The association between markers of type I collagen synthesis and echocardiographic response to spironolactone in patients at risk of heart failure: findings from the HOMAGE trial

Kobayashi, M. et al. (2022) The association between markers of type I collagen synthesis and echocardiographic response to spironolactone in patients at risk of heart failure: findings from the HOMAGE trial. European Journal of Heart Failure, (doi: 10.1002/ejhf.2579) (PMID:35703355) (Early Online Publication)

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Background: Procollagen type I C-terminal propeptide (PICP) and procollagen type III N-terminal propeptide (PIIINP) are markers reflecting collagen synthesis in cardiac fibrosis. However, they may be influenced by the presence of noncardiac comorbidities (e.g., ageing, obesity, renal impairment). Understanding the associations between markers of collagen synthesis and abnormalities of cardiac structure and function is important to screen for myocardial fibrosis and monitor the antifibrotic effect of medications. Methods: The HOMAGE (Heart OMics in Aging) trial showed that spironolactone decreased serum PICP concentrations and improved cardiac remodeling over 9 months in a population at risk of developing heart failure (HF). We evaluated the associations between echocardiographic variables, PICP, PIIINP and galectin-3 at baseline and during the course of the trial. Results: Among 527 individuals (74±7years, 26% women), median serum concentrations of PICP, PIIINP and galectin-3 were 80.6μg/L (65.1-97.0), 3.9μg/L (3.1-5.0) and 16.1μg/L (13.5-19.7), respectively. After adjustment for potential confounders, higher serum PICP was significantly associated with left ventricular hypertrophy, left atrial enlargement, and greater ventricular stiffness (all p-values<0.05), whereas serum PIIINP and galectin-3 were not (all p-values>0.05). In patients treated with spironolactone, a reduction in serum PICP during the trial was associated with a decrease in E/e′ (adjusted-beta [95% CI] =0.93 [0.14-1.73]; p=0.022). Conclusions: In individuals at high risk of developing HF, serum PICP was associated with cardiac structural and functional abnormalities, and a decrease in PICP with spironolactone was correlated with improved diastolic dysfunction as assessed by E/e′. In contrast, no such associations were present for serum PIIINP and galectin-3.

Item Type:Articles
Additional Information:The research leading to these results has received funding from the European Union Commission’s Seventh Framework programme under grant agreement N° 305507 (HOMAGE). SH acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation, Dutch Cardiovascular AllianceCVON2016-Early HFPEF, 2015-10, CVON She-PREDICTS, grant 2017-21; Furthermore, we acknowledge the support of FWO G091018N and FWO G0B5930N to S.H. AG was supported by the Instituto de Salud Carlos III (PI18/01469 co-financed by FEDER funds). SH receives personal fees for scientific advice to Astra-Zeneca, Cellprothera and CSL Behring; unrestricted research grant from Pfizer.
Status:Early Online Publication
Glasgow Author(s) Enlighten ID:Cleland, Professor John and Ferreira, Mr Joao Pedro and Pellicori, Dr Pierpaolo
Authors: Kobayashi, M., Girerd, N., Ferreira, J. P., Kevin, D., Huttin, O., González, A., Bozec, E., Clark, A. L., Cosmi, F., Cuthbert, J., Diez, J., Edelmann, F., Hazebroek, M., Heymans, S., Mariottoni, B., Pellicori, P., Petutschnigg, J., Pieske, B., Staessen, J. A., Verdonschot, J. A.J., Rossignol, P., Cleland, J. G.F., and Zannad, F.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
Journal Name:European Journal of Heart Failure
ISSN (Online):1879-0844
Published Online:15 June 2022

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190666HOMAGE: Heart OMics in AGEingChristian DellesEuropean Commission (EC)305507Institute of Cardiovascular & Medical Sciences