Therapeutic approach for patients with HTG1,2
Triglycerides < 10 mmol/l (< 885 mg/dl)
Primary goal:
cardiovascular risk reduction
- Depending on the overall risk, consider further reduction of non-HDL-C
- Consider further LDL-C reduction
Triglycerides ≥ 10 mmol/l (≥ 885 mg/dl)
Primary goal:
prevention of pancreatitis
- TG reduction < 10 mmol/l (885 mg/dl) or below the individual pancreatitis threshold
- Involve lipidologists
C, cholesterol; HDL, high density lipoprotein; LDL, low density lipoproteins
Management of monogenetic severe HTG, familial chylomicronemia
FCS management includes dietary control, pharmacological treatment, and treatment of acute pancreatitis.
Dietary control
Regardless of the cause of moderately or severely high triglyceride levels, dietary control is paramount to maintain plasma triglyceride levels below 11.3 mmol/L (1000 mg/dL) and stave off pancreatitis.3,4
<10–15% daily caloric intake from fat or 15–20 g of fat per day3-6
Limited carbohydrates and simple sugars3,6
Avoid drugs known to increase TG levels such as such as thiazides, beta blockers, and exogenous estrogen3,5
Avoid alcohol3,5,6
Dietary materials
FCS cookbook
The FCS cookbook provides recipes suitable for those following the FCS diet, helping patients to make the dietary changes necessary to maintain optimal health.
Download as PDF
Nutritional brochure
The FCS cookbook contains recipes suitable for those following the FCS diet and aims to support patients in making the changes necessary to maintain good health.
Download as PDFPharmacological treatment
Fibrates, niacine, and omega-3 unsaturated fatty acids have been used alongside a low-fat diet for triglyceride reduction, but a typical patient with FCS is unlikely to respond to these interventions.7,8
- Novel treatments targeting proteins that regulate LPL (Apo C3 and ANGPTL3) are either available or under development, with reported triglyceride level reductions of 50-70%.1,9
For more detailed information on FCS and to learn more about treatment with an antisense oligonucleotide, you can access the Sobi HCP-gated website through the link below:
Treatment of acute pancreatitis
The aim of treating acute pancreatitis is to control the condition and manage symptoms in the hospital setting.
Management principles of hypertriglyceridaemia-induced acute pancreatitis.10
| Intervention | Mechanism of Action | Comments |
|---|---|---|
| Bowel rest, NBM, IVF, Analgesia (Standard of Care) | Pancreatic rest maintains blood flow to the pancreas, reduces chylomicrons and VLDL production, and reduces HTG burden. | Severe pancreatitis may require a prolonged period of fasting; consider post-ligament of Treitz, enteral feeding or parenteral feeding. Consider fat-free/low-fat enteral parenteral feed. Avoid the use of oil-based medication, e.g., Propofol. |
| Insulin Infusion | Activates LPL activity to accelerate chylomicron degredation and lower TG levels. | Continuous insulin infusion. The risk of hypoglycaemia may outweigh any potential benefits in patients without diabetes. Consider if CBG is persistently >10.0 mmol/L. |
| Herparin Infusion | The initial increase in lipoprotein lipase activity converts TG to FFA. | Risk of rebound hypertriglyceridaemia, worsening of lipotoxicity from FFA, and risk of bleeding in pancreatic bed. Not recommended. |
| Lipoprotein apheresis / Plasma exchange | Removes TG and inflammatory cytokines. Provides functional LPL (plasma exchange). | May be considered in SHTG with organ failure, worsening systemic inflammation, or acidosis. However, there is no convincing evidence to support including TPE as one of the standard therapies. |
References
- Laufs U, et al. Clinical review on triglycerides. European Heart Journal (2020) 41, 99–109.
- Ginsberg HN, et al. Triglyceride-rich lipoproteins and their remnants: metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies-a consensus statement from the European Atherosclerosis Society. Eur Heart J. 14;42(47):4791-4806 (2021).
- Williams L, et al. Familial chylomicronemia syndrome: Bringing to life dietary recommendations throughout the life span. J Clin Lipidol. 2018; 12:908–19.
- Burnett JR, Hooper AJ, Hegele RA. Familial Lipoprotein Lipase Deficiency. 1999 Oct 12 [Updated 2017 Jun 22]. In: Adam MP, Mirzaa GM, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1308/.
- Davidson M, et al. The burden of familial chylomicronemia syndrome: Results from the global IN-FOCUS study. J Clin Lipidol. 2018;12(4):898–907.
- Alexander L, et al. Familial chylomicronaemia Syndrome (FCS): Medical Nutrition Therapy for Patients and Providers. Presented at NLA Scientific Sessions; Philadelphia,PA; 17–20 May, 2017.
- Hegele RA, et al. Rare dyslipidaemias, from phenotype to genotype to management: a European Atherosclerosis Society task force consensus statement Lancet Diabetes Endocrinol 2020; 8: 50–67.
- Brahm AJ, Hegele RA, hylomicronemia and current diagnosis and future therapies, Nat. Rev. Endocrinol. 11 (6) (2015) 352e362.
- Witzum JL, et al. Volanesorsen and Triglyceride Levels in Familial Chylomicronemia Syndrome. N Eng J Med. 2019;381(6):531-42.
- Bashir B, et al. Severe Hypertriglyceridaemia and Chylomicronaemia Syndrome— Causes, Clinical Presentation, and Therapeutic Options. Metabolites. 2023; 13(5):621.
Causes and Pathophysiology
FCS is a monogenic disease with different pattern of inheritance. In 80-90% of patients with FCS, low activity of lipoprotein lipase (LPL) is caused by mutations in the gene that encodes this enzyme.
Symptoms and complications
Learn more about the broad spectrum of signs and symptoms that are associated with FCS.
Diagnosis
FCS diagnosis is based on a three-step approach:
- High triglyceride evaluation
- Identification of candidates for FCS genetic testing
- Genetic test of possible affected genes