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Mortality and morbidity in relation to changes in albuminuria, glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies

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Abstract

Aims/hypothesis

Urinary albumin excretion is a strong predictor of cardiovascular disease. It is uncertain whether improvement from microalbuminuria or deterioration from normoalbuminuria over time in patients with differing changes in glucose and BP change their cardiovascular risk.

Methods

Data on mortality, cardiovascular and renal outcomes were analysed in 22,984 patients from two large parallel randomised clinical trials followed for 56 months. A central laboratory analysed first morning spot urine samples at baseline and after 24 months, and events were recorded over the subsequent 32 months. Patients were stratified by changes in albuminuria, glucose status and mean systolic BP over 2 years.

Results

There was a strong association between albuminuria status and all-cause and cardiovascular mortality and combined cardiovascular and renal endpoints (all p < 0.0001). Changes in systolic BP control had no effect on mortality, whereas glucose status was significantly associated with all outcomes. Irrespective of BP control or glucose status, patients showing an improvement from microalbuminuria to normoalbuminuria after 2 years were at a lower risk of all outcome measures than patients showing deterioration from normoalbuminuria to microalbuminuria (HR for all-cause mortality 0.65 [0.52–0.83], p = 0.0004).

Conclusions/interpretation

Patients who showed improvement to normoalbuminuria over 2 years were at lower risk of all-cause and cardiovascular mortality and of cardiovascular and renal events than those who deteriorated to microalbuminuria over time. Albuminuria over time was significantly better than glucose status and BP control in predicting mortality and both cardiovascular and renal outcomes in patients at a high cardiovascular risk.

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Abbreviations

eGFR:

Estimated GFR

FPG:

Fasting plasma glucose

ONTARGET:

ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial

TRANSCEND:

The Telmisartan Randomised AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease

UACR:

Urinary albumin/creatinine ratio

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Funding

Funding for this research was provided by Boehringer Ingelheim.

Duality of interest statement

RES, MB, GM, MAW, KT and SY report receiving consulting and lecture fees and research grants from Boehringer Ingelheim and from other companies manufacturing angiotensin receptor blockers, ACE inhibitors and other BP-lowering drugs; HS is an employee of Boehringer Ingelheim. All other authors declare no conflict of interest.

Contribution statement

All authors substantially contributed to the conception and design of the manuscript, acquisition and interpretation of data and approved the final version. The analysis was planned by RES, HS, MB, KT and SY; data were analysed by HS. MM was responsible for the laboratory analysis and made critical revisions. RES, RS and HS drafted the article; and MB, GM, MAW, KT and SY critically revised it for important intellectual content.

All authors had full access to the data. No medical writer or other people were involved in the design, analysis or writing of this manuscript. A full list of all investigators has been published [22]. RES is guarantor of this work.

Author information

Authors and Affiliations

  1. Department of Nephrology and Hypertension, University Hospital of the University Erlangen-Nuremberg, Ulmenweg 18, 91054, Erlangen, Germany

    Roland E. Schmieder

  2. Hypertension in Africa Research Team, North-West University, Potchefstroom, South Africa

    Rudolph Schutte

  3. Boehringer Ingelheim, Ingelheim, Germany

    Helmut Schumacher

  4. Medizinische Fakultät der Universität des Saarlandes, Universitätsklinikum des Saarlandes (UKS), Homburg, Germany

    Michael Böhm

  5. Clinica Medica, University of Milan-Bicoca, S. Gerardo Hospital, Monza, Italy

    Giuseppe Mancia

  6. Cardiology Division, State University of New York Downstate College of Medicine, Brooklyn, NY, USA

    Michael A. Weber

  7. Population Health Research Institute, McMaster University, Hamilton, ON, Canada

    Matthew McQueen, Koon Teo & Salim Yusuf

Authors
  1. Roland E. Schmieder
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  2. Rudolph Schutte
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  5. Giuseppe Mancia
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  7. Matthew McQueen
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  8. Koon Teo
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  9. Salim Yusuf
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Consortia

on behalf of the ONTARGET/TRANSCEND investigators

Corresponding author

Correspondence to Roland E. Schmieder.

Additional information

Rudolph Schutte and Roland E. Schmieder contributed equally to writing this article

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Schmieder, R.E., Schutte, R., Schumacher, H. et al. Mortality and morbidity in relation to changes in albuminuria, glucose status and systolic blood pressure: an analysis of the ONTARGET and TRANSCEND studies. Diabetologia 57, 2019–2029 (2014). https://doi.org/10.1007/s00125-014-3330-9

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  • DOI: https://doi.org/10.1007/s00125-014-3330-9

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