Abstract
Familial hypercholesterolemia (FH) is an autosomal codominant lipoprotein disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease. Definitions for FH rely on complex algorithms that are on the basis of levels of total or LDL-C, clinical features, family history, and DNA analysis that are often difficult to obtain. We propose a novel simplified definition for FH. Definite FH includes: (1) elevated LDL-C (>= 8.50 mmol/L); or (2) LDL-C >= 5.0 mmol/L (for age 40 years or older; >= 4.0 mmol/L if age younger than 18 years; and >= 4.5 mmol/L if age is between 18 and 39 years) when associated with at least 1 of: (1) tendon xanthomas; or (2) causal DNA mutation in the LDLR, APOB, or PCSK9 genes in the proband or first-degree relative. Probable FH is defined as subjects with an elevated LDL-C (>= 5.0 mmol/L) and the presence of premature atherosclerotic cardiovascular disease in the patient or a first-degree relative or an elevated LDL-C in a first-degree relative. LDL-C cut points were determined from a large database comprising > 3.3 million subjects. To compare the proposed definition with currently used algorithms (ie, the Simon Broome Register and Dutch Lipid Clinic Network), we performed concordance analyses in 5987 individuals from Canada. The new FH definition showed very good agreement compared with the Simon Broome Register and Dutch Lipid Clinic Network criteria (kappa = 0.969 and 0.966, respectively). In conclusion, the proposed FH definition has diagnostic performance comparable to existing criteria, but adapted to the Canadian population, and will facilitate the diagnosis of FH patients.