At what level of hypertriglyceridemia (elevated triglycerides) is treatment required?

Treatment Thresholds for Hypertriglyceridemia

Treatment for hypertriglyceridemia should be initiated based on specific triglyceride levels, with different approaches required for moderate versus severe elevations.

Classification of Hypertriglyceridemia

• Moderate hypertriglyceridemia: Triglyceride levels 175-499 mg/dL (2.0-5.6 mmol/L) 1
• Severe hypertriglyceridemia: Triglyceride levels ≥500 mg/dL (≥5.6 mmol/L) 1
• Very severe hypertriglyceridemia: Triglyceride levels ≥1,000 mg/dL (≥11.3 mmol/L) 2, 3

Treatment Approach for Moderate Hypertriglyceridemia (175-499 mg/dL)

• Primary intervention should focus on addressing lifestyle factors and secondary causes 1, 4
• Key lifestyle modifications include:
  • Weight loss if overweight/obese 4
  • Reduced intake of saturated fats, trans fats, and simple carbohydrates 4
  • Increased physical activity 4
  • Restriction or elimination of alcohol consumption 4
• Address secondary causes including:
  • Diabetes mellitus and insulin resistance 1, 4
  • Obesity and metabolic syndrome 1, 4
  • Medications that increase triglycerides 1
  • Hypothyroidism, kidney disease, or liver disease 1, 4
• For adults 40-75 years with moderate hypertriglyceridemia and ASCVD risk ≥7.5%, consider statin therapy after addressing lifestyle and secondary factors 1

Treatment Approach for Severe Hypertriglyceridemia (≥500 mg/dL)

• The primary goal is to reduce triglycerides below 500 mg/dL to prevent acute pancreatitis 2, 3
• Implement more aggressive dietary modifications:
  • Restrict dietary fat to 20-25% of total calories 3
  • For triglycerides ≥1,000 mg/dL, implement a very low-fat diet (10-15% of total calories) 2, 3
  • Eliminate added sugars completely 2, 3
  • Completely restrict alcohol consumption 2, 3
• Pharmacologic therapy should be considered:
  • Fibrates are first-line therapy for severe hypertriglyceridemia to prevent acute pancreatitis 3, 5
  • Prescription omega-3 fatty acids may be considered as adjunctive therapy 2, 3
• For adults with severe hypertriglyceridemia and ASCVD risk ≥7.5%, address reversible causes and initiate statin therapy 1

Treatment Approach for Very Severe Hypertriglyceridemia (≥1,000 mg/dL)

• Implement extreme dietary fat restriction (<5% of total calories as fat) until triglyceride levels are ≤1,000 mg/dL 2
• Consider insulin therapy for acute management, especially in patients with poor glycemic control 2, 3
• The risk of acute pancreatitis is significantly increased (14% incidence) 2
• Address glycemic control first in patients with diabetes, then re-evaluate triglyceride levels 2, 3

Pharmacologic Considerations

• Fibrates are effective for reducing triglycerides in severe hypertriglyceridemia 5, 6
• In clinical trials, fenofibrate reduced triglycerides by 46.2% in patients with triglycerides 350-499 mg/dL and by 54.5% in patients with triglycerides 500-1500 mg/dL 5
• Statin plus fibrate combination therapy has not been shown to improve cardiovascular outcomes and has increased risk of myositis 1
• Statin plus niacin combination therapy is generally not recommended 1
• For patients with ASCVD or cardiovascular risk factors on a statin with controlled LDL but elevated triglycerides (135-499 mg/dL), consider adding icosapent ethyl 1

Long-term Management

• Continue lifestyle modifications indefinitely to maintain triglyceride levels <500 mg/dL 2, 3
• Regular monitoring of triglyceride levels is essential 7
• For patients with cardiovascular risk factors and controlled hypertriglyceridemia, statin therapy should be considered 1, 3

Common Pitfalls and Caveats

• Failure to identify and address secondary causes can lead to persistent hypertriglyceridemia 1, 4
• Combination therapy (statin and fibrate) increases the risk of myopathy and rhabdomyolysis, particularly with gemfibrozil (fenofibrate has lower risk) 1, 4
• The effectiveness of pharmacotherapy may be limited for triglycerides ≥1,000 mg/dL as these agents primarily reduce triglyceride synthesis rather than clear circulating chylomicrons 2
• Renal function should be assessed before initiating fibrate therapy, as dose adjustment is needed in renal impairment 4