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https://www.readbyqxmd.com/read/28927707/pcsk9-inhibition-and-type-2-diabetes
#1
Luca A Lotta, Simon J Griffin
No abstract text is available yet for this article.
September 14, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28927706/cardiovascular-safety-and-efficacy-of-the-pcsk9-inhibitor-evolocumab-in-patients-with-and-without-diabetes-and-the-effect-of-evolocumab-on-glycaemia-and-risk-of-new-onset-diabetes-a-prespecified-analysis-of-the-fourier-randomised-controlled-trial
#2
Marc S Sabatine, Lawrence A Leiter, Stephen D Wiviott, Robert P Giugliano, Prakash Deedwania, Gaetano M De Ferrari, Sabina A Murphy, Julia F Kuder, Ioanna Gouni-Berthold, Basil S Lewis, Yehuda Handelsman, Armando Lira Pineda, Narimon Honarpour, Anthony C Keech, Peter S Sever, Terje R Pedersen
BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab reduced LDL cholesterol and cardiovascular events in the FOURIER trial. In this prespecified analysis of FOURIER, we investigated the efficacy and safety of evolocumab by diabetes status and the effect of evolocumab on glycaemia and risk of developing diabetes. METHODS: FOURIER was a randomised trial of evolocumab (140 mg every 2 weeks or 420 mg once per month) versus placebo in 27 564 patients with atherosclerotic disease who were on statin therapy, followed up for a median of 2·2 years...
September 14, 2017: Lancet Diabetes & Endocrinology
https://www.readbyqxmd.com/read/28926730/impact-of-evolocumab-treatment-on-low-density-lipoprotein-cholesterol-levels-in-heterozygous-familial-hypercholesterolemic-patients-withdrawing-from-regular-apheresis
#3
Masa-Aki Kawashiri, Atsushi Nohara, Toshinori Higashikata, Hayato Tada, Chiaki Nakanishi, Hirofumi Okada, Tetsuo Konno, Kenji Sakata, Kenshi Hayashi, Akihiro Inazu, Hiroshi Mabuchi, Masakazu Yamagishi
BACKGROUND AND AIMS: Low-density lipoprotein (LDL) apheresis has been used to treat refractory hyperlipidemia such as familial hypercholesterolemia (FH). Evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor used in clinical settings, can reduce LDL cholesterol (LDL-C) levels by >70%. Therefore, this study aimed to assess the impact of evolocumab on withdrawal from regular LDL apheresis in patients with heterozygous FH (HeFH). METHODS: Eleven patients with HeFH undergoing biweekly LDL apheresis were enrolled and were subsequently switched to a biweekly subcutaneous injection of 140 mg of evolocumab...
September 9, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28926398/association-of-a-3-untranslated-region-polymorphism-in-pcsk9-with-hiv-viral-load-and-cd4-levels-in-hiv-hepatitis-c-virus-co-infected-women
#4
Mark H Kuniholm, Hua Liang, Kathryn Anastos, Deborah Gustafson, Seble Kassaye, Marek Nowicki, Beverly E Sha, Emilia J Pawlowski, Stephen J Gange, Bradley E Aouizerat, Tatiana Pushkarsky, Michael I Bukrinsky, Vinayaka R Prasad
OBJECTIVE: To assess variation in genes that regulate cholesterol metabolism in relation to the natural history of HIV infection. DESIGN: Cross-sectional and longitudinal analysis of the Women's Interagency HIV Study (WIHS). METHODS: We examined 2,050 single nucleotide polymorphisms (SNPs) in 19 genes known to regulate cholesterol metabolism in relation to HIV viral load and CD4 T cell levels in a multiracial cohort of 1,066 antiretroviral therapy (ART) naïve women...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28919772/anti-pcsk9-antibodies-for-the-treatment-of-heterozygous-familial-hypercholesterolemia-patient-selection-and-perspectives
#5
REVIEW
Alberico Luigi Catapano, Angela Pirillo, Giuseppe Danilo Norata
Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol levels from birth, which exposes the arteries to high levels of atherogenic lipoproteins lifelong and results in a significantly increased risk of premature cardiovascular events. The diagnosis of FH, followed by an appropriate and early treatment is critical to reduce the cardiovascular burden in this population. Phase I-III clinical trials showed the benefit of proprotein convertase subtilisin kexin 9 inhibitors, both alirocumab and evolocumab, in these patients with an average low-density lipoprotein cholesterol reduction ranging from -40% to -60%...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28915766/should-an-ldl-cholesterol-target-based-approach-be-readopted
#6
C Michael White, Erin R Weeda, Elaine Nguyen
OBJECTIVE: To review clinical trials driving the evolution of hyperlipidemic guidelines, discuss whether low-density lipoprotein (LDL) targets and adjunctive therapy on top of statins should be used, and summarize the pharmacist's role in helping achieve LDL goals. DATA SOURCES: MEDLINE search (1/1980-5/2017) using terms including LDL, lipid, and statin, with forward and backward citation tracking. STUDY SELECTION AND DATA EXTRACTION: English-language studies and guidelines assessing LDL-lowering therapy were included...
July 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28914630/strategies-for-the-use-of-nonstatin-therapies
#7
Angela Pirillo, Giuseppe D Norata, Alberico L Catapano
PURPOSE OF REVIEW: Dyslipidaemias are a major risk factor for cardiovascular disease (CVD); in particular, high levels of low-density lipoprotein cholesterol (LDL-C) have been associated to a higher cardiovascular risk. Reducing LDL-C levels decreases the risk of coronary heart disease (CHD), and the greater the LDL-C reduction, the greater the decrease in cardiovascular risk. Although statins represent the first line lipid-lowering therapy, many patients do not reach the recommended goals or exhibit adverse side effects leading to therapy discontinuation; in addition, a significant percentage of statin-treated patients continue to experience cardiovascular events even in the presence of well controlled LDL-C levels, because of alterations in other lipid/lipoprotein classes, including triglycerides and high-density lipoprotein cholesterol...
September 12, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28913715/oxidized-low-density-lipoprotein-oxldl-affects-load-free-cell-shortening-of-cardiomyocytes-in-a-proprotein-convertase-subtilisin-kexin-9-pcsk9-dependent-way
#8
Klaus-Dieter Schlüter, Annemarie Wolf, Martin Weber, Rolf Schreckenberg, Rainer Schulz
Recent studies have documented that oxidized low-density lipoprotein cholesterol (oxLDL) levels directly impact myocardial structure and function. However, the molecular mechanisms by which oxLDL affects cardiac myocytes are not well established. We addressed the question whether oxLDL modifies load-free cell shortening, a standardized readout of cardiac cellular function, and investigated whether proprotein convertase subtilisin/kexin-9 (PCSK9) is involved on oxLDL-dependent processes. Adult rat ventricular cardiomyocytes were isolated and incubated for 24 h with oxLDL...
September 14, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28913682/-therapeutic-options-in-hyperlipidemia
#9
Robert Berent, Theresa Berent, Helmut Sinzinger
Treatment of lipid disorders (dyslipidemia) is the cornerstone of atherosclerosis prevention and reduction of progression. Lifestyle modification is the first step to improve the plasma lipid profile. Statins play a central role in the reduction of LDL cholesterol. Whether and to what extent other lipids such as triglycerides or lipoprotein(a) should also be treated depends on the extent of atherosclerotic disease and its progression over time. Especially in residential cardiac rehabilitation we have the opportunity to encourage adherence and adapt medication as necessary due to a face to face contact over 4 weeks...
September 14, 2017: Wiener Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28911509/exploration-of-pcsk9-as-a-cardiovascular%C3%A2-risk-factor-is-there-a-link-to-the-platelet
#10
EDITORIAL
Paul A Gurbel, Eliano P Navarese, Udaya S Tantry
No abstract text is available yet for this article.
September 19, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28911508/relationship-of-pcsk9-and-urinary%C3%A2-thromboxane-excretion-to%C3%A2-cardiovascular-events-in-patients%C3%A2-with%C3%A2-atrial-fibrillation
#11
Daniele Pastori, Cristina Nocella, Alessio Farcomeni, Simona Bartimoccia, Maria Santulli, Fortunata Vasaturo, Roberto Carnevale, Danilo Menichelli, Francesco Violi, Pasquale Pignatelli
BACKGROUND: Soluble proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular events (CVEs) in patients who are at high cardiovascular risk. No data on the effect of PCSK9 levels in patients with atrial fibrillation (AF) are available. OBJECTIVES: This study investigated the association between PCSK9 and CVEs in AF as well as the relationship between PCSK9 and urinary 11-dehydro-thromboxane B2 (11-dh-TxB2), a marker of platelet activation...
September 19, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28903137/nationwide-coverage-and-cost-sharing-for-pcsk9-inhibitors-among-medicare-part-d-plans
#12
Dhruv S Kazi, Christine Y Lu, Grace A Lin, Colette DeJong, R Adams Dudley, Randi Chen, Chien-Wen Tseng
No abstract text is available yet for this article.
September 13, 2017: JAMA Cardiology
https://www.readbyqxmd.com/read/28902717/new-approaches-to-address-dyslipidemia
#13
Klaus G Parhofer
PURPOSE OF REVIEW: Although lipid-lowering treatment with statins, ezetimibe, and PCSK9 inhibitors is a very successful strategy to prevent cardiovascular events, there is a need for further drug developments. Not all patients respond sufficiently to the available therapy (very high baseline values, intolerance). Furthermore, patients may be characterized by dyslipidemias not accessible to available drugs such as patients with homozygous familial hypercholesterolemia, chylomicronemia syndrome, or elevated lipoprotein(a)...
September 11, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28894089/heparan-sulfate-proteoglycans-present-pcsk9-to-the-ldl-receptor
#14
Camilla Gustafsen, Ditte Olsen, Joachim Vilstrup, Signe Lund, Anika Reinhardt, Niels Wellner, Torben Larsen, Christian B F Andersen, Kathrin Weyer, Jin-Ping Li, Peter H Seeberger, Søren Thirup, Peder Madsen, Simon Glerup
Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels of cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary artery disease by inducing lysosomal degradation of the LDL receptor (LDLR) in the liver and thereby reducing LDL clearance. Here, we show that liver heparan sulfate proteoglycans are PCSK9 receptors and essential for PCSK9-induced LDLR degradation. The heparan sulfate-binding site is located in the PCSK9 prodomain and formed by surface-exposed basic residues interacting with trisulfated heparan sulfate disaccharide repeats...
September 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28886926/2017-focused-update-of-the-2016%C3%A2-acc%C3%A2-expert-consensus-decision-pathway-on-the-role-of-non-statin-therapies-for-ldl-cholesterol-lowering-in%C3%A2-the-management-of-atherosclerotic-cardiovascular-disease-risk-a-report-of-the-american-college-of-cardiology-task-force
#15
Donald M Lloyd-Jones, Pamela B Morris, Christie M Ballantyne, Kim K Birtcher, David D Daly, Sondra M DePalma, Margo B Minissian, Carl E Orringer, Sidney C Smith
In 2016, the American College of Cardiology published the first expert consensus decision pathway (ECDP) on the role of non-statin therapies for low-density lipoprotein (LDL)-cholesterol lowering in the management of atherosclerotic cardiovascular disease (ASCVD) risk. Since the publication of that document, additional evidence and perspectives have emerged from randomized clinical trials and other sources, particularly considering the longer-term efficacy and safety of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors in secondary prevention of ASCVD...
August 30, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28884604/novel-treatment-options-for-the-management-of-heterozygous-familial-hypercholesterolemia
#16
Georgios Polychronopoulos, Konstantinos Tziomalos
Even though statins represent the mainstay of treatment of heterozygous familial hypercholesterolemia (FH), their low-density lipoprotein cholesterol (LDL-C) lowering efficacy is finite and most patients with FH will not achieve LDL-C targets with statin monotherapy. Addition of ezetimibe with or without bile acid sequestrants will also not lead to treatment goals in many of these patients, particularly in those with established cardiovascular disease. In this selected subgroup of the FH population, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide substantial reductions in LDL-C levels, reduce cardiovascular morbidity and appear to be safe...
September 8, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28879791/incorporation-of-pcsk9-inhibitors-into-prevention-of-atherosclerotic-cardiovascular-disease
#17
Cezary Wójcik
Primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) has become recently more complex than ever, leaving the clinicians perplexed with outdated guidelines and emerging evidence about new LDL-C lowering therapies. 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines have focused on high intensity statin therapy for specific groups of patients, while abandoning long established LDL-C goals, a strategy which no longer seems valid. PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors have emerged as the add-on therapy on top of statins and/or ezetimibe for the treatment of hypercholesterolemia and ASCVD prevention...
September 7, 2017: Postgraduate Medicine
https://www.readbyqxmd.com/read/28873201/mutational-screening-in-the-ldlr-gene-among-patients-presenting-familial-hypercholesterolemia-in-the-southeast-of-brazil
#18
G A Molfetta, D L Zanette, J E Santos, W A Silva
Familial hypercholesterolemia (FH) is a dominant, autosomal disease characterized by high LDL levels in blood plasma, and is caused by a defect in the gene encoding the LDL receptor (LDLR). The clinical diagnosis is based on personal and familial history, physical examination findings, and measures of high LDL cholesterol concentrations. LDLR is a cell-surface glycoprotein that controls the level of blood plasma cholesterol and triglyceride by LDLR-mediated endocytosis. Here we sequenced the entire LDLR gene-coding region to screen for mutations in 32 patients diagnosed with FH, and we have found 20 mutations including synonymous, missense, and intronic mutations...
August 31, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28871349/recent-insights-into-pharmacologic-cardiovascular-risk-reduction-in-type-2-diabetes-mellitus
#19
Scott L Purga, Mandeep Sidhu, Michael Farkouh, Joshua Schulman-Marcus
Diabetes mellitus (DM) affects nearly 30 million Americans and carries an increased risk of macrovascular complications of myocardial infarction, stroke, and cardiovascular death. While aggressive cardiovascular risk factor reduction has long been advocated in patients with diabetes, clinical trials have only recently demonstrated that such reductions result in improved outcomes. This review discusses recent evidence for risk reduction strategies and therapies with a focus on the management of glycemia, dyslipidemia, and hypertension...
September 4, 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28870033/-the-expression-and-clinical-significance-of-proprotein-convertase-subtilisin-kexin-9-in-rheumatoid-arthritis
#20
Q Du, X J Yu, H J Li, S Q Guan, Z Y Zhang, Y F Mei
Objective: To assess the expression and significance of proprotein convertase subtilisin kexin 9 (PCSK9) in patients with rheumatoid arthritis (RA). Methods: Sixty-five RA patients and forty-seven healthy controls were recruited in this study. The body mass index (BMI) and serum total cholesterol(TC), triglyceride(TG), high density lipoprotein(HDL), lipoprotein a, low density lipoprotein(LDL), very low density lipoprotein(VLDL), apolipoprotein A(ApoA), apolipoprotein B(ApoB) and the ratio of LDL-C/HDL-C were tested...
September 1, 2017: Zhonghua Nei Ke za Zhi [Chinese Journal of Internal Medicine]
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