title: Temporal Reduction in Chronotropic Index Predicts Risk of Cardiovascular Death Among Healthy Middle-Aged Men: a 28-Year Follow-Up Study.
abstract: Chronotropic index is a standardized measure of heart rate (HR) increment during exercise that reflects the combined effects of age, resting HR, and physical fitness. Low chronotropic index has been reported to predict disease and death. We tested whether temporal change in chronotropic index over 7 years influenced risk of cardiovascular death through up to 28 years.
  
  
  
  Chronotropic index was calculated ([achieved maximal HR-resting HR]/[age-predicted maximal HR-resting HR]) after a symptom-limited bicycle ECG exercise test in 1420 healthy men at 2 examinations 7 years apart, in 1972 and 1979. Events of cardiovascular death were registered by manual scrutiny of all participants' hospital charts and the Norwegian Cause of Death Registry. The participants were divided into quartiles of temporal change in chronotropic index, with quartile one having the most negative value. Cox proportional hazard regression models were used to estimate risks and adjusted for classical cardiovascular risk factors. Incidence of cardiovascular death was 310 (22%) during median of 21 years of follow-up. After multivariable adjustment, and comparison with quartile four (mean +0.11), quartiles one (-0.16), two (-0.04), and three (+0.02) were associated with hazard ratios 1.50 (95% CI 1.10-2.05), 1.10 (0.79-1.53), and 1.04 (0.74-1.45) for cardiovascular death. Results remained robust also after exclusion of 31 participants with exercise ECG-induced signs of coronary ischemia.
  
  
  
  Temporal reduction in chronotropic index was associated with increased long-term risk of cardiovascular death and might be a clinically important predictor when assessing risk in healthy individuals over a longer time.
authors.affiliation: Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway engekr@gmail.com.|Faculty of Medicine, University of Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Engeseth
authors.affiliation: Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway.|Faculty of Medicine, University of Oslo, Norway.
authors.forename: Christian
authors.initials: C
authors.lastname: Hodnesdal
authors.affiliation: Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway.|Centre for Clinical Heart Research, Oslo University Hospital, Oslo, Norway.
authors.forename: Irene
authors.initials: I
authors.lastname: Grundvold
authors.affiliation: Department of Informatics, University of Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Liestøl
authors.affiliation: Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway.|Faculty of Medicine, University of Oslo, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Gjesdal
authors.affiliation: Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway.|Faculty of Medicine, University of Oslo, Norway.
authors.forename: Sverre E
authors.initials: SE
authors.lastname: Kjeldsen
authors.affiliation: Faculty of Medicine, University of Oslo, Norway.
authors.forename: Jan E
authors.initials: JE
authors.lastname: Erikssen
authors.affiliation: Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway.
authors.forename: Johan
authors.initials: J
authors.lastname: Bodegard
authors.affiliation: Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo, Norway.
authors.forename: Per Torger
authors.initials: PT
authors.lastname: Skretteberg
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology*; D002423:Cause of Death / Q000639:trends; D005080:Exercise Test; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D011237:Predictive Value of Tests; D012016:Reference Values; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D015996:Survival Rate / Q000639:trends
keywords: all‐cause death prediction; cardiovascular outcomes; chronotropic index; exercise testing; heart rate; physical exercise; risk prediction