Hypertriglyceridemia

Hypertriglyceridemia is a topic covered in the 5-Minute Clinical Consult.

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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.
    • TGs are packaged into chylomicrons and very low-density lipoproteins (VLDL).
  • HTG is a risk factor for acute pancreatitis at levels ≥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 at levels ≥200 mg/dL.
    • 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.
    • The degree to which excess TGs cause atherosclerosis is uncertain and debatable. Evidence for a causal relationship comes mainly from Mendelian randomization studies.
    • Lowering TG has not been proven to reduce cardiovascular risk.
  • The American Association of Clinical Endocrinologists classifies HTG as follows based on fasting TG levels:
    • Normal: <150 mg/dL
    • Borderline high: 150 to 199 mg/dL
    • High: 200 to 499 mg/dL
    • Very high: ≥500 mg/dL
    • Divide by 88.5 to convert to mmol/L.
  • TGs are considered high in children when TGs exceed the 95th percentiles for age:
    • ≥100 mg/dL for ages 0 to 9 years
    • ≥130 mg/dL for ages 10 to 19 years

Epidemiology

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

Prevalence
  • 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
    • Obesity and overweight
    • Physical inactivity
    • Cigarette smoking
    • Excess alcohol intake
    • Very high carbohydrate diets (>60% of total caloric intake)
    • Certain medications
      • Atypical antipsychotics (e.g., quetiapine)
      • β-Blockers other than carvedilol
      • Cyclosporine
      • Glucocorticoids
      • Interferon α
      • Isotretinoin
      • Oral estrogens
      • Protease inhibitors (e.g., ritonavir, darunavir)
      • Tamoxifen
    • Medical conditions
      • Type 2 diabetes mellitus
      • Hypothyroidism
      • Chronic renal failure, nephrotic syndrome
      • Autoimmune disorders (e.g., systemic lupus erythematosus)
      • Paraproteinemias (e.g., macroglobulinemia, myeloma, lymphoma, lymphocytic leukemia)
      • Pregnancy (usually physiologic and transient)

Genetics
  • Familial chylomicronemia (type 1 dyslipidemia): autosomal recessive inheritance of lipoprotein lipase deficiency; 0.0001% 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
  • Diabetes
  • Alcoholism
  • Certain medications (see “Etiology and Pathophysiology”)
  • Medical conditions (see “Etiology and Pathophysiology”)

General Prevention

  • Weight reduction
  • Moderation of dietary fat and carbohydrates
  • Regular aerobic exercise

Commonly Associated Conditions

  • Coronary artery disease
  • Diabetes mellitus type 2 and insulin resistance
  • Dyslipidemias
    • Decreased high-density lipoprotein (HDL) cholesterol
    • Increased LDL, non-HDL, and total cholesterol
    • Small, dense LDL particles
  • Metabolic syndrome (three of the following):
    • Abdominal obesity (waist circumference >40 inches in men, >35 inches in women)
    • TG ≥150 mg/dL
    • Low levels of HDL cholesterol (<40 mg/dL in men, <50 mg/dL in women)
    • BP ≥130/85 mm Hg
    • Fasting glucose ≥100 mg/dL
  • Nonalcoholic steatohepatitis
  • Pancreatitis
  • Polycystic ovary syndrome

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