Triglyceride Function and Management of High Levels
Triglycerides are essential energy storage molecules in the body, but elevated levels require lifestyle modifications as first-line treatment, followed by pharmacological intervention for severe cases to reduce cardiovascular risk and prevent pancreatitis. 1
Physiological Function of Triglycerides
- Triglycerides make up the majority of dietary fat consumed in industrialized nations and serve as the body's primary mechanism for efficient energy storage 1, 2
- They play a crucial role in energy metabolism, serving as a concentrated source of calories that can be stored in adipose tissue and mobilized during periods of energy need 1
- When properly regulated, triglycerides are part of normal lipid metabolism, but dysregulation leads to hypertriglyceridemia with associated health risks 3
Classification of Triglyceride Levels
- The American Heart Association classifies triglyceride levels as:
- Normal: <150 mg/dL
- Borderline high: 150-199 mg/dL
- High: 200-499 mg/dL
- Very high: ≥500 mg/dL 4
- Optimal fasting triglyceride levels for cardiovascular health are considered to be <100 mg/dL 4, 5
Health Implications of Elevated Triglycerides
- Elevated triglycerides are associated with:
- Very high triglyceride levels (≥500 mg/dL) increase risk for pancreatitis, while moderate elevations (200-499 mg/dL) are more associated with atherosclerotic risk 5
- Hypertriglyceridemia alters lipoprotein metabolism by increasing remnant cholesterol particles, which are causally linked to atherosclerosis 5, 3
Management of Elevated Triglycerides
Assessment for Secondary Causes
- Evaluate for secondary causes of hypertriglyceridemia:
Lifestyle Modifications (First-Line Treatment)
- Weight loss: A 5-10% reduction in body weight can lower triglycerides by approximately 20% 4, 7
- Dietary changes:
- Reduce carbohydrate intake, especially added sugars and fructose 4, 5
- Eliminate dietary trans fatty acids 4
- Increase omega-3 fatty acid consumption 4
- Moderate fat intake with emphasis on unsaturated fats 4
- For severe hypertriglyceridemia (≥1000 mg/dL), implement extreme dietary fat restriction (<5% of total calories as fat) 7
- Physical activity: Aim for at least 150 minutes per week of moderate-intensity aerobic activity 4, 7
- Complete elimination of alcohol consumption, especially for those with severe hypertriglyceridemia 7
Pharmacological Treatment
- For high triglyceride levels (200-499 mg/dL):
- For severe hypertriglyceridemia (≥500 mg/dL):
- Fibrates are the first-line treatment for triglycerides ≥1500 mg/dL 7, 9
- Fenofibrate is indicated as adjunctive therapy to diet for treatment of adult patients with severe hypertriglyceridemia 9
- Consider adding prescription omega-3 fatty acids if response to fibrate is inadequate 7
- Avoid statins as monotherapy for severe hypertriglyceridemia (≥1500 mg/dL), as they are not effective as first-line treatment for this condition 7
Important Considerations and Caveats
- Despite the use of statin therapy, ASCVD event rates remain high in patients with elevated triglycerides, suggesting they represent a marker of residual cardiovascular risk 5, 10
- While triglyceride levels serve as a biomarker for cardiovascular risk, there is insufficient evidence that lowering triglyceride levels alone improves cardiovascular outcomes beyond LDL-C and non-HDL-C targets 4
- Fenofibrate at a dose equivalent to 160 mg was not shown to reduce coronary heart disease morbidity and mortality in a large, randomized controlled trial of patients with type 2 diabetes mellitus 9
- Markedly elevated levels of serum triglycerides (e.g., > 2,000 mg/dL) may increase the risk of developing pancreatitis, but the effect of fenofibrate therapy on reducing this risk has not been adequately studied 9
- Patients with impaired renal function should start with lower doses of fenofibrate (54 mg per day), and the medication should be avoided in patients with severe renal impairment 9