What are the secondary causes of elevated triglycerides?

Secondary Causes of Elevated Triglycerides

The main secondary causes of elevated triglycerides include obesity, metabolic syndrome, diabetes mellitus, chronic liver or kidney disease, nephrotic syndrome, hypothyroidism, and medications that increase triglycerides. 1, 2

Common Secondary Causes

Medical Conditions

• Diabetes mellitus: Poor glycemic control significantly influences plasma lipid levels and can exacerbate hypertriglyceridemia 1
• Obesity and metabolic syndrome: Major contributors to hypertriglyceridemia 1
• Chronic liver disease: Impairs lipid metabolism 1
• Chronic kidney disease and nephrotic syndrome: Alter lipid metabolism 1
• Hypothyroidism: Decreases lipid clearance 1, 2

Lifestyle Factors

• Excessive alcohol consumption: Directly increases triglyceride production 1, 2
• High carbohydrate diet: Particularly refined carbohydrates and added sugars 2, 3
• Physical inactivity: Contributes to metabolic dysfunction 3
• Excessive caloric intake: Leading to weight gain 2

Medication-Induced Hypertriglyceridemia

The 2018 ACC/AHA guideline specifically identifies several medications that can raise triglycerides 1:

• Hormonal therapies: Oral estrogens, tamoxifen, raloxifene
• Cardiovascular medications: Beta-blockers, thiazide diuretics
• Immunosuppressive drugs: Cyclosporine, sirolimus, tacrolimus
• Psychiatric medications: Atypical antipsychotics
• Other medications:
  • Retinoids
  • Interferon
  • Protease inhibitors
  • Glucocorticoids
  • Rosiglitazone
  • Bile acid sequestrants
  • L-asparaginase
  • Cyclophosphamide

Genetic Factors and Predisposition

While not strictly "secondary," genetic predisposition increases the likelihood and severity of elevated triglycerides when secondary factors are present 1. The 2021 ACC expert consensus highlights that multifactorial chylomicronemia syndrome is 40-60 times more prevalent than monogenic conditions like autosomal recessive familial chylomicronemia syndrome 1.

Clinical Approach to Secondary Causes

When evaluating patients with hypertriglyceridemia, it's important to:

1. Obtain at least two fasting lipid panels, preferably 2 weeks apart 1
2. Systematically evaluate for secondary causes before attributing to primary hypertriglyceridemia 4
3. Address modifiable factors first, as this may normalize triglyceride levels without pharmacological intervention 1

Clinical Implications

The clinical significance of hypertriglyceridemia varies based on severity:

• Moderate hypertriglyceridemia (175-499 mg/dL): Associated with increased cardiovascular risk 1
• Severe hypertriglyceridemia (≥500 mg/dL): Primary concern is risk of acute pancreatitis 1, 3

Management Considerations

When secondary causes are identified:

• Optimize glycemic control in patients with diabetes before reassessing triglyceride levels 2
• Consider medication changes when possible for patients on triglyceride-raising drugs 1, 5
• Address lifestyle factors including weight loss, exercise, dietary modification, and alcohol reduction 2, 3

Common Pitfalls

1. Failure to identify multiple contributing factors: Most cases of severe hypertriglyceridemia are multifactorial 1
2. Overlooking medication effects: Always review the patient's complete medication list 1
3. Premature attribution to primary hypertriglyceridemia: Secondary causes should be thoroughly investigated before making this diagnosis 4
4. Inadequate attention to glycemic control: In diabetic patients, poor glycemic control can significantly worsen hypertriglyceridemia 1

Understanding and addressing these secondary causes is essential for effective management of hypertriglyceridemia and prevention of its complications, including pancreatitis and cardiovascular disease.