated-with-atherogenic-dyslipidemia-with-special-attention-to-residual-risk-spanish-adaptation-of-a-european-consensus-of-experts
#7
Juan F Ascaso, Roberto Ferrari
This document has discussed clinical approaches to managing cardiovascular risk in clinical practice, with special focus on residual cardiovascular risk associated with lipid abnormalities, especially atherogenic dyslipidaemia (AD). A simplified definition of AD was proposed to enhance understanding of this condition, its prevalence and its impact on cardiovascular risk. AD can be defined by high fasting triglyceride levels (≥2.3mmol/L / ≥200mg/dL) and low high-density lipoprotein cholesterol (HDL-c) levels (≤1,0 / 40 and ≤1,3mmol/L / 50mg/dL in men and women, respectively) in statin-treated patients at high cardiovascular risk...
April 19, 2017: Clínica e Investigación en Arteriosclerosis
https://www.readbyqxmd.com/read/28432645/efficacy-of-lomitapide-in-the-treatment-of-familial-homozygous-hypercholesterolemia-results-of-a-real-world-clinical-experience-in-italy
#8
Laura D'Erasmo, Angelo Baldassare Cefalù, Davide Noto, Antonina Giammanco, Maurizio Averna, Paolo Pintus, Paolo Medde, Giovanni Battista Vigna, Cesare Sirtori, Laura Calabresi, Chiara Pavanello, Marco Bucci, Carlo Sabbà, Patrizia Suppressa, Francesco Natale, Paolo Calabrò, Tiziana Sampietro, Federico Bigazzi, Francesco Sbrana, Katia Bonomo, Fulvio Sileo, Marcello Arca
INTRODUCTION: Homozygous familial hypercholesterolaemia (HoFH) is a rare form of inherited dyslipidemia resistant to conventional cholesterol-lowering medications so that lipoprotein apheresis (LA) is usually required. Lomitapide has been approved for the treatment of HoFH. The aim of this study was to evaluate the benefits of lomitapide in HoFH patients followed with the usual clinical care. METHODS: Clinical and biochemical data were retrospectively collected in 15 HoFH patients (10 with mutations in the LDLR gene and 5 in the LDLRAP1 gene) treated for at least 6 months with lomitapide in addition to lipid-lowering therapies (LLT) in different Lipid Clinics across Italy...
April 21, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28432573/clinical-outcomes-in-trials-evaluating-lipid-lowering-drugs
#9
REVIEW
Julie Butters, Alex Brown, Liddy Griffith, Susan Kim, Stephen J Nicholls
While statins have formed the cornerstone of strategies for cardiovascular prevention, the residual risk related to low-density lipoprotein cholesterol (LDL-C) and other lipoprotein factors provides a landscape for development of new therapies. However, a number of lipid-modifying therapies have failed to reduce cardiovascular event rates in contemporary clinical trials of statin-treated patients. The factors considered in outcome measure selection for clinical trials of novel lipid-lowering therapies are reviewed...
April 21, 2017: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
https://www.readbyqxmd.com/read/28428116/cycloastragenol-improves-hepatic-steatosis-by-activating-farnesoid-x-receptor-signalling
#10
Ming Gu, Shiying Zhang, Yuanyuan Zhao, Jinwen Huang, Yahui Wang, Yin Li, Shengjie Fan, Li Yang, Guang Ji, Qingchun Tong, Cheng Huang
Non-alcoholic fatty liver disease (NAFLD) has become a global health problem. However, there is no approved therapy for NAFLD. Farnesoid X receptor (FXR) is a potential drug target for treatment of NAFLD. In an attempt to screen FXR agonists, we found that cycloastragenol (CAG), a natural occurring compound in Astragali Radix, stimulated FXR transcription activity. In animal studies, we demonstrated that CAG treatment resulted in obvious reduction of high-fat diet induced lipid accumulation in liver accompanied by lowered blood glucose, serum triglyceride levels and hepatic bile acid pool size...
April 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28427339/cardiovascular-disease-risk-among-chinese-antiretroviral-na%C3%A3-ve-adults-with-advanced-hiv-disease
#11
Fuping Guo, Evelyn Hsieh, Wei Lv, Yang Han, Jing Xie, Yanling Li, Xiaojing Song, Taisheng Li
BACKGROUND: Cardiovascular disease (CVD) is an important cause of mortality among HIV-infected patients, however little is known about the burden of CVD among this population in Asia. We sought to quantify prevalence of CVD risk factors, 10-year CVD risk, and patterns of CVD risk factor treatment in a group of individuals with HIV in China. METHODS: We retrospectively analyzed baseline data from treatment-naïve HIV-infected adults enrolled in two multicenter clinical trials in China...
April 20, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28426890/fine-mapping-of-lipid-regions-in-global-populations-discovers-ethnic-specific-signals-and-refines-previously-identified-lipid-loci
#12
Niha Zubair, Mariaelisa Graff, Jose Luis Ambite, William S Bush, Gleb Kichaev, Yingchang Lu, Ani Manichaikul, Wayne H-H Sheu, Devin Absher, Themistocles L Assimes, Suzette J Bielinski, Erwin P Bottinger, Petra Buzkova, Lee-Ming Chuang, Ren-Hua Chung, Barbara Cochran, Logan Dumitrescu, Omri Gottesman, Jeffrey W Haessler, Christopher Haiman, Gerardo Heiss, Chao A Hsiung, Yi-Jen Hung, Chii-Min Hwu, Jyh-Ming J Juang, Loic Le Marchand, I-Te Lee, Wen-Jane Lee, Li-An Lin, Danyu Lin, Shih-Yi Lin, Rachel H Mackey, Lisa W Martin, Bogdan Pasaniuc, Ulrike Peters, Irene Predazzi, Thomas Quertermous, Alex P Reiner, Jennifer Robinson, Jerome I Rotter, Kelli K Ryckman, Pamela J Schreiner, Eli Stahl, Ran Tao, Michael Y Tsai, Lindsay L Waite, Tzung-Dau Wang, Steven Buyske, Yii-Der Ida Chen, Iona Cheng, Dana C Crawford, Ruth J F Loos, Stephen S Rich, Myriam Fornage, Kari E North, Charles Kooperberg, Cara L Carty
Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians...
December 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28424973/pcsk9-inhibitors-in-hyperlipidemia-current-status-and-clinical-outlook
#13
Belinda Di Bartolo, Daniel J Scherer, Alex Brown, Peter J Psaltis, Stephen J Nicholls
The clinical reality of residual risk despite statin (HMG-CoA reductase inhibitor) therapy and emergence of statin intolerance support the need to develop additional lipid-lowering strategies. Proprotein convertase subtilisin kexin type 9 (PCSK9) has received considerable attention by virtue of genetic and clinical studies that have revealed its pivotal role in the regulation of cholesterol homeostasis. Monoclonal antibodies have been developed targeting PCSK9, which have been demonstrated to produce profound low-density lipoprotein cholesterol (LDL-C) lowering when provided as monotherapy or in combination with statins...
April 19, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/28424436/-dyslipidemia-and-cardiovascular-risk-assessment-in-hiv-positive-patients
#14
Serhat Uysal, Mürşide Tuncel Başoğlu, Bahar Boydak, Deniz Gökengin
OBJECTIVE: Dyslipidemia is a major complication of antiretroviral treatment. Aim of the present study was to screen baseline lipid levels and cardiovascular disease risk in HIV-positive patients and analyze change in those parameters after initiation of antiretroviral treatment (ART). METHODS: HIV-positive patients who presented at our clinic between April 2011 and August 2012 were included. Study included 19 female (22.1%) and 67 male (77.9%) patients (mean age 39...
March 2017: Türk Kardiyoloji Derneği Arşivi: Türk Kardiyoloji Derneğinin Yayın Organıdır
https://www.readbyqxmd.com/read/28423226/rvx-208-a-novel-bet-protein-inhibitor-role-as-an-inducer-of-apo-a-i-hdl-and-beyond
#15
Gopal C Ghosh, Rajarshi Bhadra, Raktim K Ghosh, Kinjal Banerjee, Anjan Gupta
Low density cholesterol (LDL) has been the prime target of currently available lipid-lowering therapies although current research is expanding the focus beyond LDL lowering and has included high density cholesterol (HDL) also as the target. Bromo and extra-terminal (BET) proteins are implicated in the regulation of transcription of several regulatory genes and regulation of pro-inflammatory pathways. As atherosclerosis is an inflammatory pathway and studies showed that BET inhibition has a role in inhibiting inflammation, the concept of BET inhibition came in the field of atherosclerosis...
April 19, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28421159/mammalian-swi-snf-enzymes-and-the-epigenetics-of-tumor-cell-metabolic-reprogramming
#16
REVIEW
Jeffrey A Nickerson, Qiong Wu, Anthony N Imbalzano
Tumor cells reprogram their metabolism to survive and grow in a challenging microenvironment. Some of this reprogramming is performed by epigenetic mechanisms. Epigenetics is in turn affected by metabolism; chromatin modifying enzymes are dependent on substrates that are also key metabolic intermediates. We have shown that the chromatin remodeling enzyme Brahma-related gene 1 (BRG1), an epigenetic regulator, is necessary for rapid breast cancer cell proliferation. The mechanism for this requirement is the BRG1-dependent transcription of key lipogenic enzymes and regulators...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28418481/comparison-of-recommended-eligibility-for-primary-prevention-statin-therapy-based-on-the-us-preventive-services-task-force-recommendations-vs-the-acc-aha-guidelines
#17
Neha J Pagidipati, Ann Marie Navar, Hillary Mulder, Allan D Sniderman, Eric D Peterson, Michael J Pencina
Importance: There are important differences among guideline recommendations for using statin therapy in primary prevention. New recommendations from the US Preventive Services Task Force (USPSTF) emphasize therapy based on the presence of 1 or more cardiovascular disease (CVD) risk factors and a 10-year global CVD risk of 10% or greater. Objective: To determine the difference in eligibility for primary prevention statin treatment among US adults, assuming full application of USPSTF recommendations compared with the American College of Cardiology/American Heart Association (ACC/AHA) guidelines...
April 18, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28411172/computational-study-on-human-sphingomyelin-synthase-1-hsms1
#18
Stefano Piotto, Lucia Sessa, Pio Iannelli, Simona Concilio
Human sphingomyelin synthase 1 (hSMS1) is the last enzyme for sphingomyelin (SM) biosynthesis. It has been discovered that in different human tumor tissues the SM levels are lower compared to normal tissues and the activation of hSMS1, to restore the normal levels of SM, inhibits cell cycle proliferation of cancer cells. Since the importance of SM and other lipid metabolism genes in the malignant transformation, we decided to explore the hSMS1 mechanism of action. Enzymes capable to regulate the formation of lipids are therefore of paramount importance...
April 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28410617/treatment-with-high-dose-n-3-pufas-has-no-effect-on-platelet-function-coagulation-metabolic-status-or-inflammation-in-patients-with-atherosclerosis-and-type-2-diabetes
#19
Malgorzata Poreba, Magdalena Mostowik, Aleksander Siniarski, Renata Golebiowska-Wiatrak, Krzysztof Piotr Malinowski, Maciej Haberka, Ewa Konduracka, Jadwiga Nessler, Anetta Undas, Grzegorz Gajos
BACKGROUND: Despite numerous studies on cardioprotective effects of omega-3 polyunsaturated fatty acids (n-3 PUFAs), there is limited evidence for n-3 PUFA-mediated effects, especially at its higher dose, on cardiovascular risk in patients with type 2 diabetes (DM2) and established atherosclerosis. PURPOSE: To investigate the effect of daily treatment with a higher dose (2 g) of n-3 PUFAs on platelet function, coagulation parameters, fibrin clot properties, markers of systemic inflammation and metabolic status, in patients with atherosclerotic vascular disease and DM2 who receive optimal medical therapy...
April 14, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28407684/atorvastatin-inhibits-the-immediate-early-response-gene-egr1-and-improves-the-functional-profile-of-cd4-t-lymphocytes-in-acute-coronary-syndromes
#20
Anna Severino, Chiara Zara, Mara Campioni, Davide Flego, Giulia Angelini, Daniela Pedicino, Ada Francesca Giglio, Francesco Trotta, Simona Giubilato, Vincenzo Pazzano, Claudia Lucci, Antonio Iaconelli, Aureliano Ruggio, Luigi Marzio Biasucci, Filippo Crea, Giovanna Liuzzo
Background- Adaptive immune-response is associated with a worse outcome in acute coronary syndromes. Statins have anti-inflammatory activity beyond lowering lipid levels. We investigated the effects of ex-vivo and in-vivo atorvastatin treatment in acute coronary syndromes on CD4+T-cells, and the underlying molecular mechanisms.Approach and results- Blood samples were collected from 50 statin-naïve acute coronary syndrome patients. We assessed CD4+T-cell activation by flow-cytometry, the expression of 84 T-helper transcription-factors and 84 T-cell related genes by RT-qPCR, and protein expression by Western-blot, before and after 24-hours incubation with increasing doses of atorvastatin: 3-10-26 μg/ml (corresponding to blood levels achieved with doses of 10-40-80 mg, respectively)...
March 14, 2017: Oncotarget
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