title: Pharmacogenetic Risk Stratification in Angiotensin-Converting Enzyme Inhibitor-Treated Patients with Congestive Heart Failure: A Retrospective Cohort Study.
abstract: BACKGROUND
  Evidence for pharmacogenetic risk stratification of angiotensin-converting enzyme inhibitor (ACEI) treatment is limited. Therefore, in a cohort of ACEI-treated patients with congestive heart failure (CHF), we investigated the predictive value of two pharmacogenetic scores that previously were found to predict ACEI efficacy in patients with ischemic heart disease and hypertension, respectively. Score A combined single nucleotide polymorphisms (SNPs) of the angiotensin II receptor type 1 gene (rs275651 and rs5182) and the bradykinin receptor B1 gene (rs12050217). Score B combined SNPs of the angiotensin-converting enzyme gene (rs4343) and ABO blood group genes (rs495828 and rs8176746).
  
  
  METHODS
  Danish patients with CHF enrolled in the previously reported Echocardiography and Heart Outcome Study were included. Subjects were genotyped and categorized according to pharmacogenetic scores A and B of ≤1, 2 and ≥3 each, and followed for up to 10 years. Difference in cumulative incidences of cardiovascular death and all-cause death were assessed by the cumulative incidence estimator. Survival was modeled by Cox proportional hazard analyses.
  
  
  RESULTS
  We included 667 patients, of whom 80% were treated with ACEIs. Differences in cumulative incidences of cardiovascular death (P = 0.346 and P = 0.486) and all-cause death (P = 0.515 and P = 0.486) were not significant for score A and B, respectively. There was no difference in risk of cardiovascular death or all-cause death between subjects with score A ≤1 vs. 2 (HR 1.03 [95% CI 0.79-1.34] and HR 1.11 [95% CI 0.88-1.42]), score A ≤1 vs. ≥3 (HR 0.80 [95% CI 0.59-1.08] and HR 0.91 [95% CI 0.70-1.20]), score B ≤1 vs. 2 (HR 1.02 [95% CI 0.78-1.32] and HR 0.98 [95% CI 0.77-1.24]), and score B ≤1 vs. ≥3 (HR 1.03 [95% CI 0.75-1.41] and HR 1.05 [95% CI 0.79-1.40]), respectively.
  
  
  CONCLUSIONS
  We found no association between either of the analyzed pharmacogenetic scores and fatal outcomes in ACEI-treated patients with CHF.
authors.affiliation: Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.
authors.forename: Karl Emil
authors.initials: KE
authors.lastname: Nelveg-Kristensen
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
authors.forename: Majbritt
authors.initials: M
authors.lastname: Busk Madsen
authors.affiliation: Institute of Health, Science and Technology, Aalborg University, Aalborg, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Torp-Pedersen
authors.affiliation: The Heart Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: Department of Nephrology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Egfjord
authors.affiliation: Institute of Biological Psychiatry, Mental Health Centre Sct. Hans, Copenhagen University Hospital, Roskilde, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Berg Rasmussen
authors.affiliation: Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Riis Hansen
mesh_terms: D000368:Aged; D000483:Alleles; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006333:Heart Failure / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics*; D043783:Receptor, Bradykinin B1 / Q000235:genetics*; D012189:Retrospective Studies; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D044140:Receptor, Angiotensin, Type 1; D043783:Receptor, Bradykinin B1