Cardiology > Hypertriglyceridemia    

Background 

Hypertriglyceridemia refers to elevated levels of triglycerides in the bloodstream, typically defined as fasting triglyceride levels >150 mg/dL. It is an important component of dyslipidemia and is associated with increased risk of atherosclerotic cardiovascular disease (ASCVD), insulin resistance, and acute pancreatitis when levels are severely elevated.

II) Classification/Types

By Severity (based on fasting triglycerides) 

• • Normal: <150 mg/dL 

• • Borderline High: 150–199 mg/dL 

• • High: 200–499 mg/dL 

• • Very High: ≥500 mg/dL 

• • Severe: ≥1,000 mg/dL (risk of pancreatitis) 

By Cause: 

• • Primary (genetic): 

• • • Familial hypertriglyceridemia 

• • • Familial combined hyperlipidemia 

• • • Type I, IV, or V hyperlipoproteinemia 

• • Secondary: 

• • • Due to lifestyle or medical conditions (see etiology) 

III) Pathophysiology 

Triglycerides are transported in chylomicrons and very low-density lipoproteins (VLDL). Overproduction, impaired lipolysis, or decreased clearance of these particles results in hypertriglyceridemia. Insulin resistance plays a key role by promoting hepatic VLDL production and reducing lipoprotein lipase activity. Extremely high levels may cause chylomicronemia, leading to pancreatitis. 

IV) Epidemiology

• • Affects ~25–30% of adults in the U.S. 

• • More prevalent in individuals with metabolic syndrome, obesity, or diabetes 

• • Strongly linked to sedentary lifestyle and poor diet 

• • Increases with age and is more common in men 

Etiology 

I) Causes

Primary (genetic disorders): 

• • • Familial hypertriglyceridemia 

• • • Familial dysbetalipoproteinemia 

• • • Familial combined hyperlipidemia 

Secondary: 

• • • Uncontrolled diabetes mellitus 

• • • Obesity/metabolic syndrome 

• • • Excessive alcohol use 

• • • Hypothyroidism 

• • • Chronic kidney disease 

• • • Pregnancy 

• • • Certain medications (estrogens, corticosteroids, beta-blockers, protease inhibitors, retinoids, antipsychotics) 

II) Risk Factors

• • Obesity 

• • Sedentary lifestyle 

• • High carbohydrate intake 

• • Excessive alcohol consumption 

• • Poorly controlled diabetes 

• • Genetic predisposition 

• • Chronic renal or liver disease 

• • Use of certain medications 

Clinical Presentation 

I) History (Symptoms)

• • Often asymptomatic 

• • Symptoms when triglycerides >1,000 mg/dL: 

• • Abdominal pain (pancreatitis) 

• • Nausea/vomiting 

• • History of recurrent pancreatitis 

• • Fatigue 

• • Eruptive skin lesions (eruptive xanthomas) 

II) Physical Exam (Signs)

• • Eruptive xanthomas: small yellow papules on extensor surfaces 

• • Lipemia retinalis: milky appearance of retinal vessels (severe cases) 

• • Hepatosplenomegaly (in familial forms) 

• • Signs of associated conditions: central obesity, acanthosis nigricans (insulin resistance) 

Differential Diagnosis (DDx) 

• • Familial combined hyperlipidemia 

• • Dysbetalipoproteinemia (ApoE mutations) 

• • Diabetic ketoacidosis (may cause secondary elevation) 

• • Acute pancreatitis from other causes 

• • Cholestatic liver disease 

• • Hypothyroidism 

• • Nephrotic syndrome 

Diagnostic Tests 

Initial Work-Up 

• • Fasting lipid panel (total cholesterol, LDL, HDL, triglycerides) 

• • HbA1c, fasting glucose (for diabetes evaluation) 

• • TSH (rule out hypothyroidism) 

• • CMP: liver and kidney function 

• • Urinalysis: proteinuria (if nephrotic syndrome suspected) 

• • Amylase/lipase: if symptoms of pancreatitis present 

Advanced Testing 

• • ApoB and lipoprotein analysis 

• • Genetic testing (if familial disorder suspected) 

• • Lipoprotein electrophoresis 

• • Imaging: abdominal ultrasound or CT if pancreatitis suspected 

Treatment 

I) Initial Approach

• • Assess for secondary causes and treat accordingly 

• • Initiate lifestyle modification for all patients 

• • Immediate triglyceride reduction if >500–1,000 mg/dL to prevent pancreatitis 

• • Consider pharmacologic therapy if triglycerides persistently >200 mg/dL and ASCVD risk is elevated 

II) Medications

Patient Education, Screening, Vaccines 

Education 

• • Low-carbohydrate, low-sugar, low-fat diet 

• • Avoid alcohol completely if TG >500 mg/dL 

• • Regular aerobic exercise (≥150 min/week) 

• • Weight loss for overweight or obese patients 

• • Medication adherence 

Screening 

• • Lipid panel: 

• • Adults ≥20 years: every 4–6 years if low risk 

• • Annually if on therapy or high risk 

• • Screen earlier in those with family history of hyperlipidemia or pancreatitis 

Vaccinations 

• • Influenza, pneumococcal, and COVID-19 (especially in patients with ASCVD or diabetes) 

Consults/Referrals 

• • Endocrinology: uncontrolled diabetes or insulin resistance 

• • Cardiology: if high ASCVD risk or established disease 

• • Gastroenterology: for pancreatitis evaluation 

• • Lipid specialist/geneticist: suspected familial hypertriglyceridemia 

• • Nutritionist: dietary modification plan 

• • Nephrology or Hepatology: if associated renal or liver disease 

Follow-Up 

Short-Term 

• • Recheck fasting triglycerides 4–12 weeks after therapy 

• • Monitor for side effects of medications (LFTs, myopathy with statins) 

Long-Term 

• • Lifelong risk reduction through diet and physical activity 

• • Monitor for cardiovascular disease and pancreatitis 

• • Reinforce lifestyle modification at every visit 

Prognosis 

• • Good if triglycerides are controlled and secondary causes addressed 

• • Poor if untreated, with high risk for pancreatitis and cardiovascular events 

• • Familial cases may be more severe and require intensive management