title: Reduced Cardiovascular Reserve in Chronic Kidney Failure: A Matched Cohort Study.
abstract: BACKGROUND
  Patients with chronic kidney failure (CKF) experience impaired functional cardiovascular reserve with reduced oxygen consumption at peak exercise (VO(2peak)). No studies have examined whether this is related to impaired cardiovascular compliance as a consequence of loss of adaptive structural alterations, resulting from chronic uremia or hypertension.
  
  
  METHODS
  Prospective matched-cohort study.
  
  
  METHODS
  We assessed CKF in parallel with patients with essential hypertension but without cardiovascular disease. Patients with CKF were either scheduled for kidney transplantation or transplant waitlisted. 80 patients with CKF and 80 with essential hypertension matched in age, sex, and body mass index were evaluated. 61 patients with CKF (76.3%) were dialysis dependent.
  
  
  METHODS
  CKF versus essential hypertension without cardiovascular disease.
  
  
  METHODS
  VO(2peak) was measured during maximal exercise testing. 2-dimensional echocardiography and arterial applanation tonometry were performed prior to exercise testing. To evaluate for the difference in VO(2peak) between study groups, statistically significant predictors of VO(2peak) in multiple regression models were additionally assessed by fitting models comprising the interaction term of patient group with the predictor variable of interest.
  
  
  RESULTS
  VO(2peak) was significantly lower in patients with CKF than those with essential hypertension (18.8 vs 24.5 mL/min·kg; P<0.001). Independent predictors of VO(2peak) for CKF included left ventricular (LV) filling pressure (E/mean e'; unstandardized regression coefficient: change in VO(2peak) [in mL/min·kg] per 1-unit change of variable = -5.1) and pulse wave velocity (-4.0); in essential hypertension, these were LV mass index (0.2), LV end-diastolic volume index (0.4), peak heart rate (0.2), and pulse wave velocity (-8.8). The interaction effect of VO(2peak) between patient groups with LV mass index (P<0.001), LV end-diastolic volume index (P<0.001), and peak heart rate (P<0.01) were significantly stronger in the hypertension group, whereby higher values led to greater VO(2peak).
  
  
  CONCLUSIONS
  Skeletal muscle strength was not assessed.
  
  
  CONCLUSIONS
  This study suggests that maladaptive LV changes, as well as blunted chronotropic response, are important mechanistic factors resulting in reduced cardiovascular reserve in patients with CKF, beyond predominantly vascular changes associated with hypertension.
authors.affiliation: Division of Nephrology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom; Division of Metabolic and Vascular Health, The University of Warwick, Coventry, United Kingdom. Electronic address: stephen_ting@yahoo.com.
authors.forename: Stephen M S
authors.initials: SM
authors.lastname: Ting
authors.affiliation: Division of Health Sciences Statistics and Epidemiology, The University of Warwick, Coventry, United Kingdom.
authors.forename: Thomas
authors.initials: T
authors.lastname: Hamborg
authors.affiliation: Division of Nephrology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
authors.forename: Gordon
authors.initials: G
authors.lastname: McGregor
authors.affiliation: Research Institutes of Sports and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Oxborough
authors.affiliation: Division of Nephrology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Lim
authors.affiliation: Division of Cardiology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
authors.forename: Sudheer
authors.initials: S
authors.lastname: Koganti
authors.affiliation: Division of Nephrology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Aldridge
authors.affiliation: Division of Vascular and Renal Transplantation Surgery, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
authors.forename: Chris
authors.initials: C
authors.lastname: Imray
authors.affiliation: Division of Metabolic and Vascular Health, The University of Warwick, Coventry, United Kingdom.
authors.forename: Rosemary
authors.initials: R
authors.lastname: Bland
authors.affiliation: Division of Nephrology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Fletcher
authors.affiliation: Division of Nephrology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
authors.forename: Nithya S
authors.initials: NS
authors.lastname: Krishnan
authors.affiliation: Division of Nephrology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Higgins
authors.affiliation: Division of Cardiology, University Hospital Birmingham, Birmingham, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Townend
authors.affiliation: Division of Cardiology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom.
authors.forename: Prithwish
authors.initials: P
authors.lastname: Banerjee
authors.affiliation: Division of Nephrology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom; Division of Metabolic and Vascular Health, The University of Warwick, Coventry, United Kingdom. Electronic address: d.zehnder@warwick.ac.uk.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zehnder
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000209:etiology / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010101:Oxygen Consumption; D011446:Prospective Studies; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000503:physiopathology*
keywords: Cardiovascular reserve; cardiopulmonary exercise testing (CPET); cardiovascular disease (CVD); chronic kidney failure; dialysis; end-stage renal disease (ESRD); exercise capacity; exercise intolerance; hypertension; left ventricular mass index (LVMI); oxygen consumption; pulse wave velocity (PWV); vascular compliance