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

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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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“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
“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
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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
Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet
Mutungi, G., Waters, D. D., Ratliff, J. C., Puglisi, M. J., Clark, R. M., Volek, J. S., & Fernández, M. L. (2009) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2008.12.011 · Cited by 78
“Similarly, low levels of HDL cholesterol (HDLC) and increased plasma triglycerides (TG) have been associated with CHD risk [2].”
Background
Therapeutic potential of herbal medicine for the management of hyperlipidemia: latest updates
Rauf, A., Akram, M., Anwar, H., Daniyal, M., Munir, N., Bawazeer, S., Bawazeer, S. S., Ребезов, М. Б., Bouyahya, A., Shariati, M. A., et al. (2022) · Environmental Science and Pollution Research · doi:10.1007/s11356-022-19733-7 · Cited by 78
“They also include multiple myeloma, SLE, glycogen storage disease, diabetes mellitus, chronic liver disorder, lipodystrophy, overweight, drug intolerance like beta-blockers, isotretinoin, estrogen, interferons, thiazides, resins, bile acids, glucocorticoids, bexarotene, sirolimus, anabolic steroids and mirtazapine (Yu…”
Background
Consumption of medium- and long-chain triacylglycerols decreases body fat and blood triglyceride in Chinese hypertriglyceridemic subjects
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Emerging Pharmacological Targets for the Treatment of Nonalcoholic Fatty Liver Disease, Insulin Resistance, and Type 2 Diabetes
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Monogenic pediatric dyslipidemias: Classification, genetics and clinical spectrum
Rahalkar, A. R., & Hegele, R. A. (2007) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2007.10.007 · Cited by 77
Therapeutic apheresis for severe hypertriglyceridemia in pregnancy
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“Poorly controlled diabetes mellitus, drugs, nephrotic syndrome, obesity, or heavy alcohol intake are secondary causes of severe hypertriglyceridemia [11].”
Background
Clinical Management of Hypertriglyceridemia in the Prevention of Cardiovascular Disease and Pancreatitis
Hernández, P., Passi, N., Modarressi, T., Kulkarni, V., Soni, M., Burke, F., Bajaj, A., & Soffer, D. E. (2021) · Current Atherosclerosis Reports · doi:10.1007/s11883-021-00962-z · Cited by 77
Severe hypertriglyceridemia and factors associated with acute pancreatitis in an integrated health care system
Rashid, N., Sharma, P. P., Scott, R. D., Lin, K. J., & Toth, P. P. (2016) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2016.02.019 · Cited by 66
High‐Fat Diet Alters Serum Fatty Acid Profiles in Obesity Prone Rats: Implications for InVitro Studies
Cross, T.-W., Heden, T. D., Morris, E. M., Fritsche, K. L., Vieira‐Potter, V. J., & Thyfault, J. P. (2015) · Lipids · doi:10.1007/s11745-015-4061-5 · Cited by 69
“Obesity has been casually linked with elevated circulating lipids including both FFA [6] and TAG [7–9], which correlates strongly with insulin resistance [10].”
Background
Spectrum of Mutations and Long-Term Clinical Outcomes in Genetic Chylomicronemia Syndromes
D’Erasmo, L., Costanzo, A. D., Cassandra, F., Minicocci, I., Polito, L., Montali, A., Ceci, F., & Arca, M. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313401 · Cited by 69
RNA Interference Therapy Targeting Apolipoprotein C-III in Hypertriglyceridemia
Gaudet, D., Clifton, P., Sullivan, D., Baker, J., Schwabe, C., Thackwray, S., Scott, R., Hamilton, J., Given, B., Melquist, S., et al. (2023) · NEJM Evidence · doi:10.1056/evidoa2200325 · Cited by 71
Impact of Fish Oil-Based Lipid Emulsion on Serum Triglyceride, Bilirubin, and Albumin Levels in Children With Parenteral Nutrition-Associated Liver Disease
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“Hypertriglyceridemia, or high plasma triglyceride levels, indicates a physiologic derangement in the balance of fat intake, storage, usage, and excretion, which itself is a marker of poor metabolic homeostasis (13).”
Background
Approach to Hypertriglyceridemia in the Pediatric Population
Valaiyapathi, B., Sunil, B., & Ashraf, A. P. (2017) · Pediatrics in Review · doi:10.1542/pir.2016-0138 · Cited by 68
A Functional Variant in APOA5/A4/C3/A1 Gene Cluster Contributes to Elevated Triglycerides and Severity of CAD by Interfering With MicroRNA 3201 Binding Efficiency
Cui, G., Li, Z., Li, R., Huang, J., Wang, H., Zhang, L., Ding, H., & Wang, D. W. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.03.050 · Cited by 68
“Individuals with HTG were unrelated subjects with a diagnosis of Fredrickson HTG phenotypes (16), defined as having a fasting plasma triglyceride level >10 mmol/l, from a the Department of Clinical Chemistry, Tongji Hospital.”
Novel LMF1 Nonsense Mutation in a Patient with Severe Hypertriglyceridemia
Cefalu, A. B., Noto, D., Arpi, M. L., Yin, F., Spina, R., Hilden, H., Barbagallo, C. M., Carroccio, A., Tarugi, P., Squatrito, S., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0594 · Cited by 65
Ezetimibe-associated adverse effects: what the clinician needs to know
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Hypertriglyceridemia-induced acute pancreatitis treated with insulin and heparin
Twilla, J. D., & Mancell, J. (2012) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp110144 · Cited by 64
Spectrum and Management of Hypertriglyceridemia Among Children in Clinical Practice
Manlhiot, C., Larsson, P., Gurofsky, R. C., Smith, R. W., Fillingham, C., Clarizia, N. A., Chahal, N., Clarke, J., & McCrindle, B. W. (2009) · PEDIATRICS · doi:10.1542/peds.2008-0367 · Cited by 64
Lupin protein compared to casein lowers the LDL cholesterol:HDL cholesterol-ratio of hypercholesterolemic adults
Weiße, K., Brandsch, C., Zernsdorf, B., Nembongwe, G. S. N., Hofmann, K., Eder, K., & Stangl, G. I. (2009) · European Journal of Nutrition · doi:10.1007/s00394-009-0049-3 · Cited by 65
“The participants of our study were under ‘‘uncontrolled’’ nutrition conditions and plasma triglycerides are known to be influenced by a series of dietary factors such as n-3 polyunsaturated fatty acids, refined carbohydrates, trans fatty acids and alcohol [ 23 ].”
Background
Double Filtration Plasma Apheresis Shortens Hospital Admission Duration of Patients With Severe Hypertriglyceridemia-Associated Acute Pancreatitis
Chang, C.-T., Tsai, T., Liao, H.-Y., Chang, C., Jheng, J.-S., Huang, W.-H., Chou, C., & Chen, C. (2015) · Pancreas · doi:10.1097/mpa.0000000000000507 · Cited by 63
“Pharmacologically, fenofibrates, gemfibrozil, niacin, heparin, and insulin are agents used to lower serum triglyceride, whereas nonpharmacologically, therapeutic apheresis has also been implemented for STAP treatment.(3,12) Although the American Society of Apheresis categorized therapeutic apheresis as a class III tre…”
Background
Etiology and risk of lactescent plasma and severe hypertriglyceridemia
Tremblay, K., Méthot, J., Brisson, D., & Gaudet, D. (2010) · Journal of clinical lipidology · doi:10.1016/j.jacl.2010.11.004 · Cited by 63
Medicinal plants in treatment of hypertriglyceridemia: A review based on their mechanisms and effectiveness
Mollazadeh, H., Mahdian, D., & Hosseinzadeh, H. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.09.024 · Cited by 64
APOA5 genetic variants are markers for classic hyperlipoproteinemia phenotypes and hypertriglyceridemia
Wang, J., Ban, M. R., Kennedy, B. A., Anand, S. S., Yusuf, S., Huff, M. W., Pollex, R. L., & Hegele, R. A. (2008) · Nature Clinical Practice Cardiovascular Medicine · doi:10.1038/ncpcardio1326 · Cited by 60
Hypertriglyceridemia: phenomics and genomics
Hegele, R. A., & Pollex, R. L. (2009) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-008-0005-1 · Cited by 60
“DNA mutation Single nucleotide polymorphism Hypertriglyceridemia refers to fasting plasma triglyceride (or triacylglycerol; TG) concentration that is increased typically [95th percentile for age and sex, although additional quantitative or qualitative lipoprotein abnormalities can be present [1].”
BackgroundInfluential
Medium‐ and Long‐Chain Triacylglycerols Reduce Body Fat and Blood Triacylglycerols in Hypertriacylglycerolemic, Overweight but not Obese, Chinese Individuals
Zhang, Y., Liu, Y., Wang, J., Zhang, R., Jing, H., Yu, X., Zhang, Y., Qin, X., Zhang, J., Zheng, Z., et al. (2010) · Lipids · doi:10.1007/s11745-010-3418-z · Cited by 59
“There is a suggestion that choosing the right type of dietary fat could be an effective strategy for preventing weight gain or fat deposition and reducing the blood levels of triacylglycerols (TAG) under an appropriate dietary regimen [3, 5].”
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Association Between Triglycerides and Risk of Dementia in Community-Dwelling Older Adults
Zhou, Z., Ryan, J. L., Tonkin, A. M., Zoungas, S., Lacaze, P. A., Wolfe, R. S., Orchard, S. G., Murray, A. M., McNeil, J. J., Yu, C., et al. (2023) · Neurology · doi:10.1212/wnl.0000000000207923 · Cited by 62
Familial chylomicronemia syndrome: An expert clinical review from the National Lipid Association
Javed, F., Hegele, R. A., Garg, A., Patni, N., Gaudet, D., Williams, L., Khan, M., Li, Q., & Ahmad, Z. (2025) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2025.03.013 · Cited by 60
Fenofibrate-associated nephrotoxicity: A review of current evidence
Attridge, R. L., Frei, C. R., Ryan, L., Koeller, J. M., & Linn, W. D. (2013) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp120131 · Cited by 57
Allelic and phenotypic spectrum of plasma triglycerides
Johansen, C. T., & Hegele, R. A. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2011.10.007 · Cited by 59
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Hypertriglyceridemia and omega-3 fatty acids: Their often overlooked role in cardiovascular disease prevention
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“However, it may also occur as a result of medication use; common culprit agents are corticosteroids, estrogens, tamoxifen, isotretinoin and the cardioselective bblockers [20].”
BackgroundInfluential
Heparan sulfate proteoglycans and triglyceride-rich lipoprotein metabolism
Bishop, J. R., Stanford, K. I., & Esko, J. D. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3282feec2d · Cited by 49
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Hypertriglyceridemia and Atherosclerosis: Using Human Research to Guide Mechanistic Studies in Animal Models
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NMR-determined lipoprotein subclass profile predicts type 2 diabetes
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Metabolic Health Status and the Obesity Paradox in Older Adults
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Hypertriglyceridemia: new approaches in management and treatment
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Current innovations in nutraceuticals and functional foods for intervention of non-alcoholic fatty liver disease
Zhao, M., Chen, S., Ji, X., Shen, X., You, J., Liang, X., Yin, H., & Zhao, L. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105517 · Cited by 50
Intravenous Injection of Apolipoprotein A-V Reconstituted High-Density Lipoprotein Decreases Hypertriglyceridemia in apoav −/− Mice and Requires Glycosylphosphatidylinositol-Anchored High-Density Lipoprotein–Binding Protein 1
Shu, X., Nelbach, L., Weinstein, M. M., Burgess, B. L., Beckstead, J. A., Young, S. G., Ryan, R. O., & Forte, T. M. (2010) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.110.210815 · Cited by 47
“Taken together, the data suggest that the heparin-binding region of apoA-V plays an important role in its capacity to lower TG. Previously, we proposed a mechanism whereby apoA-V could facilitate VLDL metabolism.7 Briefly, under conditions of increased TG, apoA-V exchanges from HDL onto VLDL, which in turn interacts w…”
Background

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 › Cardiology and Cardiovascular Medicine › 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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