title: Relationship between heart rate variability and pulse wave velocity and their association with patient outcomes in chronic kidney disease.
abstract: BACKGROUND
  Arterial stiffness and low heart rate variability (HRV) have each been associated with increased cardiovascular risk in a variety of patient populations. We explored the relationship between HRV and pulse wave velocity (PWV measure of arterial stiffness) in patients with chronic kidney disease (CKD prior to ESRD) along with examining their association with the outcomes of cardiovascular disease (CVD), death, and progression to end stage renal disease (ESRD).
  
  
  METHODS
  The RRI-CKD Study is a 4-center prospective cohort study of CKD stages 3 - 5 (n = 834). A subset underwent both HRV testing by 24-hour Holter and carotid-femoral PWV (n = 240). Multiple linear regression was used to assess predictors of PWV and Cox regression to investigate the association of HRV and PWV with time to first CVD event or death and ESRD.
  
  
  RESULTS
  Although several HRV measures were inversely correlated with PWV, this association was attenuated after adjustment for age and/or diabetes and no longer significant after adjustment for C-reactive protein. Low HRV and high PWV were individually associated with increased risk of the composite endpoint of CVD/death in multivariable analysis. The risk of the composite of CVD/death was highest for patients with both low HRV and high PWV.
  
  
  CONCLUSIONS
  Age, diabetes, and inflammation together explained the inverse association between HRV and PWV. Inflammation may play a role in the pathogenesis of both low HRV and high PWV. The combination of low HRV and high PWV showed the strongest association with a composite CVD outcome. Mechanisms underlying abnormalities in PWV and HRV, and the role of these measures as intermediate outcomes in future trials in CKD patients, merit further study.
authors.affiliation: Department of Internal Medicine, University of Maryland, Baltimore, MD, University of Michigan-Kidney Epidemiology and Cost Center, Ann Arbor, MI, Renal Research Institute, New York, NY, Department of Internal Medicine, University of North Carolina, Chapel Hill, NC, Hospital of St. Raphael Yale University, New Haven, CT, Department of Internal Medicine, University of North Carolina, Chapel Hill, NC, Department of Cardiovascular Medicine, Ohio State University, Columbus, OH, Oakwood Healthcare System, Dearborn, MI, and Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Preeti
authors.initials: P
authors.lastname: Chandra
authors.forename: Robin L
authors.initials: RL
authors.lastname: Sands
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Gillespie
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Levin
authors.forename: Peter
authors.initials: P
authors.lastname: Kotanko
authors.forename: Margaret
authors.initials: M
authors.lastname: Kiser
authors.forename: Fredric
authors.initials: F
authors.lastname: Finkelstein
authors.forename: Alan
authors.initials: A
authors.lastname: Hinderliter
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: David
authors.initials: D
authors.lastname: Sengstock
authors.forename: Rajiv
authors.initials: R
authors.lastname: Saran
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000209:etiology; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D063177:Pulse Wave Analysis; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology*
chemical_list: D002097:C-Reactive Protein