What investigations should be done in a patient with hypertriglyceridemia (elevated triglycerides)?

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Investigations for Hypertriglyceridemia

Initial Lipid Assessment

Obtain at least two fasting lipid panels, preferably 2 weeks apart, to confirm the diagnosis and guide treatment decisions 1. Fasting measurements are essential to accurately classify severity and identify patients at risk for pancreatitis 1.

  • Measure fasting triglycerides, total cholesterol, HDL-C, and calculate LDL-C using the Martin-Hopkins method for more accurate LDL-C assessment in hypertriglyceridemia 1
  • Calculate non-HDL cholesterol (total cholesterol minus HDL-C) with a target goal of <130 mg/dL for moderate hypertriglyceridemia 1
  • Classify severity: Mild (150-199 mg/dL), Moderate (200-499 mg/dL), Severe (500-999 mg/dL), Very Severe (≥1,000 mg/dL) 1, 2

Evaluation for Secondary Causes

Screen systematically for reversible causes before initiating pharmacotherapy, as treating these conditions may eliminate the need for lipid-lowering medications 1.

Metabolic and Endocrine Testing

  • Hemoglobin A1c and fasting glucose to assess for diabetes mellitus or prediabetes, as poor glycemic control is often the primary driver of severe hypertriglyceridemia 1, 2
  • Thyroid-stimulating hormone (TSH) to rule out hypothyroidism 1
  • Serum creatinine and estimated GFR to assess for chronic kidney disease or nephrotic syndrome 1

Hepatic Assessment

  • Liver function tests (AST, ALT, alkaline phosphatase, gamma-GT) to screen for non-alcoholic fatty liver disease and assess baseline hepatic function before initiating fibrate therapy 1, 3

Additional Laboratory Tests

  • Urinalysis to screen for proteinuria suggesting nephrotic syndrome 3
  • Serum amylase and lipase if triglycerides ≥500 mg/dL and any abdominal symptoms are present, as the risk of acute pancreatitis is 14% at this level 2, 4

Cardiovascular Risk Assessment

Evaluate for other components of metabolic syndrome and cardiovascular risk factors to guide comprehensive management 1.

  • Assess for central obesity (waist circumference), hypertension, and abnormal glucose metabolism 1
  • Calculate 10-year ASCVD risk using the pooled cohort equations for patients aged 40-75 years to determine statin therapy indications 1, 2
  • Obtain detailed family history of premature cardiovascular disease, dyslipidemia, and genetic lipid disorders 1

Medication and Lifestyle Review

Conduct a thorough medication review and assess lifestyle factors that contribute to hypertriglyceridemia 1.

  • Review medications that elevate triglycerides: thiazide diuretics, beta-blockers, estrogen therapy, corticosteroids, bile acid sequestrants, antiretroviral protease inhibitors, immunosuppressants, and antipsychotics 1
  • Quantify alcohol consumption, as even 1 ounce daily increases triglycerides by 5-10%, and complete abstinence is mandatory for severe hypertriglyceridemia (≥500 mg/dL) 1, 2
  • Assess dietary intake of added sugars, saturated fats, and total fat consumption 1, 2

Special Considerations for Severe Hypertriglyceridemia

For patients with triglycerides ≥500 mg/dL, prioritize urgent evaluation to prevent acute pancreatitis 2, 4.

  • Measure serum amylase and lipase immediately if any abdominal symptoms are present 4
  • Consider genetic testing for familial chylomicronemia syndrome or familial combined hyperlipidemia in cases of severe primary hypertriglyceridemia, especially if family history is positive 1
  • Assess for multifactorial chylomicronemia syndrome, which is 40-60 fold more prevalent than monogenic conditions and results from genetic predisposition combined with secondary factors 1

Monitoring Parameters

Establish baseline values before initiating therapy and schedule appropriate follow-up 2, 4.

  • Baseline creatine kinase (CK) if fibrate or combination lipid therapy is planned, particularly in patients >65 years or with renal disease 1, 2
  • Reassess fasting lipid panel in 6-12 weeks after implementing lifestyle modifications, or 4-8 weeks after initiating or adjusting pharmacotherapy 1, 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Hypertriglyceridemia Management

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2026

Research

Hypertriglyceridemia.

Journal of the American Board of Family Medicine : JABFM, 2006

Guideline

Management of Severe Hypertriglyceridemia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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