Hypertriglyceridemia Workup

  • Author: Elena Citkowitz, MD, PhD, FACP; Chief Editor: George T Griffing, MD   more...
 
Updated: Jan 5, 2010
 

Laboratory Studies

  • Lipid analysis
    • Elevated triglycerides are determined by direct laboratory analysis of serum or plasma after a 10- to 12-hour fast. Determining which lipoprotein abnormality is the cause of hypertriglyceridemia is less straightforward.
    • VLDLs are increased and chylomicrons are absent when triglyceride levels are elevated but below 1000 mg/dL. If triglyceride levels are above 1000 mg/dL, both VLDL and chylomicrons are usually present.
    • If the triglycerides are elevated but less than 1000 mg/dL and the total cholesterol is elevated, the lipoprotein abnormality may be caused by either (1) elevations of both LDL and VLDL, which is type IIb or mixed hyperlipoproteinemia, or (2) increased remnant VLDL or IDL, which is type III hyperlipidemia or dysbetahyperlipoproteinemia.
    • The 2 disorders may be distinguished by obtaining a direct LDL-c analysis, which is available at most commercial laboratories. If the direct LDL-c is significantly lower than the calculated LDL-c, a diagnosis of type III hyperlipoproteinemia is likely.
    • The only procedure that reliably distinguishes between a mixed hyperlipoproteinemia (increased LDL-c and triglycerides) and type III hyperlipoproteinemia (increased IDL) is beta quantification. This expensive analysis involves ultracentrifugation followed by electrophoresis. It is not performed by most commercial or hospital laboratories. Specialized lipid centers, such as those at Tufts and Johns Hopkins Medical Centers, should be contacted if type IIb or III must be confirmed. In most clinical settings, however, distinguishing between these entities is rarely necessary because the treatment of both conditions is essentially the same. Diet modification, exercise, and appropriate weight loss improve both. Type IIb and III also respond to the same medications—niacin and/or fibric acid derivatives.[9] Therefore, no matter which diagnosis applies to a given patient, the treatment is the same.
  • Chylomicron determination
    • If the triglyceride levels are greater than 1000 mg/dL and the presence of chylomicrons must be confirmed, the simplest and most cost-effective test involves overnight refrigeration of an upright tube of plasma or serum.
    • If a creamy supernatant is seen the next day, chylomicrons are present.
    • If the infranatant is cloudy, high levels of VLDL are present (type V hyperlipidemia).
    • If the infranatant is clear, the VLDL content is normal and type I hypercholesterolemia (elevated chylomicrons only) should be suspected.
  • Type I hyperlipoproteinemia (pure hyperchylomicronemia)
    • To make a definitive diagnosis of type I hypercholesterolemia, deficiency of either LPL or apo C-II must be confirmed. The presence of LPL activity may be measured in plasma following intravenous heparin administration (50 IU of heparin per kg body weight) or by analysis of muscle or adipose tissue biopsy samples.
    • Defective or absent apo C-II must be determined at a lipid center that performs 1 of the 3 following assays: (1) gel electrophoresis, (2) radioimmunoassay, or (3) confirmation that LPL added to the patient's plasma is not active.
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Other Tests

Rule out secondary causes of hypertriglyceridemia, including diabetes mellitus and hypothyroidism.

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Procedures

If the diagnosis of eruptive xanthomas is in doubt, obtaining a biopsy of the suspicious lesions will reveal accumulations of fat (not cholesterol).

Normally, in patients with acute pancreatitis secondary to severe hypertriglyceridemia, triglyceride levels rapidly decrease, often by 1000 mg/dL each day when treated with standard medical therapy: NPO, IV hydration, and if needed, parenteral insulin to reduce plasma glucose levels. If triglyceride levels do not decrease or, more ominously, if they increase, more aggressive intervention with plasmapheresis is probably warranted.

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Contributor Information and Disclosures
Author

Elena Citkowitz, MD, PhD, FACP  Clinical Professor of Medicine, Yale University School of Medicine; Director, Cholesterol Management Center, Director, Cardiac Rehabilitation, Department of Medicine, Hospital of St Raphael

Elena Citkowitz, MD, PhD, FACP is a member of the following medical societies: American College of Physicians, American Heart Association, National Lipid Association, and Sigma Xi

Disclosure: Nothing to disclose.

Specialty Editor Board

Steven R Gambert, MD  Professor of Medicine, Johns Hopkins University School of Medicine; Director of Geriatric Medicine, University of Maryland Medical Center and R. Adams Cowley Shock Trauma Center

Steven R Gambert, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Yoram Shenker, MD  Chief of Endocrinology Section, Veterans Affairs Medical Center of Madison; Interim Chief, Associate Professor, Department of Internal Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Wisconsin at Madison

Yoram Shenker, MD is a member of the following medical societies: American Heart Association, Central Society for Clinical Research, and Endocrine Society

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

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Eruptive xanthomas on the back of a patient admitted with a triglyceride level of 4600 mg/dL and acute pancreatitis.
Close-up of eruptive xanthomas.
Composition of triglyceride-rich lipoproteins.
Lipoprotein lipase (LPL) releases free fatty acids from chylomicrons and produces chylomicron remnants that are small enough to take part in the atherosclerotic process.
Once very low-density lipoprotein (VLDL) has been metabolized by lipoprotein lipase, VLDL remnants in the form of intermediate-density lipoprotein (IDL) can be metabolized by hepatic lipase, producing LDL, or they can be taken up by the LDL receptor via either apolipoprotein B (apo B) or apo E.
Table 1. Fredrickson Classification of Hyperlipoproteinemia
Type Serum elevation Lipoprotein elevation
ICholesterol and triglyceridesChylomicrons
IIaCholesterolLDL*
IIbCholesterol and triglyceridesLDL, VLDL**
IIICholesterol and triglyceridesIDL***
IVTriglyceridesVLDL
VCholesterol and triglyceridesVLDL, chylomicrons
*LDL (low-density lipoprotein)



**VLDL (very low-density lipoprotein)



***IDL (intermediate-density lipoprotein)



Table 2. Classification of Triglycerides (TG)
ClassificationTG level, mg/dL
Normal TG level< 150
Borderline-high TG level150-199
High TG level200-499
Very high TG level>500
Table 3. Classification of LDL Cholesterol and Non-HDL Cholesterol
ClassificationLDL Goal,



mg/dL



Non-HDL Goal,



mg/dL



CHD* and CHD risk equivalent, diabetes mellitus, and the following:10-year risk for CHD >20%< 100< 130
Two or more risk factors and the following:10-year risk < 20%< 130< 160
0-1 risk factor< 160< 190
*Coronary heart disease
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