Association of systolic blood pressure with mortality in patients with heart failure with reduced ejection fraction: A complex relationship

Sameer Ather, Wenyaw Chan, Annirudha Chillar, David Aguilar, Allison M. Pritchett, Kumudha Ramasubbu, Xander H.T. Wehrens, Anita Deswal, Biykem Bozkurt

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


Background: In ambulatory patients with heart failure with reduced ejection fraction (HFrEF), high systolic blood pressure (SBP) is associated with better outcomes. However, it is not known whether there is a ceiling beyond which high SBP has a detrimental effect. Thus, our aim was to assess the linearity of association between SBP and mortality. Methods: We used the External Peer Review Program (EPRP) and Digitalis Investigation Group (DIG) trial databases of HFrEF patients. Linearity of association of SBP with mortality was assessed by plotting Martingale residuals against SBP. To assess the patterns of relationship of SBP with mortality, we used restricted cubic spline analysis with Cox proportional hazards model. Results: In patients with mild-to-moderate left ventricular systolic dysfunction (LVSD) (30% ≤ LVEF < 50%), SBP had a nonlinear association with mortality in both EPRP (n = 3,693) and DIG (n = 3,263) databases. In these patients, SBP had a significant U-shaped association with mortality in EPRP and a trend toward U-shaped relationship in DIG database. In patients with severe LVSD (LVEF <30%), SBP had a linear association with mortality in both EPRP (n = 2,906) and DIG (n = 3,537) databases, with lower SBP being associated with increased mortality. Conclusions: Systolic blood pressure has a complex nonlinear association with mortality in patients with heart failure. Whereas it has a U-shaped association in patients with mild-to-moderate LVSD, it has a linear association with mortality in patients with severe LVSD. Recognition of this pattern of association of blood pressure profile may help clinicians in providing better care for their patients and help improve existing prediction models.

Original languageEnglish
Pages (from-to)567-573
Number of pages7
JournalAmerican Heart Journal
Issue number3
StatePublished - Mar 3 2011

Bibliographical note

Funding Information:
D.A. is a recipient of a NIH Mentored Career Development Award (5K01-HL092585-02). X.H.T.W. is a W.M. Keck Foundation Distinguished Young Scholar in Medical Research, and is also supported by NIH/NHLBI grants R01-HL089598 and R01HL091947 . DA is supported by VA Health Services Research and Development Service grant IIR02-082-1. B.B. is supported by NIH 3U01DE017793 and 9K30RR02229. The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the paper and its final contents.


  • COPD
  • DBP
  • DIG
  • Digitalis Investigation Group
  • EPRP
  • External Peer Review Program
  • HFrEF
  • HR
  • LVEF
  • LVSD
  • PH
  • SBP
  • chronic obstructive pulmonary disease
  • diastolic blood pressure
  • hazard ratio
  • heart Failure with reduced ejection fraction
  • left ventricular ejection fraction
  • left ventricular systolic dysfunction
  • proportional hazards
  • systolic blood pressure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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