title: Adverse prognostic value of a blunted circadian rhythm of heart rate in essential hypertension.
abstract: BACKGROUND
  Previous studies revealed a direct association between resting heart rate and risk of mortality in essential hypertension. However, resting heart rate is a highly variable measure since it is affected by the alerting reaction to the visit.
  
  
  OBJECTIVE
  To investigate whether the heart rate values recorded during the 24 h of ambulatory blood pressure monitoring are independent predictors of survival of uncomplicated subjects with essential hypertension.
  
  
  METHODS
  We followed up 1942 initially untreated and uncomplicated subjects with essential hypertension (mean age 51.7 years, 52% men) for an average of 3.6 years (range 0-10 years). All subjects underwent baseline procedures including 24 h non-invasive blood pressure monitoring with simultaneous assessment of heart rate, one reading every 15 min for 24 h.
  
  
  METHODS
  All-cause mortality and cardiovascular morbidity.
  
  
  RESULTS
  During follow-up there were 74 deaths from all causes (1.06 per 100 person-years) and 182 total (fatal plus non-fatal) cardiovascular morbid events (2.66 per 100 person-years). Clinic, average 24 h, daytime and night-time heart rates exhibited no association with total mortality. However, the subjects who subsequently died had had a blunted reduction of heart rate on going from day to night during the baseline examination. After adjustment for age (P < 0.001), diabetes (P < 0.001) and average 24 h systolic blood pressure (SBP, P= 0.002) in a Cox model, for each 10% less reduction in the heart rate from day to night the relative risk of mortality was 1.30 (95% confidence interval 1.02-1.65, P = 0.04). Rates of death were 0.38, 0.71, 0.94 and 2.0 per 100 person-years among subjects in the four quartiles of the distribution of the percentage reduction in heart rate from day to night The baseline day-night changes in the heart rate exhibited an inverse correlation to age and to clinic and ambulatory SBP and a direct association with the day-night changes in blood pressure. The degree of reduction of heart rate from day to night also had an independent inverse association with total cardiovascular morbidity after adjustment for age, diabetes and left ventricular hypertrophy, but this association did not remain significant when average 24 h SBP and the degree of day-night reduction in SBP were entered into the equation.
  
  
  CONCLUSIONS
  A flattened diurnal rhythm of heart rate in uncomplicated subjects with essential hypertension is a marker of risk for subsequent all-cause mortality and this association persists after adjustment for several risk factors. For assessing these subjects, a limited and uniformly distributed period of ambulatory heart rate recording during the 24 h is clinically valuable.
authors.affiliation: Area Omogenea di Cardiologia e Medicina, Ospedale Regionale Raffaello Silvestrini, Perugia, Italy. verdec@tin.it
authors.forename: P
authors.initials: P
authors.lastname: Verdecchia
authors.forename: G
authors.initials: G
authors.lastname: Schillaci
authors.forename: C
authors.initials: C
authors.lastname: Borgioni
authors.forename: A
authors.initials: A
authors.lastname: Ciucci
authors.forename: M P
authors.initials: MP
authors.lastname: Telera
authors.forename: S
authors.initials: S
authors.lastname: Pede
authors.forename: R
authors.initials: R
authors.lastname: Gattobigio
authors.forename: C
authors.initials: C
authors.lastname: Porcellati
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001795:Blood Pressure Determination; D018660:Blood Pressure Monitoring, Ambulatory; D002318:Cardiovascular Diseases / Q000401:mortality; D002940:Circadian Rhythm / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000401:mortality / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009819:Office Visits; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D000959:Antihypertensive Agents