Description

• Hypertriglyceridemia (HTG) is a common form of dyslipidemia characterized by an excess fasting plasma concentration of triglycerides (TGs).
  • TGs are fatty molecules that occur naturally in vegetable oils and animal fats and are major sources of dietary energy.
  • Absorbed TGs are packaged into very-low-density lipoproteins (VLDL) and chylomicrons.
• HTG is a risk factor for acute pancreatitis at levels ≥500 mg/dL and especially ≥1,000 mg/dL.
  • Risk is 10–20% at these TG levels.
  • Third leading cause of acute pancreatitis
• HTG also is independently associated with cardiovascular disease (atherosclerotic cardiovascular disease [ASCVD]) at levels ≥175 mg/dL.
  • The American Heart Association (AHA) and the American College of Cardiology (ACC) consider persistent HTG as a risk-enhancing factor.
  • A large Danish population study in 2018 showed that TG ≥264 mg/dL conferred a 10-year risk of major adverse cardiovascular events comparable to that of statin eligible individuals.
  • However, a causal relationship between HTG and ASCVD has not been firmly established.
  • Moreover, lowering TG has not been proven to reduce cardiovascular risk.
• AHA and ACC classify HTG into two categories:
  • Moderate: 175 to 499 mg/dL (2.0 to 5.6 mmol/L), characterized mainly by excess VLDL
  • Severe: ≥500 mg/dL (≥5.6 mmol/L), characterized by excess VLDL and chylomicrons

Epidemiology

• Predominant gender: male > female
• Predominant race: Hispanic, white > black

Prevalence

• 25-33% of U.S. population has TG levels ≥150 mg/dL.
• 1.7% has TG levels ≥500 mg/dL.
• Highest prevalence at age 50 to 70 years
• The most common genetic syndromes with HTG, familial combined hyperlipidemia and familial HTG, each affect ≤1% of general population.

Etiology and Pathophysiology

• Primary
  • Familial
  • Acquired (sporadic)
• Secondary
  • Lifestyle factors
    • Obesity and overweight
    • Physical inactivity
    • Cigarette smoking
    • Excess alcohol intake
    • High-carbohydrate diets (>60% of total caloric intake)
  • Medical conditions
    • Type 2 diabetes mellitus
    • Metabolic syndrome/insulin resistance
    • Hypothyroidism
    • Chronic liver disease
    • Chronic kidney disease, nephrotic syndrome
    • Autoimmune disorders (e.g., systemic lupus erythematosus)
    • Paraproteinemias (e.g., macroglobulinemia, myeloma, lymphoma, lymphocytic leukemia)
    • Pregnancy (usually physiologic and transient)
  • Medications
    • Acitretin
    • β-Blockers
    • Bile acid sequestrants
    • Cyclophosphamide
    • Cyclosporine
    • Glucocorticoids
    • Isotretinoin
    • Oral estrogens
    • Protease inhibitors
    • Second-generation antipsychotics
    • Tamoxifen and raloxifene
    • Thiazides

Genetics

• Familial chylomicronemia (type 1 dyslipidemia): autosomal recessive inheritance of lipoprotein lipase deficiency; 0.0001% population prevalence
• Familial combined hyperlipidemia (type IIb): usually autosomal dominant, caused by overproduction of apolipoprotein (APO) B-100; approximately 1% prevalence
• Familial dysbetalipoproteinemia (type III): usually autosomal recessive, caused by lipoprotein overproduction due to inheritance of two APOE2 variants; 0.01% prevalence
• Familial HTG (type IV): autosomal dominant, caused by an inactivating mutation of the lipoprotein lipase gene; 1% prevalence
• Primary mixed HTG (type V)

Risk Factors

• Genetic susceptibility
• Obesity, overweight
• Lack of exercise
• Type 2 diabetes mellitus
• Alcoholism
• Certain medical conditions and drugs (See “Etiology and Pathophysiology.”)

General Prevention

• Maintain healthy body weight.
• Moderation of dietary fat and refined carbohydrates
• Regular aerobic exercise
• Avoid excess alcohol.

Commonly Associated Conditions

• Pancreatitis
• Coronary artery disease
• Type 2 diabetes mellitus and insulin resistance
• Dyslipidemias
• Metabolic syndrome
• Nonalcoholic steatohepatitis (NASH)
• Polycystic ovarian syndrome