What causes elevated triglycerides?

Causes of Elevated Triglycerides

Elevated triglycerides are primarily caused by genetic factors, obesity, diabetes, excessive alcohol intake, certain medications, and various medical conditions, with most cases resulting from a combination of these factors.

Primary (Genetic) Causes

• Familial hypertriglyceridemia - characterized by triglyceride levels of 200-1000 mg/dL, not typically associated with coronary heart disease unless metabolic syndrome features are present 1
• Familial combined hyperlipidemia (FCHL) - a common genetic disorder (1-2% in white populations) with increased production of apolipoprotein B lipoproteins 1
• Lipoprotein lipase deficiency - rare genetic disorder causing severely elevated triglycerides and increased risk of pancreatitis 1
• Apolipoprotein CII deficiency - rare genetic cause of severe hypertriglyceridemia 1
• Apolipoprotein AV deficiency - genetic disorder affecting triglyceride metabolism 1
• Dysbetalipoproteinemia - rare autosomal recessive disorder with defective apolipoprotein E, requiring a second "hit" for clinical expression 1

Secondary Causes

Metabolic and Endocrine Disorders

• Obesity and overweight - major contributors to mild-to-moderate hypertriglyceridemia (2-10 mmol/L or 176-880 mg/dL) 1, 2
• Metabolic syndrome - frequently associated with elevated triglycerides 1, 2
• Poorly controlled diabetes mellitus - can cause severely elevated triglycerides 1, 2
• Hypothyroidism - affects lipid metabolism leading to elevated triglycerides 1

Lifestyle Factors

• Excessive alcohol intake - particularly when combined with high saturated-fat diet 1, 2
• Physical inactivity - contributes to elevated triglycerides 1, 2
• Diet high in refined carbohydrates - increases triglyceride production 2

Medications

• Atypical antipsychotics - particularly clozapine and olanzapine 3
• Beta-blockers - especially atenolol 1
• Bile acid resins - can significantly raise triglycerides in predisposed individuals 1
• Estrogens - oral formulations more than transdermal 1, 4
• Protease inhibitors - used in HIV treatment 1
• Retinoic acid drugs - can affect lipid metabolism 1
• Sirolimus - immunosuppressant that can raise triglycerides 1
• Steroids - affect lipid metabolism 1
• Tamoxifen - can raise triglycerides 1
• Thiazide diuretics - commonly prescribed antihypertensives 1, 4

Other Medical Conditions

• Pregnancy - especially in the third trimester 1
• Chronic kidney disease - affects lipid metabolism 1
• Autoimmune disorders - such as systemic lupus erythematosus 1
• Chronic idiopathic urticaria - associated with lipid abnormalities 1

Classification of Hypertriglyceridemia

• Mild: 150-199 mg/dL (1.7-2.3 mmol/L) 1
• Moderate: 200-999 mg/dL (2.3-11.3 mmol/L) 1
• Severe: 1,000-1,999 mg/dL (11.3-22.6 mmol/L) 1
• Very severe: ≥2,000 mg/dL (≥22.6 mmol/L) 1

Clinical Implications

• Mild to moderate hypertriglyceridemia (150-999 mg/dL) may increase cardiovascular disease risk 1, 2
• Severe hypertriglyceridemia (≥1,000 mg/dL) significantly increases the risk of acute pancreatitis 1, 2
• Very severe hypertriglyceridemia (≥2,000 mg/dL) poses an immediate risk for pancreatitis 1

Evaluation Approach

• Assess for secondary causes including diet, alcohol intake, medications, and underlying medical conditions 1, 4
• Screen for other components of metabolic syndrome (abdominal obesity, hypertension, low HDL-C, elevated fasting glucose) 2
• Consider genetic testing in cases of severe hypertriglyceridemia without obvious secondary causes, especially with family history 1
• Calculate non-HDL cholesterol and remnant cholesterol to better assess cardiovascular risk 1

Management Considerations

• Address underlying secondary causes before initiating specific triglyceride-lowering therapy 4, 5
• For medication-induced hypertriglyceridemia, consider alternative agents when possible 1, 3
• Lifestyle modifications including weight reduction, limiting alcohol, reducing refined carbohydrates, and increasing physical activity are first-line interventions 4
• Pharmacotherapy depends on triglyceride levels and cardiovascular risk 4, 5