title: Femoral atherosclerosis in heterozygous familial hypercholesterolemia: influence of the genetic defect.
abstract: OBJECTIVE
  The purpose of this study was to assess femoral atherosclerosis by ultrasound in patients with molecularly defined heterozygous familial hypercholesterolemia (FH) in comparison with matched control subjects and in relation to mutational class in the LDL receptor and apolipoprotein B (APOB) genes.
  
  
  RESULTS
  Femoral intima-media thickness (IMT) and plaque were evaluated in 146 FH patients carrying null alleles (n=48), defective-receptor alleles (n=62), undetermined-function alleles (n=25), or APOB defects (n=11) and in 193 healthy subjects. Twenty-three patients had coronary heart disease (CHD). The frequency of both tendon xanthomas and CHD was approximately 2-fold higher and average LDL cholesterol was 30 mg/dL higher in null-allele genotype compared with receptor-defective mutations. All femoral measurements were increased in FH patients versus controls (P<0.001), and null-allele mutations showed higher age-, sex-, and LDL cholesterol-adjusted maximum IMT than receptor-defective or APOB defects (P for trend, 0.001). By multivariate analysis, independent associations of mean IMT, a measure of early atherosclerosis, were age, LDL cholesterol, sex, and systolic blood pressure. Age, null-allele genotype, sex, and smoking explained 42% of the variability of maximum IMT, a measure of advanced atherosclerosis.
  
  
  CONCLUSIONS
  FH patients have increased femoral IMT in relation to mutational class. The findings support the usefulness of genetic testing in FH beyond securing the diagnosis.
authors: Unitat de Lípids, Servei d'Endocrinologia i Nutrició, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic, Barcelona, Spain.
authors: Mireia
authors: M
authors: Junyent
authors: Rosa
authors: R
authors: Gilabert
authors: Daniel
authors: D
authors: Zambón
authors: Miguel
authors: M
authors: Pocoví
authors: Miguel
authors: M
authors: Mallén
authors: Montserrat
authors: M
authors: Cofán
authors: Isabel
authors: I
authors: Núñez
authors: Fernando
authors: F
authors: Civeira
authors: Diego
authors: D
authors: Tejedor
authors: Emilio
authors: E
authors: Ros
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D005263:Femoral Artery; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011336:Probability; D012016:Reference Values; D017678:Sex Distribution; D017539:Tunica Intima / Q000473:pathology; D018608:Ultrasonography, Doppler
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL