Diagnostic Criteria for Familial Hypercholesterolemia (FH)

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The clinical diagnosis of FH is founded on personal and family history, physical examination, and lipid concentrations. Three groups have developed clinical diagnostic tools for FH: the US MedPed Program, the Simon Broome Register Group in the United Kingdom, and the Dutch Lipid Clinic Network.

US MEDPED Criteria for FH Diagnosis

Age, y First-Degree Relative With FH Second-Degree Relative With FH Third-Degree Relative With FH General Population
<20 220 mg/dL (5.7 mmol/L) 230 mg/dL (5.9 mmol/L) 240 mg/dL (6.2 mmol/L) 270 mg/dL (7.0 mmol/L)
20–29 240 mg/dL (6.2 mmol/L) 250 mg/dL (6.5 mmol/L) 260 mg/dL (6.7 mmol/L) 290 mg/dL (7.5 mmol/L)
30–39 270 mg/dL (7.0 mmol/L) 280 mg/dL (7.2 mmol/L) 290 mg/dL (7.5 mmol/L) 340 mg/dL (8.8 mmol/L)
≥40 290 mg/dL (7.5 mmol/L) 300 mg/dL (7.8 mmol/L) 310 mg/dL (8.0 mmol/L) 360 mg/dL (9.3 mmol/L)

FH Is Diagnosed if Total Cholesterol Exceeds These Cut-Off Points in mg/dL (mmol/L)*

FH indicates familial hypercholesterolemia; MEDPED, Make Early Diagnosis to Prevent Early Death.
*The total cholesterol cut-off points for FH are dependent upon the confirmed cases of FH in the family. If FH is not diagnosed in the family, then the cut-off point for diagnosis is as per “general population.”

 

Simon Broome Criteria for the Diagnosis of FH (UK FH Registers Criteria)

Possibility Criteria
Definite In adults: TC >7.5 mmol/L (290.0 mg/dL) (or when available, LDL-C >4.9 mmol/L [189.5 mg.dL])
In pediatric patients: TC >6.7 mmol/L (259.1 mg/dL), or LDL-C >4 mmol/L (154.7 mg/dL), AND
Tendon xanthoma in the patient or first/second-degree relative, OR alternatively:
Presence of LDL-R, ApoB, or PCSK9 mutation
Possible In adults: TC >7.5 mmol/L (290.0 mg/dL) (or when available, LDL-C >4.9 mmol/L [189.5 mg.dL])
In pediatric patients: TC >6.7 mmol/L (259.1 mg/dL), or LDL-C >4 mmol/L (154.7 mg/dL), AND
Family history of MI <50 y old in second-degree relative or <60 y old in first-degree relative OR alternatively
Family history of TC >7.5 mmol/L (290.0 mg/dL) in a first- or second-degree relative.

To convert LDL-C in mmol/L to mg/dL, multiply by 38.67. ApoB indicates apolipoprotein B; FH, familial hypercholesterolemia; LDL, low-density lipoprotein; LDL-R, low-density lipoprotein receptor; MI, myocardial infarction; PCSK9, proprotein convertase subtilisin/kexin type 9; TC, total cholesterol.

 

Dutch Lipid Network Criteria for Diagnosis of FH

Criteria Score
Family history
Premature CVD (men <55 y old, women <60 y old) in first-degree relative, OR 1
LDL >95th percentile in first-degree relative AND/OR 1
Tendon xanthoma and/or arcus cornealis in first-degree relative, OR 2
LDL >95th percentile in children <18 y old 2
Personal history
Premature CAD in patient (men <55 y old, women <60 y old) 2
Premature cerebral or peripheral vascular disease (men <55 y old, women <60 y old) 1
Clinical examination
Tendon xanthomas, OR 6
Corneal arcus younger than 45 y old 4
LDL
>330 mg/dL (8.5 mmol/L) 8
250–329 mg/dL (6.5–8.5 mmol/L) 5
190–249 mg/dL (4.9–6.4 mmol/L) 3
155–189 mg/dL (4.0–4.9 mmol/L) 1
Presence of functional LDL-R mutation (in the LDL-R, ApoB, or PCSK9 gene) 8
Diagnosis based on the overall score
Definite >8
Probable 6–8
Possible 3–5
Unlikely <3

ApoB indicates apolipoprotein B; CAD, coronary artery disease; CVD, cardiovascular disease; FH, familial hypercholesterolemia; LDL, low-density lipoprotein; LDL-R, low-density lipoprotein receptor; PCSK9, proprotein convertase subtilisin/kexin type 9.

 

References:

  1. McGowan MP, Hosseini Dehkordi SH, Moriarty PM, Duell PB. Diagnosis and Treatment of Heterozygous Familial Hypercholesterolemia. J Am Heart Assoc. 2019;8(24):e013225. [Medline]
  2. Sturm AC, Knowles JW, Gidding SS, et al. Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. J Am Coll Cardiol. 2018;72(6):662-680. [Medline]

Created Aug 27, 2020.