{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,25]],"date-time":"2026-01-25T21:42:35Z","timestamp":1769377355404,"version":"3.49.0"},"reference-count":31,"publisher":"BMJ","issue":"4","funder":[{"name":"HOMAGE"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Heart"],"accepted":{"date-parts":[[2018,7,26]]},"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>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 \u2018Anglo-Scandinavian Cardiac Outcomes\u2019 trial (ASCOT).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>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\u2009months before versus after spironolactone treatment was also performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Patients included in the between-person analysis (n=146) were well matched: the mean age was 63\u00b17 years and 11% were woman. Serum concentrations of PIIINP and PICP rose in \u2018controls\u2019 and fell during spironolactone treatment (adjusted means +0.52 (\u22120.05 to 1.09) vs \u22120.41 (\u22120.97 to 0.16)\u2009ng\/mL, p=0.031 for PIIINP and +4.54(\u22121.77 to 10.9) vs \u22126.36 (\u221212.5 to \u22120.21) 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=\u221211.82(\u221217.53 to \u22126.10) ng\/mL, p&lt;0.001) but not in PIIINP levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/heartjnl-2018-313182","type":"journal-article","created":{"date-parts":[[2018,8,18]],"date-time":"2018-08-18T12:15:38Z","timestamp":1534594538000},"page":"307-314","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure"],"prefix":"10.1136","volume":"105","clinical-trial-number":[{"clinical-trial-number":"nct02556450","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02556450","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2304-6138","authenticated-orcid":false,"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"Centre d\u2019Investigations Cliniques Plurith\u00e9matique Inserm 1433, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"CHRU de Nancy, Inserm U1116, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"FCRIN INI-CRCT, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"Department of Physiology, University of Porto, Porto, Portugal"},{"name":"Department of Cardiothoracic Surgery, University of Porto, Porto, Portugal"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigations Cliniques Plurith\u00e9matique Inserm 1433, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"CHRU de Nancy, Inserm U1116, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"FCRIN INI-CRCT, Universit\u00e9 de Lorraine, Nancy, France"}]},{"given":"Anne","family":"Pizard","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigations Cliniques Plurith\u00e9matique Inserm 1433, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"CHRU de Nancy, Inserm U1116, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"FCRIN INI-CRCT, Universit\u00e9 de Lorraine, Nancy, France"}]},{"given":"Jean-Loup","family":"Machu","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigations Cliniques Plurith\u00e9matique Inserm 1433, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"CHRU de Nancy, Inserm U1116, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"FCRIN INI-CRCT, Universit\u00e9 de Lorraine, Nancy, France"}]},{"given":"Timothy","family":"Collier","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigations Cliniques Plurith\u00e9matique Inserm 1433, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"CHRU de Nancy, Inserm U1116, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"FCRIN INI-CRCT, Universit\u00e9 de Lorraine, Nancy, France"}]},{"given":"Anne-C\u00e9cile","family":"Huby","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigations Cliniques Plurith\u00e9matique Inserm 1433, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"CHRU de Nancy, Inserm U1116, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"FCRIN INI-CRCT, Universit\u00e9 de Lorraine, Nancy, France"}]},{"given":"Arantxa","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA, University of Navarra and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Pamplona, Spain"},{"name":"CIBERCV, Carlos III Institute of Health, Madrid, Spain"}]},{"given":"Javier","family":"Diez","sequence":"additional","affiliation":[{"name":"Program of Cardiovascular Diseases, CIMA, University of Navarra and Instituto de Investigaci\u00f3n Sanitaria de Navarra (IdiSNA), Pamplona, Spain"},{"name":"CIBERCV, Carlos III Institute of Health, Madrid, Spain"},{"name":"Department of Cardiology and Cardiac Surgery, University of Navarra Clinic, Pamplona, Spain"}]},{"given":"Bego\u00f1a","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"CIBERCV, Carlos III Institute of Health, Madrid, Spain"}]},{"given":"Naveed","family":"Sattar","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK"}]},{"given":"John G","family":"Cleland","sequence":"additional","affiliation":[{"name":"Robertson Centre for Biostatistics and Clinical Trials, University of Glasgow, Glasgow, UK"},{"name":"National Heart and Lung Institute, Imperial College London, London, UK"}]},{"given":"Peter S","family":"Sever","sequence":"additional","affiliation":[{"name":"International Centre for Circulatory Health, Imperial College London, London, UK"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigations Cliniques Plurith\u00e9matique Inserm 1433, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"CHRU de Nancy, Inserm U1116, Universit\u00e9 de Lorraine, Nancy, France"},{"name":"FCRIN INI-CRCT, Universit\u00e9 de Lorraine, Nancy, 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