title: Impact of genetic defects on coronary atherosclerosis in patients suspected of having familial hypercholesterolaemia.
abstract: BACKGROUND
  In the present study we assessed whether the presence of genetic mutations typical of familial hypercholesterolaemia (FH) was associated with greater atherosclerosis in the coronary vessels in patients with severe hypercholesterolaemia and a family history of early cardiovascular disease.
  
  
  METHODS
  Two hundred and thirty-five patients selected for having severe hypercholesterolaemia and a family history of cardiovascular disease were classified as FH (57 men and 38 women) or non-FH (84 men and 56 women) according to a genetic analysis of the LDL-R or ApoB genes. Coronary atherosclerosis was evaluated by performing a thoracic CT scan and exercise stress testing.
  
  
  RESULTS
  Familial hypercholesterolaemia individuals had a significantly higher prevalence of coronary calcification than the non-FH patients from among both the men (OR = 3.90; 95% CI 1.86-8.19; P < 0.001) and the women (OR = 2.34; 95% CI 1.01-5.48; P = 0.05). In exercise stress testing, ECG abnormalities suggestive of cardiac ischaemia were found with a higher prevalence in the FH patients than the non-FH patients from among both the men (OR 6.15; 95% CI 2.16-17.5; P < 0.001) and the women (OR 4.76; 95% CI 0.91-24.6; P = 0.06). All differences were statistically significant after adjusting for age and cholesterol and for most classical risk factors that differed between the FH and non-FH groups.
  
  
  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 prevalence of coronary artery calcifications and a positive exercise stress test. These results suggest that despite a similar phenotype, patients carrying mutations suggestive of FH may have a greater cardiovascular risk than patients without these mutations.
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: R
authors.initials: R
authors.lastname: Luwaert
authors.forename: F R
authors.initials: FR
authors.lastname: Heller
mesh_terms: D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000235:genetics; D002114:Calcinosis / Q000235:genetics; D003324:Coronary Artery Disease / Q000209:etiology / Q000235:genetics*; D005080:Exercise Test; D005260:Female; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000150:complications / Q000235:genetics*; D017270:Lipoprotein(a) / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011973:Receptors, LDL / Q000235:genetics; D012307:Risk Factors
chemical_list: D001055:Apolipoproteins B; D017270:Lipoprotein(a); D011973:Receptors, LDL