What are the implications of elevated Triglycerides (hypertriglyceridemia)?

From the Guidelines

To address elevated triglycerides, focus on lifestyle modifications including a low-carbohydrate diet, regular exercise, weight loss if overweight, and avoiding alcohol, as recommended by the 2021 ACC expert consensus decision pathway 1. The goal of treatment is to reduce the risk of cardiovascular disease and pancreatitis, with a target triglyceride level below 150 mg/dL. Key lifestyle modifications include:

• A low-carbohydrate diet, especially limiting refined carbs and sugars
• Regular exercise, aiming for 150 minutes of moderate activity weekly
• Weight loss if overweight, with a goal of 5-10% reduction in body weight
• Avoiding alcohol Additionally, increasing omega-3 fatty acids through fatty fish consumption or supplements (1-4 grams daily of fish oil) may be beneficial. For medication, fibrates like fenofibrate (145mg daily) are first-line for severe hypertriglyceridemia (>500 mg/dL), while statins like atorvastatin (10-80mg daily) are preferred when LDL is also elevated, as noted in the 2021 ACC expert consensus decision pathway 1. Regular monitoring every 3-6 months is recommended to assess treatment effectiveness, with adjustments to lifestyle and medication as needed to achieve the target triglyceride level. It is essential to consider the individual patient's risk factors, such as family history of dyslipidemia and cardiovascular disease, and to assess for other cardiovascular risk factors, such as central obesity, hypertension, abnormal glucose metabolism, and liver dysfunction, as recommended by the Endocrine Society guidelines 1. By prioritizing lifestyle modifications and evidence-based medication, patients with elevated triglycerides can reduce their risk of cardiovascular disease and pancreatitis, improving overall morbidity, mortality, and quality of life.

From the FDA Drug Label

Fenofibrate tablets are indicated as adjunctive therapy to diet to reduce elevated low-density lipoprotein cholesterol (LDL-C), total cholesterol (Total-C), Triglycerides and apolipoprotein B (Apo B), and to increase high-density lipoprotein cholesterol (HDL-C) in adult patients with primary hypercholesterolemia or mixed dyslipidemia. Fenofibrate tablets are also indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia.

Fenofibrate is used to treat elevated triglycerides. It works by activating peroxisome proliferator activated receptor α (PPARα), which increases lipolysis and elimination of triglyceride-rich particles from plasma. The resulting decrease in TG produces an alteration in the size and composition of LDL from small, dense particles to large buoyant particles.

• Key benefits of fenofibrate:
  • Reduces triglycerides
  • Increases HDL-C
  • Decreases LDL-C and Apo B
• Important considerations:
  • Should be used as adjunctive therapy to diet
  • May increase the risk of pancreatitis in patients with markedly elevated levels of serum triglycerides (> 2,000 mg/dL) 2

From the Research

Definition and Risks of Elevated Triglycerides

• Elevated triglycerides, or hypertriglyceridemia, is defined as fasting serum triglyceride levels of 150 mg per dL or higher 3.
• Hypertriglyceridemia is associated with an increased risk of cardiovascular disease and, in severe cases (500 mg per dL or higher), pancreatitis 3, 4, 5.
• The risk of pancreatitis is particularly high in individuals with extremely high levels of triglycerides (TG) 5.

Causes and Risk Factors of Hypertriglyceridemia

• Common risk factors for hypertriglyceridemia include obesity, metabolic syndrome, and type 2 diabetes mellitus 3.
• Less common risk factors include excessive alcohol use, physical inactivity, being overweight, use of certain medications, and genetic disorders 3.
• Both genetic and lifestyle factors play significant roles in the pathophysiology of hypertriglyceridemia 5.

Management and Treatment of Hypertriglyceridemia

• Management of high triglyceride levels starts with dietary changes and physical activity to lower cardiovascular risk 3.
• Lowering carbohydrate intake (especially refined carbohydrates) and increasing fat (especially omega-3 fatty acids) and protein intake can lower triglyceride levels 3.
• Moderate- to high-intensity physical activity can lower triglyceride levels, as well as improve body composition and exercise capacity 3.
• Medications such as statins, fibrates, omega-3 fatty acids, or niacin may be considered for patients with high or severely elevated triglyceride levels 3, 4, 6, 7.
• For patients at high risk who continue to have high triglyceride levels despite statin use, high-dose icosapent (purified eicosapentaenoic acid) can reduce cardiovascular mortality 3.