Hypertriglyceridemia

BASICS

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.
    • The liver also converts excess carbohydrates to TGs. This is a major contributor to HTG for most patients.
  • 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 is also 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
      • Diet high in refined carbohydrates or excess calories
      • High intake of ultra-processed foods
      • Excess alcohol intake
      • Physical inactivity
      • Obesity and overweight
    • 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 ovary syndrome

There's more to see -- the rest of this topic is available only to subscribers.

© 2000–2025 Unbound Medicine, Inc. All rights reserved
All content is protected by copyright and may not be used for AI model training or other unauthorized purposes.