Management of Hypertriglyceridemia

Introduction

Hypertriglyceridemia is classified by severity, with levels ranging from mild (150-199 mg/dL) to very severe (≥2,000 mg/dL), as recommended by the Endocrine Society guidelines 1
The American Diabetes Association recommends initiating treatment for hypertriglyceridemia at triglyceride levels ≥500 mg/dL to reduce pancreatitis risk, while levels 150-499 mg/dL warrant treatment based on cardiovascular risk factors 2

Patients with hypertriglyceridemia should be assessed for secondary causes, including diabetes, obesity, metabolic syndrome, chronic liver or kidney disease, hypothyroidism, and excessive alcohol consumption 2, 1, 3
Identifying and addressing potential secondary causes of hypertriglyceridemia is crucial for effective management 1, 3
Underlying genetic lipid disorders, such as familial hypertriglyceridemia and familial combined hyperlipidemia, increase the risk of hypertriglyceridemia 3
Poor glycemic control, obesity, and metabolic syndrome are primary drivers of hypertriglyceridemia 1, 3

The American College of Cardiology recommends reducing total fat to 20-25% of calories and eliminating refined carbohydrates and added sugars for patients with triglycerides 500-999 mg/dL 3
For patients with triglycerides ≥1,000 mg/dL, the American College of Cardiology suggests implementing a very-low-fat diet (10-15% of calories) and eliminating alcohol consumption 3
Restricting added sugars to <6% and total fat to 30-35% of daily calories is recommended for general cardiovascular health, and further restricting added sugars to <5% and total fat to 20-25% for intensified lifestyle modifications 3
Increasing soluble fiber intake to 10-25g/day and adding plant stanols/sterols (2g/day) can improve lipid profiles and glucose control 4, 5

Lifestyle modifications, including dietary changes and physical activity, are first-line therapy for hypertriglyceridemia 2, 3
The American College of Cardiology recommends at least 150 minutes/week of moderate-intensity or 75 minutes/week of vigorous aerobic activity for cardiovascular health 3
Targeting 5-10% weight reduction is recommended for overweight or obese patients 3
Regular endurance exercise training is suggested for improving cardiovascular health 3

The American College of Cardiology recommends statins as first-line therapy, especially if LDL-C is also elevated, as they provide a 10-30% dose-dependent reduction in triglycerides 3
Prescription omega-3 fatty acids (4g/day) are effective for reducing triglyceride levels in patients with severe hypertriglyceridemia (≥500 mg/dL) 3
Icosapent ethyl (IPE) is FDA-approved for severe hypertriglyceridemia (≥500 mg/dL) and cardiovascular risk reduction in patients with triglycerides ≥150 mg/dL with established cardiovascular disease or diabetes plus ≥2 risk factors, according to the American College of Cardiology 3
Omega-3 carboxylic acids (OM3CA) are FDA-approved for severe hypertriglyceridemia (≥500 mg/dL), as stated by the American College of Cardiology 3
Combination therapy may be considered for refractory cases with combined hyperlipidemia 6, 7

Patients should be monitored for triglyceride response after 8-12 weeks and for potential increases in LDL-C levels 3
Liver and renal function should be monitored with pharmacological therapy, especially when using fibrates 8, 9, 10, 3, 11, 12
Target goals for triglycerides, LDL cholesterol, and non-HDL cholesterol are <150 mg/dL, <100 mg/dL, and <130 mg/dL, respectively 8, 1

For severe hypertriglyceridemia (≥500 mg/dL), prescription omega-3 fatty acids (4g/day) should be used as adjunct to diet, and IPE should be considered if concerned about LDL-C elevation, as recommended by the American College of Cardiology 3
For patients with established ASCVD or diabetes with ≥2 risk factors and triglycerides ≥150 mg/dL, IPE (4g/day) should be used as adjunct to maximally tolerated statin therapy, according to the American College of Cardiology 3
Clinicians should evaluate the potential net benefit of prescription omega-3 fatty acids in patients at high risk of atrial fibrillation, as stated by the American College of Cardiology 3
Non-prescription fish oil supplements should not be substituted for prescription products when treating hypertriglyceridemia, as recommended by the American College of Cardiology 3
Icosapent ethyl (4g/day) may be considered as add-on therapy for patients with atherosclerotic cardiovascular disease or other cardiovascular risk factors on a statin with controlled LDL but elevated triglycerides (135-499 mg/dL) 13