title: T2238C ANP gene variant and risk of recurrent acute coronary syndromes in an Italian cohort of ischemic heart disease patients.
abstract: BACKGROUND
  The role of C2238/atrial natriuretic peptide (ANP) minor allele, at the T2238C ANP gene variant, as a predisposing risk factor for acute cardiovascular events, has been previously reported. We aimed at evaluating, by a retrospective approach, the long-term impact of C2238/ANP-minor allele carrier status toward the risk of recurrent acute coronary syndromes (re-ACS) in an Italian cohort of ischemic heart disease patients.
  
  
  METHODS
  A total of 379 patients (males = 80.5%; mean age = 62.5 ± 9.2 years) presenting with ACS were retrospectively analyzed. Mean follow-up was 5.1 ± 3.5 years (range 1-26 years). Occurrence of new episodes of unstable angina, non-ST-segment elevation myocardial infarction and STE myocardial infarction over the years was recorded and compared between subjects not carrying and carrying C2238/ANP-minor allele.
  
  
  RESULTS
  At univariate analysis, C2238/ANP-minor allele carrier status and treatment with beta-blocker, aspirin and statin were associated with risk of re-ACS. Multivariate analysis confirmed that hypercholesterolemia (P < 0.0001) and C2238/ANP-minor allele carrier status (P < 0.05) were both significantly and independently associated with increased risk of re-ACS. Both treatments with beta-blocker and with statin were significantly associated with reduced risk of re-ACS (P = 0.01 and P < 0.01, respectively). Age above 55 years was associated with recurrence of ACS in C2238/ANP-minor allele carriers (hazard ratio 1.427, 95% confidence interval 1.066-1.911, P = 0.017). Kaplan-Meier curves confirmed highest risk of new events occurrence in C2238/ANP-minor allele carriers (P = 0.035).
  
  
  CONCLUSIONS
  The present results demonstrate that C2238/ANP-minor allele carrier status is an independent risk factor for ACS recurrence in an Italian cohort of ischemic heart disease patients over the long term, and they support the role of C2238/ANP-minor allele as a negative prognostic factor in coronary artery disease patients.
authors.affiliation: aIRCCS Neuromed, Pozzilli bDept. of Clinical and Molecular Medicine, School of Medicine and Psychology, Sapienza University of Rome, Ospedale S. Andrea, Rome cDept. of Science of Public Health and Infectious Diseases, School of Pharmacy and Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.forename: Marco
authors.initials: M
authors.lastname: De Giusti
authors.forename: Alessio
authors.initials: A
authors.lastname: Farcomeni
authors.forename: Sofia
authors.initials: S
authors.lastname: Abbolito
authors.forename: Filomena
authors.initials: F
authors.lastname: Comito
authors.forename: Sara
authors.initials: S
authors.lastname: Cangianiello
authors.forename: Ettore S
authors.initials: ES
authors.lastname: Greco
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dito
authors.forename: Beniamino
authors.initials: B
authors.lastname: Pagliaro
authors.forename: Maria
authors.initials: M
authors.lastname: Cotugno
authors.forename: Rosita
authors.initials: R
authors.lastname: Stanzione
authors.forename: Simona
authors.initials: S
authors.lastname: Marchitti
authors.forename: Franca
authors.initials: F
authors.lastname: Bianchi
authors.forename: Sara
authors.initials: S
authors.lastname: Di Castro
authors.forename: Allegra
authors.initials: A
authors.lastname: Battistoni
authors.forename: Simone
authors.initials: S
authors.lastname: Burocchi
authors.forename: Massimo
authors.initials: M
authors.lastname: Caprinozzi
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pierelli
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Sciarretta
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D054058:Acute Coronary Syndrome / Q000235:genetics*; D000368:Aged; D000483:Alleles; D000789:Angina, Unstable / Q000188:drug therapy / Q000235:genetics*; D001241:Aspirin / Q000627:therapeutic use; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000235:genetics*; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D009320:Atrial Natriuretic Factor; D001241:Aspirin