title: Impact of genetic defects on atherosclerosis in patients suspected of familial hypercholesterolaemia.
abstract: BACKGROUND
  Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, we assessed whether patients with mutations of low-density lipoprotein (LDL) receptor and apolipoprotein B genes related to familial hypercholesterolaemia (FH) have a different degree of atherosclerosis than those without such mutations.
  
  
  METHODS
  In our lipid clinics, 273 patients were selected on the basis of a severe hypercholesterolaemia (cholesterol above 95th percentile) and a family history of early cardiovascular disease. By molecular genetic test, 122 patients were classified as FH. Atherosclerosis was evaluated by the ultrasonographic measurement of intima-media thickness (IMT) in the carotid and femoral arteries.
  
  
  RESULTS
  Despite the fact that non-FH individuals had a higher prevalence of obesity, hypertension, diabetes and hypertriglyceridaemia, FH individuals had significantly greater carotid and femoral IMT than non-FH patients: difference between carotid and femoral IMT, respectively, 0.19 mm (95% CI, 0.08-0.29; P < 0.001) and 0.20 mm (95% CI, 0.09-0.35; P = 0.001), respectively. These differences remained statistically significant after adjustment for the various risk factors as well as in sub-analysis restricted to the patients with LDL-cholesterol between 240 and 300 mg dL-1 (range with similar distribution in the two groups). When classified according to the severity of their mutations, FH individuals with null LDL receptor allele tended to have thicker carotid IMT than FH individuals carrying the LDL receptor-defective allele.
  
  
  CONCLUSIONS
  Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher degree of atherosclerosis. This suggests that molecular genetic identification of FH may be helpful to evaluate better the coronary heart disease risk in these patients.
authors.affiliation: Department of Internal Medicine, Centre Hospitalier Jolimont-Lobbes, Rue Ferrer 159, B-7100 Haine-Saint-Paul, Belgium. descaoli@skypro.be
authors.forename: O S
authors.initials: OS
authors.lastname: Descamps
authors.forename: J P
authors.initials: JP
authors.lastname: Gilbeau
authors.forename: X
authors.initials: X
authors.lastname: Leysen
authors.forename: F
authors.initials: F
authors.lastname: Van Leuven
authors.forename: F R
authors.initials: FR
authors.lastname: Heller
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000235:genetics*; D001161:Arteriosclerosis / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*; D012307:Risk Factors; D014463:Ultrasonography
chemical_list: D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D011973:Receptors, LDL