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Journal of Clinical Lipidology

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https://www.readbyqxmd.com/read/29784574/highly-efficacious-long-term-triglyceride-lowering-with-rituximab-therapy-in-a-patient-with-autoimmune-hypertriglyceridemia
#1
Sophie Béliard, Mathilde Di Filippo, Gilles Kaplanski, René Valéro
We report the first case of an autoimmune hypertriglyceridemia successfully treated with rituximab, an anti-CD20-targeted monoclonal antibody. A 45-year-old man, with prior autoimmune conditions, developed severe, acquired hypertriglyceridemia resistant to traditional triglyceride lowering therapies. After the elimination of secondary or genetic causes, we detected the presence of anti-LPL-IgG by immunoblot. After 3 infusions of rituximab, we observed a marked improvement of his hypertriglyceridemia, concomitant with a reduction in plasma anti-LPL antibody titer and B-lymphocytes counts...
April 30, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29784573/phactr1-genotype-predicts-coronary-artery-disease-in-patients-with-familial-hypercholesterolemia
#2
Martine Paquette, Robert Dufour, Alexis Baass
BACKGROUND: Familial hypercholesterolemia (FH) is the most frequent autosomal codominant disease worldwide and is characterized by elevated low-density lipoprotein cholesterol and premature coronary artery disease (CAD). Polymorphisms in phosphatase and actin regulator 1 (PHACTR1) have been shown to be associated with cardiovascular risk in large genome-wide association studies studies. OBJECTIVE: The aim of the present study is to evaluate the association between the rs12526453 polymorphism in the PHACTR1 gene and the prevalence of CAD in FH patients...
April 30, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29784572/the-burden-of-familial-chylomicronemia-syndrome-results-from-the-global-in-focus-study
#3
Michael Davidson, Michael Stevenson, Andrew Hsieh, Zahid Ahmad, Jeanine Roeters van Lennep, Caroline Crowson, Joseph L Witztum
BACKGROUND: Familial chylomicronemia syndrome (FCS) is a rare genetic disorder characterized by a deficiency of lipoprotein lipase leading to extreme hypertriglyceridemia. Patients' burden of illness and quality of life have been poorly addressed in the literature. OBJECTIVE: To understand the ways in which FCS impacts patients' lives. METHODS: Investigation of Findings and Observations Captured in Burden of Illness Survey (IN-FOCUS) was a global web-based survey open to patients with FCS...
April 26, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29784571/familial-hypercholesterolemia-with-extensive-coronary-artery-disease-and-tuberous-and-tendinous-xanthomas-a-case-report-and-mutation-analysis
#4
Deniz Agirbasli, Tommy Hyatt, Mehmet Agirbasli
This is a case report of a 38-year-old Syrian refugee male with early-onset extensive atherosclerosis. The physical and laboratory examination were remarkable with severe xanthomas in the upper and lower extremities and with low-density lipoprotein cholesterol (LDL-C) 417 mg/dL, total cholesterol 495 mg/dL, high-density lipoprotein cholesterol 30 mg/dL, and triglycerides 242 mg/dL. LDL-C level responded poorly to the high-dose statin treatment. The genetic analysis indicated that the patient had a large homozygous deletion in LDL receptor gene including the exons 7-14...
April 26, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29779997/variations-in-time-to-benefit-among-clinical-trials-of-cholesterol-lowering-drugs
#5
Philip J Barter, David D Waters
BACKGROUND: Time to benefit (TTB) in clinical trials of cholesterol-lowering drugs is important because it may provide a clue as to the potential mechanism of action of the drug, it is helpful in determining when to stop a trial for futility, and it may inform treatment decisions in subjects with reduced life expectancy. OBJECTIVE: To compare TTB among clinical trials of cholesterol-lowering drugs. METHODS: We examined TTB in 24 trials of cholesterol-lowering drugs with positive outcomes...
April 21, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29773422/a-novel-homozygous-abca1-variant-in-an-asymptomatic-man-with-profound-hypoalphalipoproteinemia
#6
Yaser Carcora, Robert D Brook, Linda Farhat, Cristen J Willer, Melvyn Rubenfire, Daniel Seung Kim
Low high-density lipoprotein cholesterol (HDL-C) can be caused by several acquired secondary causes as well as primary genetic disorders. However, only a few conditions are associated with profoundly reduced levels below 10 mg/dL. We present an unusual case of a healthy man with severely decreased HDL-C because of a novel homozygous variant causing a Proline > Arginine amino acid change at position 1312 in the ATP-binding cassette transporter A1 gene. Homozygous variations in ATP-binding cassette transporter A1 typically cause Tangier disease, a rare autosomal recessive condition linked with several other abnormalities (eg, enlarged discolored tonsils)...
April 21, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29773421/r46l-polymorphism-in-the-pcsk9-gene-relationship-to-lipid-levels-subclinical-vascular-disease-and-erectile-dysfunction
#7
Jose M Mostaza, Carlos Lahoz, Miguel A Salinero-Fort, Olaya de Dios, Elisa Castillo, Teresa González-Alegre, Francisca García-Iglesias, Eva Estirado, Fernando Laguna, Concesa Sabín, Silvia López, Victor Cornejo, Carmen de Burgos, Vanesa Sanchez, Carmen Garcés
BACKGROUND: The R46L variant of the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene has been related to lipid levels and cardiovascular disease. OBJECTIVE: To evaluate the influence of this polymorphism on subclinical vascular disease and erectile dysfunction (ED). METHODS: We analyzed the association of the PCSK9 rs11591147 single-nucleotide polymorphism with lipid levels, intima-media thickness (IMT), and the ankle-brachial index, in 1188 adults free of cardiovascular disease, randomly selected from the population...
April 21, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29753733/coronary-computed-tomographic-angiography-findings-and-their-therapeutic-implications-in-asymptomatic-patients-with-familial-hypercholesterolemia-lessons-from-the-safeheart-study
#8
Leopoldo Pérez de Isla, Rodrigo Alonso, Ovidio Muñiz-Grijalvo, José Luis Díaz-Díaz, Daniel Zambón, José Pablo Miramontes, Francisco Fuentes, José Juan Gómez de Diego, Aurora González-Estrada, Nelva Mata, Adriana Saltijeral, Manuel Barreiro, Marta Tomás, Raimundo de Andrés, Rosa Argüeso, Maria Pilar Serrano Gotarredona, Silvia Navarro Herrero, Rosario J Perea Palazón, Teresa M de Caralt, Luisa Arrojo Suárez de Centi, Svetlana Zhilina, Simona Espejo Pérez, Teresa Padró, Pedro Mata
BACKGROUND: Familial hypercholesterolemia (FH) confers an increased risk of premature atherosclerotic disease. Coronary computed tomographic angiography (CTA) can assess preclinical coronary atherosclerosis. OBJECTIVES: To describe coronary CTA findings in asymptomatic molecularly defined FH individuals, to identify those factors related to its presence and extension, and to assess the impact of these results in patients' care and estimated risk. METHODS: Four hundred and forty individuals with FH, without clinical cardiovascular disease, were consecutively enrolled and underwent a coronary CTA that was used to analyze coronary atherosclerosis based on coronary calcium score (CCS), sum of stenosis severity, and plaque composition sum (PCS)...
April 17, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29731282/rethinking-reverse-cholesterol-transport-and-dysfunctional-high-density-lipoproteins
#9
REVIEW
Baiba K Gillard, Corina Rosales, Bingqing Xu, Antonio M Gotto, Henry J Pownall
Human plasma high-density lipoprotein cholesterol concentrations are a negative risk factor for atherosclerosis-linked cardiovascular disease. Pharmacological attempts to reduce atherosclerotic cardiovascular disease by increasing plasma high-density lipoprotein cholesterol have been disappointing so that recent research has shifted from HDL quantity to HDL quality, that is, functional vs dysfunctional HDL. HDL has varying degrees of dysfunction reflected in impaired reverse cholesterol transport (RCT). In the context of atheroprotection, RCT occurs by 2 mechanisms: one is the well-known trans-hepatic pathway comprising macrophage free cholesterol (FC) efflux, which produces early forms of FC-rich nascent HDL (nHDL)...
April 12, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29730187/identification-of-proresolving-and-inflammatory-lipid-mediators-in-human-psoriasis
#10
Alexander V Sorokin, Paul C Norris, Justin T English, Amit K Dey, Abhishek Chaturvedi, Yvonne Baumer, Joanna Silverman, Martin P Playford, Charles N Serhan, Nehal N Mehta
BACKGROUND: Psoriasis (PSO) is an immune-mediated inflammatory disease associated with metabolic and cardiovascular comorbidities. It is now known that resolution of inflammation is an active process locally controlled by specialized proresolving mediators (SPMs), named resolvins (Rvs), protectins, and maresins. OBJECTIVE: It is unknown whether these potent lipid mediators (LMs) are involved in PSO pathophysiology and if the skin and blood have disease-specific SPMs phenotype profiles...
April 6, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29748148/clinical-and-biochemical-features-of-different-molecular-etiologies-of-familial-chylomicronemia
#11
Robert A Hegele, Amanda J Berberich, Matthew R Ban, Jian Wang, Andres Digenio, Veronica J Alexander, Laura D'Erasmo, Marcello Arca, Alan Jones, Eric Bruckert, Erik S Stroes, Jean Bergeron, Fernando Civeira, Joseph L Witztum, Daniel Gaudet
BACKGROUND: Familial chylomicronemia syndrome (FCS) is an ultra-rare phenotype that is usually caused by biallelic mutations in the LPL gene encoding lipoprotein lipase, or less often in APOC2, APOA5, LMF1, or GPIHBP1 genes encoding cofactors or interacting proteins. OBJECTIVES: We evaluated baseline phenotypes among FCS participants in a phase 3 randomized placebo-controlled trial of volanesorsen (NCT02211209). METHODS: Baseline clinical, fasting, and postfat load metabolic markers were assessed...
April 4, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29778561/severe-xanthomatosis-in-heterozygous-familial-hypercholesterolemia
#12
Sumayah Aljenedil, Isabelle Ruel, Kevin Watters, Jacques Genest
BACKGROUND: Familial hypercholesterolemia is a genetic lipoprotein disorder characterized by elevated plasma low-density lipoprotein cholesterol level, (tendinous xanthomas, xanthelasmas, and premature arcus corneus) and early onset atherosclerotic cardiovascular disease. Familial hypercholesterolemia is caused by mutations in the low-density lipoprotein receptor, apolipoprotein B or proprotein convertase subtilisin/kexin type 9 genes. Rare mutations in low-density lipoprotein receptor adapter protein 1, APOE p...
April 3, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29703625/elevated-lipoprotein-a-and-low-density-lipoprotein-cholesterol-as-predictors-of-the-severity-and-complexity-of-angiographic-lesions-in-patients-with-premature-coronary-artery-disease
#13
David Chieng, Jing Pang, Katrina L Ellis, Graham S Hillis, Gerald F Watts, Carl J Schultz
BACKGROUND: Elevated lipoprotein(a) (Lp[a]) and low-density lipoprotein (LDL) cholesterol are important inheritable risk factors for premature coronary artery disease (CAD). Lp(a) mediates cardiovascular risk through prothrombotic, proinflammatory, and proatherogenic properties. The association of Lp(a) and LDL cholesterol with angiographic disease severity and complexity in patients with premature CAD has yet to be established. OBJECTIVE: To investigate the relationship of Lp(a) and LDL cholesterol with the severity and complexity of coronary artery lesions using the SYNergy between percutaneous coronary intervention with TAXUS and Cardiac Surgery (SYNTAX) and Gensini scores, in patients with premature CAD...
April 3, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29699916/posttranslational-modification-of-proprotein-convertase-subtilisin-kexin-type-9-is-differentially-regulated-in-response-to-distinct-cardiometabolic-treatments-as-revealed-by-targeted-proteomics
#14
Marie-Soleil Gauthier, Zuhier Awan, Annie Bouchard, Josée Champagne, Sylvain Tessier, Denis Faubert, Katherine Chabot, Pierre Y Garneau, Rémi Rabasa-Lhoret, Nabil G Seidah, Paul M Ridker, Jacques Genest, Benoit Coulombe
BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secreted protein that interacts with the low-density lipoprotein (LDL) receptor at the surface of hepatocytes to regulate circulating LDL cholesterol levels. High circulating PCSK9 levels have been associated with elevated LDL cholesterol. Recently, the Food and Drug Administration of the United States approved new LDL cholesterol-lowering drugs that specifically target the inhibition of PCSK9. Similar to most human proteins, PCSK9 exists in multiple forms as it is the target of posttranslational modifications (PTMs) such as proteolytic cleavage, phosphorylation, and others, which can affect its biological activity...
April 3, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29699915/dyslipidemia-is-associated-with-pediatric-nonalcoholic-fatty-liver-disease
#15
Shima Dowla, Stella Aslibekyan, Amy Goss, Kevin Fontaine, Ambika P Ashraf
BACKGROUND: With the increasing prevalence of childhood obesity, nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of pediatric chronic liver disorder. Factors underlying the pathophysiology of NAFLD remain poorly defined. OBJECTIVE: This study aimed to describe the metabolic characteristics of children with NAFLD differing in race/ethnicity and to test associations between dyslipidemia and NAFLD. METHODS: A retrospective chart review was conducted at a tertiary referral university hospital among 309 children with a diagnosis of NAFLD...
April 3, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29685591/cardiovascular-event-reduction-with-pcsk9-inhibition-among-1578-patients-with-familial-hypercholesterolemia-results-from-the-spire-randomized-trials-of-bococizumab
#16
Paul M Ridker, Lynda M Rose, John J P Kastelein, Raul D Santos, Caimiao Wei, James Revkin, Carla Yunis, Jean-Claude Tardif, Charles L Shear
BACKGROUND: Familial hypercholesterolemia (FH) is a dominant genetic disorder associated with elevated low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic events. Although therapeutic monoclonal antibodies that inhibit proprotein convertase subtilisin-kexin type 9 (PCSK9) are indicated for LDL-C reduction among adult patients with FH, placebo-controlled outcome data among FH patients are scant. OBJECTIVE: Directly compare the efficacy of PCSK9 inhibition as compared to placebo on hard cardiovascular outcomes in FH patients enrolled in the Studies of PCSK9 Inhibition and the Reduction of vascular Events (SPIRE) program...
April 3, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29703626/temporal-changes-in-statin-prescription-and-intensity-at-discharge-and-impact-on-outcomes-in-patients-with-newly-diagnosed-atherosclerotic-cardiovascular-disease-real-world-experience-within-a-large-integrated-health-care-system-the-impres-study
#17
Jeffrey L Anderson, Kirk U Knowlton, Heidi T May, Tami L Bair, Shannon O Armstrong, Donald L Lappé, Joseph B Muhlestein
BACKGROUND: Statins are indicated for secondary atherosclerotic cardiovascular disease (ASCVD) prevention; however, multiple surveys have found treatment gaps in clinical application. OBJECTIVE: To determine trends over 15 years in the prevalence and impact of a statin prescription and dose intensity at discharge after a first ASCVD event. METHODS: The Intermountain Enterprise Data Warehouse was searched to identify all adults with a first encounter for ASCVD between January 1, 1999 and December 31, 2013, including coronary artery disease, cerebrovascular disease, and peripheral arterial disease, who survived the index event and were followed for ≥3 years or until death...
March 30, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29699917/high-density-lipoprotein-cholesterol-and-causes-of-death-in-chronic-kidney-disease
#18
Sankar D Navaneethan, Jesse D Schold, Carl P Walther, Susana Arrigain, Stacey E Jolly, Salim S Virani, Wolfgang C Winkelmayer, Joseph V Nally
BACKGROUND: Recent data suggest a U-shaped association between high-density lipoprotein cholesterol (HDL-c) and death in chronic kidney disease (CKD). However, whether the increased mortality in patients with extreme levels is explained by specific causes of death remains unclear. OBJECTIVES: We studied the associations between HDL-c and cause-specific deaths in CKD. METHODS: We included 38,377 patients with estimated glomerular filtration rate 15-59 mL/min/1...
March 30, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29685592/clinical-features-and-outcomes-of-severe-very-severe-and-extreme-hypertriglyceridemia-in-a-regional-health-service
#19
Barak Zafrir, Ayman Jubran, Rawan Hijazi, Chen Shapira
BACKGROUND: Comprehensive data on severe hypertriglyceridemia (HTG) in the general population setting are limited and of importance due to the increase in metabolic risk factors and novel therapies under development. OBJECTIVE: To investigate contributing causes and outcomes of severe to extreme HTG. METHODS: Regional database retrospectively analyzed for subjects with severe HTG. Adverse outcomes were investigated in correlation to HTG severity, with follow-up initiating at first documentation of HTG > 1000 mg/dL...
March 30, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29753732/niacin-action-in-the-atherogenic-mixed-dyslipidemia-of-metabolic-syndrome-insights-from-metabolic-biomarker-profiling-and-network-analysis
#20
Martin Adiels, M John Chapman, Paul Robillard, Michel Krempf, Martine Laville, Jan Borén
BACKGROUND: Niacin as an adjunct to statin treatment to reduce cardiovascular risk is questioned. OBJECTIVE: To evaluate interrelationships between the effects of niacin on mixed dyslipidemia and a spectrum of metabolic and inflammatory biomarkers. METHODS: Obese, nondiabetic, hypertriglyceridemic males (n = 19) with low high-density lipoprotein-cholesterol levels received extended-release nicotinic acid for 8 weeks. Multiple biomarkers were measured using enzyme-linked immunosorbent assay, enzymatic/absorptiometric, or multiplex biochip assays...
March 29, 2018: Journal of Clinical Lipidology
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