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Cholesterol  2014 

Severe/Extreme Hypertriglyceridemia and LDL Apheretic Treatment: Review of the Literature, Original Findings

DOI: 10.1155/2014/109263

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Hypertriglyceridemia (HTG) is a feature of numerous metabolic disorders including dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 and can increase the risk of premature coronary artery disease. HTG may also be due to genetic factors (called primary HTG) and particularly the severe/extreme HTG (SEHTG), which is a usually rare genetic disorder. Even rarer are secondary cases of SEHTG caused by autoimmune disease. This review considers the causes of SEHTG, and their management including treatment with low density lipoprotein apheresis and analyzes the original findings. 1. Introduction A positive correlation between high triglycerides (TGs) concentration and coronary heart disease (CHD) has been established in numerous studies [1–11]. Hypertriglyceridemia (HTG) is prevalent in 18.6% of men and 4.2% of women between 16 and 65 years of age. The Adult Treatment Panel (ATP) III guidelines, published 13 years ago [12], described normal TGs concentration <150?mg/dL (<1.6?mmol/L), borderline-high TGs as 150 to 199?mg/dL (1.6–2.2?mmol/L), high TGs as 200 to 499?mg/dL (2.2–5.6?mmol/L), and very high TGs as >500?mg/dL (>5.6?mmol/L). However, severe/extreme hypertriglyceridemia (SEHTG) should be considered when values are greater than 1,000?mg/dL (11.2?mmol/L) because this places individuals at significant increased risk of pancreatitis. With TG values less than 1,000?mg/dL (5.6?mmol/L) one should be focused on the risk of premature CHD [13]. HTG is a feature of numerous metabolic disorders including dyslipidemias, metabolic syndrome, and diabetes mellitus type 2 (DMT2) and can increase the risk of premature CHD [14, 15]. These metabolic disorders may be caused by interactions between genetic and nongenetic factors since those subjects present usually similar clinical features (android type of obesity, ectopic fat deposition, thin arms and legs, increased waist circumference, upper body obesity, and in case of SEHTG eruptive xanthomas) [16, 17]. Visceral fat is considered to behave as ectopic fat deposition. It accumulates TGs in cases when body fat storage exceeds the capacity of fat stores. Furthermore, subjects with HTG usually present insulin resistance, hepatic steatosis, and DMT2. Thus, all the above can be called “hypertriglyceridemic phenotype.” Additionally, several studies (including ours) showed that postprandial HTG is manifested in subjects with hypertriglyceridemic phenotype [18]. HTG may also be due to genetic factors (called primary HTG) and particularly the SEHTG, which is a usually rare genetic disorder. Even rarer are secondary


[1]  J. Válek, V. Brodan, E. Kuhn, and J. Pechar, “Postprandial lipemia and ischemic heart disease,” Cesko-Slovenska Gastroenterologie a Vyziva, vol. 24, no. 2, pp. 74–78, 1970.
[2]  D. W. Barritt, “Alimentary lipaemia in men with coronary artery disease and in controls,” British Medical Journal, vol. 2, no. 4993, pp. 640–644, 1956.
[3]  M. A. Denborough, “Alimentary lipaemia in ischaemic heart disease,” Clinical Science, vol. 25, pp. 115–122, 1963.
[4]  W. R. Harlan Jr. and D. E. Beischer, “Changes in serum lipoproteins after a large fat meal in normal individuals and in patients with ischemic heart disease,” American Heart Journal, vol. 66, no. 1, pp. 61–67, 1963.
[5]  J. R. Patsch, G. Miesenbock, T. Hopferwieser et al., “Relation of triglyceride metabolism and coronary artery disease: studies in the postprandial state,” Arteriosclerosis and Thrombosis, vol. 12, no. 11, pp. 1336–1345, 1992.
[6]  J. R. Moreton, “Atherosclerosis and alimentary hyperlipemia,” Science, vol. 106, no. 2748, pp. 190–191, 1947.
[7]  P. T. Kuo and C. R. Joyner Jr., “Angina pectoris induced by fat ingestion in patients with coronary artery disease; ballistocardiographic and electrocardiographic findings,” The Journal of the American Medical Association, vol. 158, no. 12, pp. 1008–1013, 1955.
[8]  M. J. Albrink and E. B. Man, “Serum triglycerides in coronary artery disease,” Archives of Internal Medicine, vol. 103, pp. 4–8, 1959.
[9]  T. Regan, G. Timmis, M. Gray, et al., “Myocardial oxygen consumption during exercise in fasting and lipemic subjects,” The Journal of Clinical Investigation, vol. 40, pp. 624–630, 1961.
[10]  T. Zsoter, W. M. Fam, and M. Mcgregor, “The effect of lipemia on peripheral blood flow,” Canadian Medical Association journal, vol. 90, pp. 1203–1205, 1964.
[11]  D. B. Zilversmit, “Atherogenesis: a postprandial phenomenon,” Circulation, vol. 60, no. 3, pp. 473–485, 1979.
[12]  J. I. Cleeman, “Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III),” The Journal of the American Medical Association, vol. 285, no. 19, pp. 2486–2497, 2001.
[13]  L. Berglund, J. D. Brunzell, A. C. Goldberg et al., “Evaluation and treatment of hypertriglyceridemia: an endocrine society clinical practice guideline,” Journal of Clinical Endocrinology and Metabolism, vol. 97, no. 9, pp. 2969–2989, 2012.
[14]  G. D. Kolovou, K. K. Anagnostopoulou, and D. V. Cokkinos, “Pathophysiology of dyslipidaemia in the metabolic syndrome,” Postgraduate Medical Journal, vol. 81, no. 956, pp. 358–366, 2005.
[15]  G. D. Kolovou, K. K. Anagnostopoulou, P. M. Kostakou, H. Bilianou, and D. P. Mikhailidis, “Primary and secondary hypertriglyceridaemia,” Current Drug Targets, vol. 10, no. 4, pp. 336–343, 2009.
[16]  N. J. Switzer, H. S. Mangat, and S. Karmali, “Current trends in obesity: body composition assessment, weight regulation, and emerging techniques in managing severe obesity,” Journal of Interventional Gastroenterology, vol. 3, pp. 34–36, 2013.
[17]  A. Viljoen and A. S. Wierzbicki, “Diagnosis and treatment of severe hypertriglyceridemia,” Expert Review of Cardiovascular Therapy, vol. 10, no. 4, pp. 505–514, 2012.
[18]  G. D. Kolovou, K. K. Anagnostopoulou, A. N. Pavlidis et al., “Metabolic syndrome and gender differences in postprandial lipaemia,” European Journal of Cardiovascular Prevention and Rehabilitation, vol. 13, no. 4, pp. 661–664, 2006.
[19]  E. Zerem, G. Imamovi?, A. Su?i?, and B. Hara?i?, “Step-up approach to infected necrotising pancreatitis: a 20-year experience of percutaneous drainage in a single centre,” Digestive and Liver Disease, vol. 43, no. 6, pp. 478–483, 2011.
[20]  F. Anderson, S. R. Thomson, D. L. Clarke, and I. Buccimazza, “Dyslipidaemic pancreatitis clinical assessment and analysis of disease severity and outcomes,” Pancreatology, vol. 9, no. 3, pp. 252–257, 2009.
[21]  W. Kimura and J. M?ssner, “Role of hypertriglyceridemia in the pathogenesis of experimental acute pancreatitis in rats,” International Journal of Pancreatology, vol. 20, no. 3, pp. 177–184, 1996.
[22]  S. Nielsen and F. Karpe, “Determinants of VLDL-triglycerides production,” Current Opinion in Lipidology, vol. 23, no. 4, pp. 321–326, 2012.
[23]  T. D. Dayspring and G. Pokrywka, “Impact of triglycerides on lipid and lipoprotein biology in women,” Gender Medicine, vol. 7, no. 3, pp. 189–205, 2010.
[24]  M. M. Hussain, S. Fatma, X. Pan, and J. Iqbal, “Intestinal lipoprotein assembly,” Current Opinion in Lipidology, vol. 16, no. 3, pp. 281–285, 2005.
[25]  J. Iqbal and M. M. Hussain, “Intestinal lipid absorbtion,” The American Journal of Physiology—Endocrinology and Metabolism, vol. 296, pp. E1183–E1194, 2009.
[26]  S. Tiwari and S. A. Siddiqi, “Intracellular trafficking and secretion of VLDL,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 32, no. 5, pp. 1079–1086, 2012.
[27]  S.-Q. Xiang, K. Cianflone, D. Kalant, and A. D. Sniderman, “Differential binding of triglyceride-rich lipoproteins to lipoprotein lipase,” Journal of Lipid Research, vol. 40, no. 9, pp. 1655–1663, 1999.
[28]  B. Klop, A. T. D. Rego, and M. C. Cabezas, “Alcohol and plasma triglycerides,” Current Opinion in Lipidology, vol. 24, no. 4, pp. 321–326, 2013.
[29]  J. B. Whitfield, A. C. Heath, P. A. F. Madden, M. L. Pergadia, G. W. Montgomery, and N. G. Martin, “Metabolic and biochemical effects of low-to-moderate alcohol consumption,” Alcoholism: Clinical and Experimental Research, vol. 37, no. 4, pp. 575–586, 2013.
[30]  G. D. Kolovou, K. D. Salpea, K. K. Anagnostopoulou, and D. P. Mikhailidis, “Alcohol use, vascular disease, and lipid-lowering drugs,” Journal of Pharmacology and Experimental Therapeutics, vol. 318, no. 1, pp. 1–7, 2006.
[31]  M. C. Nierman, J. Rip, J. Twisk et al., “Gene therapy for genetic lipoprotein lipase deficiency: from promise to practice,” Netherlands Journal of Medicine, vol. 63, no. 1, pp. 14–19, 2005.
[32]  H. H. Wittrup, A. Tybj?rg-Hansen, and B. G. Nordestgaard, “Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease: a meta-analysis,” Circulation, vol. 99, no. 22, pp. 2901–2907, 1999.
[33]  E. M. M. Ooi, P. H. R. Barrett, D. C. Chan, and G. F. Watts, “Apolipoprotein C-III: understanding an emerging cardiovascular risk factor,” Clinical Science, vol. 114, no. 9-10, pp. 611–624, 2008.
[34]  M. Okubo, M. Ishihara, T. Iwasaki et al., “A novel APOA5 splicing mutation IVS2+1g>a in a Japanese chylomicronemia patient,” Atherosclerosis, vol. 207, no. 1, pp. 24–25, 2009.
[35]  I. Coca-Prieto, P. Valdivielso, G. Olivecrona et al., “Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis,” BMC Gastroenterology, vol. 9, article 46, 2009.
[36]  D. N. Nevin, J. D. Brunzell, and S. S. Deeb, “The LPL gene in individuals with familial combined hyperlipidemia and decreased LPL activity,” Arteriosclerosis and Thrombosis, vol. 14, no. 6, pp. 869–873, 1994.
[37]  M. Rouis, K. A. Dugi, L. Previato et al., “Therapeutic response to medium-chain triglycerides and ω-3 fatty acids in a patient with the familial chylomicronemia syndrome,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 7, pp. 1400–1406, 1997.
[38]  T. Mizushfrna, K. Ochi, N. Matsumura et al., “Prevention of hyperlipidemic acute pancreatitis during pregnancy with medium-chain triglyceride nutritional support,” International Journal of Pancreatology, vol. 23, no. 3, pp. 187–192, 1998.
[39]  M. R. Aryal, N. R. Mainali, S. Gupta, and M. Singla, “Acute pancreatitis owing to very high triglyceride levels treated with insulin and heparin infusion,” BMJ case reports, vol. 2013, 2013.
[40]  M. Miller, N. J. Stone, C. Ballantyne et al., “Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association,” Circulation, vol. 123, no. 20, pp. 2292–2333, 2011.
[41]  W. A. Bailey, E. C. Westman, M. L. Marquart, and J. R. Guyton, “Low glycemic diet for weight loss in hypertriglyceridemic patients attending a lipid clinic,” Journal of Clinical Lipidology, vol. 4, no. 6, pp. 508–514, 2010.
[42]  T. P. Wycherley, L. J. Moran, P. M. Clifton, M. Noakes, and G. D. Brinkworth, “Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials,” The American Journal of Clinical Nutrition, vol. 96, no. 6, pp. 1281–1298, 2012.
[43]  M. I. Maraki, N. Aggelopoulou, N. Christodoulou et al., “Lifestyle intervention leading to moderate weight loss normalizes postprandial triacylglycerolemia despite persisting obesity,” Obesity, vol. 19, no. 5, pp. 968–976, 2011.
[44]  M. Maraki, F. Magkos, N. Christodoulou et al., “One day of moderate energy deficit reduces fasting and postprandial triacylglycerolemia in women: the role of calorie restriction and exercise,” Clinical Nutrition, vol. 29, no. 4, pp. 459–463, 2010.
[45]  H. Büning, “Gene therapy enters the pharma market: the short story of a long journey,” EMBO Molecular Medicine, vol. 5, no. 1, pp. 1–3, 2013.
[46]  A. Hooper and J. Burnett, “Recent developments in the genetics of LDL deficiency,” Current Opinion in Lipidology, vol. 24, no. 2, pp. 111–115, 2013.
[47]  G. Kolovou, G. Hatzigeorgiou, C. Mihas et al., “Changes in lipids and lipoproteins after selective LDL apheresis (7-year experience),” Cholesterol, vol. 2012, Article ID 976578, 5 pages, 2012.
[48]  V. Lamounier-Zepter, C. Look, M. Ehrhart-Bornstein, S. R. Bornstein, S. Fischer, and U. Julius, “Lipoprotein apheresis reduces adipocyte fatty acid-binding protein serum levels,” Atherosclerosis Supplements, vol. 14, no. 1, pp. 129–134, 2013.
[49]  L. J. Dr?ger, U. Julius, K. Kraenzle et al., “DALI—the first human whole-blood low-density lipoprotein and lipoprotein (a) apheresis system in clinical use: procedure and clinical results,” European Journal of Clinical Investigation, vol. 28, no. 12, pp. 994–1002, 1998.
[50]  D. J. Betteridge, M. Bakowski, K. G. Taylor, J. P. Reckless, S. R. de Silva, and D. J. Galton, “Treatment of severe diabetic hypertriglyceridaemia by plasma exchange,” The Lancet, vol. 1, no. 8078, p. 1368, 1978.
[51]  S. B. Iskandar and K. E. Olive, “Plasmapheresis as an adjuvant therapy for hypertriglyceridemia-induced pancreatitis,” The American Journal of the Medical Sciences, vol. 328, no. 5, pp. 290–294, 2004.
[52]  C. Stefanutti, S. di Giacomo, A. Vivenzio et al., “Therapeutic plasma exchange in patients with severe hypertriglyceridemia: a multicenter study,” Artificial Organs, vol. 33, no. 12, pp. 1096–1102, 2009.
[53]  T. Furuya, M. Komatsu, K. Takahashi et al., “Plasma exchange for hypertriglyceridemic acute necrotizing pancreatitis: report of two cases,” Therapeutic Apheresis, vol. 6, no. 6, pp. 454–458, 2002.
[54]  T. Bosch, B. Schmidt, M. Blumenstein, and H.-J. Gurland, “Lipid apheresis by hemoperfusion: in vitro efficacy and ex vivo biocompatibility of a new low-density lipoprotein adsorber compatible with human whole blood,” Artificial Organs, vol. 17, no. 7, pp. 640–652, 1993.
[55]  T. Bosch, “Direct adsorption of lipoproteins from whole blood by DALI apheresis: technique and effects,” Therapeutic Apheresis, vol. 5, no. 4, pp. 239–243, 2001.
[56]  T. Bosch, S. Gahr, U. Belschner, C. Schaefer, A. Lennertz, and J. Rammo, “Direct adsorption of low-density lipoprotein by DALI-LDL-apheresis: results of a prospective long-term multicenter follow-up covering 12 291 sessions,” Therapeutic Apheresis and Dialysis, vol. 10, no. 3, pp. 210–218, 2006.
[57]  V. Otto and A. Sch?n, “The DALI system,” Artificial Organs, vol. 24, no. 11, pp. 919–920, 2000.
[58]  T. Bosch, O. Heinemann, C. Duhr et al., “Effect of low-dose citrate anticoagulation on the clinical safety and efficacy of direct adsorption of lipoproteins (DALI apheresis) in hypercholesterolemic patients: a prospective controlled clinical trial,” Artificial Organs, vol. 24, no. 10, pp. 790–796, 2000.
[59]  M. Jansen, S. Banyai, S. Schmaldienst et al., “Direct adsorption of lipoproteins (DALI) from whole blood: first long- term clinical experience with a new LDL-apheresis system for the treatment of familial hypercholesterolaemia,” Wiener Klinische Wochenschrift, vol. 112, no. 2, pp. 61–69, 2000.
[60]  T. Bosch, A. Lennertz, B. Kordes, and W. Samtleben, “Low density lipoprotein hemoperfusion by direct adsorption of lipoproteins from whole blood (DALI apheresis): clinical experience from a single center,” Therapeutic Apheresis, vol. 3, no. 3, pp. 209–213, 1999.
[61]  C. Stefanutti, S. Di Giacomo, M. Di Caro, A. Vivenzio, and A. Musca, “DALI low-density lipoprotein apheresis in homozygous and heterozygous familial hypercholesterolemic patients using low-dose citrate anticoagulation,” Therapeutic Apheresis, vol. 5, no. 5, pp. 364–371, 2001.
[62]  A. Ramírez-Bueno, C. Salazar-Ramírez, F. Cota-Delgado, M. V. De La Torre-Prados, and P. Valdivielso, “Plasmapheresis as treatment for hyperlipidemic pancreatitis,” European Journal of Internal Medicine, vol. 25, no. 2, pp. 160–163, 2014.
[63]  F. S. C. L. de Castro, A. M. R. Nascimento, I. A. Coutinho, F. R. de Fernandez Y Alcazar, and J. M. Filho, “Plasmapheresis as a therapeutic approach for hypertriglyceridemia-induced acute pancreatitis,” Revista Brasileira de Terapia Intensiva, vol. 24, no. 3, pp. 302–307, 2012.
[64]  N. G. Maher and H. Ramaswamykanive, “Use of plasmapheresis in managing the diagnostic dilemma of symptomatic hypertriglyceridemia,” Case Reports in Gastrointestinal Medicine, vol. 2012, Article ID 501373, 3 pages, 2012.
[65]  N. Ewald and H. U. Kloer, “Treatment options for severe hypertriglyceridemia (SHTG): the role of apheresis,” Clinical Research in Cardiology Supplements, vol. 7, supplement 1, pp. 31–35, 2012.
[66]  J.-H. Yeh, J.-H. Chen, and H.-C. Chiu, “Plasmapheresis for hyperlipidemic pancreatitis,” Journal of Clinical Apheresis, vol. 18, no. 4, pp. 181–185, 2003.
[67]  D. Altun, G. Eren, Z. Cukurova, O. Hergünsel, and L. Yasar, “An alternative treatment in hypertriglyceridemia-induced acute pancreatitis in pregnancy: plasmapheresis,” Journal of Anaesthesiology Clinical Pharmacology, vol. 28, no. 2, pp. 252–254, 2012.
[68]  R. Basar, A. K. Uzum, B. Canbaz et al., “Therapeutic apheresis for severe hypertriglyceridemia in pregnancy,” Archives of Gynecology and Obstetrics, vol. 287, no. 5, pp. 839–843, 2013.
[69]  P. Reper, R. Attou, L. Gucciardo, P. Gottignies, J. Devriendt, and J. Massaut, “Early plasmapheresis as a successful treatment in hypertriglyceridemia-induced acute pancreatitis in first trimester pregnancy following in vitro fertilization,” European Journal of Obstetrics Gynecology and Reproductive Biology, vol. 179, pp. 257–258, 2014.
[70]  L. Vandenbroucke, S. Seconda, L. Lassel, G. Le Bouar, and P. Poulain, “Acute pancreatitis induced by major hypertriglyceridemia during pregnancy. A case report,” Journal de Gynecologie Obstetrique et Biologie de la Reproduction, vol. 38, no. 5, pp. 436–439, 2009.
[71]  J. Niro, V. Sapin, J. M. Constantin et al., “Management of gestational hypertriglyceridemia by plasmapheresis,” Gynecologie Obstetrique Fertilite, vol. 35, no. 11, pp. 1133–1135, 2007.
[72]  V. Exbrayat, J. Morel, J.-P. De Filippis, G. Tourne, R. Jospe, and C. Auboyer, “Hypertriglycideraemia-induced pancreatitis in pregnancy. A case report,” Annales Francaises d'Anesthesie et de Reanimation, vol. 26, no. 7-8, pp. 677–679, 2007.
[73]  M. Madhra, R. M. Noh, N. N. Zammitt, A. W. Patrick, and C. D. B. Love, “A complicated pregnancy in a patient with lipodystrophic diabetes attributable to a peroxisome proliferator-activated receptor gamma (PPARG) mutation,” Diabetic Medicine, vol. 29, no. 10, pp. e398–e401, 2012.
[74]  J.-P. Routy, G. H. R. Smith, D. W. Blank, and B. M. Gilfix, “Plasmapheresis in the treatment of an acute pancreatitis due to protease inhibitor-induced hypertriglyceridemia,” Journal of Clinical Apheresis, vol. 16, no. 3, pp. 157–159, 2001.
[75]  W. J. Flynn, P. G. Freeman, and L. G. Wickboldt, “Pancreatitis associated with isotretinoin-induced hypertriglyceridemia,” Annals of Internal Medicine, vol. 107, no. 1, article 63, 1987.
[76]  J. Seah, K. Lin, D. Tai, S. T. Lim, and A. Chan, “Conservative management of L-asparaginase-induced hypertriglyceridemia in an adult patient: a case report and review of the literature,” Onkologie, vol. 35, no. 10, pp. 596–598, 2012.
[77]  E.-C. Zborovszky, L. Santana-Cabrera, A. Ramírez Rodríguez, and C. Díaz Mendoza, “Plasmapheresis in the treatment of an acute pancreatitis due to hypertriglyceridemia,” Medicina Clinica, vol. 142, no. 6, p. 282, 2014.
[78]  C. Stefanutti, S. Di Giacomo, and G. Labbadia, “Timing clinical events in the treatment of pancreatitis and hypertriglyceridemia with therapeutic plasmapheresis,” Transfusion and Apheresis Science, vol. 45, no. 1, pp. 3–7, 2011.
[79]  F. Anderson, S. Z. Mbatha, and S. R. Thomson, “The early management of pancreatitis associated with hypertriglyceridaemia,” South African Journal of Surgery, vol. 49, no. 2, pp. 82–84, 2011.
[80]  J. Schwartz, J. L. Winters, A. Padmanabhan et al., “Guidelines on the use of therapeutic apheresis in clinical practice—evidence-based approach from the writing committee of the american society for apheresis: the sixth special issue,” Journal of Clinical Apheresis, vol. 28, no. 3, pp. 145–284, 2013.


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