title: Impact of atorvastatin treatment in first-degree relatives of patients with premature coronary artery disease with endothelial dysfunction: a double-blind, randomized, placebo-controlled crossover trial.
abstract: BACKGROUND
  A family history of premature coronary artery disease (CAD) is a well-known risk factor for cardiovascular events.
  
  
  OBJECTIVE
  Atorvastatin may improve endothelial dysfunction (ED) in the first-degree relatives (FDRs) of patients with premature CAD with ED.
  
  
  METHODS
  Thirty-five FDRs (median age, 52 years [interquartile range (IQR), 46-57 years], 21 male) of patients with premature CAD with ED were recruited in a prospective trial with a crossover double-blind design: 6 weeks of treatment with atorvastatin 40 mg/day followed by placebo, or vice versa. After each treatment, the digital pulse wave amplitude was determined by EndoPAT to obtain the reactive hyperemia index (RHI), a measure for endothelial function. The primary outcome was the difference of RHI between atorvastatin and placebo treatment.
  
  
  RESULTS
  Low-density lipoprotein cholesterol was lower after atorvastatin compared with placebo treatment (124 [102-145] mg/dL vs 67 [50-73] mg/dL, P < 0.001). However, RHI was not different after atorvastatin compared with placebo treatment (1.9 [1.5-2.4] vs 1.9 [1.6-2.2], P = 0.902). Also, the augmentation index was similar after each treatment. These results were observed both in subjects who had indications for statin treatment (31%) and those who did not (69%) according to National Cholesterol Education Program Adult Treatment Panel III guidelines.
  
  
  CONCLUSIONS
  Despite improvement in the lipid profile, atorvastatin failed to improve ED in the FDRs of patients with premature CAD with ED. Although we identified those with ED in FDRs of patients with premature CAD as a high-risk group for future cardiovascular events, atorvastatin treatment may not be a beneficial primary prevention strategy for this population.
authors.affiliation: Division of Cardiology, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sung-Jin
authors.initials: SJ
authors.lastname: Hong
authors.forename: Hyuk-Jae
authors.initials: HJ
authors.lastname: Chang
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.forename: Dae Ryong
authors.initials: DR
authors.lastname: Kang
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Shin
authors.forename: In-Jeong
authors.initials: IJ
authors.lastname: Cho
authors.forename: Chi Young
authors.initials: CY
authors.lastname: Shim
authors.forename: Geu-Ru
authors.initials: GR
authors.lastname: Hong
authors.forename: Jong-Won
authors.initials: JW
authors.lastname: Ha
authors.forename: Namsik
authors.initials: N
authors.lastname: Chung
mesh_terms: D017668:Age of Onset; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D011322:Primary Prevention / Q000379:methods*; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D056910:Republic of Korea; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D011758:Pyrroles; D000069059:Atorvastatin