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. 2023 Jun;11(6):662-674.
doi: 10.1016/j.jchf.2023.01.016. Epub 2023 Apr 12.

Regional Handling and Prognostic Performance of Circulating Insulin-Like Growth Factor Binding Protein-7 in Heart Failure

Eugene S J Tan  1 , Siew-Pang Chan  1 , Yeunhyang C Choi  2 , Chris J Pemberton  3 , Richard Troughton  3 , Katrina Poppe  4 , Mayanna Lund  5 , Gerry Devlin  6 , Robert N Doughty  4 , A Mark Richards  7
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Free article

Regional Handling and Prognostic Performance of Circulating Insulin-Like Growth Factor Binding Protein-7 in Heart Failure

Eugene S J Tan et al. JACC Heart Fail. 2023 Jun.
Free article

Abstract

Background: Regional handling and the prognostic performance of insulin-like growth factor binding protein (IGFBP)-7, in contrast or in combination with other candidate biomarkers, in chronic heart failure (CHF) remain uncertain.

Objectives: The authors investigated the regional handling of plasma IGFBP-7 and its association with long-term outcomes in CHF in comparison with selected circulating biomarkers.

Methods: Plasma concentrations of IGFBP-7, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T, growth differentiation factor-15, and high-sensitivity C-reactive protein were measured prospectively in a cohort with CHF (n = 863). The primary outcome was the composite of heart failure (HF) hospitalization or all-cause mortality. In a separate non-HF cohort (n = 66) undergoing cardiac catheterization, transorgan gradients of plasma IGFBP-7 concentrations were evaluated.

Results: Among 863 patients (age 69 ± 14 years, 30% female, 36% HF with preserved ejection fraction), IGFBP-7 (median: 121 [IQR: 99-156] ng/mL) related inversely to left ventricular volumes but directly to diastolic function. Above the optimal cutoff, IGFBP-7 ≥110 ng/mL was independently associated with 32% increased hazard of the primary outcome: 1.32 (95% CI: 1.06-1.64). Among the 5 markers, IGFBP-7 had the highest hazard for a proportional increment in plasma concentrations independent of HF phenotype in single- and double-biomarker models, and provided incremental prognostic value beyond clinical predictors plus NT-proBNP, high-sensitivity troponin-T, and high-sensitivity C-reactive protein (P < 0.05). Assessment of regional concentrations indicated renal secretion of IGFBP-7 in contrast to renal extraction of NT-proBNP, possible cardiac extraction of IGFBP-7 in contrast to secretion of NT-proBNP, and common hepatic extraction of both peptides.

Conclusions: Transorgan regulation of IGFBP-7 is distinct from NT-proBNP. Circulating IGFBP-7 independently predicts adverse outcomes in CHF with a strong prognostic performance when compared with other well-recognized cardiac-specific or noncardiac prognostic markers.

Keywords: biomarkers; heart failure; insulin-like growth factor binding protein (IGFBP)-7; prognosis.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the following research grants: A∗STAR-NZ HRC (Grant Number: JGC 10_027), New Zealand Heart Foundation Project Grant, TM Hosking Trust (Auckland); Waikato Medical Research Foundation; HRC Programme Grant; New Zealand Heart Foundation Chair in Cardiovascular Studies (Dr Richards); and New Zealand Heart Foundation Chair of Heart Health (Dr Doughty), Auckland Medical Research Foundation. Dr Richards has received grants from the Health Research Council of New Zealand and the Heart Foundation of New Zealand; and has received grants and nonfinancial support from Roche Diagnostics during the conduct of the study. Dr Poppe has received grants from the Heart Foundation of New Zealand and the Health Research Council outside of the submitted work. Dr Lund has received grants from the Health research council, Auckland Medical Research Foundation, and the Lottery Health Research during the conduct of the study. Dr Troughton has received grants and personal fees from Roche Diagnostics during the conduct of the study; and has received grants and personal fees from Merck outside of the submitted work. Dr Doughty has received grants from the Heart Foundation of New Zealand, the Health Research Council of New Zealand, and Roche Diagnostics during the conduct of the study. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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