There are currently three accepted resources for FH diagnosis: the Simon Broom Criteria, the MEDPED Criteria, and the FH Dutch Lipid Clinic Criteria.
|SIMON BROOME DIAGNOSTIC CRITERIA FOR FAMILIAL HYPERCHOLESTEROLEMIA1|
|1|| Total cholesterol levels > 290mg/dL (7.5 mmol/L) or LDL-C > 190 mg/dL (4.9 mmol/L) in adults. Total cholesterol levels > 260 mg/dL (6.7 mmol/L) or LDL-C > 155 mg/dL (4.0 mmol/L)|
|2|| Tendon xanthomas in the patient or tendon xanthomas in a first or second degree relative.|
|3|| DNA-based evidence of an LDL-receptor mutation, familial defective apo B-100, or a PCSK9 mutation.|
|4|| Family history of myocardial infarction before age 50 years in a second degree relative or before age 60 years in a first degree relative.|
|5|| Family history of elevated total cholesterol > 290 mg/dL (7.5 mmol/L) in an adult first or second-degree relative.
Family history of elevated totacl cholesterol > 260 mg/dL (6.7 mmol/L) in a child, brother, or sister 16 years or younger.|
|Definite familial hypercholesterolemia = 1+2 or 3
Possible familial hypercholesterolemia = 1+4 or 5|
1 Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. American journal of epidemiology. 2004;160:407-420.
|DUTCH LIPID CLINIC NETWORK DIAGNOSTIC CRITERIA FOR FAMILIAL HYPERCHOLESTEROLEMIA1-3|
| First-degree relative with known premature* coronary and vascular disease OR
First-degree relative with known LDL-C level above the 95th percentile.||1|
| First-degree relative with tendinous xanthomata and/or arcus cornealis OR
Children aged less than 18 years with LDL-C level above the 95th percentile.||2|
| Patient with premature* coronary artery disease.||2|
| Patient with premature* cerebral or peripheral vascular disease.||1|
| Tendinous xanthomata||6|
| Arcus cornealis prior to age 45 years.||4|
|Cholesterol levels mg/dl (mmol/liter)|
| LDL-C >= 330 mg/dL ( ≥ 8.5)||8|
| LDL-C 250 – 329 mg/dL (6.5 – 8.4)||5|
| LDL-C 190 – 249 mg/dL (5.0 – 6.4)||3|
| LDL-C 155 – 189 mg/dL (4.0 – 4.9)||1|
| Functional mutation in the LDLR, apo B or PCSK9 gene||8|
|Diagnosis (diagnosis is based on the total number of points obtained)|
| Defnite familial hypercholesterolemia||>8|
| Probable familial hypercholesterolemia||6 – 8|
| Possible familial hypercholesterolemia||3 – 5|
| Unlikely familial hypercholesterolemia||<3|
*Premature = < 55 years in men; < 60 years in women
LDL-C = low density lipoprotein cholesterol; FH, familial hypercholesterolemia.
LDLR = low density lipoprotein receptor
Apo B = apolipoprotein B
PCSK9 = Proprotein convertase subtilisin/kexin type 9
1Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. American journal of epidemiology. 2004;160:407-420.2Haase A, Goldberg AC. Identi cation of people with heterozygous familial hypercholesterolemia. Current opinion in lipidology.
3Nordestgaard BG, Chapman MJ, Humphries SE, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in
the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European
Atherosclerosis Society. European heart journal. 2013;34:3478-3490a.
|MEDPED DIAGNOSTIC CRITERIA FOR FAMILIAL HYPERCHOLESTEROLEMIA*1-3|
|FH is diagnosed if total cholesterol exceeds these cutpoints in mg/dL (mmol/L)|
|Age (years)||First degree relative with FH||Second degree relative with FH||Third degree relative with FH||General population|
|<20||220 (5.7)||230 (5.9)||240 (6.2)||270 (7.0)|
|20 – 29||240 (6.2)||250 (6.5)||260 (6.7)||290 (7.5)|
|30 – 39||270 (7.0)||280 (7.2)||290 (7.5)||340 (8.8)|
|≥40||290 (7.5)||300 (7.8)||310 (8.0)||360 (9.3)|
*The total cholesterol cutpoints for FH is dependent upon the confirmed cases of FH in the family.
If FH is not diagnosed in the family, then the cutpoint for diagnosis is as per “general population.”
1Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. American journal of epidemiology. 2004;160:407-420.2Haase A, Goldberg AC. Identi cation of people with heterozygous familial hypercholesterolemia. Current opinion in lipidology. 2012;23:282-289.3Williams RR, Hunt SC, Schumacher MC, et al. Diagnosing heterozygous familial hypercholesterolemia using new practical
criteria validated by molecular genetics. The American journal of cardiology. 1993;72:171-176.