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Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anemia—the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT)

Journal of Human Hypertension volume 30, pages 46–52 (2016)Cite this article

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Abstract

Pulse pressure (PP) remains an elusive cardiovascular risk factor with inconsistent findings. We clarified the prognostic value in patients with type 2 diabetes, chronic kidney disease (CKD) and anemia in the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin alfa) Therapy. In 4038 type 2 diabetes patients, darbepoetin alfa treatment did not affect the primary outcome. Risk related to PP at randomization was evaluated in a multivariable model including age, gender, kidney function, cardiovascular disease (CVD) and other conventional risk factors. End points were myocardial infarction (MI), stroke, end stage renal disease (ESRD) and the composite of cardiovascular death, MI or hospitalization for myocardial ischemia, heart failure or stroke (CVD composite). Median (interquartile range) age, gender, eGFR and PP was 68 (60–75) years, 57.3% women, 33 (27–42) ml min−1 per 1.73 m2 and 60 (50–74) mm Hg. During 29.1 months (median) follow-up, the number of events for composite CVD, MI, stroke and ESRD was 1010, 253, 154 and 668. In unadjusted analyses, higher quartiles of PP were associated with higher rates per 100 years of follow-up of all end points (P⩽0.04), except stroke (P=0.52). Adjusted hazard ratios (95% confidence interval) per one quartile increase in PP were 1.06 (0.99–1.26) for MI, 0.96 (0.83–1.11) for stroke, 1.01 (0.94–1.09) for ESRD and 1.01 (0.96–1.07) for CVD composite. Results were similar in continuous analyses of PP (per 10 mm Hg). In patients with type 2 diabetes, CKD and anemia, PP did not independently predict cardiovascular events or ESRD. This may reflect confounding by aggressive antihypertensive treatment, or PP may be too rough a risk marker in these high-risk patients.

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Acknowledgements

The TREAT trial was supported by Amgen. This study was conducted independently by the academic co-authors using the TREAT database at the Brigham and Women’s Hospital, Boston, MA, USA. EFL received research grants from Amgen. H-HP acted as Amgen consultant. MP received research grants from and acted as a consultant for Amgen. SDS received research grants from and acted as a consultant for Amgen.

Ethics approval

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study.

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Authors and Affiliations

  1. Steno Diabetes Center, Gentofte, Denmark

    S Theilade, T W Hansen & P Rossing

  2. Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

    B Claggett, H Skali, E F Lewis, S D Solomon & M Pfeffer

  3. Division of Cardiovascular Medicine, Brigham Women’s Hospital, Boston, MA, USA

    B Claggett, H Skali, E F Lewis, S D Solomon & M Pfeffer

  4. Department of Medical Endocrinology, Rigshospitalet, Copenhagen, Denmark

    H-H Parving

  5. Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    H-H Parving & P Rossing

  6. Faculty of Health Sciences, Aarhus University, Aarhus, Denmark

    H-H Parving & P Rossing

  7. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK

    J J McMurray

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Theilade, S., Claggett, B., Hansen, T. et al. Pulse pressure is not an independent predictor of outcome in type 2 diabetes patients with chronic kidney disease and anemia—the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT). J Hum Hypertens 30, 46–52 (2016). https://doi.org/10.1038/jhh.2015.22

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