Diagnostic Criteria for Familial Hypercholesterolemia (FH)

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.