Proteomic profiles of left atrial volume and its influence on response to spironolactone: Findings from the HOMAGE trial and STANISLAS cohort

Data de publicação: 01/01/2024

Autores da FMUP

João Pedro Melo Marques Pinho Ferreira

Autor

Participantes de fora da FMUP

Kobayashi M.
Duarte K.
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.
Girerd N.

Unidades de investigação

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. © 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Dados da publicação

ISSN/ISSNe:: 1388-9842, 1879-0844
Tipo:: Article
Páginas:: 1231-1241
DOI:: 10.1002/ejhf.3202
Link para outro recurso:: www.scopus.com

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Kobayashi M.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France

Department of Cardiology, Tokyo Medical University Hospital, Tokyo, Japan
Ferreira J.P.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France

Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, Porto, Portugal
Duarte K.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France
Bresso E.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France
Huttin O.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France
Bozec E.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France
Brunner La Rocca H.-P.:: Department of Cardiology, Maastricht University Medical Center, Maastricht, Netherlands
Delles C.:: School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom
Clark A.L.:: Department of Cardiology, University of Hull, Castle Hill Hospital, Yorkshire, United Kingdom
Edelmann F.:: Department of Internal Medicine and Cardiology Campus Virchow Klinikum, Charité University Medicine Berlin and German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Berlin, Germany
González A.:: CIMA Universidad de Navarra, Department of Pathology, Anatomy and Physiology Universidad de Navarra and IdiSNA, Pamplona, Spain

CIBERCV, Carlos III Institute of Health, Madrid, Spain
Heymans S.:: Department of Cardiology, Maastricht University Medical Center, Maastricht, Netherlands
Pellicori P.:: School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom
Petutschnigg J.:: Department of Internal Medicine and/Cardiology, Campus Virchow Klinikum, Charité University Medicine Berlin, and German Heart Center Berlin, and Berlin Institute of Health (BIH), and German Centre for Cardiovascular research (DZHK), Berlin, Germany
Verdonschot J.A.J.:: Department of Cardiology, Maastricht University Medical Center, Maastricht, Netherlands
Rossignol P.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France

Medical Specialties and Nephrology Dialysis Departments, Monaco Princess Grace Hospital and Monaco Private Hemodialysis Centre, Monaco, Monaco
Cleland J.G.F.:: School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom
Zannad F.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France
Girerd N.:: Université de Lorraine, INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Inserm U1116, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France

Keywords

Aged; Biomarkers; Female; Heart Atria; Heart Failure; Humans; Male; Matrix Metalloproteinase 2; Middle Aged; Mineralocorticoid Receptor Antagonists; Natriuretic Peptide, Brain; Peptide Fragments; Proteomics; Spironolactone; Stroke Volume; amino terminal pro brain natriuretic peptide; angiotensin receptor antagonist; decorin; insulin; matrix metalloproteinase; metalloproteinase; natriuretic factor; procollagen; procollagen type I c terminal propeptide; somatomedin binding protein 2; spironolactone; transforming growth factor beta; unclassified drug; vascular cell adhesion molecule 1; biological marker; brain natriuretic peptide; gelatinase A; mineralocorticoid antagonist; peptide fragment; pro-brain natriuretic peptide (1-76); spironolactone; Article; atrial fibrillation; blood pressure; body mass; body surface; cardiac index; cardiovascular parameters; cardiovascular risk; clinical trial; cohort analysis; collagen synthesis; controlled study; coronary artery disease; diabetes mellitus;