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Original research article
Inverse association of pulse pressure augmentation during exercise with heart failure and death
  1. Mahmoud Al Rifai1,2,
  2. Michael J Blaha2,
  3. Faisal Rahman2,
  4. Jonathan K Ehrman3,
  5. Clinton A Brawner3,
  6. Steven J Keteyian3,
  7. Mouaz H Al-Mallah3,4,
  8. John William McEvoy2,5
  1. 1 Department of Medicine, University of Kansas School of Medicine, Wichita, Kansas, USA
  2. 2 The Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  3. 3 Henry Ford Hospital, Detroit, Michigan, USA
  4. 4 Cardiovascular Imaging and PET, Houston Methodist DeBakey Heart & Vascular Center, Houston Texas, Texas, USA
  5. 5 Cardiology, National Institute for Preventive Cardiology and National University of Ireland, Galway Campus, Galway, Ireland
  1. Correspondence to Dr John William McEvoy, Ciccarone Center for the Prevention of Heart Disease, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA; jmcevoy1{at}


Objective Resting pulse pressure (PP) is a risk factor for heart failure (HF); however, whether PP augmentation during exercise, a parameter easily obtained from routine treadmill stress testing, is associated with incident HF is unknown. Thus, we aimed to study the relationship between a novel parameter, the pulse pressure stress index (P2SI), and adverse outcomes among adults undergoing clinical exercise stress testing in the Henry Ford Exercise Testing Project.

Methods The P2SI was calculated as PP at peak exercise divided by resting PP and was analysed continuously and categorically using quartiles. Cox models examined the association between P2SI and adjusted HR (aHR) of incident HF, myocardial infarction (MI) or death. Receiver operating curve (ROC) analyses tested the optimal prognostic cut-point for P2SI.

Results Among 55 524 participants without prior MI or HF, mean (SD) age was 53 (13) years, 51% were men and 29% black. A total of 2516 HF, 1606 MI and 6224 mortality outcomes occurred. Quartile 3 P2SI (2.0–2.4) was chosen as the reference category based on ROC analyses. There was a graded inverse association of low P2SI with excess HF (aHR of 1.3 (95% CI 1.1 to 1.5) for quartile 2 and 1.5 (95% CI 1.2 to 1.8) for quartile 1, p for trend<0.001) and mortality (aHR of 1.1 (95% CI 1.01 to 1.2) for quartile 2 and 1.3 (95% CI 1.2 to 1.5) for quartile 1, p for trend<0.001). There was no association between P2SI and MI after adjustment. P2SI added significant prognostic information to more established stress testing parameters such as peak systolic blood pressure, per cent maximal predicted heart rate achieved and metabolic equivalents of task achieved.

Conclusions Poor augmentation of PP with exercise, specifically a P2SI below 2, is a novel and readily quantifiable exercise-based risk feature for HF and death.

  • pulse pressure
  • exercise
  • heart failure
  • death
  • risk factor

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  • Contributors Drafting: MA-R, JW. Statistical analysis: MA-R, JWM. Data acquisition: FR, CAB, SJK, JKE, MHA-M. Critical revision of the manuscript for important intellectual content: FR, CAB, SJK, JKE, MHA-M. Supervision: MJB, JWM.

  • Funding JWM is supported by a grant from the American Heart Association (17MCPRP33400031).

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval This study has been approved by the Henry Ford Health System Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data, analytic methods and study materials will not be made available to other researchers.