Severe Hypertriglyceridemia

How to Cite This Chapter: Attalla M, Curnew G, Pare G, Cybulska B, Kłosiewicz-Latoszek L, Szostak W. Severe Hypertriglyceridemia. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. Accessed April 16, 2024.
Last Updated: February 2, 2022
Last Reviewed: February 2, 2022
Chapter Information

Etiology and PathogenesisTop

Classification and etiology of severe hypertriglyceridemia (ie, fasting triglyceride [TG] concentrations >10.0 mmol/L):

1) Polygenic hypertriglyceridemia (type V hyperlipoproteinemia according to the Fredrickson classification): A combination of genetic, demographic, and clinical factors. Causes include obesity, diabetes mellitus, untreated hypothyroidism, HIV infection, lipodystrophy, anorexia, Cushing syndrome, sarcoidosis, systemic lupus erythematosus, alcohol consumption, and certain drugs (oral estrogen, glucocorticoids, protease inhibitors, hydrochlorothiazide, nonselective beta-blockers, retinoic acid, tamoxifen, raloxifene, cyclosporine [INN ciclosporin], sirolimus).

2) Familial chylomicronemia syndrome: Genetic (type I hyperlipoproteinemia according to the Fredrickson classification).

Both forms are associated with fasting chylomicronemia and high very low–density lipoprotein (VLDL) levels. However, familial chylomicronemia syndrome tends to be more severe and resistant to treatment. Hypertriglyceridemia has been linked to an increased risk of cardiovascular disease and acute pancreatitis.

Clinical Features and DiagnosisTop

Clinical symptoms of severe hypertriglyceridemia with the presence of chylomicrons: Abdominal pain, acute pancreatitis.

Biochemical thresholds of hypertriglyceridemia:

1) Normal TG level: <1.7 mmol/L.

2) Borderline high TG level: 1.7 to 2.3 mmol/L.

3) High TG level: 2.3 to 5.6 mmol/L.

4) Very high TG level: >5.6 mmol/L.

A TG level >10.0 mmol/L is considered severely elevated and puts the patients at high risk for developing pancreatitis.

Low-density lipoprotein cholesterol (LDL-C) levels are generally low in hypertriglyceridemia, whereas total cholesterol may be high, depending on the cholesterol content of chylomicrons.

Fasting chylomicronemia is usually accompanied by fasting TG levels >10.0 mmol/L and is never considered normal. Its recognition is usually prompted either by the occurrence of acute pancreatitis or by finding turbid plasma in a fasting patient or high serum TG levels in routine laboratory tests. Genetic testing is usually necessary to distinguish polygenic hypertriglyceridemia from familial chylomicronemia syndrome.


The main goal of treatment is prevention of acute pancreatitis.

1. A very low-fat diet (<10% of daily caloric requirements covered by fats), including both saturated and unsaturated fats. Additionally, reduce the intake of carbohydrates, particularly simple carbohydrates.

2. Abstinence from alcohol.

3. Control of diabetes and weight management.

4. Fibrates (eg, fenofibrate, gemfibrozil) should be used in patients with very high TG levels (Table: Selected Fibrates). We suggest the threshold for treatment of ~5 mmol/L. In patients with a TG concentration ≥10.0 mmol/L (885 mg/dL), starting a fibrate is highly recommended for prevention of pancreatitis.

Contraindications and major adverse effects: see Atherogenic Dyslipidemia.

5. Omega-3 fatty acids: A purified, costly form of omega-3 fatty acid (eicosapentaenoic acid [EPA]) may reduce the risk for developing cardiovascular events and mortality but increases the risk for atrial fibrillation.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Bhatt DL, Steg PG, Miller M, et al; REDUCE-IT Investigators. Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia. N Engl J Med. 2019 Jan 3;380(1):11-22. doi: 10.1056/NEJMoa1812792. Epub 2018 Nov 10. PMID: 30415628. Yokoyama M, Origasa H, Matsuzaki M, et al; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007 Mar 31;369(9567):1090-8. doi: 10.1016/S0140-6736(07)60527-3. Erratum in: Lancet. 2007 Jul 21;370(9583):220. PMID: 17398308. There is no cardiovascular benefit from regular use of over-the-counter omega-3 fatty acids, although they can be effective at decreasing TG levels at a dose of 1 g tid.

6. Statins are not effective at treating hypertriglyceridemia, although patients with hypertriglyceridemia often have coexisting hypercholesterolemia.

7. Nicotinic acid at a dose of up to 3 g/d can have a limited effect on lowering plasma TG levels, increasing high-density lipoprotein cholesterol (HDL-C), and minimally lowering LDL-C concentrations, but its effect is limited by its adverse effect profile, and it is therefore generally not recommended. Adverse effects include flushing, pruritus, paresthesias, and nausea.

Contraindications: Gout, active liver disease, acute myocardial infarction, peptic ulcer disease, pregnancy, breastfeeding, diabetes mellitus (only for crystalline nicotinic acid).


Pancreatitis secondary to hypertriglyceridemia is significantly more severe than pancreatitis due to other etiologies. It is associated with higher risk for developing pancreatic necrosis, pseudocyst, and other complications, as well as with higher mortality.

While patients that develop pancreatitis due to other causes are now encouraged to maintain enteral nutrition, patients with acute pancreatitis secondary to hypertriglyceridemia should abstain from eating and should be advised to only consume water by mouth (see Acute Pancreatitis).

Apheresis can rapidly lower excessively elevated TG levels, but fasting is the most effective aspect of management of acute pancreatitis secondary to hypertriglyceridemia.

After the acute episode resolves, patients should be advised to maintain a very low–fat diet, abstain from alcohol, and start treatment with a fibrate. The risk of repeat pancreatitis is considered minimal when fasting TG levels are maintained at <10.0 mmol/L.


Table 3.12-1. Selected fibrates





400 mg once daily



600 mg bid



48 mg, 145 mg, 54 mg, 160 mg, or 67 mg once daily with main meal


200 mg, 134 mg, 40 mg, 120 mg, 43 mg, 130 mg, 30 mg, 90 mg, 50 mg, or 150 mg once daily with main meal

bid, 2 times a day.

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