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Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure.

  • Ferreira, João Pedro1, 2, 3, 4, 5
  • Rossignol, Patrick1, 2, 3
  • Pizard, Anne1, 2, 3
  • Machu, Jean-Loup1, 2, 3
  • Collier, Timothy6
  • Girerd, Nicolas1, 2, 3
  • Huby, Anne-Cécile1, 2, 3
  • Gonzalez, Arantxa7, 8
  • Diez, Javier7, 8, 9
  • López, Begoña8
  • Sattar, Naveed10
  • Cleland, John G11, 12
  • Sever, Peter S13
  • Zannad, Faiez1, 2, 3
  • 1 Centre d'Investigations Cliniques Plurithématique Inserm 1433, Université de Lorraine, Nancy, France. , (France)
  • 2 CHRU de Nancy, Inserm U1116, Université de Lorraine, Nancy, France. , (France)
  • 3 FCRIN INI-CRCT, Université de Lorraine, Nancy, France. , (France)
  • 4 Department of Physiology, University of Porto, Porto, Portugal. , (Portugal)
  • 5 Department of Cardiothoracic Surgery, University of Porto, Porto, Portugal. , (Portugal)
  • 6 Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
  • 7 Program of Cardiovascular Diseases, CIMA, University of Navarra and Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Spain. , (Spain)
  • 8 CIBERCV, Carlos III Institute of Health, Madrid, Spain. , (Spain)
  • 9 Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain. , (Spain)
  • 10 Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK.
  • 11 Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, UK.
  • 12 National Heart and Lung Institute, Imperial College London, London, UK.
  • 13 International Centre for Circulatory Health, Imperial College London, London, UK.
Published Article
Publication Date
Feb 01, 2019
DOI: 10.1136/heartjnl-2018-313182
PMID: 30121630


An increase in myocardial collagen content may contribute to the development of heart failure; this might be inhibited or reversed by mineralocorticoid receptor antagonists (MRAs). We investigated changes in serum concentrations of the collagen synthesis biomarkers N-terminal propeptide of procollagen type III (PIIINP) (primary outcome) and C-terminal propeptide of procollagen type I (PICP) (secondary outcome) after non-randomised initiation of spironolactone as add-on therapy among patients with resistant hypertension enrolled in the 'Anglo-Scandinavian Cardiac Outcomes' trial (ASCOT). An age/sex matching plus propensity-scored logistic regression model incorporating variables related to the outcome and spironolactone treatment was created to compare patients treated with spironolactone for a 9-month period versus matched controls. A within-person analysis comparing changes in serum biomarker concentrations in the 9 months before versus after spironolactone treatment was also performed. Patients included in the between-person analysis (n=146) were well matched: the mean age was 63±7 years and 11% were woman. Serum concentrations of PIIINP and PICP rose in 'controls' and fell during spironolactone treatment (adjusted means +0.52 (-0.05 to 1.09) vs -0.41 (-0.97 to 0.16) ng/mL, p=0.031 for PIIINP and +4.54(-1.77 to 10.9) vs -6.36 (-12.5 to -0.21) ng/mL, p=0.023 for PICP). For the within-person analysis (n=173), spironolactone treatment was also associated with a reduction in PICP (beta estimate=-11.82(-17.53 to -6.10) ng/mL, p<0.001) but not in PIIINP levels. Treatment with spironolactone was associated with a reduction in serum biomarkers of collagen synthesis independently of blood pressure in patients with hypertension, suggesting that spironolactone might exert favourable effects on myocardial collagen synthesis and fibrosis. Whether this effect might contribute to slowing the progression to heart failure is worth investigating. © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.

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