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Hypertriglyceridemia
What's new
The American Association of Clinical Endocrinology (AACE) has published a focused update on pharmacotherapy for dyslipidemia, including hypertriglyceridemia. Eicosapentaenoic acid (EPA) is suggested alongside statins for patients with hypertriglyceridemia (150-499 mg/dL) who have or are at high risk of atherosclerotic cardiovascular disease. Niacin should be avoided due to a lack of meaningful clinical benefits and a significant risk of adverse events. .
Background
Overview
Definition
Hypertriglyceridemia is defined as fasting triglycerides ≥ 150 mg/dL, which is associated with an increased risk for coronary heart disease.
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Pathophysiology
Underlying pathophysiology occurs through abnormalities in hepatic VLDL production, and intestinal chylomicron synthesis; dysfunctional LPL-mediated lipolysis or impaired remnant clearance. Primary etiology includes genetic mutations (LPL, APOC3, APOA5 genes), while secondary etiologies may consist of obesity, metabolic syndrome, diabetes, alcohol use, renal disease, pregnancy, and MASLD.
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Epidemiology
The prevalence of hypertriglyceridemia in the US is estimated at 29% in men and 21% in women.
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Disease course
Clinical manifestations include eruptive cutaneous xanthomata, lipemia retinalis, tuberous xanthoma, palmar crease xanthomas, hepatosplenomegaly, focal neurologic symptoms (irritability), and recurrent epigastric pain with an increased risk of pancreatitis seen mostly with both familial chylomicronemia and primary mixed hyperlipidemia. Hypertriglyceridemia is associated with an increased risk of coronary heart disease, T2DM, and acute pancreatitis with a reduction in health-related QoL.
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Prognosis and risk of recurrence
Hypertriglyceridemia with high (150-500 mg/dL) and very high levels (> 500 mg/dL) is associated with increased risk of all-cause mortality with hazard ratio of 1.49 (95% CI 1.36-1.63, p < 0.001) and 3.08 (95% CI 1.46-6.50, p < 0.01), respectively.
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Guidelines
Key sources
The following summarized guidelines for the evaluation and management of hypertriglyceridemia are prepared by our editorial team based on guidelines from the American Association of Clinical Endocrinologists (AACE 2025), the Endocrine Society (ES 2020,2012), the European Society of Cardiology (ESC/EAS 2020), and the American College of Preventive Medicine (ACPM/ADA/PCNA/ABC/ASPC/AAPA/AGS/AHA/ACC/APhA 2019).
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Screening and diagnosis
Indications for screening: as per ES 2012 guidelines, screen adults for hypertriglyceridemia with measurement of serum triglycerides as part of a lipid panel at least every 5 years.
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Diagnosis
Diagnostic investigations
Initial evaluation: as per ES 2012 guidelines, evaluate patients with elevation of fasting triglycerides for secondary causes of hypertriglyceridemia, including endocrine conditions and medications. Focus treatment on such secondary causes.
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Lipoprotein levels
Medical management
General principles: as per ES 2020 guidelines, initiate pharmacologic treatment as adjunct to dietary modifications and exercise to prevent pancreatitis in adult patients with fasting triglyceride levels > 500 mg/dL (5.6 mmol/L).
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Statins
Fibrates
PUFAs
Bile acid sequestrants
Niacin
Nonpharmacologic interventions
Lifestyle modification: as per AAPA/ABC/ACC/…/PCNA 2019 guidelines, advise implementing a very low-fat diet, avoiding refined carbohydrates and alcohol in adult patients with severe hypertriglyceridemia (fasting triglycerides ≥ 500 mg/dL; ≥ 5.7 mmol/L), especially with fasting triglycerides ≥ 1,000 mg/dL (≥ 11.3 mmol/L), if triglycerides are persistently elevated or increasing after addressing other causes of hypertriglyceridemia.
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Specific circumstances
Patients with triglyceride-induced pancreatitis
As per ES 2020 guidelines:
Avoid performing acute plasmapheresis as first-line therapy to reduce triglyceride levels in patients with triglyceride-induced pancreatitis.
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Avoid administering routine insulin infusion in patients with triglyceride-induced pancreatitis not having diabetes.
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