title: Chronic nitrate therapy is associated with different presentation and evolution of acute coronary syndromes: insights from 52,693 patients in the Global Registry of Acute Coronary Events.
abstract: OBJECTIVE
  Brief episode(s) of ischaemia may increase cardiac tolerance to a subsequent major ischaemic insult ('preconditioning'). Nitrates can pharmacologically mimic ischaemic preconditioning in animals. In this study, we investigated whether antecedent nitrate therapy affords protection toward acute ischaemic events using data from the Global Registry of Acute Coronary Events.
  
  
  RESULTS
  The dataset comprised 52,693 patients from 123 centres in 14 countries: 42,138 (80%) were nitrate-naïve and 10,555 (20%) were on chronic nitrates at admission. In nitrate-naïve patients, admission diagnosis was ST-segment elevation myocardial infarction (STEMI) in 41%, whereas 59% presented with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). In contrast, only 18% nitrate users showed STEMI, whereas 82% presented with NSTE-ACS. Thus, among nitrate users clinical presentation was tilted toward NSTE-ACS by more than four-fold, STEMI occurring in less than one of five patients (P < 0.0001). After adjustment (age, sex, medical history, prior therapy, revascularization, previous angina), chronic nitrate use remained independent predictor of NSTE-ACS (OR 1.36; 95% CI 1.26-1.46; P < 0.0001). Furthermore, regardless of presentation, within both STEMI and NSTEMI populations, antecedent nitrate use was associated with significantly lower levels of CK-MB and troponin (P < 0.0001 for all).
  
  
  CONCLUSIONS
  In this large multinational registry, chronic nitrate use was associated with a shift away from STEMI in favour of NSTE-ACS and with less release of markers of cardiac necrosis. These findings suggest that in nitrate users acute coronary events may develop to a smaller extent. Randomized, placebo-controlled trials are warranted to establish whether nitrate therapy may pharmacologically precondition the heart toward ischaemic episodes.
authors.affiliation: Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy. giuseppe.ambrosio@ospedale.perugia.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ambrosio
authors.forename: Maurizio
authors.initials: M
authors.lastname: Del Pinto
authors.forename: Isabella
authors.initials: I
authors.lastname: Tritto
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Agnelli
authors.forename: Maurizio
authors.initials: M
authors.lastname: Bentivoglio
authors.forename: Cinzia
authors.initials: C
authors.lastname: Zuchi
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Anderson
authors.forename: Joel M
authors.initials: JM
authors.lastname: Gore
authors.forename: Jose
authors.initials: J
authors.lastname: López-Sendón
authors.forename: Allison
authors.initials: A
authors.lastname: Wyman
authors.forename: Brian M
authors.initials: BM
authors.lastname: Kennelly
authors.forename: Keith A A
authors.initials: KA
authors.lastname: Fox
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D008875:Middle Aged; D032342:Muscle Cells / Q000473:pathology; D009203:Myocardial Infarction / Q000188:drug therapy*; D009336:Necrosis; D009566:Nitrates / Q000627:therapeutic use*; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D002316:Cardiotonic Agents; D009566:Nitrates