title: The heart rate response to adenosine: a simple predictor of adverse cardiac outcomes in asymptomatic patients with type 2 diabetes.
abstract: BACKGROUND
  The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study demonstrated a low 5-year hard cardiac event rate. We hypothesized that a blunted heart rate response (HRR, maximum percent change) to adenosine, a simple marker of cardiac autonomic neuropathy, will identify a cohort at higher cardiac risk.
  
  
  METHODS
  In DIAD, 518 participants were randomized to screening adenosine myocardial perfusion imaging (MPI) and had available data. HRR <20% was considered abnormal. The primary endpoint was a composite of nonfatal myocardial infarction and cardiac death.
  
  
  RESULTS
  During 4.7 ± 0.9 years of follow-up 15 (3%) participants experienced the primary outcome. Participants with lower HRR experienced more events than those with higher HRR (8%, 3%, 1%, for HRR <20% (n=79), 20-39% (n=182) and ≥ 40% (n=257), respectively, p=0.01). In a Cox proportional regression model that included MPI abnormalities and HRR, both were independently associated with cardiac events (p for model <0.001). HRR <20% was associated with 9-fold increased risk (p=0.007) and moderate/large abnormal MPI was associated with 6-fold increased risk (p=0.004). Participants with both abnormal MPI and HRR (n=8) were at highest risk for cardiac events (38%) whereas those with HRR ≥ 40%, irrespective of MPI abnormalities (n=234), were at extremely low risk (≤1%, log-rank p<0.001).
  
  
  CONCLUSIONS
  In DIAD, abnormal HRR to adenosine infusion is an independent predictor of cardiac events. This easily obtained marker of cardiac autonomic neuropathy identifies asymptomatic patients with type 2 diabetes mellitus at increased risk, particularly when associated with abnormal MPI, who may warrant further testing and more aggressive cardiovascular risk factor management.
authors.affiliation: University of Alabama at Birmingham, Birmingham, AL, USA. fadihage@uab.edu
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Hage
authors.forename: Frans J Th
authors.initials: FJ
authors.lastname: Wackers
authors.forename: Shanti
authors.initials: S
authors.lastname: Bansal
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Chyun
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Young
authors.forename: Silvio E
authors.initials: SE
authors.lastname: Inzucchi
authors.forename: Ami E
authors.initials: AE
authors.lastname: Iskandrian
mesh_terms: D000241:Adenosine; D000368:Aged; D058070:Asymptomatic Diseases / Q000453:epidemiology; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016896:Treatment Outcome
chemical_list: D000241:Adenosine