Open AccessInsulin‐like growth factor binding protein 7 (IGFBP7), a link between heart failure and senescence
Author(s) -
Bracun Valentina,
Essen Bart,
Voors Adriaan A.,
Veldhuisen Dirk J.,
Dickstein Kenneth,
Zannad Faiez,
Metra Marco,
Anker Stefan,
Samani Nilesh J.,
Ponikowski Piotr,
Filippatos Gerasimos,
Cleland John G.F.,
Lang Chim C.,
Ng Leong L.,
Shi Canxia,
Wit Sanne,
Aboumsallem Joseph Pierre,
Meijers Wouter C.,
Klip IJsbrand T.,
Meer Peter,
Boer Rudolf A.
Publication year - 2022
Publication title -
esc heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.787
H-Index - 25
ISSN - 2055-5822
DOI - 10.1002/ehf2.14120
Subject(s) - medicine , heart failure , biomarker , renal function , proportional hazards model , ejection fraction , cohort , cardiology , diabetes mellitus , endocrinology , prospective cohort study , biochemistry , chemistry
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.