Management of High Triglycerides
Lifestyle modifications are the first-line treatment for all patients with elevated triglycerides, and can reduce levels by 20-50% when combined with weight loss, dietary changes, and regular aerobic exercise. 1, 2
Classification and Risk Stratification
Triglyceride levels are classified as follows 2:
- Normal: <150 mg/dL
- Mild: 150-199 mg/dL
- Moderate: 200-499 mg/dL
- Severe: 500-999 mg/dL (14% risk of pancreatitis)
- Very severe: ≥1,000 mg/dL (dramatically increased pancreatitis risk)
Initial Assessment: Identify Secondary Causes
Before initiating treatment, evaluate and address 2, 3:
- Uncontrolled diabetes (check HgA1C—optimizing glucose control can be more effective than lipid medications) 2
- Hypothyroidism (check TSH) 2
- Excessive alcohol intake (even 1 ounce daily increases triglycerides 5-10%) 2
- Medications: thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals 2, 3
- Renal disease and liver disease 2
Lifestyle Interventions (All Triglyceride Levels)
Weight Loss
Target 5-10% body weight reduction, which produces a 20% decrease in triglycerides—the single most effective intervention. 2 In some patients, weight loss can reduce triglycerides by 50-70%. 2
Dietary Modifications by Triglyceride Level
For mild-moderate hypertriglyceridemia (150-499 mg/dL) 1, 2:
- Restrict added sugars to <6% of total daily calories (sugar directly increases hepatic triglyceride production)
- Limit total fat to 30-35% of total daily calories
- Restrict saturated fats to <7% of total calories, replacing with monounsaturated or polyunsaturated fats
- Eliminate trans fatty acids completely
- Increase soluble fiber to >10 g/day
- Consume ≥2 servings/week (8+ ounces) of fatty fish (salmon, trout, sardines, anchovies)
For severe hypertriglyceridemia (500-999 mg/dL) 1, 2:
- Restrict added sugars to <5% of total daily calories
- Limit total fat to 20-25% of total daily calories
- Complete alcohol abstinence (mandatory to prevent hypertriglyceridemic pancreatitis)
For very severe hypertriglyceridemia (≥1,000 mg/dL) 1, 2:
- Eliminate all added sugars completely
- Restrict total fat to 10-15% of daily calories (or <5% until levels fall below 1,000 mg/dL)
- Complete alcohol abstinence
- Medium-chain triglyceride oil can be added gradually for additional calories
Key dietary principle: Low-carbohydrate diets are more effective than low-fat diets for lowering triglycerides. 2
Physical Activity
Engage in ≥150 minutes/week of moderate-intensity aerobic activity (or 75 minutes/week of vigorous activity), which reduces triglycerides by approximately 11%. 1, 2, 4
Pharmacologic Therapy: Treatment Algorithm by Triglyceride Level
Severe to Very Severe Hypertriglyceridemia (≥500 mg/dL)
Initiate fenofibrate 54-160 mg daily IMMEDIATELY as first-line therapy to prevent acute pancreatitis, regardless of LDL-C levels or cardiovascular risk. 2, 3, 5 This is mandatory pharmacologic intervention—do not delay while attempting lifestyle modifications alone. 2
- Fenofibrate reduces triglycerides by 30-50% 2, 5
- Dosing: Start 54 mg daily in patients with mild-moderate renal impairment; otherwise 54-160 mg daily 3
- Take with meals to optimize bioavailability 3
- Monitor lipids at 4-8 week intervals after initiation 2, 3
- Once triglycerides fall <500 mg/dL, reassess LDL-C and add statin therapy if LDL-C is elevated or cardiovascular risk is high 2
Moderate Hypertriglyceridemia (200-499 mg/dL)
For patients with 10-year ASCVD risk ≥7.5%, initiate moderate-to-high intensity statin therapy as first-line pharmacologic treatment. 2, 5 Statins provide 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit. 2
If triglycerides remain >200 mg/dL after 3 months of optimized lifestyle modifications and statin therapy, add prescription omega-3 fatty acids (icosapent ethyl 2-4 g/day). 2, 5 This is specifically indicated for patients with:
- Established cardiovascular disease, OR
- Diabetes with ≥2 additional cardiovascular risk factors 2
Icosapent ethyl provides a 25% reduction in major adverse cardiovascular events (NNT = 21). 2, 6
Alternative: Consider fenofibrate 54-160 mg daily if icosapent ethyl criteria are not met. 2
Mild Hypertriglyceridemia (150-199 mg/dL)
For patients with 10-year ASCVD risk ≥7.5%, consider moderate-intensity statin therapy. 2 Persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor favoring statin initiation. 2
For patients with ASCVD risk 5% to <7.5%, engage in patient-clinician discussion regarding statin initiation. 2
Secondary Treatment Goals
- Non-HDL-C target: <130 mg/dL (calculated as total cholesterol minus HDL-C) 2, 5
- LDL-C target: <100 mg/dL for high-risk patients (or <70 mg/dL for very high-risk patients) 2
Combination Therapy Safety Considerations
When combining fenofibrate with statins, use lower statin doses (atorvastatin 10-20 mg maximum) to minimize myopathy risk, particularly in patients >65 years or with renal disease. 2 Fenofibrate has a significantly better safety profile than gemfibrozil when combined with statins. 2, 5
Monitor for myopathy: Check baseline and follow-up creatine kinase levels, especially in elderly patients or those with renal disease. 2
Critical Pitfalls to Avoid
- Do not delay fibrate therapy in patients with triglycerides ≥500 mg/dL while attempting lifestyle modifications alone—pharmacologic intervention is mandatory. 2
- Do not start with statin monotherapy when triglycerides are ≥500 mg/dL—statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis at this level. 2
- Do not use gemfibrozil when combining with statins—fenofibrate has a much lower myopathy risk. 2
- Do not ignore secondary causes—uncontrolled diabetes, hypothyroidism, or certain medications can be the primary driver of severe hypertriglyceridemia. 2, 3
- Monitor for atrial fibrillation with prescription omega-3 fatty acids at doses of 2-4 g daily. 2