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Haddad F, Ataam JA, Amsallem M, et al. Insulin Growth Factor Phenotypes in Heart Failure with Preserved Ejection Fraction, an INSPIRE Registry and CATHGEN Study: IGF axis in HFpEF. J Card Fail. 2021;doi: 10.1016/j.cardfail.2021.12.012.
Haddad, F., Ataam, J. A., Amsallem, M., Cauwenberghs, N., Kuznetsova, T., Rosenberg-Hasson, Y., Zamanian, R. T., Karakikes, I., Horne, B. D., Muhlestein, J. B., Kwee, L., Shah, S., Maecker, H., Knight, S., & Knowlton, K. (2021). Insulin Growth Factor Phenotypes in Heart Failure with Preserved Ejection Fraction, an INSPIRE Registry and CATHGEN Study: IGF axis in HFpEF. Journal of cardiac failure, . https://doi.org/10.1016/j.cardfail.2021.12.012
Haddad, Francois, et al. "Insulin Growth Factor Phenotypes in Heart Failure with Preserved Ejection Fraction, an INSPIRE Registry and CATHGEN Study: IGF axis in HFpEF." Journal of cardiac failure vol. (2021). doi: https://doi.org/10.1016/j.cardfail.2021.12.012
Haddad F, Ataam JA, Amsallem M, Cauwenberghs N, Kuznetsova T, Rosenberg-Hasson Y, Zamanian RT, Karakikes I, Horne BD, Muhlestein JB, Kwee L, Shah S, Maecker H, Knight S, Knowlton K. Insulin Growth Factor Phenotypes in Heart Failure with Preserved Ejection Fraction, an INSPIRE Registry and CATHGEN Study: IGF axis in HFpEF. J Card Fail. 2021 Dec 31; doi: 10.1016/j.cardfail.2021.12.012. Epub 2021 Dec 31. PMID: 34979242.
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J Card Fail. 2021 Dec 31; doi: 10.1016/j.cardfail.2021.12.012. Epub 2021 Dec 31.

Insulin Growth Factor Phenotypes in Heart Failure with Preserved Ejection Fraction, an INSPIRE Registry and CATHGEN Study: IGF axis in HFpEF.

Journal of cardiac failure

Francois Haddad, Jennifer Arthur Ataam, Myriam Amsallem, Nicholas Cauwenberghs, Tatiana Kuznetsova, Yael Rosenberg-Hasson, Roham T Zamanian, Ioannis Karakikes, Benjamin D Horne, Joseph B Muhlestein, Lydia Kwee, Svati Shah, Holden Maecker, Stacey Knight, Kirk Knowlton

Affiliations

  1. Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: [email protected].
  2. Division of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA; Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  3. Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
  4. Research Unit of Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
  5. Institute for Immunity, Transplantation, and Infection, Stanford University School of Medicine, Stanford, CA, USA.
  6. Vera Moulton Wall Center at Stanford, Stanford University School of Medicine, Stanford, CA, USA.
  7. Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Division of Cardiothoracic Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  8. Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Intermountain Medical Center, Heart Institute, Salt Lake City, UT, USA.
  9. Intermountain Medical Center, Heart Institute, Salt Lake City, UT, USA.
  10. Department of Internal Medicine, Division of Cardiology, Duke University Medical Center, Durham, North Carolina and Duke Molecular Physiology Institute, Duke University, Durham, North Carolina.

PMID: 34979242 DOI: 10.1016/j.cardfail.2021.12.012

Abstract

BACKGROUND: The insulin like growth factor (IGF) axis emerged as an important pathway in heart failure with preserved ejection (HFpEF). We aimed to identify IGF phenotypes associated with HFpEF in the context high-dimensional proteomic profiling.

METHODS: From the Intermountain INSPIRE Registry, we identified 96 patients with HFpEF and matched controls. We performed targeted proteomics including IGF-1,2, IGF binding proteins (IGFBP) 1-7 and 111 other proteins (EMD Millipore and ELISA). We used partial least square discriminant analysis (PLS-DA) to identify a set of proteins associated with prevalent HFpEF, pulmonary hypertension (PH) and 5-year-all-cause mortality. K-mean clustering was used to identify IGF phenotypes.

RESULTS: Patients with HFpEF had a high prevalence of systemic hypertension (95%) and coronary artery disease (74%). Using PLS-DA, we identified a set of biomarkers including IGF1,2 and IGFBP-1,2,7 that provided a strong discrimination of HFPEF, PH and mortality with an AUC of 0.91, 0.77 and 0.83, respectively. Using K mean clustering, we identified three IGF phenotypes that were independently associated with all-cause 5-year mortality after adjustment for age, NT-proBNP and kidney disease (p=0.004). Multivariable analysis validated the prognostic value of IGFBP-1 and 2 in the CATHGEN biorepository.

CONCLUSION: IGF phenotypes were associated with PH and mortality in HFpEF.

Copyright © 2021. Published by Elsevier Inc.

Conflict of interest statement

Declaration of Competing Interest No specific conflict of interest specific to this paper with the exception of the research funding received by Actelion Pharmaceuticals.

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