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https://www.readbyqxmd.com/read/28424373/statins-pcsk9-inhibitors-and-cholesterol-homeostasis-a-view-from-within-the-hepatocyte
#1
EDITORIAL
Allan D Sniderman, Robert Scott Kiss, Thomas Reid, George Thanassoulis, Gerald F Watts
Statins and PCSK9 inhibitors dramatically lower plasma LDL levels and dramatically increase LDL receptor number within hepatocyte cell membranes. It seems self-evident that total clearance of LDL particles from plasma and total delivery of cholesterol to the liver must increase in consequence. However, based on the results of stable isotope tracer studies, this analysis demonstrates the contrary to be the case. Statins do not change the production rate of LDL particles. Accordingly, at steady state, the clearance rate cannot change...
May 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28379036/inverse-association-of-lipoprotein-a-with-markers-of-insulin-resistance-in-dyslipidemic-subjects
#2
H Vaverková, D Karásek, M Halenka, L Cibíčková, V Kubíčková
Lipoprotein (a) [Lp(a)] is an LDL-like particle that contains an apolipoprotein B100 molecule covalently bound to a plasminogen-like glycoprotein, apolipoprotein (a) [apo(a)]. Epidemiological evidence supports a direct and causal association between Lp(a) levels and coronary risk. On the contrary, a few prospective findings demonstrate inverse association of Lp(a) levels with risk of type 2 diabetes (T2DM). The aim of our study was to evaluate the association of Lp(a) with indicators of insulin resistance (IR) and metabolic syndrome (MS), which precede development of T2DM...
April 5, 2017: Physiological Research
https://www.readbyqxmd.com/read/28342064/hdl-cholesterol-reappraisal-of-its-clinical-relevance
#3
REVIEW
Winfried März, Marcus E Kleber, Hubert Scharnagl, Timotheus Speer, Stephen Zewinger, Andreas Ritsch, Klaus G Parhofer, Arnold von Eckardstein, Ulf Landmesser, Ulrich Laufs
BACKGROUND: While several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as "good cholesterol". Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted...
March 24, 2017: Clinical Research in Cardiology: Official Journal of the German Cardiac Society
https://www.readbyqxmd.com/read/28329241/lipoprotein-a-the-revenant
#4
Baris Gencer, Florian Kronenberg, Erik S Stroes, François Mach
In the mid-1990s, the days of lipoprotein(a) [Lp(a)] were numbered and many people would not have placed a bet on this lipid particle making it to the next century. However, genetic studies brought Lp(a) back to the front-stage after a Mendelian randomization approach used for the first time provided strong support for a causal role of high Lp(a) concentrations in cardiovascular disease and later also for aortic valve stenosis. This encouraged the use of therapeutic interventions to lower Lp(a) as well numerous drug developments, although these approaches mainly targeted LDL cholesterol, while the Lp(a)-lowering effect was only a 'side-effect'...
February 17, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28260912/association-of-uremic-pruritus-in-hemodialysis-patients-with-the-number-of-days-of-high-mean-24-hour-particulate-matter-with-a-diameter-of-2-5-%C3%AE-m
#5
Ming-Hui Liu, Ming-Jen Chan, Ching-Wei Hsu, Cheng-Hao Weng, Tzung-Hai Yen, Wen-Hung Huang
Uremic pruritus (UP) is a common and incapacitating symptom in patients undergoing hemodialysis (HD). The pathogenesis of UP is multifactorial and complex. Particulate matter (PM), a major air pollutant, is a mixture of particles with various chemical compositions. PM is associated with several allergic diseases, including dermatitis. To assess the role of PM (PM with a diameter of <10 μm [PM10] and PM with a diameter of <2.5 μm [PM2.5]) and other clinical variables in UP in patients on HD, we recruited 866 patients on maintenance HD (MHD)...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28137217/anti-pcsk9-antibodies-a-new-era-in-the-treatment-of-dyslipidemia
#6
Joel Schmitz, Ioanna Gouni-Berthold
The serine protease proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to the low-density lipoprotein (LDL) receptor (LDLR) and directs it to lysosomal degradation. This results in decreased numbers of LDLR available on the cell surface to bind LDL particles and remove them from the circulation which in turn leads to an increase in circulating LDL-cholesterol (LDL-C) concentrations. Since the role PCSK9 plays in LDL-C metabolism has been discovered in 2003 there have been major efforts in finding efficient and safe methods to inhibit it...
January 30, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28125987/method-for-estimating-high-sdldl-c-by-measuring-triglyceride-and-apolipoprotein-b-levels
#7
Toshiyuki Hayashi, Shinji Koba, Yasuki Ito, Tsutomu Hirano
BACKGROUND: We previously developed an assay to directly measure small dense (sd) low-density lipoprotein cholesterol (LDL-C) levels, which is not widely used in general clinical practice. Therefore, we propose a simpler method, "LDL window," that uses conventional methods for estimating high sdLDL-C levels. METHODS: We analyzed our previous studies (2006-2008) on healthy subjects and patients with type 2 diabetes and coronary artery disease (CAD). The sdLDL-C level was measured using the precipitation method, and LDL size was determined using gradient gel electrophoresis...
January 26, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28108216/the-phenomenon-of-atherosclerosis-reversal-and-regression-lessons-from-animal-models
#8
REVIEW
Dimitry A Chistiakov, Veronika A Myasoedova, Victor V Revin, Alexander N Orekhov, Yuri V Bobryshev
Studies in non-rodent and murine models showed that atherosclerosis can be reversed. Atherosclerosis progression induced by high-fat or cholesterol-rich diet can be reduced and reversed to plaque regression after switching to a normal diet or through administration of lipid-lowering agents. The similar process should exist in humans after implementation of lipid-lowering therapy and as a result of targeting of small rupture-prone plaques that are major contributors for acute atherosclerotic complications. Lowering of low density lipoprotein (LDL) cholesterol and the activation of reverse cholesterol transport lead to a decline in foam cell content, to the depletion of plaque lipid reservoirs, a decrease in lesional macrophage numbers through the activation of macrophage emigration and, probably, apoptosis, dampening plaque inflammation, and the induction of anti-inflammatory macrophages involved in clearance of the necrotic core and plaque healing...
January 17, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28078862/a-placebo-controlled-trial-of-a-proprietary-lipid-lowering-nutraceutical-supplement-in-the-management-of-dyslipidemia
#9
RANDOMIZED CONTROLLED TRIAL
M Houston, R Rountree, J Lamb, S Phipps, S Meng, B Zhang
There is an ever growing emergence in the popularity of patient-driven care. As this health and wellness model grows, inquiries into diet, lifestyle, and supplemental approaches will continue to become a focal point for the healthcare consumer. Because of this, the aim of this study is to determine the tolerability, and overall effectiveness of a proprietary multi-ingredient lipid-lowering supplement in subjects with dyslipidemia. Forty participants were recruited for a single-center, double-blind randomized, placebocontrolled trial...
October 2016: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/28062489/lipoprotein-a-mass-levels-increase-significantly-according-to-apoe-genotype-an-analysis-of-431%C3%A2-239-patients
#10
Patrick M Moriarty, Stephen A Varvel, Philip L S M Gordts, Joseph P McConnell, Sotirios Tsimikas
OBJECTIVE: Lipoprotein(a) [Lp(a)] levels are genetically determined by hepatocyte apolipoprotein(a) synthesis, but catabolic pathways also influence circulating levels. APOE genotypes have different affinities for the low-density lipoprotein (LDL) receptor and LDL-related protein-1, with ε2 having the weakest binding to LDL receptor at <2% relative to ε3 and ε4. APPROACH AND RESULTS: APOE genotypes (ε2/ε2, ε2/ε3, ε2/ε4, ε3/ε3, ε3/ε4, and ε4/ε4), Lp(a) mass, directly measured Lp(a)-cholesterol levels, and a variety of apoB-related lipoproteins were measured in 431 239 patients...
March 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28053201/evidence-that-supports-the-prescription-of-low-carbohydrate-high-fat-diets-a-narrative-review
#11
REVIEW
Timothy David Noakes, Johann Windt
Low-carbohydrate high-fat (LCHF) diets are a highly contentious current topic in nutrition. This narrative review aims to provide clinicians with a broad overview of the effects of LCHF diets on body weight, glycaemic control and cardiovascular risk factors while addressing some common concerns and misconceptions. Blood total cholesterol and LDL-cholesterol concentrations show a variable, highly individual response to LCHF diets, and should be monitored in patients adhering to this diet. In contrast, available evidence from clinical and preclinical studies indicates that LCHF diets consistently improve all other markers of cardiovascular risk-lowering elevated blood glucose, insulin, triglyceride, ApoB and saturated fat (especially palmitoleic acid) concentrations, reducing small dense LDL particle numbers, glycated haemoglobin (HbA1c) levels, blood pressure and body weight while increasing low HDL-cholesterol concentrations and reversing non-alcoholic fatty liver disease (NAFLD)...
January 2017: British Journal of Sports Medicine
https://www.readbyqxmd.com/read/28038378/the-causal-effects-of-alcohol-on-lipoprotein-subfraction-and-triglyceride-levels-using-a-mendelian-randomization-analysis-the-nagahama-study
#12
Yasuharu Tabara, Hidenori Arai, Yuhko Hirao, Yoshimitsu Takahashi, Kazuya Setoh, Takahisa Kawaguchi, Shinji Kosugi, Yasuki Ito, Takeo Nakayama, Fumihiko Matsuda
BACKGROUND: Light-to-moderate alcohol consumption may increase circulating high-density lipoprotein cholesterol (HDL-C) levels and decrease low-density lipoprotein cholesterol (LDL-C) levels. However, the effect of alcohol on biologically important lipoprotein subfractions remains largely unknown. Here we aimed to clarify the effects of alcohol on lipoprotein subfractions using a Mendelian randomization analysis. METHODS: The study subjects consisted of 8364 general Japanese individuals...
February 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28029752/effects-of-baricitinib-on-lipid-apolipoprotein-and-lipoprotein-particle-profiles-in-a-phase-2b-study-in-patients-with-active-rheumatoid-arthritis
#13
Joel Kremer, Mark C Genovese, Edward Keystone, Peter C Taylor, Steven H Zuckerman, Giacomo Ruotolo, Douglas E Schlichting, Victoria L Crotzer, Eric Nantz, Scott D Beattie, William L Macias
Objective To assess the effects of baricitinib on lipid profile in patients with moderate-to-severe rheumatoid arthritis. Methods Once-daily baricitinib (1, 2, 4, or 8-mg) or placebo was studied in 301 randomized patients. Changes in lipid profile, particle size, and number were assessed at weeks 12/24; associations with clinical efficacy were evaluated. Apolipoproteins were assessed at weeks 4/12 for the placebo, and 4- and 8-mg baricitinib groups. Results Baricitinib treatment resulted in dose-dependent increases by week 12 in serum lipids (low-density lipoprotein cholesterol [LDL-C]: 3...
December 28, 2016: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28025677/pcsk9-inhibition-the-dawn-of-a-new-age-in-cholesterol-lowering
#14
REVIEW
David Preiss, Marion Mafham
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating enzyme of hepatic origin that plays a key role in LDL receptor turnover. Genetic studies have confirmed that individuals with gain-of-function PCSK9 mutations have increased PCSK9 activity, elevated LDL-cholesterol levels and a severe form of familial hypercholesterolaemia. Those with variants leading to reduced PCSK9 have lower LDL-cholesterol levels and a reduced risk of coronary heart disease, and this has led to the development of various strategies aimed at reducing circulating PCSK9...
March 2017: Diabetologia
https://www.readbyqxmd.com/read/27927162/use-of-low-density-lipoprotein-particle-number-levels-as-an-aid-in-statin-treatment-decisions-for-intermediate-risk-patients-a-cost-effectiveness-analysis
#15
Dov Shiffman, Andre R Arellano, Michael P Caulfield, Judy Z Louie, Lance A Bare, James J Devlin, Olle Melander
BACKGROUND: The 2013 ACC/AHA guideline recommended either no statin therapy or moderate-intensity statin therapy (MST) for intermediate risk patients-those with 5-7.5% 10-year risk and without cardiovascular disease (CVD), hypercholesterolemia or diabetes. The guideline further suggested that the therapy choice be based on patient-clinician discussions of risks and benefits. Since low-density lipoprotein particle (LDL-P) levels were reported to be associated with CVD independently of traditional risk factors in intermediate and low risk patients, we investigated the cost-effectiveness of using LDL-P levels to identify intermediate risk patients likely to benefit from initiating or intensifying statin therapy...
December 7, 2016: BMC Cardiovascular Disorders
https://www.readbyqxmd.com/read/27903361/-evaluation-of-health-effect-among-occupational-population-exposed-to-nano-titanium-dioxide-a-cross-sectional-study
#16
H D Xu, J W Zhou, S C Tang, F L Kong, X W Li, Z L Shen, L Yan, Z J Chen, L Zhao, G Jia, J Zhang
Objective: To characterize the health effects of nano-titanium dioxide exposure in an occupational cohort. Methods: Eighty-five male employees of a nano-titanium dioxide manufacturing enterprise in Shandong Province were evaluated in September 2014. Forty-four were exposed to nano-titanium dioxide (exposure group), and 41 were not exposed to nano-titanium dioxide (control group). We collected employees' basic information, smoking and drinking history, previous medical history, family history, and occupational history...
November 6, 2016: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/27887691/cost-effectiveness-of-achieving-targets-of-low-density-lipoprotein-particle-number-versus-low-density-lipoprotein-cholesterol-level
#17
Michael Grabner, Deborah A Winegar, Rajeshwari S Punekar, Ralph A Quimbo, Mark J Cziraky, William C Cromwell
A recent analysis of a commercially insured US population found fewer cardiovascular disease (CVD) events in high-risk patients attaining low levels of low-density lipoprotein (LDL), as measured by LDL particle number (LDL-P) versus low LDL cholesterol (LDL-C). Here, we investigated the cost effectiveness of LDL-lowering therapy guided by LDL-P. Patients were selected from the HealthCore Integrated Research Database and followed for 12 to 36 months. Patients who achieved LDL-P <1,000 nmol/l were placed into the LDL-P cohort, whereas those without LDL-P tests, but who achieved LDL-C <100 mg/dl, were placed into the LDL-C cohort...
February 1, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/27866534/-dihydrotestosterone-inhibits-foam-cell-formation-via-a-lectin-like-ox-low-density-lipoprotein-receptor-mediated-mechanism-in-j774-1-cell-line
#18
Y Qiu, H D Hu, B Q Hu, X Y Chen, P Y Xu, L Cui, P Li, C Liu, L Li
Objective: To investigate the effect of dihydrotestosterone (DHT) on lectin-like ox- low-density lipoprotein (LDL) receptor(LOX-1)expression and foam cell formation in the female macrophage cell line J774.1. Methods: In cultured J774.1 cells, after pretreated with DHT at concentrations of 1×10(-9) mol/L and 1×10(-8) mol/L, ox-LDL-induced LOX-1 expression and foam cell formation were investigated by quantitative real-time PCR, Western blotting, and oil-red O staining. Results: DHT at concentrations of 1×10(-9) mol/L and 1×10(-8) mol/L inhibited ox-LDL-induced LOX-1 mRNA (2...
November 15, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27816804/persistent-changes-in-lipoprotein-lipids-after-a-single-infusion-of-ascending-doses-of-mdco-216-apoa-imilano-popc-in-healthy-volunteers-and-stable-coronary-artery-disease-patients
#19
Herman J Kempen, Monica Gomaraschi, Sara Simonelli, Laura Calabresi, Matthijs Moerland, James Otvos, Elias Jeyarajah, David Kallend, Peter L J Wijngaard
BACKGROUND AND AIMS: Effects of single ascending doses of MDCO-216 on plasma lipid and lipoprotein levels were assessed in human healthy volunteers and in patients with stable coronary artery disease (CAD). METHODS: MDCO-216 was infused at a single dose of 5, 10, 20, 30 or 40 mg/kg over 2 h and blood was collected at 2, 4, 8, 24, 48, 168 and 720 h after start of infusion (ASOI). Lipoprotein lipids were assessed by FLPC and by 1H NMR. RESULTS: Plasma concentrations of free cholesterol (FC) displayed a rapid and dose-dependent rise, peaking at 8 h, but remaining above baseline until 48 h ASOI, whereas levels of esterified cholesterol (CE) increased at lower doses but not at higher doses, and even decreased below baseline at the highest dose...
December 2016: Atherosclerosis
https://www.readbyqxmd.com/read/27784733/comprehensive-analysis-of-established-dyslipidemia-associated-loci-in-the-diabetes-prevention-program
#20
Tibor V Varga, Alexandra H Winters, Kathleen A Jablonski, Edward S Horton, Prajakta Khare-Ranade, William C Knowler, Santica M Marcovina, Frida Renström, Karol E Watson, Ronald Goldberg, José C Florez, Toni I Pollin, Paul W Franks
BACKGROUND: We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (versus placebo control) on lipid and lipid subfraction levels in the Diabetes Prevention Program randomized controlled trial. METHODS AND RESULTS: We tested gene treatment interactions in relation to baseline-adjusted follow-up blood lipid concentrations (high-density lipoprotein [HDL] and low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) and lipoprotein subfraction particle concentrations and size in 2993 participants with pre-diabetes...
December 2016: Circulation. Cardiovascular Genetics
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