The US MEDPED (Make Early Diagnosis to Prevent Early Death) criteria is a widely recognized clinical tool for diagnosing Familial Hypercholesterolemia (FH) in the United States. Unlike other diagnostic systems like the Dutch Lipid Clinic Network or Simon Broome, which incorporate physical signs (such as xanthomas) or genetic testing, the MEDPED criteria rely primarily on total cholesterol levels, age, and family history (Williams et al., 1993).

This approach was designed to be a high-specificity screening tool suitable for “cascade testing”—a process where the relatives of a known FH patient are systematically screened to find additional cases early (McGowan et al., 2019).

The MEDPED Diagnostic Criteria

The diagnosis is based on whether a patient’s total cholesterol exceeds a specific threshold (cutoff). These thresholds are tiered based on how closely related the patient is to a person with a confirmed diagnosis of FH.

Total Cholesterol Cutoff Points (mg/dL)

(Source: Williams et al., 1993; McGowan et al., 2019)

Defining Degrees of Relatives

• 1st-Degree: Parents, siblings, or children.
• 2nd-Degree: Grandparents, aunts, uncles, nieces, or nephews.
• 3rd-Degree: First cousins or great-grandparents.

Clinical Logic and Performance

The MEDPED criteria operate on the principle that if a genetic mutation for FH is already known to exist in a family, the “bar” for diagnosing a relative should be lower.

• High Specificity: The MEDPED thresholds are set to maintain a specificity of approximately 98%. This means that if a person meets these criteria, there is a very low chance of a “false positive” diagnosis (Williams et al., 1993).
• Sensitivity: The sensitivity varies. It is highest (approx. 88%) when testing first-degree relatives of a known patient and lowest (approx. 54%) when screening the general population without a known family link.
• Focus on Total Cholesterol: While modern medicine often emphasizes LDL-C, MEDPED originally utilized total cholesterol because it was the most commonly available and standardized measurement during the program’s inception.

Strengths and Limitations

Strengths

• Simplicity: Does not require specialized physical exams (searching for tendon xanthomas) or expensive genetic sequencing to provide a clinical diagnosis.
• Effective for Families: It is the premier tool for “cascade screening,” allowing clinicians to trace the condition through family trees efficiently.

Limitations

• Excludes Other Factors: It ignores physical findings like corneal arcus or tendon xanthomas, which are included in the Simon Broome or Dutch Lipid Clinic Network criteria.
• General Population Use: It is significantly less effective at identifying FH in individuals who do not yet have a diagnosed relative (the “index case”).

References

1. Williams, R. R., et al. (1993). Selection, and screening for familial hypercholesterolemia. American Journal of Cardiology, 72(2), 161-176.
2. McGowan, M. P., et al. (2019). Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia. Journal of the American Heart Association, 8(24), e013225. https://doi.org/10.1161/JAHA.119.013225
3. Gidding, S. S., et al. (2015). The CASCADE FH Registry: Design, Baseline Characteristics, and Follow-up. Journal of Clinical Lipidology.
4. National Center for Biotechnology Information (NCBI). Screening for Lipid Disorders in Children and Adolescents: MEDPED Criteria. [Online Table].