Kobayashi, M. et al. (2024) Proteomic profiles of left atrial volume and its influence on response to spironolactone: findings from the HOMAGE trial and STANISLAS cohort. European Journal of Heart Failure, 26(5), pp. 1231-1241. (doi: 10.1002/ejhf.3202) (PMID:38528728)
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Abstract
Aims: High left ventricular filling pressure increases left atrial volume and causes myocardial fibrosis, which may decrease with spironolactone. We studied clinical and proteomic characteristics associated with left atrial volume indexed by body surface area (LAVi), and whether LAVi influences the response to spironolactone on biomarker expression and clinical variables. Methods and results: In the HOMAGE trial, where people at risk of heart failure were randomized to spironolactone or control, we analysed 421 participants with available LAVi and 276 proteomic measurements (Olink) at baseline, month 1 and 9 (mean age 73 ± 6 years; women 26%; LAVi 32 ± 9 ml/m2). Circulating proteins associated with LAVi were also assessed in asymptomatic individuals from a population-based cohort (STANISLAS; n = 1640; mean age 49 ± 14 years; women 51%; LAVi 23 ± 7 ml/m2). In both studies, greater LAVi was significantly associated with greater left ventricular masses and volumes. In HOMAGE, after adjustment and correction for multiple testing, greater LAVi was associated with higher concentrations of matrix metallopeptidase-2 (MMP-2), insulin-like growth factor binding protein-2 (IGFBP-2) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (false discovery rates [FDR] <0.05). These associations were externally replicated in STANISLAS (all FDR <0.05). Among these biomarkers, spironolactone decreased concentrations of MMP-2 and NT-proBNP, regardless of baseline LAVi (pinteraction > 0.10). Spironolactone also significantly reduced LAVi, improved left ventricular ejection fraction, lowered E/e', blood pressure and serum procollagen type I C-terminal propeptide (PICP) concentration, a collagen synthesis marker, regardless of baseline LAVi (pinteraction > 0.10). Conclusion: In individuals without heart failure, LAVi was associated with MMP-2, IGFBP-2 and NT-proBNP. Spironolactone reduced these biomarker concentrations as well as LAVi and PICP, irrespective of left atrial size.
Item Type: | Articles |
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Additional Information: | Funding: The research leading to these results has received funding from the European Union Commission's Seventh Framework programme under grant agreement N° 305507 (HOMAGE). S.H. acknowledges 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. A.G. was supported by the Instituto de Salud Carlos III (PI18/01469 co-financed by FEDER funds). S.H. receives personal fees for scientific advice to AstraZeneca, Cellprothera and CSL Behring; unrestricted research grant from Pfizer. |
Keywords: | Heart failure, spironolactone, left atrial volume, echocardiogram, biomarkers. |
Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Cleland, Professor John and Delles, Professor Christian and Ferreira, Mr Joao Pedro and Pellicori, Dr Pierpaolo |
Authors: | Kobayashi, M., Ferreira, J. P., Kevin, D., Bresso, E., Huttin, O., Bozec, E., Brunner La Rocca, H.-P., Delles, C., Clark, A. L., Edelmann, F., González, A., Heymans, S., Pellicori, P., Petutschnigg, J., Verdonschot, J. A.J., Rossignol, P., Cleland, J. G.F., Zannad, F., and Girerd, N. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | European Journal of Heart Failure |
Publisher: | Wiley |
ISSN: | 1388-9842 |
ISSN (Online): | 1879-0844 |
Published Online: | 25 March 2024 |
Copyright Holders: | Copyright © 2024 The Author(s) |
First Published: | First published in European Journal of Heart Failure 26(5):1231-1241 |
Publisher Policy: | Reproduced under a creative commons licence |
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