In which patients should triglycerides be reduced, particularly those with high-risk cardiovascular profiles, such as established cardiovascular disease, diabetes, or a family history of cardiovascular disease?

Triglyceride Reduction: Target Populations

All patients with triglycerides ≥150 mg/dL should have triglycerides reduced through lifestyle modifications, with pharmacologic therapy intensity determined by absolute triglyceride level and cardiovascular risk stratification. 1, 2

Risk-Based Treatment Thresholds

Severe to Very Severe Hypertriglyceridemia (≥500 mg/dL)

• Immediate pharmacologic intervention is mandatory regardless of cardiovascular risk to prevent acute pancreatitis, which occurs in 14% of patients at this level. 1, 3
• Initiate fenofibrate 54-160 mg daily as first-line therapy before addressing LDL cholesterol. 1, 2
• The primary goal is rapid reduction to <500 mg/dL to eliminate pancreatitis risk, followed by further reduction to <200 mg/dL for cardiovascular protection. 1, 2
• Implement extreme dietary fat restriction (10-25% of total calories for 500-999 mg/dL; <5% for ≥1,000 mg/dL) and complete elimination of added sugars and alcohol. 1, 3

Moderate Hypertriglyceridemia (200-499 mg/dL)

• Patients with 10-year ASCVD risk ≥7.5%, established cardiovascular disease, or diabetes should receive statin therapy as first-line, providing 10-30% dose-dependent triglyceride reduction plus proven cardiovascular benefit. 1, 3
• For patients on maximally tolerated statins with controlled LDL-C but persistent triglycerides 135-499 mg/dL who have established cardiovascular disease OR diabetes with ≥2 additional risk factors, add icosapent ethyl 2g twice daily (25% reduction in major adverse cardiovascular events, NNT=21). 1, 2, 4
• Target non-HDL-C <130 mg/dL as a secondary goal when triglycerides remain in this range. 1, 5

Mild Hypertriglyceridemia (150-199 mg/dL)

• Persistently elevated nonfasting triglycerides ≥175 mg/dL constitute a cardiovascular risk-enhancing factor that favors statin initiation in borderline (5-7.4%) or intermediate (7.5-19.9%) risk patients. 1, 5
• For patients with 10-year ASCVD risk ≥7.5%, consider moderate-intensity statin therapy. 1, 5
• Lifestyle modifications are the cornerstone: 5-10% weight loss produces 20% triglyceride reduction, restrict added sugars to <6% of calories, limit total fat to 30-35% of calories, and engage in ≥150 minutes/week of moderate-intensity aerobic activity. 1, 3, 5

High-Risk Populations Requiring Aggressive Triglyceride Management

Established Cardiovascular Disease

• All patients with prior MI, stroke, or documented coronary artery disease should have triglycerides reduced to <150 mg/dL through statin therapy, with icosapent ethyl added if triglycerides remain ≥150 mg/dL on maximally tolerated statins. 1, 2, 4

Diabetes Mellitus

• Diabetic patients aged 40-75 years require statin therapy regardless of baseline triglyceride levels, as diabetes itself is a high-risk condition. 1, 3
• Optimizing glycemic control is paramount—poor glucose control is often the primary driver of severe hypertriglyceridemia and can reduce triglycerides independent of lipid medications. 1, 3
• For diabetic patients with triglycerides ≥150 mg/dL on statins who have ≥2 additional cardiovascular risk factors (hypertension, smoking, low HDL-C, family history), add icosapent ethyl 2g twice daily. 1, 2, 4

Metabolic Syndrome

• Patients meeting metabolic syndrome criteria (fasting triglycerides ≥150 mg/dL is one diagnostic criterion) have increased cardiovascular risk and should receive intensive lifestyle intervention plus statin therapy if 10-year ASCVD risk ≥7.5%. 1, 5

Family History of Premature Cardiovascular Disease

• Family history of premature ASCVD is a risk-enhancing factor that, combined with persistent hypertriglyceridemia ≥175 mg/dL, favors early statin initiation even in borderline risk patients. 1

Critical Secondary Causes Requiring Correction First

• Uncontrolled diabetes mellitus must be optimized before adding lipid medications—hyperglycemia should be treated first, then hypertriglyceridemia re-evaluated. 1, 3
• Screen for hypothyroidism, chronic kidney disease, nephrotic syndrome, and chronic liver disease, as these conditions elevate triglycerides and require specific treatment. 1, 3, 5
• Assess medications that raise triglycerides (thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, antiretrovirals, antipsychotics) and discontinue or substitute if possible. 1, 3
• Alcohol consumption of even 1 ounce daily increases triglycerides by 5-10%—complete abstinence is mandatory for severe hypertriglyceridemia (≥500 mg/dL). 1, 3

Common Pitfalls to Avoid

• Do NOT delay fibrate therapy while attempting lifestyle modifications alone when triglycerides ≥500 mg/dL—pharmacologic intervention is mandatory to prevent pancreatitis. 1, 2
• Do NOT start with statin monotherapy when triglycerides ≥500 mg/dL—statins provide only 10-30% triglyceride reduction and are insufficient for preventing pancreatitis at this level. 1
• Do NOT use gemfibrozil when combining with statins—fenofibrate has a significantly better safety profile with lower myopathy risk. 1, 2
• Do NOT add niacin to statin therapy for cardiovascular risk reduction—the AIM-HIGH trial showed no benefit and increased risk of new-onset diabetes. 1, 6
• Do NOT use over-the-counter fish oil supplements as substitutes for prescription omega-3 formulations—only icosapent ethyl has proven cardiovascular benefit. 1, 2, 4
• Do NOT ignore the increased risk of atrial fibrillation with icosapent ethyl (3.1% vs 2.1% placebo)—monitor appropriately. 1, 2