What is the workup for a patient with severely elevated triglycerides (hypertriglyceridemia)?

Workup and Management for Triglycerides Over 1,000 mg/dL

For patients with triglycerides over 1,000 mg/dL, immediate implementation of extreme dietary fat restriction (<15% of total calories) along with evaluation for secondary causes is essential to prevent acute pancreatitis. 1, 2

Initial Assessment and Risk Stratification

• Severely elevated triglycerides (≥1,000 mg/dL) significantly increase the risk of acute pancreatitis (14% incidence) 1, 2
• The primary goal is to reduce triglycerides below 500 mg/dL to prevent acute pancreatitis 2, 3
• Evaluate for secondary causes of hypertriglyceridemia:
  • Uncontrolled diabetes mellitus 1, 3
  • Excessive alcohol consumption 1, 3
  • Hypothyroidism 3, 4
  • Chronic kidney disease or nephrotic syndrome 3
  • Medications (estrogen therapy, thiazide diuretics, beta-blockers) 5, 6
  • Genetic disorders (familial hypertriglyceridemia, lipoprotein lipase deficiency) 7

Immediate Management

Dietary Modifications

• Implement very-low-fat diet (<10-15% of total calories or <20-40g total fat/day) 1, 2
• Eliminate all added sugars 2, 3
• Implement a diet low in simple and refined carbohydrates 1, 2
• Include high amounts of soluble fiber (>10 g/day) 1, 2
• Completely restrict alcohol consumption 1, 2, 3

Pharmacologic Management

• Initiate fibrate therapy (fenofibrate or gemfibrozil) as first-line medication for severe hypertriglyceridemia 5, 6, 5
• For patients with diabetes, address glycemic control first, as hyperglycemia can worsen hypertriglyceridemia 2, 3
• Consider insulin therapy for acute management of very severe hypertriglyceridemia, especially in patients with poor glycemic control 2, 8
• Prescription omega-3 fatty acids may be considered as adjunctive therapy 2, 3

Management of Acute Pancreatitis Due to Hypertriglyceridemia

• If acute pancreatitis develops, insulin infusion can rapidly lower triglyceride levels 2, 8
• Plasmapheresis should be considered if triglyceride levels remain ≥1,000 mg/dL despite conservative management 9, 10
• Avoid lipid-containing parenteral nutrition during acute management 2

Long-term Management

• Continue lifestyle modifications indefinitely to maintain triglyceride levels <500 mg/dL 2, 3
• Maintain fibrate therapy as the cornerstone of long-term management 9, 7
• For patients with cardiovascular risk factors, consider adding statin therapy once triglycerides are controlled 3, 10
• Caution: Statin plus fibrate combination therapy has increased risk of myositis 4
• Regular monitoring of triglyceride levels is essential, with adjustments to therapy as needed 5

Common Pitfalls and Caveats

• When triglycerides are ≥1,000 mg/dL, the effectiveness of pharmacotherapy may be limited as these agents primarily reduce triglyceride synthesis rather than clear circulating chylomicrons 2
• Dietary non-compliance is a major cause of treatment failure - emphasize the importance of strict dietary adherence 1, 11
• Fibrates are often overlooked as first-line therapy for severe hypertriglyceridemia 11
• Improving glycemic control in diabetic patients with fasting chylomicronemia will often reduce the need for pharmacologic intervention 5