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Hypertriglyceridemia: HELP
Articles from Copenhagen
Based on 20 articles published since 2008
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These are the 20 published articles about Hypertriglyceridemia that originated from Copenhagen during 2008-2019.
 
+ Citations + Abstracts
1 Editorial Nonfasting Lipid Profiles: The Way of the Future. 2015

Langsted, Anne / Nordestgaard, Børge G. ·Department of Clinical Biochemistry and the Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. ·Clin Chem · Pubmed #26206883.

ABSTRACT: -- No abstract --

2 Review GPIHBP1 and Plasma Triglyceride Metabolism. 2016

Fong, Loren G / Young, Stephen G / Beigneux, Anne P / Bensadoun, André / Oberer, Monika / Jiang, Haibo / Ploug, Michael. ·Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address: lfong@mednet.ucla.edu. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. Electronic address: sgyoung@mednet.ucla.edu. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. · Division of Nutritional Science, Cornell University, Ithaca, NY 14853, USA. · Institute of Molecular Biosciences, University of Graz and BioTechMed, Graz, Austria. · Centre for Microscopy, Characterisation, and Analysis, The University of Western Australia. · Finsen Laboratory, Rigshospitalet, 2200 Copenhagen N, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, 220 Copenhagen N, Denmark. Electronic address: m-ploug@finsenlab.dk. ·Trends Endocrinol Metab · Pubmed #27185325.

ABSTRACT: GPIHBP1, a GPI-anchored protein in capillary endothelial cells, is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs). GPIHBP1 shuttles lipoprotein lipase (LPL) to its site of action in the capillary lumen and is essential for the margination of TRLs along capillaries - such that lipolytic processing can proceed. GPIHBP1 also reduces the unfolding of the LPL catalytic domain, thereby stabilizing LPL catalytic activity. Many different GPIHBP1 mutations have been identified in patients with severe hypertriglyceridemia (chylomicronemia), the majority of which interfere with folding of the protein and abolish its capacity to bind and transport LPL. The discovery of GPIHBP1 has substantially revised our understanding of intravascular triglyceride metabolism but has also raised many new questions for future research.

3 Review Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease: New Insights From Epidemiology, Genetics, and Biology. 2016

Nordestgaard, Børge G. ·From the Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark; and Institute of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Boerge.Nordestgaard@regionh.dk. ·Circ Res · Pubmed #26892957.

ABSTRACT: Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need to reduce levels to no advice on treatment. New insight in epidemiology now suggests that these lipoproteins, marked by high triglycerides, are strong and independent predictors of ASCVD and all-cause mortality, and that their cholesterol content or remnant cholesterol likewise are strong predictors of ASCVD. Of all adults, 27% have triglycerides >2 mmol/L (176 mg/dL), and 21% have remnant cholesterol >1 mmol/L (39 mg/dL). For individuals in the general population with nonfasting triglycerides of 6.6 mmol/L (580 mg/dL) compared with individuals with levels of 0.8 mmol/L (70 mg/dL), the risks were 5.1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate that triglyceride-rich lipoproteins are causally associated with ASCVD and all-cause mortality. Finally, genetic evidence also demonstrates that high concentrations of triglyceride-rich lipoproteins are causally associated with low-grade inflammation. This suggests that an important part of inflammation in atherosclerosis and ASCVD is because of triglyceride-rich lipoprotein degradation and uptake into macrophage foam cells in the arterial intima. Taken together, new insights now strongly suggest that elevated triglyceride-rich lipoproteins represent causal risk factors for low-grade inflammation, ASCVD, and all-cause mortality.

4 Review Triglycerides and cardiovascular disease. 2014

Nordestgaard, Børge G / Varbo, Anette. ·Department of Clinical Biochemistry and The Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ·Lancet · Pubmed #25131982.

ABSTRACT: After the introduction of statins, clinical emphasis first focussed on LDL cholesterol-lowering, then on the potential for raising HDL cholesterol, with less focus on lowering triglycerides. However, the understanding from genetic studies and negative results from randomised trials that low HDL cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride-lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence as to whether lowering triglycerides reduces the risk of cardiovascular disease.

5 Review The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. 2014

Hegele, Robert A / Ginsberg, Henry N / Chapman, M John / Nordestgaard, Børge G / Kuivenhoven, Jan Albert / Averna, Maurizio / Borén, Jan / Bruckert, Eric / Catapano, Alberico L / Descamps, Olivier S / Hovingh, G Kees / Humphries, Steve E / Kovanen, Petri T / Masana, Luis / Pajukanta, Päivi / Parhofer, Klaus G / Raal, Frederick J / Ray, Kausik K / Santos, Raul D / Stalenhoef, Anton F H / Stroes, Erik / Taskinen, Marja-Riitta / Tybjærg-Hansen, Anne / Watts, Gerald F / Wiklund, Olov / Anonymous2400791. ·Department of Medicine, Western University, London, ON, Canada. Electronic address: hegele@robarts.ca. · Irving Institute for Clinical and Translational Research, Columbia University, New York, NY, USA. · Dyslipidaemia and Atherosclerosis Research Unit, INSERM U939, Pitié-Salpêtrière University Hospital, Paris, France. · Department of Diagnostic Sciences, Herlev Hospital, University of Copenhagen, Denmark. · Department of Molecular Genetics, University Medical Center Groningen, University of Groningen, Netherlands. · Department of Internal Medicine, University of Palermo, Palermo, Italy. · Strategic Research Center, Sahlgrenska Center for Cardiovascular and Metabolic Research, University of Gothenburg, Gothenburg, Sweden. · Department of Endocrinology and Metabolism, Endocrinology and Cardiovascular Disease Prevention, Hôpital Pitié-Salpêtrière, Paris, France. · Department of Pharmacological Sciences, University of Milan and Multimedica IRCSS, Milan, Italy. · Centre de Recherche Médicale, Lipid Clinic, Hopital de Jolimont, Haine Saint-Paul, Belgium. · Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. · Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, London, UK. · Wihuri Research Institute, Helsinki, Finland. · Vascular Medicine and Metabolism Unit, Sant Joan University Hospital, Universitat Rovira & Virgili, IISPV, CIBERDEM, Reus, Spain. · Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. · Department of Endocrinology and Metabolism, University of Munich, Munich, Germany. · Division of Endocrinology and Metabolism, Director of the Carbohydrate and Lipid Metabolism Research Unit, University of the Witwatersrand, Johannesburg, South Africa. · Cardiovascular Sciences Research Centre, St George's Hospital NHS Trust, London, UK. · Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil. · Department of Internal Medicine, Radboud University Medical Center, Nijmegen, Netherlands. · Cardiovascular Research Group, Heart and Lung Centre, Helsinki University Central Hospital and Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. · Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. · School of Medicine and Pharmacology, Royal Perth Hospital Unit, The University of Western Australia, Perth, WA, Australia. · Department of Cardiology, Wallenberg Laboratory, Sahlgrenska University Hospital, Gothenburg, Sweden. ·Lancet Diabetes Endocrinol · Pubmed #24731657.

ABSTRACT: Plasma triglyceride concentration is a biomarker for circulating triglyceride-rich lipoproteins and their metabolic remnants. Common mild-to-moderate hypertriglyceridaemia is typically multigenic, and results from the cumulative burden of common and rare variants in more than 30 genes, as quantified by genetic risk scores. Rare autosomal recessive monogenic hypertriglyceridaemia can result from large-effect mutations in six different genes. Hypertriglyceridaemia is exacerbated by non-genetic factors. On the basis of recent genetic data, we redefine the disorder into two states: severe (triglyceride concentration >10 mmol/L), which is more likely to have a monogenic cause; and mild-to-moderate (triglyceride concentration 2-10 mmol/L). Because of clustering of susceptibility alleles and secondary factors in families, biochemical screening and counselling for family members is essential, but routine genetic testing is not warranted. Treatment includes management of lifestyle and secondary factors, and pharmacotherapy. In severe hypertriglyceridaemia, intervention is indicated because of pancreatitis risk; in mild-to-moderate hypertriglyceridaemia, intervention can be indicated to prevent cardiovascular disease, dependent on triglyceride concentration, concomitant lipoprotein disturbances, and overall cardiovascular risk.

6 Review Clinical relevance of non-fasting and postprandial hypertriglyceridemia and remnant cholesterol. 2011

Nordestgaard, Børge G / Freiberg, Jacob J. ·Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark. brno@heh.regionh.dk ·Curr Vasc Pharmacol · Pubmed #21314630.

ABSTRACT: Non-fasting triglycerides are measured at any time within up to 8 h (14 h) after any normal meal, while postprandial triglycerides are measured at a fixed time point within up to 8 h (14 h) of a standardised fat tolerance test. The simplest possible way of evaluating remnant cholesterol is non-fasting/postprandial total cholesterol minus low-density lipoprotein (LDL) cholesterol minus high-density lipoprotein (HDL) cholesterol. Elevated levels of non-fasting/postprandial triglycerides directly correlate with elevated remnant cholesterol. In the general population, 38% of men have non-fasting/postprandial triglycerides > 2mmol/L (>176 mg/dL) while 45% of men have non-fasting/postprandial triglyceride levels of 1-2 mmol/L (89-176 mg/dL); corresponding fractions in women are 20% and 47%. Also, 31% of men have remnant cholesterol levels > 1mmol/L (>39 mg/dL) while 46% of men have remnant cholesterol levels of 0.5-1 mmol/L (19-39 mg/dL); corresponding fractions in women are 15% and 43%. Non-fasting triglycerides ≥5 mmol/L vs. <1 mmol/L marked a 17 and 5 fold increased risk of myocardial infarction, a 5 and 3 fold increased risk of ischemic stroke, and a 4 and 2 fold increased risk of early death in women and men in the general population. As all cells can degrade triglycerides it is biologically unlikely that it is the triglyceride molecules themselves that cause atherosclerosis and cardiovascular disease. However, elevated remnant cholesterol may lead to cholesterol entrapment in the arterial intima and consequently to accelerated atherosclerosis and cardiovascular disease.

7 Article Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis. 2019

Birrane, Gabriel / Beigneux, Anne P / Dwyer, Brian / Strack-Logue, Bettina / Kristensen, Kristian Kølby / Francone, Omar L / Fong, Loren G / Mertens, Haydyn D T / Pan, Clark Q / Ploug, Michael / Young, Stephen G / Meiyappan, Muthuraman. ·Division of Experimental Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095. · Discovery Therapeutics, US Drug Discovery, Shire Pharmaceuticals, Cambridge, MA 02142. · Finsen Laboratory, Rigshospitalet, DK-2200 Copenhagen, Denmark. · Biotech Research and Innovation Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark. · BIOSAXS Group, European Molecular Biology Laboratory Hamburg, D-22607 Hamburg, Germany. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; sgyoung@mednet.ucla.edu mmeiyappan@shire.com. · Discovery Therapeutics, US Drug Discovery, Shire Pharmaceuticals, Cambridge, MA 02142; sgyoung@mednet.ucla.edu mmeiyappan@shire.com. ·Proc Natl Acad Sci U S A · Pubmed #30559189.

ABSTRACT: Lipoprotein lipase (LPL) is responsible for the intravascular processing of triglyceride-rich lipoproteins. The LPL within capillaries is bound to GPIHBP1, an endothelial cell protein with a three-fingered LU domain and an N-terminal intrinsically disordered acidic domain. Loss-of-function mutations in

8 Article GPIHBP1 autoantibodies in a patient with unexplained chylomicronemia. 2017

Hu, Xuchen / Dallinga-Thie, Geesje M / Hovingh, G Kees / Chang, Sandy Y / Sandoval, Norma P / Dang, Tiffany Ly P / Fukamachi, Isamu / Miyashita, Kazuya / Nakajima, Katsuyuki / Murakami, Masami / Fong, Loren G / Ploug, Michael / Young, Stephen G / Beigneux, Anne P. ·Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. · Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands. · Immuno-Biological Laboratories (IBL) Co, Ltd, Fujioka, Gunma, Japan. · Immuno-Biological Laboratories (IBL) Co, Ltd, Fujioka, Gunma, Japan; Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. · Department of Clinical Laboratory Medicine, Gunma University, Graduate School of Medicine, Maebashi, Japan. · Finsen Laboratory, Rigshospitalet, Copenhagen, Denmark; Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA; Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: sgyoung@mednet.ucla.edu. · Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: abeigneux@mednet.ucla.edu. ·J Clin Lipidol · Pubmed #28666713.

ABSTRACT: BACKGROUND: GPIHBP1, a glycolipid-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) in the interstitial spaces and transports it to the capillary lumen. GPIHBP1 deficiency prevents LPL from reaching the capillary lumen, resulting in low intravascular LPL levels, impaired intravascular triglyceride processing, and severe hypertriglyceridemia (chylomicronemia). A recent study showed that some cases of hypertriglyceridemia are caused by autoantibodies against GPIHBP1 ("GPIHBP1 autoantibody syndrome"). OBJECTIVE: Our objective was to gain additional insights into the frequency of the GPIHBP1 autoantibody syndrome in patients with unexplained chylomicronemia. METHODS: We used enzyme-linked immunosorbent assays to screen for GPIHBP1 autoantibodies in 33 patients with unexplained chylomicronemia and then used Western blots and immunocytochemistry studies to characterize the GPIHBP1 autoantibodies. RESULTS: The plasma of 1 patient, a 36-year-old man with severe hypertriglyceridemia, contained GPIHBP1 autoantibodies. The autoantibodies, which were easily detectable by Western blot, blocked the ability of GPIHBP1 to bind LPL. The plasma levels of LPL mass and activity were low. The patient had no history of autoimmune disease, but his plasma was positive for antinuclear antibodies. CONCLUSIONS: One of 33 patients with unexplained chylomicronemia had the GPIHBP1 autoantibody syndrome. Additional studies in large lipid clinics will be helpful for better defining the frequency of this syndrome and for exploring the best strategies for treatment.

9 Article Hypertriglyceridemia and Pancreatitis-New Evidence That Less Is More-Reply. 2017

Pedersen, Simon B / Langsted, Anne / Nordestgaard, Børge G. ·Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. ·JAMA Intern Med · Pubmed #28460108.

ABSTRACT: -- No abstract --

10 Article Asparaginase-associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia. 2017

Raja, Raheel Altaf / Schmiegelow, Kjeld / Sørensen, Ditte Nørbo / Frandsen, Thomas Leth. ·Department of Pediatrics and Adolescent Medicine, University Hospital Rigshospitalet, Copenhagen, Denmark. · Institute of Clinical Medicine, Faculty of Medicine, University of Copenhagen, Copenhagen, Denmark. · Section of Biostatistics, Department of Public Health, University of Copenhagen, Denmark. ·Pediatr Blood Cancer · Pubmed #27555294.

ABSTRACT: BACKGROUND: l-Asparaginase is an important drug for treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with serious toxicities, including pancreatitis and hypertriglyceridemia (HTG). Asparaginase-associated pancreatitis (AAP) is a common reason for stopping asparaginase treatment. The aim of this study was to explore if HTG or early elevations in pancreatic enzymes were associated with the subsequent development of AAP. METHOD: Children (1.0-17.9 years) diagnosed with ALL, treated with asparaginase for 30 weeks, according to the NOPHO ALL2008 protocol at the University Hospital Rigshospitalet, Copenhagen, Denmark, were eligible. Pancreatic enzymes, triglycerides, and cholesterol were measured regularly. RESULTS: Thirty-one patients were included. Seven patients were diagnosed with AAP. HTG was most evident when PEG-asparaginase and dexamethasone were administered concomitantly. Overall, there was no significant difference in triglyceride levels in patients who experienced AAP and patients who did not. An increase in triglyceride levels during concomitant dexamethasone therapy in delayed intensification was significantly associated with an increase in pancreas-specific amylase levels two weeks later (P = 0.005). CONCLUSIONS: AAP does not seem to be associated with HTG. Continuous monitoring of pancreas enzymes does not predict AAP.

11 Article Nonfasting Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis. 2016

Pedersen, Simon B / Langsted, Anne / Nordestgaard, Børge G. ·Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark3The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark. · Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark2Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark3The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev, Denmark4The Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Frederiksberg, Denmark. ·JAMA Intern Med · Pubmed #27820614.

ABSTRACT: Importance: Severe hypertriglyceridemia is associated with increased risk of acute pancreatitis. However, the threshold above which triglycerides are associated with acute pancreatitis is unclear. Objective: To test the hypothesis that nonfasting mild-to-moderate hypertriglyceridemia (177-885 mg/dL; 2-10 mmol/L) is also associated with acute pancreatitis. Design, Setting, and Participants: This prospective cohort study examines individuals from the Copenhagen General Population Study in 2003 to 2015 and the Copenhagen City Heart Study initiated in 1976 to 1978 with follow-up examinations in 1981 to1983, 1991 to 1994, and in 2001 to 2003. Median follow-up was 6.7 years (interquartile range, 4.0-9.4 years); and includes 116 550 individuals with a triglyceride measurement from the Copenhagen General Population Study (n = 98 649) and the Copenhagen City Heart Study (n = 17 901). All individuals were followed until the occurrence of an event, death, emigration, or end of follow-up (November 2014), whichever came first. Exposures: Plasma levels of nonfasting triglycerides. Main Outcomes and Measures: Hazard ratios (HRs) for acute pancreatitis (n = 434) and myocardial infarction (n = 3942). Results: Overall, 116 550 individuals were included in this study (median [interquartile range] age, 57 [47-66] years). Compared with individuals with plasma triglyceride levels less than 89 mg/dL (<1 mmol/L), the multivariable adjusted HRs for acute pancreatitis were 1.6 (95% CI, 1.0-2.6; 4.3 events/10 000 person-years) for individuals with triglyceride levels of 89 mg/dL to 176 mg/dL (1.00 mmol/L-1.99 mmol/L), 2.3 (95% CI, 1.3-4.0; 5.5 events/10 000 person-years) for 177 mg/dL to 265 mg/dL (2.00 mmol/L-2.99 mmol/L), 2.9 (95% CI, 1.4-5.9; 6.3 events/10 000 person-years) for 366 mg/dL to 353 mg/dL (3.00 mmol/L-3.99 mmol/L), 3.9 (95% CI, 1.5-10.0; 7.5 events/10 000 person-years) for 354 mg/dL-442 mg/dL (4.00 mmol/L-4.99 mmol/L), and 8.7 (95% CI, 3.7-20.0; 12 events/10 000 person-years) for individuals with triglyceride levels greater than or equal to 443 mg/dL (≥5.00 mmol/L) (trend, P = 6 × 10-8). Corresponding HRs for myocardial infarction were 1.6 (95% CI, 1.4-1.9; 41 events/10 000 person-years), 2.2 (95% CI, 1.9-2.7; 57 events/10 000 person-years), 3.2 (95% CI, 2.6-4.1; 72 events/10 000 person-years), 2.8 (95% CI, 2.0-3.9; 68 events/10 000 person-years), and 3.4 (95% CI, 2.4-4.7; 78 events/10 000 person-years) (trend, P = 6 × 10-31), respectively. The multivariable adjusted HR for acute pancreatitis was 1.17 (95% CI, 1.10-1.24) per 89 mg/dL (1 mmol/L) higher triglycerides. When stratified by sex, age, education, smoking, hypertension, statin use, study cohort, diabetes, body mass index (calculated as weight in kilograms divided by height in meters squared), alcohol intake, and gallstone disease, these results were similar with no statistical evidence of interaction. Conclusions and Relevance: Nonfasting mild-to-moderate hypertriglyceridemia from 177 mg/dL (2 mmol/L) and above is associated with high risk of acute pancreatitis, with HR estimates higher than for myocardial infarction.

12 Article Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency. 2016

Rodrigues, Rute / Artieda, Marta / Tejedor, Diego / Martínez, Antonio / Konstantinova, Pavlina / Petry, Harald / Meyer, Christian / Corzo, Deyanira / Sundgreen, Claus / Klor, Hans U / Gouni-Berthold, Ioanna / Westphal, Sabine / Steinhagen-Thiessen, Elisabeth / Julius, Ulrich / Winkler, Karl / Stroes, Erik / Vogt, Anja / Hardt, Phillip / Prophet, Heinrich / Otte, Britta / Nordestgaard, Borge G / Deeb, Samir S / Brunzell, John D. ·Progenika Biopharma, Bizkaia, Spain. Electronic address: rute.rodrigues@grifols.com. · Progenika Biopharma, Bizkaia, Spain. · uniQure NV, Amsterdam, The Netherlands. · Director of the German HITRIG, Third Medical Department and Policlinic, Giessen University Hospital, Justus-Liebig-University of Giessen, Giessen, Germany. · Center for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany. · Institute of Clinical Chemistry, Lipid Clinic, Magdeburg, Germany. · Charité-Universitätsmedizin Berlin, Berlin, Germany. · Universitätsklinikum Carl Gustav Carus an der Technischen Universität, Medizinische Klinik III, Dresden, Germany. · Institute of Clinical Chemistry and Laboratory Medicine and Lipid Outpatient Clinic, University Hospital Freiburg, Freiburg, Germany. · Department of Vascular Medicine, Amsterdam Medical Center/University of Amsterdam, Amsterdam, The Netherlands. · LMU Klinikum der Universität München, Medizinische Klinik und Poliklinik 4, München, Germany. · Gießen and Marburg University Hospital, Giessen, Germany. · Lipidambulanz, Rostock, Germany. · Universitätsklinikum Münster, Medizinische Klinik D, Med. Clinic, Münster, Münster, Germany. · Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. · Department of Medicine (Division of Medical Genetics), University of Washington, Seattle, WA, USA; Department of Genome Sciences, University of Washington, Seattle, WA, USA. · Department of Medicine (Division of Metabolism, Endocrinology and Nutrition), University of Washington, Seattle, WA, USA. ·J Clin Lipidol · Pubmed #27055971.

ABSTRACT: BACKGROUND: Lipoprotein lipase (LPL) deficiency is a serious lipid disorder of severe hypertriglyceridemia (SHTG) with chylomicronemia. A large number of variants in the LPL gene have been reported but their influence on LPL activity and SHTG has not been completely analyzed. Gaining insight into the deleterious effect of the mutations is clinically essential. METHODS: We used gene sequencing followed by in-vivo/in-vitro and in-silico tools for classification. We classified 125 rare LPL mutations in 33 subjects thought to have LPL deficiency and in 314 subjects selected for very SHTG. RESULTS: Of the 33 patients thought to have LPL deficiency, only 13 were homozygous or compound heterozygous for deleterious mutations in the LPL gene. Among the 314 very SHTG patients, 3 were compound heterozygous for pathogenic mutants. In a third group of 51,467 subjects, from a general population, carriers of common variants, Asp9Asn and Asn291Ser, were associated with mild increase in triglyceride levels (11%-35%). CONCLUSION: In total, 39% of patients clinically diagnosed as LPL deficient had 2 deleterious variants. Three patients selected for very SHTG had LPL deficiency. The deleterious mutations associated with LPL deficiency will assist in the diagnosis and selection of patients as candidates for the presently approved LPL gene therapy.

13 Article Do Genetic Factors Modify the Relationship Between Obesity and Hypertriglyceridemia? Findings From the GLACIER and the MDC Studies. 2016

Ali, Ashfaq / Varga, Tibor V / Stojkovic, Ivana A / Schulz, Christina-Alexandra / Hallmans, Göran / Barroso, Inês / Poveda, Alaitz / Renström, Frida / Orho-Melander, Marju / Franks, Paul W. ·From the Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit (A.A., T.V.V., A.P., F.R., P.W.F.) and Department of Clinical Sciences, Diabetes & Cardiovascular Disease-Genetic Epidemiology (I.A.S., C.-A.S., M.O.-M.), Lund University, Malmö, Sweden · Department of Systems Medicine, Steno Diabetes Center, Gentofte, Denmark (A.A.) · Department of Biobank Research (G.H., F.R.) and Department of Public Health & Clinical Medicine (P.W.F.), Umeå University, Umeå, Sweden · Human Genetics Programme, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton (I.B.) · NIHR Cambridge Biomedical Research Centre, Institute of Metabolic Science (I.B.) and University of Cambridge, Metabolic Research Laboratories Institute of Metabolic Science (I.B.), Addenbrooke's Hospital, Cambridge, United Kingdom · Department of Genetics, Physical Anthropology & Animal Physiology, University of the Basque Country (UPV/EHU), Bilbao, Spain (A.P.) · and Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA (P.W.F.). ·Circ Cardiovasc Genet · Pubmed #26865658.

ABSTRACT: BACKGROUND: Obesity is a major risk factor for dyslipidemia, but this relationship is highly variable. Recently published data from 2 Danish cohorts suggest that genetic factors may underlie some of this variability. METHODS AND RESULTS: We tested whether established triglyceride-associated loci modify the relationship of body mass index (BMI) and triglyceride concentrations in 2 Swedish cohorts (the Gene-Lifestyle Interactions and Complex Traits Involved in Elevated Disease Risk [GLACIER Study; N=4312] and the Malmö Diet and Cancer Study [N=5352]). The genetic loci were amalgamated into a weighted genetic risk score (WGRSTG) by summing the triglyceride-elevating alleles (weighted by their established marginal effects) for all loci. Both BMI and the WGRSTG were strongly associated with triglyceride concentrations in GLACIER, with each additional BMI unit (kg/m(2)) associated with 2.8% (P=8.4×10(-84)) higher triglyceride concentration and each additional WGRSTG unit with 2% (P=7.6×10(-48)) higher triglyceride concentration. Each unit of the WGRSTG was associated with 1.5% higher triglyceride concentrations in normal weight and 2.4% higher concentrations in overweight/obese participants (Pinteraction=0.056). Meta-analyses of results from the Swedish cohorts yielded a statistically significant WGRSTG×BMI interaction effect (Pinteraction=6.0×10(-4)), which was strengthened by including data from the Danish cohorts (Pinteraction=6.5×10(-7)). In the meta-analysis of the Swedish cohorts, nominal evidence of a 3-way interaction (WGRSTG×BMI×sex) was observed (Pinteraction=0.03), where the WGRSTG×BMI interaction was only statistically significant in females. Using protein-protein interaction network analyses, we identified molecular interactions and pathways elucidating the metabolic relationships between BMI and triglyceride-associated loci. CONCLUSIONS: Our findings provide evidence that body fatness accentuates the effects of genetic susceptibility variants in hypertriglyceridemia, effects that are most evident in females.

14 Article Unclear effect of fish oil supplementation on adolescent hypertriglyceridemia. 2015

Lauritzen, Lotte / Damsgaard, Camilla Trab. ·University of Copenhagen, Copenhagen, Denmark. ·J Pediatr · Pubmed #25722277.

ABSTRACT: -- No abstract --

15 Article n-3 PUFA esterified to glycerol or as ethyl esters reduce non-fasting plasma triacylglycerol in subjects with hypertriglyceridemia: a randomized trial. 2015

Hedengran, Anne / Szecsi, Pal B / Dyerberg, Jørn / Harris, William S / Stender, Steen. ·Department of Clinical Biochemistry, Copenhagen University Hospital Gentofte, Niels Andersensvej 65, 2900, Hellerup, Denmark, anne.hedengran.nedergaard.02@regionh.dk. ·Lipids · Pubmed #25403919.

ABSTRACT: To date, treatment of hypertriglyceridemia with long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been investigated solely in fasting and postprandial subjects. However, non-fasting triacylglycerols are more strongly associated with risk of cardiovascular disease. The objective of this study was to investigate the effect of long-chain n-3 PUFA on non-fasting triacylglycerol levels and to compare the effects of n-3 PUFA formulated as acylglycerol (AG-PUFA) or ethyl esters (EE-PUFA). The study was a double-blinded randomized placebo-controlled interventional trial, and included 120 subjects with non-fasting plasma triacylglycerol levels of 1.7-5.65 mmol/L (150-500 mg/dL). The participants received approximately 3 g/day of AG-PUFA, EE-PUFA, or placebo for a period of eight weeks. The levels of non-fasting plasma triacylglycerols decreased 28% in the AG-PUFA group and 22% in the EE-PUFA group (P < 0.001 vs. placebo), with no significant difference between the two groups. The triacylglycerol lowering effect was evident after four weeks, and was inversely correlated with the omega-3 index (EPA + DHA content in erythrocyte membranes). The omega-3 index increased 63.2% in the AG-PUFA group and 58.5% in the EE-PUFA group (P < 0.001). Overall, the heart rate in the AG-PUFA group decreased by three beats per minute (P = 0.045). High-density lipoprotein (HDL) cholesterol increased in the AG-PUFA group (P < 0.001). Neither total nor non-HDL cholesterol changed in any group. Lipoprotein-associated phospholipase A2 (LpPLA2) decreased in the EE-PUFA group (P = 0.001). No serious adverse events were observed. Supplementation with long-chain n-3 PUFA lowered non-fasting triacylglycerol levels, suggestive of a reduction in cardiovascular risk. Regardless of the different effects on heart rate, HDL, and LpPLA2 that were observed, compared to placebo, AG-PUFA, and EE-PUFA are equally effective in reducing non-fasting triacylglycerol levels.

16 Article Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: the EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial. 2014

Kastelein, John J P / Maki, Kevin C / Susekov, Andrey / Ezhov, Marat / Nordestgaard, Borge G / Machielse, Ben N / Kling, Douglas / Davidson, Michael H. ·Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands. Electronic address: j.j.kastelein@amc.uva.nl. · Biofortis Clinical Research, Addison, IL, USA. · Russian Cardiology Scientific Production Complex, Federal State University, Moscow, Russian Federation. · Copenhagen University Hospital, University of Copenhagen, Herlev, Denmark. · Omthera Pharmaceuticals, Inc, Princeton, NJ, USA. ·J Clin Lipidol · Pubmed #24528690.

ABSTRACT: BACKGROUND: Omega-3 fatty acids in free fatty acid form have enhanced bioavailability, and plasma levels are less influenced by food than for ethyl ester forms. OBJECTIVE: The aim was to evaluate the safety and lipid-altering efficacy in subjects with severe hypertriglyceridemia of an investigational pharmaceutical omega-3 free fatty acid (OM3-FFA) containing eicosapentaenoic acid and docosahexaenoic acid. METHODS: This was a multinational, double-blind, randomized, out-patient study. Men and women with triglycerides (TGs) ≥ 500 mg/dL, but <2000 mg/dL, took control (olive oil [OO] 4 g/d; n = 99), OM3-FFA 2 g/d (plus OO 2 g/d; n = 100), OM3-FFA 3 g/d (plus OO 1 g/d; n = 101), or OM3-FFA 4 g/d (n = 99) capsules for 12 weeks in combination with the National Cholesterol Education Program Therapeutic Lifestyle Changes diet. RESULTS: Fasting serum TGs changed from baseline by -25.9% (P < .01 vs OO), -25.5% (P < .01 vs OO), and -30.9% (P < .001 vs OO) with 2, 3, and 4 g/d OM3-FFA, respectively, compared with -4.3% with OO. Non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol-to-HDL-C ratio, very low-density lipoprotein cholesterol, remnant-like particle cholesterol, apolipoprotein CIII, lipoprotein-associated phospholipase A2, and arachidonic acid were significantly lowered (P < .05 at each OM3-FFA dosage vs OO); and plasma eicosapentaenoic acid and docosahexaenoic acid were significantly elevated (P < .001 at each OM3-FFA dosage vs OO). With OM3-FFA 2 and 4 g/d (but not 3 g/d), low-density lipoprotein cholesterol was significantly increased compared with OO (P < .05 vs OO). High-sensitivity C-reactive protein responses with OM3-FFA did not differ significantly from the OO response at any dosage. Fewer subjects reported any adverse event with OO vs OM3-FFA, but frequencies across dosage groups were similar. Discontinuation due to adverse event, primarily gastrointestinal, ranged from 5% to 7% across OM3-FFA dosage groups vs 0% for OO. CONCLUSIONS: OM3-FFA achieved the primary end point for TG lowering and secondary end point of non-HDL-C lowering at 2, 3, and 4 g/d in persons with severe hypertriglyceridemia. This trial was registered at www.clinicaltrials.gov as NCT01242527.

17 Article Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. 2013

Jørgensen, Anders Berg / Frikke-Schmidt, Ruth / West, Anders Sode / Grande, Peer / Nordestgaard, Børge G / Tybjærg-Hansen, Anne. ·Department of Clinical Biochemistry KB3011, Section for Molecular Genetics, Rigshospitalet, Copenhagen University Hospitals and Faculty of Health Sciences, University of Copenhagen, Denmark. ·Eur Heart J · Pubmed #23248205.

ABSTRACT: AIMS: Elevated non-fasting triglycerides mark elevated levels of remnant cholesterol. Using a Mendelian randomization approach, we tested whether genetically increased remnant cholesterol in hypertriglyceridaemia due to genetic variation in the apolipoprotein A5 gene (APOA5) associates with an increased risk of myocardial infarction (MI). METHODS AND RESULTS: We resequenced the core promoter and coding regions of APOA5 in individuals with the lowest 1% (n = 95) and highest 2% (n = 190) triglyceride levels in the Copenhagen City Heart Study (CCHS, n = 10 391). Genetic variants which differed in frequency between the two extreme triglyceride groups (c.-1131T > C, S19W, and c.*31C > T; P-value: 0.06 to <0.001), thus suggesting an effect on triglyceride levels, were genotyped in the Copenhagen General Population Study (CGPS), the CCHS, and the Copenhagen Ischemic Heart Disease Study (CIHDS), comprising a total of 5705 MI cases and 54 408 controls. Genotype combinations of these common variants associated with increases in non-fasting triglycerides and calculated remnant cholesterol of, respectively, up to 68% (1.10 mmol/L) and 56% (0.40 mmol/L) (P < 0.001), and with a corresponding odds ratio for MI of 1.87 (95% confidence interval: 1.25-2.81). Using APOA5 genotypes in instrumental variable analysis, the observational hazard ratio for a doubling in non-fasting triglycerides was 1.57 (1.32-2.68) compared with a causal genetic odds ratio of 1.94 (1.40-1.85) (P for comparison = 0.28). For calculated remnant cholesterol, the corresponding values were 1.67(1.38-2.02) observational and 2.23(1.48-3.35) causal (P for comparison = 0.21). CONCLUSION: These data are consistent with a causal association between elevated levels of remnant cholesterol in hypertriglyceridaemia and an increased risk of MI. Limitations include that remnants were not measured directly, and that APOA5 genetic variants may influence other lipoprotein parameters.

18 Article [Extreme levels of hyperlipidaemia as a cause of acute pancreatitis]. 2010

Johansen, Maria Egede / Mattsson, Nick / Larsen, Mogens Lytken. ·Kobenhavn Universitet, Panum Instituttet, Denmark. mariaj@stud.ku.dk ·Ugeskr Laeger · Pubmed #20926048.

ABSTRACT: Hypertriglyceridaemia is an uncommon cause of acute pancreatitis, accounting for 1-4% of cases. In the case of lipoprotein-lipase mutations, lipid levels may rise to extreme levels during acute pancreatitis. In this case a 29-year-old female was hospitalized several times due to acute pancreatitis. She presented with extreme lipid levels and difficulty in blood testing. While the correlation of acute pancreatitis and hyperlipidaemia is known, awareness of its association with defects in lipid metabolism could, in this case, have furthered diagnostic and prevented repeated hospitalizations.

19 Article [Fatal course of a patient during in vitro fertilisation treatment]. 2010

Sørensen, Martin Kryspin / Møller-Sørensen, Hasse / Svane, Christian / Jensen, Carsten Huus / Lange, Kai Henrik Wiborg / Tybjaerg-Hansen, Anne. ·Anaestesi- og Operationsklinikken, HovedOrtoCentret, Rigshospitalet, 2100 København Ø, Denmark. martin@kryspin.dk ·Ugeskr Laeger · Pubmed #20483102.

ABSTRACT: Chylomicronaemia syndrome is a rare disorder primarily caused by a genetic defect which increases triglycerides, combined with a secondary inducing factor. We describe the fatal course of a 33-year-old, pregnant woman with known dyslipidaemia who had been treated with in vitro fertilisation and developed chylomicronaemia syndrome with severe hypertriglyceridaemia, hypertriglyceridaemia-induced acute pancreatitis and septic shock. Appropriate treatment including close monitoring, severe restriction of dietary fat intake and early plasmapheresis is emphasized - especially during pregnancy.

20 Article Fish oil in combination with high or low intakes of linoleic acid lowers plasma triacylglycerols but does not affect other cardiovascular risk markers in healthy men. 2008

Damsgaard, Camilla T / Frøkiaer, Hanne / Andersen, Anders D / Lauritzen, Lotte. ·Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, DK-1958 Frederiksberg C, Denmark. ctd@life.ku.dk ·J Nutr · Pubmed #18492834.

ABSTRACT: Both (n-3) long-chain PUFA (LCPUFA) and linoleic acid [LA, 18:2(n-6)] improve cardiovascular disease (CVD) risk factors, but a high-LA intake may weaken the effect of (n-3) LCPUFA. In a controlled, double-blind, 2 x 2-factorial 8-wk intervention, we investigated whether fish oil combined with a high- or low-LA intake affects overall CVD risk profile. Healthy men (n = 64) were randomized to 5 mL/d fish oil capsules (FO) [mean intake 3.1 g/d (n-3) LCPUFA] or olive oil capsules (control) and to oils and spreads with either a high (S/B) or a low (R/K) LA content, resulting in a 7.3 g/d higher LA intake in the S/B groups than in the R/K groups. Diet, (n-3) LCPUFA in peripheral blood mononuclear cells, blood pressure (BP), heart rate (HR), and plasma CVD risk markers were measured before and after the intervention. FO lowered fasting plasma triacylglycerol (TAG) (P < 0.001) by 51% and 19% in the FO+R/K-group and FO+S/B-group, respectively, which was also reflected in postprandial TAG measured after the intervention (P < 0.01). Although a fat x FO interaction was found for monocyte chemoattractant protein-1, neither the FO nor fat intervention affected fasting plasma cholesterol, glucose, insulin, fibrinogen, C-reactive protein, interleukin-6, vascular cell adhesion molecule-1, P-selectin, oxidized LDL, cluster of differentiation antigen 40 ligand (CD40L), adiponectin, or fasting or postprandial BP or HR after adjustment for body weight changes. In conclusion, neither fish oil supplementation nor the LA intake had immediate pronounced effects on the overall CVD risk profile in healthy men, but fish oil lowered plasma TAG in healthy subjects with initially low concentrations.