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. 2016 Oct 21;16(1):199.
doi: 10.1186/s12872-016-0376-2.

Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction

Michael Coll Barroso  1 , Frank Kramer  2 , Stephen J Greene  3 , Daniel Scheyer  4 , Till Köhler  4 , Martin Karoff  1 , Melchior Seyfarth  4 , Mihai Gheorghiade  5 , Wilfried Dinh  6   7
Affiliations

Serum insulin-like growth factor-1 and its binding protein-7: potential novel biomarkers for heart failure with preserved ejection fraction

Michael Coll Barroso et al. BMC Cardiovasc Disord. .

Abstract

Background: Insulin-like growth factor binding protein-7 (IGFBP-7) modulates the biological activities of insulin-like growth factor-1 (IGF-1). Previous studies demonstrated the prognostic value of IGFBP-7 and IGF-1 among patients with systolic heart failure (HF). This study aimed to evaluate the IGF1/IGFBP-7 axis in HF patients with preserved ejection fraction (HFpEF).

Methods: Serum IGF-1 and IGFBP-7 levels were measured in 300 eligible consecutive patients who underwent comprehensive cardiac assessment. Patients were categorized into 3 groups including controls with normal diastolic function (n = 55), asymptomatic left ventricular diastolic dysfunction (LVDD, n = 168) and HFpEF (n = 77).

Results: IGFBP-7 serum levels showed a significant graded increase from controls to LVDD to HFpEF (median 50.30 [43.1-55.3] vs. 54.40 [48.15-63.40] vs. 61.9 [51.6-69.7], respectively, P < 0.001), whereas IGF-1 levels showed a graded decline from controls to LVDD to HFpEF (120.0 [100.8-144.0] vs. 112.3 [88.8-137.1] vs. 99.5 [72.2-124.4], p < 0.001). The IGFBP-7/IGF-1 ratio increased from controls to LVDD to HFpEF (0.43 [0.33-0.56] vs. 0.48 [0.38-0.66] vs. 0.68 [0.55-0.88], p < 0.001). Patents with IGFB-7/IGF1 ratios above the median demonstrated significantly higher left atrial volume index, E/E' ratio, and NT-proBNP levels (all P ≤ 0.02).

Conclusion: In conclusion, this hypothesis-generating pilot study suggests the IGFBP-7/IGF-1 axis correlates with diastolic function and may serve as a novel biomarker in patients with HFpEF. A rise in IGFBP-7 or the IGFBP-7/IGF-1 ratio may reflect worsening diastolic function, adverse cardiac remodeling, and metabolic derangement.

Keywords: Heart failure; IGF-1; IGFBP-7; Preserved.

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Figures

Fig. 1
Fig. 1
Comparison of serum insulin-like growth factor-1 (IGF-1) (a), and insulin-like growth factor-binding protein-7 concentrations (IGFBP-7) (b), and the insulin-like growth factor axis (the molar ratio of IGFBP-7 and IGF-1) (c) between controls, LVDD and HFpEF. Log IGFBP-7, log IGF-1 and the IGFBP7/IGF-1 levels are presented as box (25th percentile, median, 75th percentile), and whiskers plots, with outliers expressed as dots. All comparisons, P <0.001. LVDD, asymptomatic left ventricular diastolic dysfunction; HFpEF, heart failure with preserved ejection fraction
Fig. 2
Fig. 2
Correlation between log IGFBP-7/IGF-1 ratio and log NT-proBNP. NT-proBNP, N-terminal pro-B-type natriuretic peptide
Fig. 3
Fig. 3
IGFBP-7/IGF-1 ratio between controls, LVDD, and HFpEF, stratified by soluble ST2 level < or ≥ 35 ng/mL. LVDD, asymptomatic left ventricular diastolic dysfunction; HFpEF, heart failure with preserved ejection fraction
Fig. 4
Fig. 4
Comparison of left atrial volume index (a), average E/E’ ratio (septal and lateral averaged) (b), and NT-proBNP levels (c) for patients above and below the median IGFBP-7/IGF-1 ratio
See this image and copyright information in PMC

References

    1. Shah RV, Desai AS, Givertz MM. The effect of renin-angiotensin system inhibitors on mortality and heart failure hospitalization in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis. J Card Fail. 2010;16(3):260–267. doi: 10.1016/j.cardfail.2009.11.007. - DOI - PubMed
    1. Shah SJ. Matchmaking for the optimization of clinical trials of heart failure with preserved ejection fraction: no laughing matter. J Am Coll Cardiol. 2013;62(15):1339–1342. doi: 10.1016/j.jacc.2013.07.010. - DOI - PMC - PubMed
    1. Chen D, Yoo BK, Santhekadur PK, Gredler R, Bhutia SK, Das SK, Fuller C, Su ZZ, Fisher PB, Sarkar D. Insulin-like growth factor-binding protein-7 functions as a potential tumor suppressor in hepatocellular carcinoma. Clin Cancer Res. 2011;17(21):6693–6701. doi: 10.1158/1078-0432.CCR-10-2774. - DOI - PMC - PubMed
    1. Oh Y, Nagalla SR, Yamanaka Y, Kim HS, Wilson E, Rosenfeld RG. Synthesis and characterization of insulin-like growth factor-binding protein (IGFBP)-7. Recombinant human mac25 protein specifically binds IGF-I and -II. J Biol Chem. 1996;271(48):30322–30325. doi: 10.1074/jbc.271.48.30322. - DOI - PubMed
    1. Sacca L, Cittadini A, Fazio S. Growth hormone and the heart. Endocr Rev. 1994;15(5):555–573. doi: 10.1210/edrv-15-5-555. - DOI - PubMed

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