title: Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.
abstract: OBJECTIVE
  Intensive therapy targeting normal blood glucose increased mortality compared with standard treatment in a randomized clinical trial of 10,251 participants with type 2 diabetes at high-risk for cardiovascular disease (CVD) events. We evaluated whether the presence of cardiac autonomic neuropathy (CAN) at baseline modified the effect of intensive compared with standard glycemia treatment on mortality outcomes in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial participants.
  
  
  METHODS
  CAN was assessed by measures of heart rate variability (HRV) and QT index (QTI) computed from 10-s resting electrocardiograms in 8,135 ACCORD trial participants with valid measurements (mean age 63.0 years, 40% women). Prespecified CAN definitions included a composite of the lowest quartile of HRV and highest QTI quartile in the presence or absence of peripheral neuropathy. Outcomes were all-cause and CVD mortality. Associations between CAN and mortality were evaluated by proportional hazards analysis, adjusting for treatment group allocation, CVD history, and multiple prespecified baseline covariates.
  
  
  RESULTS
  During a mean 3.5 years follow-up, there were 329 deaths from all causes. In fully adjusted analyses, participants with baseline CAN were 1.55-2.14 times as likely to die as participants without CAN, depending on the CAN definition used (P < 0.02 for all). The effect of allocation to the intensive group on all-cause and CVD mortality was similar in participants with or without CAN at baseline (P(interaction) > 0.7).
  
  
  CONCLUSIONS
  Whereas CAN was associated with increased mortality in this high-risk type 2 diabetes cohort, these analyses indicate that participants with CAN at baseline had similar mortality outcomes from intensive compared with standard glycemia treatment in the ACCORD cohort.
authors.affiliation: Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, Michigan, USA. rpbusui@umich.edu
authors.forename: Rodica
authors.initials: R
authors.lastname: Pop-Busui
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Evans
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
authors.forename: Vivian
authors.initials: V
authors.lastname: Fonseca
authors.forename: Jerome L
authors.initials: JL
authors.lastname: Fleg
authors.forename: Byron J
authors.initials: BJ
authors.lastname: Hoogwerf
authors.forename: Saul
authors.initials: S
authors.lastname: Genuth
authors.forename: Richard H
authors.initials: RH
authors.lastname: Grimm
authors.forename: Marshall A
authors.initials: MA
authors.lastname: Corson
authors.forename: Ronald
authors.initials: R
authors.lastname: Prineas
mesh_terms: D000368:Aged; D001342:Autonomic Nervous System Diseases / Q000401:mortality*; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality*; D003929:Diabetic Neuropathies / Q000401:mortality*; D005260:Female; D005500:Follow-Up Studies; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000401:mortality*; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents