title: Assessment of carotid atherosclerosis in normocholesterolemic individuals with proven mutations in the low-density lipoprotein receptor or apolipoprotein B genes.
abstract: BACKGROUND
  Genetic cascade screening for heterozygous familial hypercholesterolemia (FH) revealed that 15% of individuals given this diagnosis do not exhibit elevated low-density lipoprotein cholesterol (LDL-C) levels. We assessed whether cardiovascular risk for these individuals differs from that of hypercholesterolemic FH heterozygotes and unaffected relatives.
  
  
  RESULTS
  Individuals aged 18 to 55 years were recruited within 18 months after genetic screening. Three groups were studied: subjects given a molecular diagnosis of FH and with LDL-C levels at genetic screening below the 75th percentile (FH-low), subjects with FH and an LDL-C level above the 90th percentile (FH-high), and subjects without FH (no-FH). We measured carotid intima-media thickness (IMT) by ultrasonography. Differences in carotid IMT among the groups were assessed using multivariate linear regression analyses. Mean carotid IMT of 114 subjects in the FH-low group (0.623 mm; 95% CI, 0.609 to 0.638 mm) was significantly smaller than that of 162 subjects in the FH-high group (0.664 mm; 95% CI, 0.648 to 0.679 mm; P<0.001) and did not significantly differ from the mean carotid IMT in 145 subjects in the no-FH group (0.628 mm; 95% CI, 0.613 to 0.642 mm; P=0.67).
  
  
  CONCLUSIONS
  Our findings suggest that the risk of cardiovascular disease in patients with FH to a large extent is related to LDL-C levels and not to the presence of a mutation per se. Consequently, this study cautiously suggests that individuals with an FH genotype without expression of hypercholesterolemia may not require a pharmaceutical intervention that is as aggressive as the standard for subjects with FH.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, The Netherlands. r.huijgen@amc.uva.nl
authors.forename: Roeland
authors.initials: R
authors.lastname: Huijgen
authors.forename: Maud N
authors.initials: MN
authors.lastname: Vissers
authors.forename: Iris
authors.initials: I
authors.lastname: Kindt
authors.forename: Mieke D
authors.initials: MD
authors.lastname: Trip
authors.forename: Eric
authors.initials: E
authors.lastname: de Groot
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Hutten
mesh_terms: D000293:Adolescent; D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology; D002340:Carotid Artery Diseases / Q000175:diagnosis*; D059168:Carotid Intima-Media Thickness; D002784:Cholesterol / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*; D055815:Young Adult
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D011973:Receptors, LDL; D002784:Cholesterol