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Hypertriglyceridemia: HELP
Articles from Illinois
Based on 45 articles published since 2008

These are the 45 published articles about Hypertriglyceridemia that originated from Illinois during 2008-2019.
+ Citations + Abstracts
Pages: 1 · 2
1 Review Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial. 2018

Nicholls, Stephen J / Lincoff, A Michael / Bash, Dianna / Ballantyne, Christie M / Barter, Philip J / Davidson, Michael H / Kastelein, John J P / Koenig, Wolfgang / McGuire, Darren K / Mozaffarian, Dariush / Pedersen, Terje R / Ridker, Paul M / Ray, Kausik / Karlson, Björn W / Lundström, Torbjörn / Wolski, Kathy / Nissen, Steven E. ·South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, Australia. · Department of Cardiovascular Medicine and Cleveland Clinic Coordinating Center for Clinical Research, Cleveland Clinic, Cleveland, Ohio. · Baylor College of Medicine, Houston, Texas. · University of New South Wales, Sydney, Australia. · University of Chicago, Chicago, Illinois. · Academic Medical Center, Amsterdam, The Netherlands. · Deutsches Herzzentrum München, Technische Universität München, and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany. · Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas. · Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts. · Oslo University Hospital, Oslo, Norway. · Harvard Medical School, Boston, Massachusetts. · Imperial College of London, London, UK. · Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. · AstraZeneca Pharmaceuticals, Gothenburg, Sweden. ·Clin Cardiol · Pubmed #30125052.

ABSTRACT: It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.

2 Review Not every patient needs a triglyceride check, but all can get pancreatitis: a systematic review and clinical characterization of isotretinoin-associated pancreatitis. 2017

Opel, D / Kramer, O N / Chevalier, M / Bigby, M / Albrecht, J. ·Division of Dermatology, Department of Medicine, Loyola University Medical Center, Maywood, IL, U.S.A. · Medical School, University of Illinois, Chicago, IL, U.S.A. · Apex Dermatology, Littleton, CO, U.S.A. · Department of Dermatology, Harvard Medical School and Beth Israel Deaconess Medical Center, Boston, MA, U.S.A. · Division of Dermatology, Department of Medicine, J.H. Stroger Hospital of Cook County, Chicago, IL, U.S.A. · Department of Dermatology, Rush Medical College, Chicago, IL, U.S.A. ·Br J Dermatol · Pubmed #27893168.

ABSTRACT: Monitoring of triglycerides for patients on isotretinoin is practised primarily to avoid hypertriglyceridaemia-associated pancreatitis. The aim of this study was to describe clinically the published cases of hypertriglyceride-associated pancreatitis. A comprehensive search strategy using MEDLINE, Embase and grey literature was conducted (1960 to January 2016) to identify all case reports of isotretinoin-associated pancreatitis and all relevant studies of isotretinoin and triglycerides for any indication (≥ 20 patients). Terms related to isotretinoin, triglycerides and pancreatitis were searched with all available synonyms. Any studies that used isotretinoin and mentioned triglycerides or pancreatitis were searched in full text, where available, for cases of pancreatitis. Studies from all countries and published in any language were included, but Korean and Turkish studies could not be analysed. Two authors independently reviewed the publications to determine eligibility, and for data extraction. In total, 125 papers fulfilled the inclusion criteria and were searched for cases of pancreatitis. Eleven papers with 25 cases of pancreatitis associated with isotretinoin were identified; four of these cases were likely due to hypertriglyceridaemia. Three patients had elevated baseline triglycerides, but no monitoring. Pancreatitis occurred 6 and 7 weeks, and 6 months after initiation of therapy. For the fourth patient who was treated for glioblastoma and died, no detailed clinical information was available. Idiosyncratic pancreatitis associated with isotretinoin is the most frequent pancreatitis on isotretinoin, and patients should be warned about it. Hypertriglyceride-associated pancreatitis is an exceedingly rare adverse event of isotretinoin therapy. Our data cannot give a frequency or risk for either adverse event. Based on the clinical information of the patients available, we conclude that for patients without elevated baseline triglycerides, or risk thereof, monitoring of triglycerides during therapy is of little value.

3 Review Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia. 2016

Benes, Lane B / Bassi, Nikhil S / Davidson, Michael H. ·Department of Medicine, Section of Cardiology. · Department of Medicine, University of Chicago, Chicago, IL, USA. ·Vasc Health Risk Manag · Pubmed #28003756.

ABSTRACT: The 2013 American College of Cardiology/American Heart Association guidelines on cholesterol management placed greater emphasis on statin therapy given the well-established benefits in primary and secondary prevention of cardiovascular disease. Residual risk may remain after statin initiation, in part because of triglyceride-rich lipoprotein cholesterol. Several large trials have failed to show benefit with non-statin cholesterol-lowering medications in the reduction of cardiovascular events. Yet, subgroup analyses showed a benefit in those with hypertriglyceridemia and lower high-density lipoprotein cholesterol level, a high-risk pattern of dyslipidemia. This review discusses the benefits of omega-3 carboxylic acids, a recently approved formulation of omega-3 fatty acid with enhanced bioavailability, in the treatment of dyslipidemia both as monotherapy and combination therapy with a statin.

4 Review Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease. 2016

Toth, Peter P. ·Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Preventive Cardiology, CGH Medical Center, Sterling, IL, USA. ·Vasc Health Risk Manag · Pubmed #27226718.

ABSTRACT: Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels are associated with increased cardiovascular disease (CVD) risk, and severe hypertriglyceridemia (TG levels ≥500 mg/dL [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma TG levels correspond to the sum of the TG content in TG-rich lipoproteins (TRLs; ie, very low-density lipoproteins plus chylomicrons) and their remnants. There remains some uncertainty regarding the direct causal role of TRLs in the progression of atherosclerosis and CVD, with cardiovascular outcome studies of TG-lowering agents, to date, having produced inconsistent results. Although low-density lipoprotein cholesterol (LDL-C) remains the primary treatment target to reduce CVD risk, a number of large-scale epidemiological studies have shown that elevated TG levels are independently associated with increased incidence of cardiovascular events, even in patients treated effectively with statins. Genetic studies have further clarified the causal association between TRLs and CVD. Variants in several key genes involved in TRL metabolism are strongly associated with CVD risk, with the strength of a variant's effect on TG levels correlating with the magnitude of the variant's effect on CVD. TRLs are thought to contribute to the progression of atherosclerosis and CVD via a number of direct and indirect mechanisms. They directly contribute to intimal cholesterol deposition and are also involved in the activation and enhancement of several proinflammatory, proapoptotic, and procoagulant pathways. Evidence suggests that non-high-density lipoprotein cholesterol, the sum of the total cholesterol carried by atherogenic lipoproteins (including LDL, TRL, and TRL remnants), provides a better indication of CVD risk than LDL-C, particularly in patients with hypertriglyceridemia. This article aims to provide an overview of the available epidemiological, clinical, and genetic evidence relating to the atherogenicity of TRLs and their role in the progression of CVD.

5 Review Asparaginase-associated toxicity in children with acute lymphoblastic leukemia. 2016

Hijiya, Nobuko / van der Sluis, Inge M. ·a Division of Hematology/Oncology/Stem Cell Transplant, Ann & Robert H. Lurie Children's Hospital of Chicago and Department of Pediatrics, Feinberg School of Medicine , Northwestern University , Chicago , IL , USA ; · b Department of Pediatric Oncology/Hematology , Erasmus MC-Sophia Children's Hospital , Rotterdam , The Netherlands. ·Leuk Lymphoma · Pubmed #26457414.

ABSTRACT: Asparaginase is an integral component of multiagent chemotherapy regimens for the treatment of children with acute lymphoblastic leukemia. Positive outcomes are seen in patients who are able to complete their entire prescribed course of asparaginase therapy. Toxicities associated with asparaginase use include hypersensitivity (clinical and subclinical), pancreatitis, thrombosis, encephalopathy, and liver dysfunction. Depending on the nature and severity of the toxicity, asparaginase therapy may be altered or discontinued in some patients. Clinical hypersensitivity is the most common asparaginase-associated toxicity requiring treatment discontinuation, occurring in up to 30% of patients receiving Escherichia coli-derived asparaginase. The ability to rapidly identify and manage asparaginase-associated toxicity will help ensure patients receive the maximal benefit from asparaginase therapy. This review will provide an overview of the common toxicities associated with asparaginase use and recommendations for treatment management.

6 Review Hypertriglyceridemia and Cardiovascular Outcomes. 2016

Malhotra, Gurveen / Sethi, Ankur / Arora, Rohit. ·1Department of Internal Medicine, Mount Sinai Hospital, Chicago, IL; 2Department of Cardiology, Mount Sinai Hospital, Chicago, IL; and 3Department of Medicine, James Lovell Federal Health Care Center, North Chicago, IL. ·Am J Ther · Pubmed #25415545.

ABSTRACT: Cardiovascular disease, particularly ischemic heart disease, is one of the most common causes of morbidity and mortality in the United States. Atherosclerosis, the root cause of ischemic heart disease, is promoted by risk factors like elevated plasma low-density lipoprotein, low plasma high-density lipoprotein, smoking, hypertension, and diabetes mellitus. Even 66 years after a relation between triglycerides (TG) and cardiovascular disease was first suspected, TGs still continue to be a controversial risk factor and target for therapy. Some previous studies did not show any significant positive relationship between TG and cardiovascular mortality; however, recent meta-analyses found otherwise. The role of elevated TG in patients with low low-density lipoprotein and interventions to lower TG to reduce cardiovascular mortality and morbidity is an area of active research.

7 Review Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease. 2014

Rosenson, Robert S / Davidson, Michael H / Hirsh, Benjamin J / Kathiresan, Sekar / Gaudet, Daniel. ·Mount Sinai Heart, Cardiometabolic Disorders, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: robert.rosenson@mssm.edu. · Division of Cardiology, Pritzker School of Medicine, University of Chicago, Chicago, Illinois. · Mount Sinai Heart, Mount Sinai Hospital, New York, New York. · Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts. · ECOGENE-21 and Lipid Clinic, Department of Medicine, Université de Montreal, Chicoutimi, Quebec, Canada. ·J Am Coll Cardiol · Pubmed #25500239.

ABSTRACT: Triglycerides represent 1 component of a heterogeneous pool of triglyceride-rich lipoproteins (TGRLs). The reliance on triglycerides or TGRLs as cardiovascular disease (CVD) risk biomarkers prompted investigations into therapies that lower plasma triglycerides as a means to reduce CVD events. Genetic studies identified TGRL components and pathways involved in their synthesis and metabolism. We advocate that only a subset of genetic mechanisms regulating TGRLs contribute to the risk of CVD events. This "omic" approach recently resulted in new targets for reducing CVD events.

8 Review Addition of omega-3 carboxylic acids to statin therapy in patients with persistent hypertriglyceridemia. 2014

Davidson, Michael H / Phillips, Alyssa K / Kling, Douglas / Maki, Kevin C. ·Department of Medicine, The University of Chicago, 5841 S. Maryland Avenue, MC 6080, Chicago, IL 60637, USA. ·Expert Rev Cardiovasc Ther · Pubmed #25089906.

ABSTRACT: The incidence of hypertriglyceridemia has grown alongside that of obesity. Statin therapy has been widely recommended for the treatment of dyslipidemias. Omega-3 (OM3) fatty acid concentrates are commonly prescribed concurrently with statins in patients with persistent hypertriglyceridemia for additional lowering of triglyceride and non-HDL cholesterol. The bioavailability of currently available OM3 ethyl ester drugs is limited by their need for hydrolysis by pancreatic lipases, largely stimulated by dietary fat, prior to intestinal absorption. This review will discuss the chemistry, pharmacokinetics and clinical efficacy of a novel OM3 carboxylic acid drug that provides polyunsaturated docosahexaenoic and eicosapentaenoic acids in the free fatty acid form, which is readily absorbed by the intestine. This drug was approved in May 2014 as an adjunct to diet to reduce triglyceride levels in adults with severe (≥500 mg/dl) hypertriglyceridemia.

9 Review Treatment options for the management of hypertriglyceridemia: strategies based on the best-available evidence. 2012

Maki, Kevin C / Bays, Harold E / Dicklin, Mary R. ·Biofortis Clinical Research, 211 E. Lake Street, Addison, IL 60101, USA. Kevin.Maki@mxns.com ·J Clin Lipidol · Pubmed #23009777.

ABSTRACT: A severe elevation in triglycerides (TG; ≥500 mg/dL) increases the risk for pancreatitis. TG levels ≥200 mg/dL are associated with a greater risk of atherosclerotic coronary heart disease (CHD). However, no outcomes trials exist to assess the efficacy of TG lowering for preventing pancreatitis in patients with severe hypertriglyceridemia. Similarly, no completed prospective outcomes trial exists to support or refute a reduction in CHD risk resulting from lipid-altering therapy in patients specifically selected for the presence of hypertriglyceridemia. This review examines the available evidence for the use of statins, omega-3 fatty acids, fibrates, and niacin in the management of hypertriglyceridemic patients. Results from CHD outcomes trials support statins as the first-line lipid-altering drug therapy to reduce CHD in hypercholesterolemic patients, and subgroup analyses suggest statins are efficacious in hypertriglyceridemic patients with fasting TG levels <500 mg/dL. Omega-3 fatty acids and fibrates are reasonable first drug options for patients with TG ≥500 mg/dL and often are used to lower TG levels with the objective of reducing pancreatitis risk, although a statin or niacin may also be reasonable options. Combination lipid drug therapy may be needed to achieve both low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol treatment goals for CHD prevention in patients with elevated TG levels, particularly those with TG ≥500 mg/dL. Additional clinical outcomes data are needed to provide a more evidence-based rationale for clinical lipid management of hypertriglyceridemic patients.

10 Review Management of severe hypertriglyceridemia in the hospital: a review. 2012

Schaefer, Eric W / Leung, Alicia / Kravarusic, Jelena / Stone, Neil J. ·Division of Hospital Medicine, Northwestern University, Chicago, Illinois, USA. eschaefe@nmh.org ·J Hosp Med · Pubmed #22128096.

ABSTRACT: For hospitalists, hypertriglyceridemia (HTG) is more than cardiovascular risk. Severe HTG occurs when serum triglycerides rise above 1000 mg/dL, and it carries a risk of abdominal pain and pancreatitis. The etiology of severe HTG is usually a combination of genetic and secondary factors. A detailed history with attention to family history, medications, and alcohol consumption can often lead to the cause. Physical examination findings may stretch across multiple organ systems. Patients with severe HTG should be admitted to the hospital for aggressive medical therapy if they develop symptoms such as abdominal pain or pancreatitis. Asymptomatic patients with severe HTG who have significant short-term risk for developing symptoms require urgent consultation that may lead to a brief hospitalization to address exacerbating factors. Treatment of severe HTG includes a combination of pharmacologic agents and a restriction on dietary triglyceride intake. If oral medications fail to adequately lower triglyceride levels, intravenous insulin and in rare cases therapeutic plasma exchange may be required. To prevent recurrent severe HTG, the patient should be counseled about adherence to long-term medications and lifestyle changes.

11 Review Novel developments in omega-3 fatty acid-based strategies. 2011

Davidson, Michael H / Kling, Douglas / Maki, Kevin C. ·University of Chicago Pritzker School of Medicine, Chicago, IL 60654, USA. mdavidso@medicine.bsd.uchicago.edu ·Curr Opin Lipidol · Pubmed #21986642.

ABSTRACT: PURPOSE OF REVIEW: Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been attributed with several health benefits, including triglyceride lowering and cardiovascular disease risk reduction. This review focuses on new prescription omega-3 fatty acid products in development and recently published data regarding omega-3 fatty acid effects on arrhythmias, heart failure, and platelet inactivation. RECENT FINDINGS: A free fatty acid form of n-3 PUFA was found to produce a four-fold higher area under the plasma n-3 PUFA curve than prescription omega-3-acid ethyl esters in patients on a low-fat diet. Eicosapentaenoic acid ethyl esters reduced triglyceride without significantly elevating LDL cholesterol in patients with severe hypertriglyceridemia and in those with mixed dyslipidemia. Recent investigations of n-3 PUFA effects on ventricular and atrial arrhythmias, including studies in patients with implanted defibrillators, failed to demonstrate a significant benefit. However, increased fatty fish or n-3 PUFA consumption was associated with a lower rate of hospitalization in heart failure patients. A further important finding was potentiation of the antiplatelet response when n-3 PUFAs were added to aspirin + clopidogrel. SUMMARY: Although n-3 PUFA therapy continues to show promise in the prevention and management of cardiovascular diseases, further research is necessary to more fully elucidate its role in specific disorders.

12 Review Chronic pancreatitis and exocrine insufficiency. 2011

Affronti, John. ·Division of Gastroenterology, Hepatology and Nutrition, Stritch School of Medicine, Loyola University of Chicago, 2160 South First Avenue, Maywood, IL 60153, USA. jaffronti@lumc.edu ·Prim Care · Pubmed #21872095.

ABSTRACT: The evaluation, management, and follow-up of patients with chronic pancreatitis (CP) can be simple, but it can also be complex, so having a good referral network of subspecialists experienced in this field is essential. Identifying the cause of CP requires a systematic review of the many potential causes when the cause is not obvious. The identification of patients with autoimmune CP is particularly important because treatment with steroids may be effective. Alterations in pain or other symptoms in patients with CP should not be attributed to worsening disease before evaluations for complications including malignancy are done.

13 Review Inhibitors of diacylglycerol acyltransferase: a review of 2008 patents. 2010

King, Andrew J / Judd, Andrew S / Souers, Andrew J. ·Global Pharmaceutical Research & Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064, USA. ·Expert Opin Ther Pat · Pubmed #20021283.

ABSTRACT: BACKGROUND: Postprandial hypertriglyceridemia has been identified as a major independent risk factor for future cardiovascular events. Therefore, inhibition of triglyceride synthesis has enormous therapeutic potential in the treatment of metabolic disorders. Diacylglycerol acyltransferase (DGAT) enzymes catalyze the final and only committed step in triglyceride biosynthesis and have thus been identified as potential therapeutic targets to combat human cardio-metabolic diseases. OBJECTIVE/METHOD: Significant interest in DGAT-1 inhibitors has emerged in the last several years. To provide a perspective on the exciting features of this enzyme for targeting metabolic diseases, a summary of the biology and pharmacology surrounding the DGAT enzymes is presented. Following this is a discussion of the various chemotypes that have been disclosed within relevant patent applications published in 2008. Specifically, the similarities and differences of the chemical structures and the biological data that are provided to support the corresponding claims are presented. CONCLUSION: Small molecule and biologic-based DGAT inhibitors have been successfully used for the preclinical validation of DGAT enzymes as targets for the treatment of metabolic diseases. Given the advanced stage in which some of the chemical matter resides, it is expected that DGAT inhibitors will enter the clinic in the coming years.

14 Review Niacin and lipoprotein(a): facts, uncertainties, and clinical considerations. 2008

Scanu, Angelo M / Bamba, Ravi. ·Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA. ascanu@medicine.bsd.uchicago.edu ·Am J Cardiol · Pubmed #18375241.

ABSTRACT: Over the years, niacin has gained recognition as an atheroprotective agent, in part because of its capacity to lower the plasma levels of cholesterol, triglycerides, and very-low- and low-density lipoproteins and to substantially raise high-density lipoprotein. In high doses, niacin has also been reported to lower the plasma level of lipoprotein(a) (Lp[a]). However, the published research on the subject suffers from a lack of uniformity regarding patient selection, drug dose, length of administration, and methods for plasma Lp(a) quantification. In this report, the authors examine the most relevant niacin-related Lp(a) studies and hypothetical mechanisms of drug action, also considering the emerging notion of Lp(a) as a potential proinflammatory entity.

15 Clinical Trial Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia. 2017

Dai Perrard, Xiao-Yuan / Lian, Zeqin / Bobotas, George / Dicklin, Mary R / Maki, Kevin C / Wu, Huaizhu. ·Department of Medicine, Baylor College of Medicine, Houston, TX, USA. · Matinas BioPharma, Inc, Bedminster, NJ, USA. · Midwest Biomedical Research/Center for Metabolic and Cardiovascular Health, Glen Ellyn, IL, USA. · Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA. Electronic address: hwu@bcm.edu. ·J Clin Lipidol · Pubmed #28942094.

ABSTRACT: BACKGROUND: Hypertriglyceridemia increases risk for atherosclerotic cardiovascular disease and may contribute to atherosclerosis by changing circulating monocyte phenotypes. High-dose n-3 polyunsaturated fatty acids reduce blood triglyceride levels. Effects of triglyceride-lowering therapy on monocyte phenotypes are not well known. OBJECTIVE: We examined effects of n-3 polyunsaturated fatty acid treatments (eicosapentaenoic acid [EPA] plus docosapentaenoic acid [MAT9001] vs EPA ethyl esters [EPA-EE]) on monocyte phenotypes in individuals with hypertriglyceridemia. METHODS: Individuals with triglycerides 200 to 400 mg/dL were recruited. Subjects received 2 treatments in randomized order for 14 days each: MAT9001 and EPA-EE, at 4 g/d. At 2 days before the start of, and on the last day of, each treatment, nile red staining for lipids and phenotypes of each monocyte subset were examined by flow cytometry after an overnight fast and postprandially after a high-fat meal. RESULTS: Treatment with MAT9001 or EPA-EE reduced fasting triglyceride levels and decreased proportions of intermediate monocytes. Only MAT9001 decreased postprandial blood triglyceride levels, lowered fasting nile red levels, indicating less lipid in classical and intermediate monocytes, and reduced postprandial CD11c levels on nonclassical monocytes. MAT9001 and EPA-EE each reduced fasting and postprandial CD11c and CD36 levels on classical and intermediate monocytes and postprandial CCR5 levels on intermediate and nonclassical monocytes, with no significant differences between the 2 treatments. CONCLUSIONS: Treatment with MAT9001 in individuals with hypertriglyceridemia reduced fasting nile red staining for lipids in classical and intermediate monocytes. MAT9001 and EPA-EE each improved fasting and postprandial monocyte phenotypes, which could potentially help to protect against atherosclerosis.

16 Clinical Trial A Novel ω-3 Acid Ethyl Ester Formulation Incorporating Advanced Lipid Technologies 2017

Lopez-Toledano, Miguel A / Thorsteinsson, Thorsteinn / Daak, Ahmed / Maki, Kevin C / Johns, Colleen / Rabinowicz, Adrian L / Sancilio, Frederick D. ·Department of Research and Development Sancilio and Company, Inc, Riviera Beach, Florida. Electronic address: mltoledano@sancilio.com. · Department of Research and Development Sancilio and Company, Inc, Riviera Beach, Florida. · Midwest Biomedical Research/Center for Metabolic and Cardiovascular Health, Glen Ellyn, Illinois. ·Clin Ther · Pubmed #28189364.

ABSTRACT: PURPOSE: The US Food and Drug Administration has approved several highly purified ω-3 fatty acid prescription drugs for the treatment of severe hypertriglyceridemia. These differ in the amounts and forms of docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). This study compared the bioavailability of SC401 (1530 mg EPA-ethyl esters [EEs] and DHA-EEs plus Advanced Lipid Technologies METHODS: This was a Phase I, randomized, open-label, single-dose, 2-way crossover study in healthy participants housed from day -3 to day 2 in each treatment period. Blood samples for pharmacokinetic measurements were collected before and after dosing, and safety profile and tolerability were assessed. FINDINGS: In unadjusted analyses, SC401 had 5% lower C IMPLICATIONS: These results indicate that SC401, an ω-3 acid EE formulation containing ALT

17 Clinical Trial Effects of omega-3 carboxylic acids on lipoprotein particles and other cardiovascular risk markers in high-risk statin-treated patients with residual hypertriglyceridemia: a randomized, controlled, double-blind trial. 2015

Dunbar, Richard L / Nicholls, Stephen J / Maki, Kevin C / Roth, Eli M / Orloff, David G / Curcio, Danielle / Johnson, Judith / Kling, Douglas / Davidson, Michael H. ·Division of Translational Medicine & Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, 8046 Maloney Building, Philadelphia, PA, 19104-2699, USA. richard.dunbar@uphs.upenn.edu. · South Australian Health & Medical Research Institute, University of Adelaide, Adelaide, Australia. stephen.nicholls@sahmri.com. · Midwest Center for Metabolic & Cardiovascular Research, Chicago, IL, USA. kmaki@mc-mcr.com. · Sterling Research Group, Cincinnati, OH, USA. eroth@sterlingresearch.org. · Medpace, Inc., Cincinnati, OH, USA. d.orloff@medpace.com. · Omthera Pharmaceuticals, Princeton, NJ, USA. dcurcio319@gmail.com. · Omthera Pharmaceuticals, Princeton, NJ, USA. judithbjohnson@gmail.com. · Omthera Pharmaceuticals, Princeton, NJ, USA. douglaskling@gmail.com. · Omthera Pharmaceuticals, Princeton, NJ, USA. mdavidson@omthera.com. · AstraZeneca, Wilmington, DE, USA. mdavidson@omthera.com. ·Lipids Health Dis · Pubmed #26328624.

ABSTRACT: BACKGROUND: This study examined the effects of a mixture of highly bioavailable omega-3 carboxylic acids (OM3-CA) on nuclear magnetic resonance spectroscopy-assessed lipoprotein particle concentrations and sizes and other cardiovascular risk markers in statin-treated patients with fasting triglycerides (TG) ≥ 2.3 mmol/L (200 mg/dL) and <5.6 mmol/L (500 mg/dL) and at high cardiovascular risk. METHODS: After a diet lead-in and statin-stabilization period, 647 patients were randomly assigned to receive capsules of control (olive oil, OO) 4 g/d, OM3-CA 2 g/d (plus OO 2 g/d), or OM3-CA 4 g/d for 6 weeks. RESULTS: Compared with OO, low-density lipoprotein (LDL) particle size was increased with OM3-CA 2 g/d (p < 0.01) and 4 g/d (p < 0.001), and very low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) particle sizes were decreased with both OM3-CA dosages vs. OO (p < 0.001 and p < 0.05 for VLDL and HDL, respectively). Total VLDL/chylomicron remnant particle concentration was reduced by 8.5 and 16.0 % with OM3-CA 2 and 4 g/d, respectively, vs. a 6.9 % reduction with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Total HDL particle concentration was also reduced by 1.5 and 3.2 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.6 % increase with OO (at least p < 0.05 for both comparisons). Changes in total LDL particle concentration were not significantly different for OO vs. OM3-CA at either dosage. Apolipoprotein (Apo) CIII levels decreased by 7.6 and 13.1 % with OM3-CA 2 and 4 g/d, respectively, vs. 3.2 % with OO (p < 0.001 for OM3-CA 4 g/d vs. OO). Lipoprotein-associated phospholipase A2 (Lp-PLA2) mass was reduced by 6.2 and 10.7 % with OM3-CA 2 and 4 g/d, respectively, vs. a 0.1 % increase with OO (p < 0.001 for both vs. OO). There were no significant differences between treatments in high-sensitivity C-reactive protein responses. CONCLUSION: OM3-CA were associated with shifts in lipoprotein particle sizes and concentrations, and reductions in Apo CIII and Lp-PLA2, in patients with hypertriglyceridemia while taking a statin. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01408303.

18 Article Diabetic Ketoacidosis and the Domino Effect. 2018

Shaikh, Bilal H / Sohaib, Muneebah / Alshantti, Raeda / Barrera, Francisco / Faridi, Farah S / Murvelashvili, Natia. ·Department of Internal Medicine, Presence Saint Francis Hospital, Evanston, IL, USA. ·Am J Case Rep · Pubmed #30413682.

ABSTRACT: BACKGROUND Severe hypertriglyceridemia is a well-known cause of acute pancreatitis. Mild elevations of triglyceride levels are common in patients presenting with diabetic ketoacidosis (DKA). Rarely, DKA can be accompanied by an elevation of serum triglyceride level severe enough to lead to AP. CASE REPORT We report one such case of a young diabetic male who presented with DKA that was complicated by hypertriglyceridemia-induced acute pancreatitis (HTGAP). We were able to treat the condition with a slightly prolonged infusion of intravenous (IV) regular insulin in an efficient and cost-effective manner with a good outcome. CONCLUSIONS From our experience, DKA-associated HTGAP can be rapidly, efficiently, and cost-effectively treated with IV regular insulin and close biochemical monitoring. A high index of suspicion for acute pancreatitis is necessary in patients with DKA, especially with co-existing hypertriglyceridemia; and all efforts should be made to diagnose it in a timely manner to prevent subsequent complications.

19 Article Evaluation of the prognostic value of neutrophil to lymphocyte ratio in patients with hypertriglyceridemia-induced acute pancreatitis. 2017

Wang, Yuchen / Fuentes, Harry E / Attar, Bashar M / Jaiswal, Palash / Demetria, Melchor. ·Department of Internal Medicine, John H Stroger Hospital of Cook County, Chicago, IL, United States. Electronic address: ywang4@cookcountyhhs.org. · Department of Internal Medicine, John H Stroger Hospital of Cook County, Chicago, IL, United States. · Department of Gastroenterology, Rush University Medical Center, Chicago, IL, United States; Division of Gastroenterology and Hepatology, John H Stroger Hospital of Cook County, Chicago, IL, United States. · Division of Gastroenterology and Hepatology, John H Stroger Hospital of Cook County, Chicago, IL, United States. ·Pancreatology · Pubmed #29030078.

ABSTRACT: INTRODUCTION: Recent studies attribute promising prognostic values to various inflammatory biomarkers in acute pancreatitis, including the following: the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and red cell distribution width (RDW). We aimed to determine the performance of these biomarkers for detecting disease severity in patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP). METHODS: We retrospectively reviewed 110 patients with HTG-AP and compared the NLR, PLR, and RDW in different severity groups. We performed receiver-operating characteristic (ROC) analysis to identify the optimal cut-off value for NLR to predict severe AP. RESULTS: NLR was significantly higher in patients with severe AP than mild and moderately severe AP (14.6 vs. 6.9, p < 0.001), and higher with organ failure upon presentation (9.1 vs. 7.1, p = 0.026). After dichotomization by the optimal cut-off value of 10 as determined by the ROC curve, the high-NLR group had a significantly longer length of stay (9.1 vs. 6.6 days, p = 0.001), duration of nil per os (4.9 vs. 3.7 days, p = 0.007), and higher rates of complications, including systemic inflammatory response syndrome (81.5% vs. 44.6%, p = 0.001) and persistent acute kidney injury (25.9% vs. 3.6%, p < 0.001). High NLR independently predicted severe acute pancreatitis in multivariate analysis (Odds ratio 6.71, p = 0.019). CONCLUSION: NLR represents an inexpensive, readily available test with a promising value to predict disease severity in HTG-AP. Among the three inflammatory biomarkers, NLR has the highest discriminatory capacity for severe HTG-AP, with an optimal cut-off value of 10.

20 Article Concurrent Diabetic Ketoacidosis in Hypertriglyceridemia-Induced Pancreatitis: How Does It Affect the Clinical Course and Severity Scores? 2017

Wang, Yuchen / Attar, Bashar M / Hinami, Keiki / Jaiswal, Palashkumar / Yap, John Erikson / Jaiswal, Radhika / Devani, Kalpit / Simons-Linares, Carlos Roberto / Demetria, Melchor V. ·From the *Department of Internal Medicine, John H. Stroger, Jr Hospital of Cook County; †Department of Gastroenterology, Rush University Medical Center; and ‡Division of Gastroenterology and Hepatology and §Collaborative Research Unit, John H. Stroger, Jr Hospital of Cook County, Chicago, IL, ∥Department of Internal Medicine, Long Island Jewish Forest Hills Hospitals, Forest Hills, NY; and ¶Department of Internal Medicine, James J. Quillen College of Medicine, East Tennessee State University, Johnson City, TN. ·Pancreas · Pubmed #28984788.

ABSTRACT: OBJECTIVES: Concurrent diabetic ketoacidosis (DKA) is highly prevalent in patients with hypertriglyceridemia-induced pancreatitis (HP). Diabetic ketoacidosis could potentially complicate the diagnosis, management, and prognosis of HP. This study aimed to directly compare the clinical course of HP with and without DKA and assess the outcomes of frequently used severity-prediction scores in such population. METHODS: We retrospectively analyzed 140 patients with HP; 37 patients (26.4%) had concurrent DKA. We compared epidemiologic characteristics, initial laboratory values, and clinical courses between the DKA and non-DKA groups. Bedside Index for Severity in Acute Pancreatitis score, Sequential Organ Failure Assessment score, Ranson criteria, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Marshall score were calculated and compared between groups. RESULTS: We observed more acute kidney injury in the DKA group. Patients with DKA more likely required intensive care unit admission, received intravenous insulin, and were discharged on subcutaneous insulin. Ranson criteria and APACHE II score were significantly higher with DKA. CONCLUSIONS: Concurrent DKA does not affect length of stay, in-hospital mortality, and readmission rate in patients with HP. Higher Ranson criteria and APACHE II score likely reflected derangement of clinical parameters secondary to DKA rather than true severity of pancreatitis in such population.

21 Article Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides. 2017

Maki, Kevin C / Palacios, Orsolya M / Lindner, Emily / Nieman, Kristin M / Bell, Marjorie / Sorce, Jennifer. ·Midwest Biomedical Research/Center for Metabolic and Cardiovascular Health, Glen Ellyn, IL; and kmaki@mbclinicalresearch.com. · Great Lakes Clinical Trials, Chicago, IL. · Midwest Biomedical Research/Center for Metabolic and Cardiovascular Health, Glen Ellyn, IL; and. ·J Nutr · Pubmed #28515160.


22 Article The burden of familial chylomicronemia syndrome: interim results from the IN-FOCUS study. 2017

Davidson, Michael / Stevenson, Michael / Hsieh, Andrew / Ahmad, Zahid / Crowson, Caroline / Witztum, Joseph L. ·a Department of Medicine , University of Chicago , Chicago , IL , USA. · b Akcea Therapeutics , Cambridge , MA , USA. · c Division of Nutrition and Metabolic Disease, Department of Internal Medicine , University of Texas Southwestern Medical Center , Dallas , TX , USA. · d Trinity Partners , Waltham , MA , USA. · e Department of Medicine, Division of Endocrinology and Metabolism , University of California San Diego , La Jolla , CA , USA. ·Expert Rev Cardiovasc Ther · Pubmed #28338353.

ABSTRACT: BACKGROUND: Familial Chylomicronemia Syndrome (FCS) is a rare genetic disorder that is caused by a decrease or an absence of lipoprotein lipase activity. FCS is characterized by marked accumulation of chylomicrons and extreme hypertriglyceridemia, which have major effects on both physical and mental health. To date, there have been no systematic efforts to characterize the impact of chylomicronemia on FCS patients' lives. In particular, the impact of FCS on the burden of illness (BoI) and quality of life (QoL) has not been fully described in the literature. METHODS: IN-FOCUS was a comprehensive web-based research survey of patients with FCS focused on capturing the BoI and impact on QoL associated with FCS. Sixty patients from the US diagnosed with FCS participated. Patients described multiple symptoms spanning across physical, emotional and cognitive domains. RESULTS: Patients on average cycled through 5 physicians of varying specialty before being diagnosed with FCS, reflecting a lengthy journey to diagnosis Nearly all respondents indicated that FCS had a major impact on BoI and QoL and significantly influenced their career choice and employment status, and caused significant work loss due to their disease. CONCLUSION: FCS imparts a considerable burden across multiple domains with reported impairment on activities of daily living and QoL.

23 Article Bioequivalence Demonstration for Ω-3 Acid Ethyl Ester Formulations: Rationale for Modification of Current Guidance. 2017

Maki, Kevin C / Johns, Colleen / Harris, William S / Puder, Mark / Freedman, Steven D / Thorsteinsson, Thorsteinn / Daak, Ahmed / Rabinowicz, Adrian L / Sancilio, Frederick D. ·Midwest Biomedical Research/Center for Metabolic and Cardiovascular Research and Department of Food Science and Nutrition, Illinois Institute of Technology, Chicago, Illinois. Electronic address: kmaki@mbclinicalresearch.com. · Sancilio and Company, Inc, Riviera Beach, Florida. · Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota; OmegaQuant Analytics, LLC, Sioux Falls, South Dakota. · Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts. · Division of Translational Research and Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. ·Clin Ther · Pubmed #28189365.

ABSTRACT: The US Food and Drug Administration (FDA) draft guidance for establishing bioequivalence (BE) of ω-3 acid ethyl esters (containing both eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA] as ethyl esters), used to treat severe hypertriglyceridemia, recommends the conduct of 2 studies: one with participants in the fasting state and one with participants in the fed state. For the fasting study, the primary measures of BE are baseline-adjusted EPA and DHA levels in total plasma lipids. For the fed study, the primary measures of BE are EPA and DHA ethyl esters in plasma. This guidance differs from that established for icosapent ethyl (EPA ethyl esters) in which the primary measure of BE is baseline-adjusted total EPA in plasma lipids for both the fasting and fed states. The FDA guidance for ω-3 acid ethyl esters is not supported by their physiologic characteristics and triglyceride-lowering mechanisms because EPA and DHA ethyl esters are best characterized as pro-drugs. This article presents an argument for amending the FDA draft guidance for ω-3 acid ethyl esters to use baseline-adjusted EPA and DHA in total plasma lipids as the primary measures of BE for both fasting and fed conditions. This change would harmonize the approaches for demonstration of BE for ω-3 acid ethyl esters and icosapent ethyl (EPA ethyl esters) products for future development programs and is the most physiologically rational approach to BE testing.

24 Article All-Cause and Acute Pancreatitis Health Care Costs in Patients With Severe Hypertriglyceridemia. 2017

Rashid, Nazia / Sharma, Puza P / Scott, Ronald D / Lin, Kathy J / Toth, Peter P. ·From the *Kaiser Permanente, Southern California Region, Drug Information Services, Downey, CA; †US Health Economics & Outcomes Research, Novartis Pharmaceuticals, Corporation, East Hanover, NJ; ‡Southern California Permanente Medical Group, Kaiser Permanente Southern California, West Los Angeles, CA; §CGH Medical Center, Sterling, IL; and ∥Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD. ·Pancreas · Pubmed #27518471.

ABSTRACT: OBJECTIVE: The aim of this study was to assess health care utilization and costs related to acute pancreatitis (AP) in patients with severe hypertriglyceridemia (sHTG) levels. METHODS: Patients with sHTG levels 1000 mg/dL or higher were identified from January 1, 2007, to June 30, 2013. The first identified incident triglyceride level was labeled as index date. All-cause, AP-related health care visits, and mean total all-cause costs in patients with and without AP were compared during 12 months postindex. A generalized linear model regression was used to compare costs while controlling for patient characteristics and comorbidities. RESULTS: Five thousand five hundred fifty sHTG patients were identified, and 5.4% of these patients developed AP during postindex. Patients with AP had significantly (P < 0.05) more all-cause outpatient visits, hospitalizations, longer length of stays during the hospital visits, and emergency department visits versus patients without AP. Mean (SD) unadjusted all-cause health care costs in the 12 months postindex were $25,343 ($33,139) for patients with AP compared with $15,195 ($24,040) for patients with no AP. The regression showed annual all-cause costs were 49.9% higher (P < 0.01) for patients with AP versus without AP. CONCLUSIONS: Patients who developed AP were associated with higher costs; managing patients with sHTG at risk of developing AP may help reduce unnecessary costs.

25 Article The effect of omega-3 carboxylic acids on apolipoprotein CIII-containing lipoproteins in severe hypertriglyceridemia. 2016

Morton, Allyson M / Furtado, Jeremy D / Lee, Jane / Amerine, William / Davidson, Michael H / Sacks, Frank M. ·Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA. · Department of Clinical Development, Marinus Pharmaceuticals, Inc, Radnor, PA, USA. · Department of Medicine, Section of Cardiology, University of Chicago, Chicago, IL, USA. · Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA. Electronic address: fsacks@hsph.harvard.edu. ·J Clin Lipidol · Pubmed #27919362.

ABSTRACT: BACKGROUND: Lipoprotein subspecies containing apoCIII adversely affect cardiovascular disease (CVD) risk; for example, low density lipoprotein (LDL) with apoCIII is a stronger CVD predictor than LDL without apoCIII. The Epanova for Lowering Very High Triglycerides (EVOLVE) trial showed that Epanova (omega-3 carboxylic acids [OM3-CA]) significantly lowered TG and apoCIII but raised LDL-C. However, it is unknown what subspecies of LDL were affected by treatment. OBJECTIVE: To determine how lipoprotein subspecies are affected by omega-3 fatty acid treatment, we studied the effect of OM3-CA on apoCIII concentrations in high density lipoprotein (HDL), LDL, and very low density lipoprotein (VLDL) and on the concentrations of subspecies of HDL, LDL, and VLDL that contain or do not contain apoCIII. METHODS: We analyzed plasma from a subset of subjects from the EVOLVE trial, a 12-week double-blind study of 399 subjects with fasting TG of 500 to 2000 mg/dL who were randomized to OM3-CA 2, 3, or 4 g/d or olive oil (placebo). RESULTS: OM3-CA significantly reduced plasma apoCIII relative to placebo, as well as apoCIII in HDL, and apoCIII in LDL. Treatment did not significantly affect the concentration of LDL with apoCIII, a subspecies highly associated with CVD risk. OM3-CA increased selectively the concentration of LDL that does not contain apoCIII, a subspecies with a weak relation to coronary heart disease. The reduction in apoCIII was associated with plasma increases in eicosapentaenoic acid, docosahexaenoic acid, and arachidonic acid and decreases in linoleic, palmitic, and oleic acids. CONCLUSION: Reduction in apoCIII may be a mechanism for the TG-lowering effects of OM3-CA. The increase in LDL-C seen in the EVOLVE trial may not be associated with increased risk of CVD.