Heart rate is associated with increased risk of major cardiovascular events, cardiovascular and all-cause death in patients with stable chronic cardiovascular disease: an analysis of ONTARGET/TRANSCEND

Clin Res Cardiol. 2014 Feb;103(2):149-59. doi: 10.1007/s00392-013-0644-4. Epub 2013 Dec 20.


Aims: Heart rate was proposed as an emergent cardiovascular (CV) risk factor. Previous studies have shown associations between increased heart rate and CV risk in various populations. We aimed to evaluate the prognostic relevance of heart rate in a large contemporaneous medically optimized cohort of patients with stable chronic CV disease.

Methods and results: In a post hoc analysis of the ONTARGET/TRANSCEND trials, we evaluated associations between baseline and average heart rate in trial with CV risk in 31, 531 patients followed for a median of 5 years. The primary outcome, major vascular events (MVE), was a composite of CV death, myocardial infarction (MI), stroke, and congestive heart failure (CHF). Pre-specified secondary outcomes included all-cause death and the individual components of the primary outcome. Associations between heart rate and outcomes were computed with heart rate as a continuous variable, baseline heart rate >70 vs ≤ 70 bpm, and across heart rate quintiles, adjusting for other markers of risk, beta-blocker and non-dihydropyridine calcium channel blocker use. For each 10 bpm increase in baseline and average heart rate, we observed a significant increase in risk of MVE, CV death, CHF and all-cause death. There was a continuous relationship between MVE and baseline and, more importantly, average in-trial heart rate, with no observed threshold. MVE, CV death, stroke, CHF, and all-cause death increased across heart rate quintiles. There was no association between MI and HR. Results were consistent in clinically relevant subgroups. There were modest but significant improvements in C-statistic and in statistical measures of model calibration for models that included heart rate for MVE, CV death, CHF and all-cause death.

Conclusions: This large study examined and quantitated associations between heart rate and CV events in a contemporary medically optimized population with stable CV disease. Resting and, in particular, in-trial average heart rate are independently associated with significant increases in CV events and all-cause death.

Trial registration: ClinicalTrials.gov NCT00153101.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / physiopathology*
  • Cause of Death
  • Chronic Disease
  • Double-Blind Method
  • Female
  • Heart Failure / mortality
  • Heart Failure / physiopathology
  • Heart Rate* / drug effects
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / mortality
  • Myocardial Infarction / physiopathology
  • Prognosis
  • Risk Assessment
  • Risk Factors
  • Stroke / mortality
  • Stroke / physiopathology
  • Time Factors


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors

Associated data

  • ClinicalTrials.gov/NCT00153101