At what triglyceride level do you initiate therapy?

Triglyceride Treatment Thresholds

For triglyceride levels ≥500 mg/dL, pharmacologic therapy should be initiated immediately to reduce the risk of pancreatitis, with fibrates or niacin as first-line options before LDL-lowering therapy. 1, 2

Classification of Hypertriglyceridemia

• Hypertriglyceridemia is classified by severity: normal (<150 mg/dL), mild (150-199 mg/dL), moderate (200-499 mg/dL), severe (500-999 mg/dL), and very severe (≥1000 mg/dL) 2
• Fasting triglyceride levels >150 mg/dL or nonfasting triglycerides >175 mg/dL are considered elevated and require attention 3
• Moderate hypertriglyceridemia (150-499 mg/dL) is associated with increased cardiovascular disease risk 2, 4
• Severe hypertriglyceridemia (≥500 mg/dL) significantly increases the risk of acute pancreatitis 2, 5

Treatment Thresholds and Approach

For Triglycerides 150-199 mg/dL (Mild)

• Implement lifestyle modifications including weight management, physical activity, and dietary changes 3
• Assess cardiovascular risk factors and consider statin therapy if 10-year ASCVD risk is elevated 4
• Target a 5-10% weight loss which can reduce triglycerides by approximately 20% 3, 6

For Triglycerides 200-499 mg/dL (Moderate)

• Continue aggressive lifestyle modifications with emphasis on weight loss, reduced alcohol consumption, and carbohydrate restriction 3
• If triglycerides are 200-499 mg/dL, non-HDL-C should be less than 130 mg/dL 1
• For patients with ASCVD risk ≥7.5%, consider statin therapy to reduce cardiovascular risk 2, 4
• Therapeutic options to reduce non-HDL-C include more intense LDL-C-lowering therapy, niacin, or fibrate therapy (after LDL-C-lowering therapy) 1

For Triglycerides ≥500 mg/dL (Severe)

• Immediate pharmacologic intervention is required to reduce the risk of acute pancreatitis 1, 2
• Fibrates or niacin should be initiated before LDL-C lowering therapy 1, 5
• The goal is to achieve non-HDL-C less than 130 mg/dL if possible 1
• For very severe hypertriglyceridemia (≥1000 mg/dL), extreme dietary fat restriction (<5% of total calories) may be necessary until triglycerides are <1000 mg/dL 2, 3

Lifestyle Interventions

• Weight loss is the most effective lifestyle intervention, with a 5-10% reduction potentially lowering triglycerides by up to 20-70% 3, 6
• Restrict added sugars to <6% of total daily calories and limit total fat to 30-35% of total daily calories for mild to moderate hypertriglyceridemia 3
• For severe hypertriglyceridemia (500-999 mg/dL), restrict dietary fat to 20-25% of total calories 3
• Engage in at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity 3
• Limit or completely avoid alcohol consumption 3, 4

Pharmacologic Therapy

• For severe hypertriglyceridemia (≥500 mg/dL), fibrates are first-line therapy to reduce pancreatitis risk 2, 7, 5
• Fenofibrate has been shown to reduce triglycerides by 46-54% in patients with severe hypertriglyceridemia 7
• For moderate hypertriglyceridemia with elevated ASCVD risk, statins can provide a 10-30% reduction in triglycerides 3, 8
• Prescription omega-3 fatty acids can be considered as adjunctive therapy for severe hypertriglyceridemia 3, 8

Special Considerations

• Always evaluate for secondary causes such as uncontrolled diabetes, hypothyroidism, renal disease, liver disease, and certain medications 3, 9
• Optimize glycemic control in patients with diabetes, as it can significantly improve triglyceride levels 3
• The combination of statins and fibrates increases the risk of myopathy and should be used with caution 3, 6
• For patients with very severe hypertriglyceridemia (≥1000 mg/dL), consider insulin infusion or plasmapheresis if triglycerides remain elevated despite conservative management 5