Hypertriglyceridaemia

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

Last reviewed: 7 Mar 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 US 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 hypertriglyceridaemia only. Olezarsen is not approved in Europe as yet.

See Management: emerging

Original source of update

Hypertriglyceridaemia (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 non-fasting TG 2.0 to 5.6 mmol/L (175-499 mg/dL) and severe HTG as fasting TG ≥5.6 mmol/L (≥500 mg/dL).[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 (>10 mmol/L [>885 mg/dL]) is associated with an increased risk of acute pancreatitis.[3][4]

History and exam

Key diagnostic factors

presence of risk factors
eruptive xanthomas
lipaemia retinalis

Full details

Other diagnostic factors

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

Full details

Risk factors

family history of hyperlipidaemia
high saturated fat diet
high carbohydrate or high glycaemic 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 investigations

1st investigations to order

triglyceride level

Full details

Investigations to consider

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

Full details

Treatment algorithm

ACUTE

chylomicronaemia

ONGOING

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

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

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.

Use of this content is subject to our disclaimer

Hypertriglyceridaemia

FDA approves olezarsen for the treatment of familial chylomicronemia syndrome

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

chylomicronaemia

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

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

Contributors

Authors

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

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Vinaya Simha, MBBS, MD

Disclosures

Differentials

Guidelines

Patient information

Hypertriglyceridaemia

FDA approves olezarsen for the treatment of familial chylomicronemia syndrome

Summary

Definition

History and exam

Diagnostic investigations

Treatment algorithm

Contributors

Authors

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

Disclosures

Acknowledgements

Disclosures

Peer reviewers

Vinaya Simha, MBBS, MD

Disclosures