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BASICS

Description

  • Excess fasting plasma triglycerides (TGs).
  • TGs are dietary fatty molecules transported mainly by VLDL and chylomicrons.
  • Risk of acute pancreatitis increases at TG β‰₯500 mg/dL, especially β‰₯1,000 mg/dL.
  • HTG is independently associated with ASCVD risk at levels β‰₯175 mg/dL.
  • Classified as moderate (175-499 mg/dL) or severe (β‰₯500 mg/dL).

Epidemiology

  • More common in males.
  • Highest prevalence between ages 50-70.
  • 25-33% of U.S. adults have TG β‰₯150 mg/dL.
  • 1.7% have TG β‰₯500 mg/dL.
  • Familial syndromes rare (<1%).

ETIOLOGY AND PATHOPHYSIOLOGY

Primary

  • Familial chylomicronemia (type 1 dyslipidemia): autosomal recessive lipoprotein lipase deficiency.
  • Familial combined hyperlipidemia (type IIb): autosomal dominant APOB overproduction.
  • Familial dysbetalipoproteinemia (type III): autosomal recessive APOE2 homozygosity.
  • Familial HTG (type IV): autosomal dominant lipoprotein lipase gene mutation.
  • Primary mixed HTG (type V).

Secondary

  • Lifestyle: obesity, inactivity, smoking, alcohol, high-carb diets.
  • Medical: type 2 diabetes, metabolic syndrome, hypothyroidism, liver/kidney disease, autoimmune disorders, paraproteinemias, pregnancy.
  • Medications: acitretin, Ξ²-blockers, glucocorticoids, isotretinoin, oral estrogens, protease inhibitors, antipsychotics, tamoxifen, thiazides.

RISK FACTORS

  • Genetic predisposition.
  • Obesity, overweight.
  • Type 2 diabetes mellitus.
  • Alcoholism.
  • Medication use.

PREVENTION

  • Healthy weight maintenance.
  • Moderate dietary fat and carb intake.
  • Regular aerobic exercise.
  • Avoid excess alcohol.

COMMONLY ASSOCIATED CONDITIONS

  • Pancreatitis.
  • Coronary artery disease.
  • Type 2 diabetes.
  • Metabolic syndrome.
  • Nonalcoholic steatohepatitis (NASH).
  • Polycystic ovarian syndrome.

DIAGNOSIS

History

  • Often asymptomatic.
  • Chylomicronemia syndrome: neurologic symptoms.
  • Pancreatitis symptoms if present.
  • Assess family cardiac history.

Physical Exam

  • Obesity.
  • Eruptive xanthomas.
  • Lipemia retinalis.
  • Epigastric tenderness (pancreatitis).
  • Hepatomegaly (NASH).

Diagnostic Tests

  • Fasting or nonfasting lipid profile.
  • Serum may appear turbid with milky supernatant.
  • Screen for secondary causes: HbA1c, creatinine, TSH, lipase, imaging as indicated.
  • ApoB measurement may be helpful but not routine.

TREATMENT

General Measures

  • Prioritize cardiovascular risk reduction through LDL lowering.
  • Lifestyle: dietary modification (limit sugars, refined carbs), weight loss, exercise.
  • Abstain from alcohol if TGs severe.
  • Treat secondary causes.

Medication

First Line

  • Statins: Preferred for ASCVD risk reduction; may lower TG by 15-30%.
  • Atorvastatin: 10-80 mg/day.
  • Rosuvastatin: 5-40 mg/day.

  • Monitor for myopathy, contraindicated in pregnancy/lactation.

  • Fibrates: For pancreatitis risk reduction in severe HTG; lower TG up to 50%.

  • Fenofibrate preferred (30-200 mg/day).
  • Gemfibrozil: 600 mg BID (avoid with statins).
  • Side effects: GI upset, hepatotoxicity, myopathy (especially combined with statins).

Second Line

  • Icosapent ethyl (Vascepa): 2 g BID for persistent HTG and ASCVD risk reduction.
  • REDUCE-IT trial showed 25% reduction in major CV events.

  • Adverse effects include atrial fibrillation/flutter, bleeding risk.

  • Other omega-3 fatty acids (Lovaza): reduce TG but not ASCVD risk; GI side effects common.

ISSUES FOR REFERRAL

  • Severe refractory HTG.
  • Familial HTG syndromes.

INPATIENT CONSIDERATIONS

  • Acute pancreatitis with TG >1,000 mg/dL:
  • Therapeutic plasma exchange (apheresis).
  • Insulin infusion (0.1-0.3 U/kg/hr IV with glucose if needed).

ONGOING CARE

Follow-Up

  • Repeat fasting lipid profile 1-3 months after therapy initiation/modification.
  • Monitor hepatic transaminases and CPK if myalgias develop.

Diet

  • Limit carbs to 50-60% of total calories.
  • Increase fiber.
  • Avoid sugars and refined carbs.
  • Limit fat to 30%, or 15% if TG β‰₯1,000 mg/dL.
  • Increase marine omega-3 fatty acids (fatty fish).
  • Avoid trans fats.
  • Mediterranean diet preferred.

PATIENT EDUCATION

  • Smoking cessation for CV risk reduction.
  • Address reversible secondary causes.

PROGNOSIS

  • Good with TG correction.
  • Lifelong treatment often required in primary HTG.

COMPLICATIONS

  • Atherosclerosis.
  • Chylomicronemia syndrome.
  • Pancreatitis.

REFERENCES

  1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC guideline on management of blood cholesterol. J Am Coll Cardiol. 2019;73(24):e285-e350.
  2. Jakob T, Nordmann AJ, Schandelmaier S, et al. Fibrates for primary prevention of cardiovascular disease events. Cochrane Database Syst Rev. 2016;11(11):CD009753.
  3. Orringer CE, Jacobson TA, Maki KC. National Lipid Association statement on icosapent ethyl in statin-treated patients. J Clin Lipidol. 2019;13(6):860-872.

Clinical Pearls

  • HTG is a risk factor for pancreatitis at TG β‰₯500-1,000 mg/dL.
  • Lifestyle modification is crucial for all patients.
  • Statins reduce ASCVD risk; fibrates best for pancreatitis prevention.
  • Icosapent ethyl reduces CV events in high-risk patients with persistent HTG.