title: Hyperlipoproteinaemia(a) is a common cause of autosomal dominant hypercholesterolaemia.
abstract: Autosomal dominant hypercholesterolaemia (ADH) are a heterogeneous group of monogenic lipid disorders. The plasma level of lipoprotein(a) (Lp(a)) is a heritable trait associated with increased coronary heart disease (CHD) risk.
  
  
  OBJECTIVE
  To evaluate the frequency of elevated Lp(a) as a cause of ADH and the characteristics of subjects with high Lp(a) (hyperLp(a)).
  
  
  METHODS
  200 healthy subjects and 933 unrelated Spanish subjects with a clinical diagnosis of ADH who were screened for low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) gene mutations. Standard cardiovascular risk factors and blood lipid levels, including Lp(a), were evaluated. HyperLp(a) was defined as Lp(a) levels >or=95th centile of control values.
  
  
  RESULTS
  Lp(a) was higher in 263 subjects without LDLR or APOB mutations (nonLDLR/nonAPOB group) than in 670 subjects with mutations (FH group): 40.0 mg/dl (interquartile range (IR) 15.0-89.0) versus 31.0 mg/dl (IR 11.0-73.7) respectively, p = 0.002. HyperLp(a) was present in 23% of ADH subjects (odds ratio (OR) 5.6 (95% CI, 2.9 to 10.7) versus controls) and 29% of nonLDLR/nonAPOB subjects (OR 7.7; 3.9 to 15.4). After adjusting for Lp(a), LDL cholesterol levels were <95th centile in 28 (10.6%) nonLDLR/nonAPOB subjects and in 9 (1.3%) FH subjects. Lp(a) levels were nonsignificantly higher in ADH subjects with early-onset CHD than in those without (43.5 mg/dl, (IR, 12.0-82.0) versus 31.7 mg/dl (11.8-76.5), respectively).
  
  
  CONCLUSIONS
  HyperLp(a) is responsible for ADH in approximately 6% of nonLDLR/nonAPOB subjects. HyperLp(a) would not appear to be a risk factor for early-onset CHD in ADH, independently of whether genetic defects have or have not been demonstrated.
authors.affiliation: Lipid Unit and Molecular Research Laboratory, Hospital Universitario Miguel Servet, Instituto Aragonés de Ciencias de la Salud, Avda Isabel La Católica 1-3, 50009, Zaragoza, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Meriño-Ibarra
authors.forename: J
authors.initials: J
authors.lastname: Puzo
authors.forename: E
authors.initials: E
authors.lastname: Jarauta
authors.forename: A
authors.initials: A
authors.lastname: Cenarro
authors.forename: D
authors.initials: D
authors.lastname: Recalde
authors.forename: A L
authors.initials: AL
authors.lastname: García-Otín
authors.forename: E
authors.initials: E
authors.lastname: Ros
authors.forename: E
authors.initials: E
authors.lastname: Martorell
authors.forename: X
authors.initials: X
authors.lastname: Pintó
authors.forename: M
authors.initials: M
authors.lastname: Franco
authors.forename: D
authors.initials: D
authors.lastname: Zambón
authors.forename: A
authors.initials: A
authors.lastname: Brea
authors.forename: M
authors.initials: M
authors.lastname: Pocoví
authors.forename: F
authors.initials: F
authors.lastname: Civeira
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D006937:Hypercholesterolemia / Q000175:diagnosis* / Q000235:genetics*; D006951:Hyperlipoproteinemias / Q000175:diagnosis* / Q000235:genetics*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms; D011973:Receptors, LDL / Q000378:metabolism; D012307:Risk Factors; D013030:Spain
chemical_list: D008055:Lipids; D020033:Protein Isoforms; D011973:Receptors, LDL