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- 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
- Predominant gender: male > female
- Predominant race: Hispanic, white > black
- 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
- Acquired (sporadic)
- 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
- Interferon α
- Oral estrogens
- Protease inhibitors (e.g., ritonavir, darunavir)
- Medical conditions
- Type 2 diabetes mellitus
- 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)
- 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)
- Genetic susceptibility
- Obesity, overweight
- Lack of exercise
- Certain medications (see “Etiology and Pathophysiology”)
- Medical conditions (see “Etiology and Pathophysiology”)
- Weight reduction
- Moderation of dietary fat and carbohydrates
- Regular aerobic exercise
Commonly Associated Conditions
- Coronary artery disease
- Diabetes mellitus type 2 and insulin resistance
- 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
- Polycystic ovary syndrome