Insulin-like growth factor binding protein 7 (IGFBP7), a link between heart failure and senescence

Valentina Bracun, Bart van Essen, Adriaan A. Voors, Dirk J. van Veldhuisen, Kenneth Dickstein, Faiez Zannad, Marco Metra, Stefan Anker, Nilesh J. Samani, Piotr Ponikowski, Gerasimos Filippatos, John G.F. Cleland, Chim C. Lang, Leong L. Ng, Canxia Shi, Sanne de Wit, Joseph Pierre Aboumsallem, Wouter C. Meijers, IJsbrand T. Klip, Peter van der MeerRudolf A. de Boer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Aims: Insulin like growth factor binding protein 7 (IGFBP7) is a marker of senescence secretome and a novel biomarker in patients with heart failure (HF). We evaluated the prognostic value of IGFBP7 in patients with heart failure and examined associations to uncover potential new pathophysiological pathways related to increased plasma IGFBP7 concentrations. Methods and results: We have measured plasma IGFBP7 concentrations in 2250 subjects with new-onset or worsening heart failure (BIOSTAT-CHF cohort). Higher IGFBP7 plasma concentrations were found in older subjects, those with worse kidney function, history of atrial fibrillation, and diabetes mellitus type 2, and in subjects with higher number of HF hospitalizations. Higher IGFBP7 levels also correlate with the levels of several circulating biomarkers, including higher NT-proBNP, hsTnT, and urea levels. Cox regression analyses showed that higher plasma IGFBP7 concentrations were strongly associated with increased risk of all three main endpoints (hospitalization, all-cause mortality, and combined hospitalization and mortality) (HR 1.75, 95% CI 1.25–2.46; HR 1.71, 95% CI 1.39–2.11; and HR 1.44, 95% CI 1.23–1.70, respectively). IGFBP7 remained a significant predictor of these endpoints in patients with both reduced and preserved ejection fraction. Likelihood ratio test showed significant improvement of all three risk prediction models, after adding IGFBP7 (P < 0.001). A biomarker network analysis showed that IGFBP7 levels activate different pathways involved in the regulation of the immune system. Results were externally validated in BIOSTAT-CHF validation cohort. Conclusions: IGFPB7 presents as an independent and robust prognostic biomarker in patients with HF, with both reduced and preserved ejection fraction. We validate the previously published data showing IGFBP7 has correlations with a number of echocardiographic markers. Lastly, IGFBP7 pathways are involved in different stages of immune system regulation, linking heart failure to senescence pathways.

Original languageEnglish
Pages (from-to)4167-4176
Number of pages10
JournalESC heart failure
Volume9
Issue number6
DOIs
Publication statusPublished - Dec 2022
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by a grant from the European Research Council (ERC CoG 818715, SECRETE‐HF). Furthermore, support was received from grants from the Netherlands Heart Foundation (CVON SHE‐PREDICTS‐HF, grant 2017‐21; CVON RED‐CVD, grant 2017‐11; CVON PREDICT2, grant 2018‐30; and CVON DOUBLE DOSE, grant 2020B005), and by a grant from the leDucq Foundation [Cure PhosphoLambaN induced Cardiomyopathy (Cure‐PLaN)].

Publisher Copyright:
© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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