title: Evidence of a synergistic association between heart rate, inflammation, and cardiovascular mortality in patients undergoing coronary angiography.
abstract: OBJECTIVE
  Both elevated inflammatory activity and sustained tachycardia reflect unfavourable cardiovascular risk profiles, and there is evidence to suggest the deleterious effects of inflammation are amplified by increased heart rate. The purpose of this study was to assess the interaction between resting heart rate and inflammation in cardiovascular mortality.
  
  
  RESULTS
  A total of 3267 patients (2283 men), aged 18-95 years, scheduled for coronary angiography, were followed prospectively. By principle component analysis, we developed an overall multi-marker index of inflammation weighting the respective coefficients of five inflammatory markers including: interleukin-6, C-reactive protein, serum amyloid A, neutrophils, and fibrinogen. Cox proportional hazard regression models were employed to evaluate the relationship between inflammation and heart rate with cardiovascular mortality. Across 29,940 person years of follow-up, there were 546 (17%) deaths due to cardiovascular disease (CVD). Significantly, we observed a strong synergistic effect of inflammatory activity and concurrent elevated heart rate. For CVD mortality, patients in the highest quartile of inflammation had an adjusted hazard ratio (95% confidence interval) of 1.84 (1.31-2.57), P < 0.0001 if their resting heart rate was <75 b.p.m. Substantially, patients had a greater adjusted HR of 7.50 (3.21-17.50), P < 0.0001 if their resting heart rate was ≥75 b.p.m.
  
  
  CONCLUSIONS
  The present analyses underline elevated inflammation as a risk factor for cardiovascular mortality. The effects of inflammation appeared to be strongly amplified by a faster resting heart rate. If confirmed by additional studies, this association may prove a useful adjunct for therapeutic approaches to alleviate symptoms and prolong survival.
authors.affiliation: Department of Internal Medicine/Geriatrics, Yale School of Medicine, Yale University, New Haven, CT 06510, USA.
authors.forename: Bríain
authors.initials: B
authors.lastname: O Hartaigh
authors.forename: Jos A
authors.initials: JA
authors.lastname: Bosch
authors.forename: Douglas
authors.initials: D
authors.lastname: Carroll
authors.forename: Karla
authors.initials: K
authors.lastname: Hemming
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Adrian
authors.initials: A
authors.lastname: Loerbroks
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Kleber
authors.forename: Tanja B
authors.initials: TB
authors.lastname: Grammer
authors.forename: Joachim E
authors.initials: JE
authors.lastname: Fischer
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: G Neil
authors.initials: GN
authors.lastname: Thomas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000401:mortality / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000503:physiopathology; D017023:Coronary Angiography / Q000401:mortality; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006339:Heart Rate / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000502:physiology; D011446:Prospective Studies; D000685:Serum Amyloid A Protein / Q000378:metabolism; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D000685:Serum Amyloid A Protein; D005340:Fibrinogen; D002097:C-Reactive Protein