Hypertriglyceridemia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 12 Apr 2025

Last updated: 05 Mar 2025

05 Mar 2025

FDA approves olezarsen for the treatment of familial chylomicronemia syndrome

Olezarsen, a ligand conjugated antisense oligonucleotide targeting apo C-III, has been shown to reduce triglyceride (TG) levels by >50% and acute pancreatitis risk by >85% in patients with familial chylomicronemia syndrome (FCS).[71] Olezarsen has been approved by the Food and Drug Administration as an adjunct to diet to reduce TG levels in adults with FCS. Note this indication is for a rare and severely affected subgroup of patients with hypertriglyceridemia only. Olezarsen is not approved in Europe as yet.

See Management: emerging

Original source of update

Hypertriglyceridemia (HTG) can be classified either according to the severity of triglyceride (TG) elevation or whether it is primary or secondary.

Primary HTG is rarely monogenic and typically polygenic in nature; secondary causes of HTG include lifestyle factors, medical conditions, and drugs.

Mild-to-moderate HTG is associated with increased risk of atherosclerotic cardiovascular disease while severe HTG may cause acute pancreatitis.

Treatment begins with lifestyle modification and control of secondary factors.

Additional therapies include statins, fibrates, and prescription omega-3 acids.

Definition

HTG is defined as elevated fasting plasma triglyceride (TG), typically >75th or >95th percentile for age and sex.[1] In the US, the American Heart Association/American College of Cardiology guidelines define moderate HTG as fasting or nonfasting TG 175-499 mg/dL (2.0 to 5.6 mmol/L) and severe HTG as fasting TG ≥500 mg/dL (≥5.6 mmol/L).[2] Other lipoprotein abnormalities are often also present.[3] Patients with HTG have an increased risk of atherosclerotic cardiovascular disease, and a severely elevated TG level (>885 mg/dL [>10 mmol/L]) is associated with an increased risk of acute pancreatitis.[3][4]

History and exam

Key diagnostic factors

eruptive xanthomas
lipemia retinalis

Full details

Other diagnostic factors

increased BMI/waist circumference
lipodystrophy
features of coronary artery disease
claudication
neurologic features
recurrent abdominal pain

Full details

Risk factors

family history of hyperlipidemia
high saturated fat diet
high carbohydrate or high glycemic index diet
excessive alcohol consumption
family or personal history of overweight/obesity
family or personal history of diabetes
insulin resistance
liver disease
renal disease
HIV infection
use of certain drugs
Cushing syndrome
inflammatory/immune disorders
organ transplant
hypothyroidism
pregnancy

Full details

Diagnostic tests

1st tests to order

triglyceride level

Full details

Tests to consider

apolipoprotein B
fasting plasma glucose
BUN, creatinine
urinary albumin/protein
serum albumin
thyroid-stimulating hormone
liver function tests
C-reactive protein

Full details

Treatment algorithm

ACUTE

chylomicronemia

ONGOING

moderate HTG (fasting TG ≥150 mg/dL [≥1.7 mmol/L] or nonfasting TG ≥175 mg/dL [≥2.0 mmol/L] and TG <500 mg/dL [<5.6 mmol/L])

severe HTG (fasting TG ≥500 mg/dL [≥5.6 mmol/L] especially fasting TG ≥1000 mg/dL [≥11.3 mmol/L])

Contributors

Authors

Robert A. Hegele, MD, FRCPC, Cert Endo, FACP, FAHA

Jacob J. Wolfe Distinguished Medical Research Chair

Martha Blackburn Chair in Cardiovascular Research

Distinguished University Professor of Medicine and Biochemistry

University of Western Ontario

London

Ontario

Canada

Disclosures

RAH reports consulting fees from Acasti, Aegerion, Akcea/Ionis, Amgen, Boston Heart, HLS Therapeutics, Novartis, Pfizer, Regeneron, Sanofi and UltraGenyx. RAH is an author of references cited in this topic.

Acknowledgements

Dr Robert A. Hegele would like to gratefully acknowledge Dr David Alexander Leaf, the previous contributor to this topic.

Disclosures

DAL declares that he has no competing interests.

Peer reviewers

Vinaya Simha, MBBS, MD

Associate Professor

Mayo Clinic

Rochester

Disclosures

VS declares that he has no competing interests.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association task force on clinical practice guidelines. Circulation. 2019 Jun 18;139(25):e1082-143.Full text Abstract

Laufs U, Parhofer KG, Ginsberg HN, et al. Clinical review on triglycerides. Eur Heart J. 2020 Jan 1;41(1):99-109c.Full text Abstract

Berglund L, Brunzell JD, Goldberg AC, et al; Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012 Sep;97(9):2969-89.Full text Abstract

Virani SS, Morris PB, Agarwala A, et al. 2021 ACC expert consensus decision pathway on the management of ASCVD risk reduction in patients with persistent hypertriglyceridemia: a report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2021 Aug 31;78(9):960-93.Full text Abstract

Mach F, Baigent C, Catapano AL, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan 1;41(1):111-88.Full text Abstract

Jellinger PS, Handelsman Y, Rosenblit PD, et al. American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017 Apr;23(Suppl 2):1-87.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Diabetes
- Lipodystrophies
- Liver disease
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Guidelines
- Guidelines for the primary prevention of stroke
- Cardiovascular disease: risk assessment and reduction, including lipid modification
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Patient information
High cholesterol
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Hypertriglyceridemia

FDA approves olezarsen for the treatment of familial chylomicronemia syndrome

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests to consider

Treatment algorithm

chylomicronemia

moderate HTG (fasting TG ≥150 mg/dL [≥1.7 mmol/L] or nonfasting TG ≥175 mg/dL [≥2.0 mmol/L] and TG <500 mg/dL [<5.6 mmol/L])

severe HTG (fasting TG ≥500 mg/dL [≥5.6 mmol/L] especially fasting TG ≥1000 mg/dL [≥11.3 mmol/L])

Contributors

Authors

Robert A. Hegele, MD, FRCPC, Cert Endo, FACP, FAHA

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Vinaya Simha, MBBS, MD

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Patient information

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice