title: Premature coronary heart disease and autosomal dominant hypercholesterolemia: Increased risk in women with LDLR mutations.
abstract: BACKGROUND
  For patients with autosomal dominant hypercholesterolemia (ADH), it remains unclear whether differences exist in the risk of premature coronary heart disease (CHD) between patients with confirmed mutations in low-density lipoprotein receptor (LDLR) vs those without detectable mutations.
  
  
  OBJECTIVE
  This study sought to assess the risk of premature CHD in ADH patients with mutations in LDLR (referred to as familial hypercholesterolemia [FH]) vs those without detectable mutations (unexplained ADH), stratified by sex.
  
  
  METHODS
  Comparative study of premature CHD in a multiethnic cohort of 111 men and 165 women meeting adult Simon-Broome criteria for ADH.
  
  
  RESULTS
  Women with FH (n = 51) had an increased risk of premature CHD compared with unexplained ADH women (n = 111; hazard ratio [HR], 2.74; 95% confidence interval, 1.40-5.34; P = .003) even after adjustment for lipid levels and traditional CHD risk factors (HR, 2.53 [1.10-5.83]; P = .005). Men with FH (n = 42), in contrast, had a similar risk of premature CHD when compared with unexplained ADH men (n = 66; unadjusted: HR, 1.48 [0.84-2.63]; P = .18; adjusted: HR, 1.04 [0.46-2.37]; P = .72). To address whether mutation status provides additional information beyond LDL-cholesterol level, we analyzed premature CHD risk for FH vs unexplained ADH at various percentiles of LDL-cholesterol: the risk ratios were significant for women at 25th percentile (HR, 4.90 [1.69-14.19]) and 50th percentile (HR, 3.44 [1.42-8.32]) but not at 75th percentile (HR, 1.99 [0.95-4.17]), and were not significant for men at any percentile.
  
  
  CONCLUSIONS
  Our findings suggest that genetic confirmation of ADH may be important to identify patient's risk of CHD, especially for female LDLR mutation carriers.
authors.affiliation: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: Zahid.ahmad@utsouthwestern.edu.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Ahmad
authors.affiliation: Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Xilong
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Jedrek
authors.initials: J
authors.lastname: Wosik
authors.affiliation: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Preethi
authors.initials: P
authors.lastname: Mani
authors.affiliation: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Joye
authors.initials: J
authors.lastname: Petr
authors.affiliation: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: George
authors.initials: G
authors.lastname: McLeod
authors.affiliation: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Shatha
authors.initials: S
authors.lastname: Murad
authors.affiliation: Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Clinical Sciences, UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Beverley
authors.initials: B
authors.lastname: Adams-Huet
authors.affiliation: Division of Nutrition and Metabolic Diseases, Center for Human Nutrition, UT Southwestern Medical Center, Dallas, TX, USA; Department of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA. Electronic address: Abhimanyu.garg@utsouthwestern.edu.
authors.forename: Abhimanyu
authors.initials: A
authors.lastname: Garg
mesh_terms: D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D003327:Coronary Disease / Q000150:complications*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011973:Receptors, LDL / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D008078:Cholesterol, LDL; D011973:Receptors, LDL
keywords: APOB; Familial hypercholesterolemia; LDLR; Lipids; Premature coronary heart disease