title: Autonomic dysfunction independently predicts poor cardiovascular outcomes in asymptomatic individuals with type 2 diabetes in the DIAD study.
abstract: OBJECTIVE
  The primary aim of this secondary analysis was to determine whether cardiac autonomic neuropathy independently predicted adverse cardiac outcomes in asymptomatic individuals with type 2 diabetes. Additional aims include the determination of the correlation of standard autonomic testing measures and power spectral analysis of heart rate variability, and the association of diabetes-related and cardiac risk factors with cardiac autonomic neuropathy measures.
  
  
  METHODS
  Cardiac autonomic neuropathy was assessed at the study entry into the Detection of Ischemia in Asymptomatic Diabetics study, using autonomic heart rate and blood pressure testing, and power spectral analysis of heart rate variability. All participants were prospectively followed for the composite clinical outcome of cardiac death, acute coronary syndromes, heart failure, or coronary revascularization.
  
  
  RESULTS
  Over 5 years of follow-up, 94 of 1119 (8.4%) subjects developed symptomatic cardiac disease. In unadjusted bivariate analyses, abnormalities in several cardiac autonomic neuropathy tests, including lower Valsalva and Standing Heart Rate Ratios, higher resting Heart Rate, greater systolic blood pressure decrease on standing, and lower low-frequency power, were predictive of symptomatic disease. Independent predictors of poor cardiac outcome were a lower Valsalva Heart Rate Ratio, non-Black ethnicity, longer diabetes duration, higher glycated hemoglobin (HbA1c), insulin use, reported numbness in the extremities, higher pulse pressure, family history of coronary artery disease, and higher waist-to-hip ratio. Clinical factors independently associated with a lower Valsalva Heart Rate Ratio were insulin use, clinical proteinuria, higher pulse pressure, use of angiotensin-converting enzyme inhibitor and non-Black ethnicity.
  
  
  CONCLUSIONS
  Cardiac autonomic neuropathy predicted adverse cardiac outcomes in asymptomatic type 2 diabetes without known cardiac disease. Clinical variables may help to identify patients who might have cardiac autonomic neuropathy and warrant consideration for autonomic testing.
authors.affiliation: College of Nursing, New York University, New York, NY, USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Chyun
authors.affiliation: Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
authors.forename: Frans J Th
authors.initials: FJ
authors.lastname: Wackers
authors.affiliation: Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
authors.forename: Silvio E
authors.initials: SE
authors.lastname: Inzucchi
authors.affiliation: Sutter Medical Group, Cardiology, Sacramento, CA, USA.
authors.forename: Powell
authors.initials: P
authors.lastname: Jose
authors.affiliation: Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Curtis
authors.initials: C
authors.lastname: Weiss
authors.affiliation: Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
authors.forename: Janice A
authors.initials: JA
authors.lastname: Davey
authors.affiliation: Division of Cardiology, Morristown Medical Center, Morristown, NJ, USA.
authors.forename: Gary V
authors.initials: GV
authors.lastname: Heller
authors.affiliation: Division of Cardiovascular Diseases, University of Alabama, Birmingham, AL, USA.
authors.forename: Ami E
authors.initials: AE
authors.lastname: Iskandrian
authors.affiliation: Section of Cardiovascular Medicine, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Young
keywords: Type 2 diabetes; asymptomatic myocardial ischemia; cardiac autonomic neuropathy; pulse pressure