Hypertriglyceridemia

Aka: Hypertriglyceridemia

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II. Pathophysiology

  1. Triglycerides are a major component of serum VLDL
  2. Hypertriglyceridemia is an independent risk factor for Coronary Artery Disease
    1. Triglycerides >500: Increases premature CAD risk by 11.4 fold
    2. Triglycerides >300 and HDL<30: Increases premature CAD risk by 17.2 fold
    3. Type III Dyslipidemia: Increases premature CAD risk by 5-10 fold
    4. (2005) JACC 45:1003-12 [PubMed]

III. Causes

  1. See Hypertriglyceridemia Causes
  2. See Drug-Induced Hypertriglyceridemia

IV. Labs

  1. Lipid Panel
  2. Serum Triglycerides
    1. Normal: <150 mg/dl
    2. High: 150 to 499 mg/dl
    3. Severe: >=500 mg/dl
  3. Serum Glucose

V. Management

  1. General therapeutic lifestyle changes
    1. Reduce body weight by at least 5-10%
      1. Weight decrease alone may decrease Serum Triglycerides by 20%
    2. Increase aerobic Exercise (esp. higher intensity) and Resistance Training
      1. Walking 3-4 miles in approximately 40 minutes daily normalizes Triglycerides within 1 week
        1. Oscai (1972) AJC 30:775-80 [PubMed]
    3. Limit Simple Sugars and simple Carbohydrate intake and focus on lower Glycemic Foods
      1. Replace simple Carbohydrates with Protein and monunsaturated fats
      2. Increase monounsaturated fat intake (e.g. Mediterranean Diet)
    4. Optimize Blood Sugar control in Diabetes Mellitus
      1. Consider Metabolic Syndrome management
  2. Serum Triglycerides 150 to 199 mg/dl (Borderline high)
    1. Therepeutic lifestyle changes above
    2. Lower LDL Cholesterol to goal (see Hyperlipidemia)
  3. Serum Triglycerides 200 to 499 (high)
    1. Therepeutic lifestyle changes above
    2. Primary goal: Lower LDL Cholesterol
      1. Statin AntiHyperlipidemics for high Cardiovascular Risk
        1. Statins also lower Serum Triglycerides 10-30%
    3. Secondary goal: Lower Triglycerides
      1. Omega 3 Fatty Acids
        1. Fish oil 2-4 g EPA/DHA daily
    4. Other agents that have been previously recommended (but fallen out of favor, lack of efficacy, side effects)
      1. Fibrate added to Statin
        1. Fenofibrate (risk of Myopathy when used with Statin)
        2. Avoid Gemfibrozil with Statin (higher risk of Myopathy than Fenofibrate)
      2. Niacin added to Statin
        1. Caution: Niacin is NOT in the official AHA guidelines and not typically recommended
        2. Combination did not show benefit beyond Statin alone in AIM-HIGH study (2011)
        3. Less effect on Triglycerides than Fibrate (consider adding Fibrate)
  4. Serum Triglycerides >500 (very high)
    1. See Hyperlipidemia to estimate ASCVD risk
    2. Therepeutic lifestyle changes above
    3. Primary goals are to reduce ASCVD risk, lower Triglycerides and reduce Pancreatitis risk
      1. First-line
        1. Statins
          1. Lower Triglycerides 10-30%
      2. Second-Line
        1. Omega 3 Fatty Acids
          1. Fish oil 2-4 g EPA/DHA daily or
          2. Vascepa 2 g orally twice daily
      3. Other agents that have been previously recommended (but fallen out of favor, lack of efficacy, side effects)
        1. Fibrate (Fenofibrate, Gemfibrozil) decreases triglcerides by 25-50%
          1. Avoid Gemfibrozil in combination with Statin
        2. Niacin with or without Fibrate
          1. Caution: Niacin is NOT in the official AHA guidelines and not typically recommended
          2. Niacin lowers Serum Triglycerides by 10-35% (but does not alter cardiovascular outcomes)
    4. Secondary goal is to lower LDL Cholesterol
      1. Consider adding a Statin to agents above
      2. Use caution due to Myopathy risk
  5. Serum Triglycerides >1000 (highest)
    1. Aggressive weight loss and Diabetes Mellitus control
    2. High level of suspicion for secondary cause
    3. Management as for Serum Triglycerides >500 mg/dl
    4. Familial Chylomicronemia syndrome
      1. Olezarsen to reduce Pancreatitis risk
    5. Manage Acute Pancreatitis
      1. Early and aggressive Serum Triglyceride lowering is associated with better outcomes
      2. Insulin Infusion 0.25 units/kg/h with dextrose infusion unless hyperglycemic OR
      3. Plasmapheresis if Insulin Infusion is not effective

VI. Complications

  1. Cardiac Risk Factor
    1. Independent risk factor for cardiovascular disease (beyond standard major CAD risk factors)
    2. Associated with Metabolic Syndrome and Diabetes Mellitus, which are also signirficant CAD risks
  2. Pancreatitis
    1. Increased risk at Serum Triglycerides >500 mg/dl
    2. Acute Pancreatitis is typically associated with Serum Triglycerides >1000 mg/dl
      1. Responsible for 2-4% of Pancreatitis cases
      2. Consider acute Serum Triglyceride lowering with Insulin Infusion, Plasmapheresis

VII. References

  1. (2021) Presc Lett 28(11): 63
  2. (2001) JAMA 285:2486-97 [PubMed]
  3. Blumenthal (2026) J Am Coll Cardiol S0735-1097(25)10254-4 +PMID: 41824590 [PubMed]
  4. Oh (2020) Am Fam Physician 102(6): 347-54 [PubMed]
  5. Oh (2007) Am Fam Physician 75:1365-71 [PubMed]
  6. Safer (2002) Am Fam Physician 65:871-80 [PubMed]

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