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 (Lead / Corresponding author)

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    24 Citations (Scopus)
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    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
    Early online date11 Sept 2022
    DOIs
    Publication statusPublished - Dec 2022

    Keywords

    • IBFBP7
    • heart failure
    • HFpEF
    • HFrEF
    • senescence
    • BIOSTAT-CHF
    • IGFBP7

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine

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