Clinical Investigation
Congestive Heart Failure
Association of systolic blood pressure with mortality in patients with heart failure with reduced ejection fraction: A complex relationship

https://doi.org/10.1016/j.ahj.2010.12.009Get rights and content

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.

Section snippets

External Peer Review Program (EPRP) database

We performed a retrospective study of a national cohort of veterans with HFrEF treated in ambulatory clinics at Veterans Affairs medical centers using the Veteran Affairs EPRP data between October 2000 and September 2002 (n = 6,608), as described previously.17, 18 This database contained qualitative left ventricular (LV) function assessments of mild-to-moderate (30% ≤ LVEF < 50%) or severe LV systolic dysfunction (LVEF < 30%), and not specific LVEF measurements. Only patients for whom LVEF was

Patient characteristics

The baseline demographic, laboratory characteristics, and comorbidities of the patients with HFrEF in the EPRP database are summarized in Table I. The follow-up duration was 631 ± 201 days. All-cause mortality was 25% in the overall group, which was significantly higher in patients with severe LVSD (29%), in comparison with patients with mild-to-moderate LVSD (23%; P < .001). Most of the baseline parameters were different between the 2 groups as detailed in Table I.

The baseline demographic,

Discussion

This study shows that in ambulatory HFrEF patients with mild-to-moderate LVSD, SBP had a nonlinear relationship with mortality. The lowest mortality was in the SBP range of 130 to 140 mm Hg, with a significantly increased mortality in patients with SBP below 110 mm Hg. In the more recent EPRP database, there was a significantly increased mortality above 150 mm Hg, whereas in the DIG database, there was only a trend toward increased mortality at similar SBP range. On the other hand, in HFrEF

Conclusion

Systolic blood pressure has a complex relationship with outcomes in HFrEF patient that varies with the severity of systolic dysfunction. Specifically, SBP has a U-shaped association with mortality in mild-to-moderate LVSD patients, with better outcomes in the range of 130 to 140 mm Hg. On the other hand, in severe LVSD patients, SBP has a relatively linear association with mortality with higher SBP portending better prognosis. Identification of these patterns of association of SBP with

Disclosures

Conflicts of interest: None of the authors have any financial or other relations that could lead to a conflict of interest.

Acknowledgements

The Digitalis Investigation Group (DIG) study is conducted and supported by the NHLBI in collaboration with the DIG Investigators. This manuscript was not prepared in collaboration with investigators of the DIG, and the views expressed in this article are those of the authors and do not necessarily reflect the opinions or views of the DIG, NHLBI, or Department of Veteran Affairs. The authors thank the Office of Quality and Performance of the Veterans Health Administration for Providing External

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