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Original article
Influence of age on the prognostic value of mid-regional pro-adrenomedullin in the general population
  1. Frank P Brouwers1,
  2. Rudolf A de Boer1,
  3. Pim van der Harst1,
  4. Joachim Struck2,
  5. Paul E de Jong3,
  6. Dick de Zeeuw4,
  7. Rijk O Gans5,
  8. Ron T Gansevoort3,
  9. Hans L Hillege1,
  10. Wiek H van Gilst1,
  11. Stephan J Bakker3
  1. 1Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  2. 2BRAHMS GmbH/ThermoFisher Scientific, Hennigsdorf, Germany
  3. 3Department of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  4. 4Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  5. 5Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Dr Frank P Brouwers, University of Groningen, University Medical Centre Groningen, Department of Cardiology, P O Box 30 001, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands; f.p.j.brouwers{at}


Objective Experimental studies have shown that adrenomedullin (ADM) has an important role in circulatory homeostasis. Mid-regional pro-ADM (MR-proADM) is a stable form of ADM. Observational studies found an important association with age, body mass index and kidney function. The aim of this study was to evaluate the prognostic performance of MR-proADM in the general population, controlling for these potential confounders.

Methods 7903 subjects (mean age 49±13 years, 49% male) from the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort with a median follow-up of 10.5 years were enrolled in a prospective cohort study.

Results Mean baseline MR-proADM was 0.39±0.14 nmol/l. In cross-sectional analyses, age, blood pressure, C reactive protein, cystatin-C, N-terminal pro-brain type natriuretic peptide and urinary albumin excretion remained as independent determinants of MR-proADM. In prospective analyses, MR-proADM was associated with the primary endpoint (combined cardiovascular mortality and cardiovascular morbidity), with event rates ranging from 8% in the lowest quintile to 45% in the highest quintile (p for trend <0.001) independent of age, sex, components of the Framingham risk score and other cardiovascular markers. Overall Net Reclassification Improvement against the Framingham risk score was 2.2%, which was non-significant. However, significant modification of the effect of MR-proADM on outcome by age was observed. In subjects aged ≤70 years (N=7475), 8.8% were correctly reclassified in a higher risk category (p=0.017) and 3.4% in a lower risk category (p<0.001). In subjects aged >70 years (N=428) there was no improvement of reclassification (p=0.32).

Conclusion This study gives a detailed overview of the distribution of ADM in a general population and provides evidence that it is a potent and interesting biomarker in predicting cardiovascular events. These results seem especially applicable to younger subjects.

  • MR-proADM
  • prognosis
  • epidemiology
  • cardiovascular disease
  • heart failure
  • renal disease
  • metabolic medicine

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  • Competing interests JS is employed by BRAHMS GmbH/ThermoFisher Scientific, a company which manufactures and holds patent rights on the MR-proADM assay.

  • Ethics approval This study was conducted with the approval of the local ethics committees and performed in accordance with the Declaration of Helsinki.

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