Hypertriglyceridemia: its etiology, effects and treatment

Yuan, G.; Al-Shali, K. Z.; Hegele, R. A.

doi:10.1503/cmaj.060963

Cited by 625Lipid metabolism and disordersLipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and Lipoproteins

Hypertriglyceridemia: its etiology, effects and treatment

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Yuan, G., Al-Shali, K. Z., Hegele, R. A.·2007·Canadian Medical Association Journal

DOI 10.1503/cmaj.060963PMC PMC1839776

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Abstract

Elevated plasma triglyceride concentration is a common biochemical finding, but the evidence for the benefit of treating this lipid disturbance remains less robust than that for treating elevated low-density lipoprotein-cholesterol. Part of the difficulty in the provision of specific recommendations has been the frequent coexistence of elevated triglycerides with other conditions that affect cardiovascular disease risk, such as depressed high-density lipoprotein-cholesterol, obesity, metabolic syndrome, proinflammatory and prothrombotic biomarkers, and type 2 diabetes. Recent investigations of outcomes of cardiovascular disease when medications are used to reduce triglyceride levels suggest that, although a net benefit probably exists, both relative and absolute risk reductions seem underwhelming when compared with the benefit of reducing low-density lipoprotein-cholesterol levels with treatment. However, the totality of evidence suggests that elevated triglyceride levels likely contribute independently to increased risk of cardiovascular disease, although there is no consensus about appropriate target levels. Furthermore, severe hypertriglyceridemia is associated with an increased risk of acute pancreatitis, irrespective of its effect on risk of cardiovascular disease. We review the causes and classification of elevated triglyceride levels, the clinical manifestations of primary hypertriglyceridemia and the management of patients with elevated triglyceride levels.

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Effectiveness of omega-3 fatty acids, routinely used in pharmacologic doses for treatment of severe HTG, has been inconsistent in patients with FCS.
“Effectiveness of omega-3 fatty acids, routinely used in pharmacologic doses for treatment of severe HTG, has been inconsistent in patients with FCS.3,[16][17][18]20”
From Familial chylomicronemia syndrome: Bringing to life dietary recommendations throughout the life span (2018) · cites this paper as [17]
Prescription omega-3 fatty acids (up to 4 grams per day) have shown inconsistent effectiveness as a treatment for HTG in patients with FCS.
“Of note, prescription omega-3 fatty acids (up to 4 grams per day) have shown inconsistent effectiveness as a treatment for HTG in patients with FCS.3,[16][17][18][19]”
From Familial chylomicronemia syndrome: Bringing to life dietary recommendations throughout the life span (2018) · cites this paper as [17]

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Hodis, H. N., Mack, W. J., Krauss, R. M., & Alaupovic, P. (1999) · Clinical Cardiology · doi:10.1002/clc.4960221404 · Cited by 43 · cited 3× · see citing works
“obesity, metabolic syndrome, proinflammatory and prothrombotic biomarkers, and type 2 diabetes mellitus.(2) The increased risk of acute pancreatitis is an additional consideration when a patient’s triglyceride level is very high (typically”
Background
Effect of Rimonabant, a Cannabinoid-1 Receptor Blocker, on Weight and Cardiometabolic Risk Factors in Overweight or Obese Patients. RIO-North America: A Randomized Controlled Trial
Bessesen, D. H. (2007) · Yearbook of Endocrinology · doi:10.1016/s0084-3741(08)70087-8 · Cited by 39 · see citing works
Correction to the FIELD study report
KEECH, A. C., Simes, J. R., Barter, P. J., Best, J. D., Scott, R. S., & Taskinen, M. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69594-9 · Cited by 35 · see citing works
Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review
Pistorius, M.-A. (2006) · Journal des Maladies Vasculaires · doi:10.1016/s0398-0499(06)76553-2 · Cited by 32 · see citing works
Metabolic risk factor profile associated with use of second generation antipsychotics: a cross sectional study in a community mental health centre
Tarricone, I., Casoria, M., Gozzi, B. F., Grieco, D., Menchetti, M., Serretti, A., Ujkaj, M., Pastorelli, F., & Berardi, D. (2006) · BMC Psychiatry · doi:10.1186/1471-244x-6-11 · Cited by 31 · cited 2× · see citing works
“Patients taking second-generation antipsychotics should be monitored regularly (every 8–12 months) for weight gain and changes in fasting plasma glucose and lipoprotein levels.(21)”
Background
Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients. RIO-North America: a randomized controlled trial
Constans, J. (2006) · Journal des Maladies Vasculaires · doi:10.1016/s0398-0499(06)76549-0 · Cited by 30 · see citing works
Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes
Isaac, M. T., & Isaac, M. (2004) · Diabetes Care · doi:10.2337/diacare.27.8.2088 · Cited by 28 · see citing works
Systematic review of lipid lowering for primary prevention of coronary heart disease in diabetes
Gami, A. S., Montori, V. M., Erwin, P. J., Khan, M. A., & Smith, S. A. (2003) · BMJ · doi:10.1136/bmj.326.7388.528 · Cited by 16 · see citing works
Complex Trait Locus Linkage Mapping in Atherosclerosis
Pollex, R. L., & Hegele, R. A. (2005) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000173307.25652.89 · Cited by 16 · cited 1× · see citing works
“A recently defined gene that may be causative for this disorder is USF1, which encodes an upstream stimulatory factor,(5) although several other genes (including APOA5 and APOC3) have been variably claimed as causative.(6) Finally, familial dysbetalipoproteinemia (hyperlipoproteinemia type 3) has a population prevalen…”
Background
Managing diabetic dyslipidaemia—beyond LDL-C:HDL-C and triglycerides
Barter, P. J. (2006) · Atherosclerosis Supplements · doi:10.1016/j.atherosclerosissup.2006.05.003 · Cited by 7 · cited 1× · see citing works
“Thus, enthusiasm for fibrate therapy is lower than that for statins, although selected patients might benefit.(42)”
Background
Gene Therapy for Lipoprotein Lipase Deficiency: Working Toward Clinical Application
Rip, J., Nierman, M. C., Sierts, J. A., Petersen, W., van den Oever, K., van Raalte, D. H., Ross, C. J., Hayden, M. R., Bakker, A. C., Dijkhuizen, P. A., et al. (2005) · Human Gene Therapy · doi:10.1089/hum.2005.16.ft-138 · Cited by 3 · see citing works

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Sorted by citations

Pathophysiology of human visceral obesity: an update
Tchernof, A., & Després, J.-P. (2013) · Physiological Reviews · doi:10.1152/physrev.00033.2011 · Cited by 2,583 · see citing works
“, risk unrelated to its impact on LDL and HDL remodeling), but this issue remains debated (16, 223, 635).”
Background
American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease
Jellinger, P. S., Handelsman, Y., Rosenblit, P. D., Bloomgarden, Z. T., Fonseca, V. A., Garber, A. J., Grunberger, G., Guerin, C. K., Bell, D. S. H., Mechanick, J. I., et al. (2017) · Endocrine Practice · doi:10.4158/ep171764.appgl · Cited by 1,094 · see citing works
The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management
Hegele, R. A., Ginsberg, H. N., Chapman, M. J., Nordestgaard, B. G., Kuivenhoven, J. A., Averna, M., Borén, J., Bruckert, E., Catapano, A. L., Descamps, O. S., et al. (2014) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70191-8 · Cited by 635 · see citing works
The Forgotten Lipids: Triglycerides, Remnant Cholesterol, and Atherosclerotic Cardiovascular Disease Risk
Sandesara, P. B., Virani, S. S., Fazio, S., & Shapiro, M. D. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00184 · Cited by 626 · see citing works
American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis
Jellinger, P. S., Smith, D. A., Mehta, A., Ganda, O. P., Handelsman, Y., Rodbard, H. W., Shepherd, M. D., & Seibel, J. A. (2012) · Endocrine Practice · doi:10.4158/ep.18.s1.1 · Cited by 527 · see citing works
Omega-3 Fatty Acids for the Management of Hypertriglyceridemia: A Science Advisory From the American Heart Association
Skulas-Ray, A. C., Wilson, P. W. F., Harris, W. S., Brinton, E. A., Kris-Etherton, P. M., Richter, C. K., Jacobson, T. A., Engler, M. B., Miller, M., Robinson, J. G., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000709 · Cited by 488 · see citing works
A Modern Approach to Dyslipidemia
Berberich, A. J., & Hegele, R. A. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab037 · Cited by 502 · see citing works
“Clinical features of chylomicronemia include failure to thrive in infants, eruptive xanthomas, lipemia retinalis, hepatosplenomegaly, recurrent abdominal pain, nausea and vomiting, and risk of acute pancreatitis (159, 160) (Table 6).”
BackgroundInfluential
Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia
Johansen, C. T., Wang, J., Lanktree, M. B., Cao, H., McIntyre, A. D., Ban, M. R., Martins, R. A., Kennedy, B. A., Hassell, R. G., Visser, M. E., et al. (2010) · Nature Genetics · doi:10.1038/ng.628 · Cited by 437 · see citing works
“Primary HTG is one such complex polygenic disease, broadly defined by fasting plasma triglyceride concentrations above the ninety-fifth percentil”
Chylomicronaemia–current diagnosis and future therapies
Brahm, A. J., & Hegele, R. A. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2015.26 · Cited by 356 · see citing works
Self-citation
Hypertriglyceridemia and acute pancreatitis
Yang, A. L., & McNabb-Baltar, J. (2020) · Pancreatology · doi:10.1016/j.pan.2020.06.005 · Cited by 333 · see citing works
Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome
Volek, J. S., Fernandez, M. L., Feinman, R. D., & Phinney, S. D. (2008) · Progress in Lipid Research · doi:10.1016/j.plipres.2008.02.003 · Cited by 288 · see citing works
Nonfasting mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis
Pedersen, S. B., Langsted, A., & Nordestgaard, B. G. (2016) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2016.6875 · Cited by 270 · see citing works
Prescription omega-3 fatty acids and their lipid effects: physiologic mechanisms of action and clinical implications
Bays, H., Tighe, A., Sadovsky, R., & Davidson, M. (2008) · Expert Review of Cardiovascular Therapy · doi:10.1586/14779072.6.3.391 · Cited by 271 · see citing works
Genetic determinants of plasma triglycerides
Johansen, C. T., Kathiresan, S., & Hegele, R. A. (2010) · Journal of Lipid Research · doi:10.1194/jlr.r009720 · Cited by 258 · see citing works
Acetyl‐CoA Carboxylase Inhibition Reverses NAFLD and Hepatic Insulin Resistance but Promotes Hypertriglyceridemia in Rodents
Goedeke, L., Bates, J. G., Vatner, D. F., Perry, R. J., Wang, T., Ramírez, R., Li, L., Ellis, M. W., Zhang, D., Wong, K. E., et al. (2018) · Hepatology · doi:10.1002/hep.30097 · Cited by 257 · see citing works
“Hypertriglyceridemia may represent an increase in VLDL-triglyceride production that overcomes peripheral clearance and/or from a decrease in clearance without a compensatory decrease in production.(26) As such, we measured triglyceride secretion in overnight-fasted ACCi-treated rats after injection of Poloxamer 405 to…”
Background
Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the management of dyslipidemia and prevention of cardiovascular disease algorithm - 2020 executive summary
Handelsman, Y., Jellinger, P. S., Guerin, C. K., Bloomgarden, Z. T., Brinton, E. A., Budoff, M. J., Davidson, M. H., Einhorn, D., Fazio, S., Fonseca, V. A., et al. (2020) · Endocrine Practice · doi:10.4158/cs-2020-0490 · Cited by 248 · see citing works
“Severe hypertriglyceridemia (triglycerides >500 mg/dL) increases the risk of acute pancreatitis and chylomicronemia syndrome (1,13).”
Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an "FCS score
Moulin, P., Dufour, R., Averna, M., Arca, M., Cefalù, A. B., Noto, D., D'Erasmo, L., Di Costanzo, A., Marçais, C., Alvarez-Sala Walther, L. A., et al. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.06.814 · Cited by 247 · see citing works
Remnant cholesterol as a cause of ischemic heart disease: Evidence, definition, measurement, atherogenicity, high risk patients, and present and future treatment
Varbo, A., Benn, M., & Nordestgaard, B. G. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2013.11.008 · Cited by 251 · see citing works
“These genetic forms of the chylomicronemia syndrome are rare; however, the more commonly observed forms are caused by the interplay of genetic factors with external factors (Yuan et al., 2007; Gotoda et al., 2012), which are typically poorly controlled diabetes mellitus, excessive alcohol intake, and high estrogen lev…”
Background
Systematic review of hypertriglyceridemia-induced acute pancreatitis: A more virulent etiology?
Carr, R. A., Rejowski, B. J., Cote, G. A., Pitt, H. A., & Zyromski, N. J. (2016) · Pancreatology · doi:10.1016/j.pan.2016.02.011 · Cited by 247 · see citing works
“Hypertriglyceridemia is generally defined as having a fasting serum triglyceride measurement that is increased above the 95th percentile for age and sex [25].”
Background
Pharmacological targeting of the atherogenic dyslipidemia complex: the next frontier in CVD prevention beyond lowering LDL cholesterol
Xiao, C., Dash, S., Morgantini, C., Hegele, R. A., & Lewis, G. F. (2016) · Diabetes · doi:10.2337/db16-0046 · Cited by 212 · see citing works
“, insulin resistance, metabolic syndrome, untreated or poorly controlled diabetes), pregnancy, and certain medications (54).”
BackgroundSelf-citation
Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement
Hegele, R. A., Borén, J., Ginsberg, H. N., Arca, M., Averna, M., Binder, C. J., Calabresi, L., Chapman, M. J., Cuchel, M., von Eckardstein, A., et al. (2020) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(19)30264-5 · Cited by 204 · see citing works
Incidence of pancreatitis, secondary causes, and treatment of patients referred to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective cohort study
Sandhu, S., Al-Sarraf, A., Taraboanta, C., Frohlich, J., & Francis, G. A. (2011) · Lipids in Health and Disease · doi:10.1186/1476-511x-10-157 · Cited by 167 · see citing works
“Insulin resistance and diabetes are associated with an increase in plasma TG for multiple reasons, including reduced insulin-dependent inhibition of lipolysis in adipocytes, increased TG and VLDL production by the liver, and impaired insulin-dependent activation of lipoprotein lipase and hydrolysis of TG-rich lipoprot…”
BackgroundInfluential
Hypertriglyceridemia and acute pancreatitis
Murphy, M. J., Sheng, X., MacDonald, T. M., & Wei, L. (2013) · JAMA Internal Medicine · doi:10.1001/2013.jamainternmed.477 · Cited by 172 · see citing works
“The warning indicated that the products were considered adulterated because DMAA is considered a new dietary ingredient(NDI).(3) NDIs require themanufacturer to submit somedocumentationdemonstrating the expectation of safety.”
Background
Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia
Gaudet, D., Pall, D., Watts, G. F., Nicholls, S. J., Rosenson, R. S., Modesto, K., San Martin, J., Hellawell, J., & Ballantyne, C. M. (2024) · JAMA Cardiology · doi:10.1001/jamacardio.2024.0959 · Cited by 172 · see citing works
Lipid Metabolism, Disorders and Therapeutic Drugs - Review
Vijayakumar, N., & Kim, S. (2021) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2021.122 · Cited by 183 · see citing works
“Because no compelling studies have been published, there is no agreement on when medical therapy should begin (Yuan et al., 2007).”
Background
Grape seed proanthocyanidins correct dyslipidemia associated with a high-fat diet in rats and repress genes controlling lipogenesis and VLDL assembling in liver
Quesada, H., Bas-Prior, J. M. D., Reguera, D. P., Díaz, S., Fernández-Larrea, J., Pinent, M., Arola, L., Salvadó, M. J., & Bladé, C. (2009) · International Journal of Obesity · doi:10.1038/ijo.2009.136 · Cited by 170 · see citing works
Effect of admission hypertriglyceridemia on the episodes of severe acute pancreatitis
Deng, L., Xue, P., Xia, Q., Yang, X.-N., & Wan, M. (2008) · World Journal of Gastroenterology · doi:10.3748/wjg.14.4558 · Cited by 168 · see citing works
Mediterranean-style diet in pregnant women with metabolic risk factors (ESTEEM): A pragmatic multicentre randomised trial
Wattar, B. H. A., Dodds, J. P., Placzek, A., Beresford, L., Spyreli, E., Moore, A. P., Carreras, F. J. G., Austin, F., Murugesu, N., Roseboom, T. J., et al. (2019) · PLoS Medicine · doi:10.1371/journal.pmed.1002857 · Cited by 168 · see citing works
“We employed the cutoff values used to define metabolic risk in the general population because the tests were done in early pregnancy, reflective of the preconception risk status [18].”
Method
Clinical and biochemical features of different molecular etiologies of familial chylomicronemia
Hegele, R. A., Berberich, A. J., Ban, M. R., Wang, J., Digenio, A., Alexander, V. J., D'Erasmo, L., Arca, M., Jones, A., Bruckert, E., et al. (2018) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2018.03.093 · Cited by 165 · see citing works
Serum triglycerides and risk of cardiovascular disease
Boullart, A. C. I., Graaf, J. D., & Stalenhoef, A. F. H. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.10.002 · Cited by 157 · see citing works
Prevalence of Severe (500 to 2,000 mg/dl) Hypertriglyceridemia in United States Adults
Christian, J. B., Bourgeois, N., Snipes, R., & Lowe, K. A. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2010.11.008 · Cited by 155 · see citing works
Hypertriglyceridemia in the genomic era: a new paradigm
Lewis, G. F., Xiao, C., & Hegele, R. A. (2015) · Endocrine Reviews · doi:10.1210/er.2014-1062 · Cited by 152 · see citing works
Self-citation
Hypertriglyceridemia
Berberich, A. J., & Hegele, R. A. (2013) · Nutrients · doi:10.3390/nu5030981 · Cited by 141 · see citing works
“It has been suggested that the pathophysiology of HTG-induced pancreatitis is related to increased activity of exocrine pancreatic lipase, which ectopically mediates hydrolysis of circulating TG within the pancreatic vasculature [1,16].”
BackgroundInfluential
Body mass index and all‐cause mortality among older adults
Cheng, F. W., Gao, X., Mitchell, D. C., Wood, C., Still, C. D., Rolston, D. D. K., & Jensen, G. L. (2016) · Obesity · doi:10.1002/oby.21612 · Cited by 133 · see citing works
“cholesterol <65 or >750 mg/dL, HDL cholesterol <10 or >120 mg/dL, LDL cholesterol <30 or >300 mg/dL, blood glucose <30 or >600 mg/dL, and triglyceride <10 or >2,000 mg/dL (17,21-24).”
Background
National lipid association annual summary of clinical lipidology 2016
Bays, H. E., Jones, P. H., Orringer, C. E., Brown, W. V., & Jacobson, T. A. (2016) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2015.08.002 · Cited by 128 · see citing works
Familial chylomicronemia syndrome: an under‐recognized cause of severe hypertriglyceridaemia
Baass, A., Paquette, M., Bernard, S., & Hegele, R. A. (2020) · Journal of Internal Medicine · doi:10.1111/joim.13016 · Cited by 144 · see citing works
Serum triglycerides and cancer risk in the metabolic syndrome and cancer (Me-Can) collaborative study
Borena, W., Stocks, T., Jönsson, H., Strohmaier, S., Nagel, G., Bjørge, T., Manjer, J., Hallmans, G., Selmer, R. M., Almquist, M., et al. (2010) · Cancer Causes & Control · doi:10.1007/s10552-010-9697-0 · Cited by 131 · see citing works
FoxO1 integrates insulin signaling to VLDL production.
Kamagate, A., & Dong, H. H. (2008) · Cell Cycle · doi:10.4161/cc.7.20.6882 · Cited by 127 · see citing works
Genetic bases of hypertriglyceridemic phenotypes
Johansen, C. T., & Hegele, R. A. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3283471972 · Cited by 127 · see citing works
Familial chylomicronemia syndrome: Bringing to life dietary recommendations throughout the life span
Williams, L., Rhodes, K. S., Karmally, W., Welstead, L. A., Alexander, L., & Sutton, L. (2018) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2018.04.010 · Cited by 125 · see citing works
Update on the molecular biology of dyslipidemias
Ramasamy, I. (2015) · Clinica Chimica Acta · doi:10.1016/j.cca.2015.10.033 · Cited by 126 · see citing works
The FGF21 analog pegozafermin in severe hypertriglyceridemia: a randomized phase 2 trial
Bhatt, D. L., Bays, H. E., Miller, M., Cain, J. E., Wasilewska, K., Andrawis, N. S., Parli, T., Feng, S., Sterling, L., Tseng, L., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02427-z · Cited by 121 · see citing works
Nutraceuticals and Functional Foods in the Management of Hyperlipidemia
Chen, G., Wang, H., Zhang, X., & Yang, S. (2013) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408398.2011.629354 · Cited by 120 · see citing works
“Severe hypertriglyceridemia is also a risk factor for pancreatitis (Yuan et al., 2007) and excessive TGs accumulated in the liver will give rise to fatty liver disease (nonalcoholic steatohepatitis) (Ferre and Foufelle, 2010).”
Background
Severe Hypertriglyceridemia‐Related Acute Pancreatitis
Stefanutti, C., Labbadia, G., & Morozzi, C. (2013) · Therapeutic Apheresis and Dialysis · doi:10.1111/1744-9987.12008 · Cited by 120 · see citing works
The Role of Lipids and Lipoproteins in Atherosclerosis
Linton, M. F., Yancey, P. G., Davies, S. S., Jerome, W. G., Linton, E. F., Song, W., Doran, A. C., & Vickers, K. C. (2015) · Europe PMC (PubMed Central) · Cited by 108 · see citing works
(−)-Epigallocatechin Gallate Suppresses Azoxymethane-Induced Colonic Premalignant Lesions in Male C57BL/KsJ-db/db Mice
Shimizu, M., Shirakami, Y., Sakai, H., Adachi, S., Hata, K., Hirose, Y., Tsurumi, H., Tanaka, T., & Moriwaki, H. (2008) · Cancer Prevention Research · doi:10.1158/1940-6207.capr-08-0045 · Cited by 108 · see citing works
Transient Infantile Hypertriglyceridemia, Fatty Liver, and Hepatic Fibrosis Caused by Mutated GPD1, Encoding Glycerol-3-Phosphate Dehydrogenase 1
Basel‐Vanagaite, L., Zevit, N., Har‐Zahav, A., Guo, L., Parathath, S., Pasmanik‐Chor, M., McIntyre, A. D., Wang, J., Albin‐Kaplanski, A., Hartman, C., et al. (2012) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.11.028 · Cited by 106 · see citing works
The association between the combined oral contraceptive pill and insulin resistance, dysglycemia and dyslipidemia in women with polycystic ovary syndrome: a systematic review and meta-analysis of observational studies
Halperin, I. J., Kumar, S. S., Stroup, D. F., & Laredo, S. (2010) · Human Reproduction · doi:10.1093/humrep/deq301 · Cited by 100 · see citing works
Adipose tissue dysfunction and hypertriglyceridemia: mechanisms and management
van de Woestijne, A. P., Monajemi, H., Kalkhoven, E., & Visseren, F. L. J. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00900.x · Cited by 99 · see citing works
“Although statins reduce plasma triglyceride levels by only 10% to 40% (12), statins are well tolerated and have a well-known beneficial effect on the incidence of cardiovascular events.”
BackgroundInfluential
An increased burden of common and rare lipid-associated risk alleles contributes to the phenotypic spectrum of hypertriglyceridemia
Johansen, C. T., Wang, J., Lanktree, M. B., McIntyre, A. D., Ban, M. R., Martins, R. A., Kennedy, B. A., Hassell, R. G., Visser, M. E., Schwartz, S. M., et al. (2011) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.111.226365 · Cited by 97 · see citing works
Self-citation
Severe Hypertriglyceridemia Influenced by Alcohol (SHIBA)
Bessembinders, K. M., Wielders, J. P. M., & van de Wiel, A. (2011) · Alcohol and Alcoholism · doi:10.1093/alcalc/agq088 · Cited by 95 · see citing works
“Causes of HT are usually divided into primary (genetic) and secondary causes including excessive alcohol use (Brunzell, 2007; Yuan et al., 2007).”
Background
Lipids and Lipid-Processing Pathways in Drug Delivery and Therapeutics
Marković, M., Ben‐Shabat, S., Aponick, A. A., Zimmermann, E. M., & Dahan, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093248 · Cited by 91 · see citing works
“Omega-3 PUFA (4g a day) were shown to decrease the TG levels by 30%, respective of the baseline levels, and can thus be used in the treatment of pancreatitis [31].”
Background
Acute hypertriglyceridaemia in humans increases the triglyceride content and decreases the anti-inflammatory capacity of high density lipoproteins
Patel, S., Puranik, R., Nakhla, S., Lundman, P., Stocker, R., Wang, X., Lambert, G. C., Rye, K.-A., Barter, P. J., Nicholls, S. J., et al. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2008.07.047 · Cited by 92 · see citing works
“[3] Yuan G, Al-Shali KZ, Hegele RA.”
Background
The Importance of Lipoprotein Lipase Regulation in Atherosclerosis
Kumari, A., Kristensen, K. K., Ploug, M., & Winther, A.-M. L. (2021) · Biomedicines · doi:10.3390/biomedicines9070782 · Cited by 95 · see citing works
“A prime focus has been on the role of HDL-C in atherosclerosis and as a potential therapeutic target for treatment of ASCVD.”
BackgroundInfluential
The Hypertension–Diabetes Continuum
Cheung, B. M. Y. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181d26430 · Cited by 88 · see citing works
“The circulating triglyceride concentration is related to adiposity and is increased in insulin resistance and glycemia.(37) In Hong Kong, an SNP in the apolipoprotein A5 gene is associated with higher plasma triglyceride concentrations.”
Background
Primary hypertriglyceridemia in children and adolescents
SHAH, A. S., & Wilson, D. P. (2015) · Journal of clinical lipidology · doi:10.1016/j.jacl.2015.04.004 · Cited by 89 · see citing works
NovelLPLmutations associated with lipoprotein lipase deficiency: two case reports and a literature review
Rahalkar, A. R., Giffen, F., Har, B., Ho, J., Morrison, K. M., Hill, J. S., Wang, J., Hegele, R. A., & JOY, T. R. (2009) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y09-005 · Cited by 86 · see citing works
“3 mmol/L (1000 mg/dL) but may be greater than 20 mmol/L (>1775 mg/dL) (Davignon and Dufour 2007; Yuan et al. 2007).”
BackgroundInfluential
Treatment of hypertriglyceridemia-induced acute pancreatitis with insulin
Coskun, A. K., Erkan, N., Yakan, S., Yıldırım, M., Cartı, E. B., Ucar, D., & Oymacı, E. (2015) · Gastroenterology Review · doi:10.5114/pg.2014.45412 · Cited by 80 · see citing works
“The generated proinflammatory non-esterified free fatty acids further damage pancreatic acinar cells and microvasculature [16].”
Background
Hepatic remnant lipoprotein clearance by heparan sulfate proteoglycans and low-density lipoprotein receptors depend on dietary conditions in mice
Foley, E. M., Gordts, P. L. S. M., Stanford, K. I., Gonzales, J. C., Lawrence, R., Stoddard, N., & Esko, J. D. (2013) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.113.301637 · Cited by 77 · see citing works
Risk factors for development of coronary artery disease in women with systemic lupus erythematosus
GOLDBERG, R. J., UROWITZ, M. B., IBAÑEZ, D., NIKPOUR, M., & GLADMAN, D. D. (2009) · The Journal of Rheumatology · doi:10.3899/jrheum.090011 · Cited by 78 · see citing works
Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet
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Authors: Yuan, G., Al-Shali, K. Z., & Hegele, R. A.
Affiliations: Western University (CA)
Corresponding author: Hegele, R. A.
ORCID: Hegele, R. A.
Venue: Canadian Medical Association Journal
Publisher: CMA Impact Inc.
Published: 2007-04-10
Volume: 176
Issue: 8
Pages: 1113-1120
ISSN: 0820-3946 (ISSN-L)
1488-2329
DOI: 10.1503/cmaj.060963
PMC: PMC1839776
OpenAlex: W1982040758
Cited by: 624
References: 77
Citations by year: 2026: 26 · 2025: 24 · 2024: 42 · 2023: 30 · 2022: 35 · 2021: 36 · 2020: 40 · 2019: 25 · 2018: 31 · 2017: 31 · 2016: 35 · 2015: 35 · 2014: 29 · 2013: 32 · 2012: 35
FWCI: 5.55
Type: journal article
Language: en
Open access: gold
doi.org
Locations: Canadian Medical Association Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Heart and Stroke Foundation of Canada
Genome Canada
Ontario Genomics
Ontario Genomics Institute
Topics: Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: hypertriglyceridemia, triglyceride-lowering therapy, cardiovascular risk, acute pancreatitis, primary hypertriglyceridemia, LDL cholesterol, HDL cholesterol, metabolic syndrome, type 2 diabetes, pro-inflammatory markers
MeSH terms: Hypolipidemic Agents, Clofibric Acid, Coronary Artery Disease, Diet, Humans, Niacin, Pancreatitis, Risk Factors, Triglycerides, Hypertriglyceridemia, Weight Loss, Exercise, Practice Guidelines as Topic, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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Hypertriglyceridemia: its etiology, effects and treatment

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