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

Ferreira, J. P. et al. (2019) Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure. Heart, 105(4), pp. 307-314. (doi: 10.1136/heartjnl-2018-313182) (PMID:30121630)

168437.pdf - Accepted Version



Background: 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). Methods: 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. Results: 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. Conclusions: 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.

Item Type:Articles
Additional Information:This work is supported by the European Union: HEALTH-F7- 305507 HOMAGE (EU FP7 305507 http://www.homage-hf.eu). The European Research Council Advanced Researcher Grant-2011-294713-EPLORE and the Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Ministry of the Flemish Community, Brussels, Belgium (G.0881.13 and G.088013), currently support the Studies Coordinating Centre in Leuven. JF, PR and FZ are supported by a public grant overseen by the French National Research Agency (ANR) as part of the second ’Investissements d’Avenir’ programme (Fighting Heart Failure reference: ANR-15- RHU-0004 and GEENAGE IMPACT Lorraine University Excellence).
Glasgow Author(s) Enlighten ID:Cleland, Professor John and Sattar, Professor Naveed
Authors: Ferreira, J. P., Rossignol, P., Pizard, A., Machu, J.-L., Collier, T., Girerd, N., Huby, A.-C., Gonzalez, A., Diez, J., López, B., Sattar, N., Cleland, J. G., Sever, P. S., and Zannad, F.
Subjects:R Medicine > R Medicine (General)
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Health and Wellbeing > Robertson Centre
Journal Name:Heart
Publisher:BMJ Publishing Group
ISSN (Online):1468-201X
Published Online:18 August 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Heart 105(4): 307-314
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
601881HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507RI CARDIOVASCULAR & MEDICAL SCIENCES