title: Resting heart rate and incident heart failure and cardiovascular mortality in older adults: role of inflammation and endothelial dysfunction: the PROSPER study.
abstract: OBJECTIVE
  Resting heart rate is a promising modifiable cardiovascular risk marker in older adults, but the mechanisms linking heart rate to cardiovascular disease are not fully understood. We aimed to assess the association between resting heart rate and incident heart failure (HF) and cardiovascular mortality, and to examine whether these associations might be attributable to systemic inflammation and endothelial dysfunction.
  
  
  RESULTS
  We studied 4084 older adults aged 70-82 years with known cardiovascular risk factors or previous cardiovascular disease, without pre-existing HF or beta-blockers in the PROSPER study. Over a 3.2-year follow-up period, we examined incident HF hospitalization and cardiovascular mortality according to resting heart rate, along with C-reactive protein (CRP), interleukin-6 (IL-6), tissue plasminogen activator (tPA), and von Willebrand factor (vWf). Mean heart rate was 67 b.p.m. for men and 70 b.p.m. for women. CRP, IL-6, tPA, and vWf levels were all positively correlated with heart rate. After multivariate adjustment, heart rate was associated with HF hospitalization [hazard ratio (HR) 1.78 for highest vs. lowest distribution third, 95% confidence interval (CI) 1.21-2.63, P= 0.003] and cardiovascular mortality (HR 1.74, 95% CI 1.23-2.47, P= 0.002). Further adjustment for both IL-6 and vWf levels decreased HR to 1.60 (95% CI 1.08-2.38, P= 0.020) for HF and to 1.50 (95% CI 1.04-2.15, P= 0.028) for cardiovascular mortality.
  
  
  CONCLUSIONS
  Increased heart rate is associated with increased systemic inflammation and endothelial dysfunction. These factors are likely to contribute to, but do not fully explain, the risk of HF and cardiovascular death associated with increased heart rate in older age.
authors.affiliation: Department of Ambulatory Care and Community Medicine, University of Lausanne, Lausanne, Switzerland. david.nanchen@chuv.ch
authors.forename: David
authors.initials: D
authors.lastname: Nanchen
authors.forename: David J
authors.initials: DJ
authors.lastname: Stott
authors.forename: Jacobijn
authors.initials: J
authors.lastname: Gussekloo
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mooijaart
authors.forename: Rudi G J
authors.initials: RG
authors.lastname: Westendorp
authors.forename: J Wouter
authors.initials: JW
authors.lastname: Jukema
authors.forename: Peter W
authors.initials: PW
authors.lastname: Macfarlane
authors.forename: Jacques
authors.initials: J
authors.lastname: Cornuz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rodondi
authors.forename: Brendan M
authors.initials: BM
authors.lastname: Buckley
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: de Craen
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000401:mortality* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood / Q000503:physiopathology*; D006339:Heart Rate / Q000502:physiology*; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011446:Prospective Studies; D012307:Risk Factors; D010959:Tissue Plasminogen Activator / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015850:Interleukin-6; D014841:von Willebrand Factor; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator