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Soluble ST2 is a biomarker for cardiovascular mortality related to abnormal glucose metabolism in high-risk subjects

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Abstract

Aims

Inflammation plays a role in the development and progression of type 2 diabetes macroangiopathy. Interleukin 33 (IL-33) drives production of Th2-associated cytokines. The soluble form of suppression of tumorigenicity 2 (sST2) acting as a decoy receptor blocks IL-33 and tones down Th2 inflammatory response. We investigated the role of sST2 as a predictor of CV and all-cause mortality in a cohort of patients affected by established atherosclerotic disease.

Methods

399 patients with atherosclerotic disease from the Tor Vergata Atherosclerosis Registry performed follow-up every year by phone interview. The primary endpoint was cardiovascular death and the secondary endpoint was death for any other disease.

Results

sST2 plasma levels were significantly increased from normal glucose-tolerant patients to patients with history of type 2 diabetes (p < 0.00001). Levels of sST2 were significantly correlated with fasting plasma glucose (R = 0.16, p = 0.002), HbA1c (R = 0.17, p = 0.002), and HOMA (R = 0.16, p = 0.004). Dividing patients in tertiles of sST2 levels, those belonging to the highest tertile showed an increased rate of all-cause and cardiovascular mortality, (all-cause mortality p = 0.045 and CVD mortality p = 0.02). A multivariate Cox analysis revealed that sST2 increased the risk in cardiovascular mortality per SD by hazard ratio 1.050 (95% CI 1.006–1.097, p = 0.025) after adjustment for age and hs-CRP while it did not significantly change the risk for all-cause mortality.

Conclusions

High circulating level of sST2 is associated to increased CVD mortality and markers of metabolic dysfunction in subjects with atherosclerotic disease.

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Funding

M. F. research was in part funded by EU-FP7 FLORINASH (Health-F2-2009-241913), Ministry of University (MIUR) Progetti di Ricerca di Interesse Nazionale (PRIN) protocol number 2015MPESJS_004, Ministry of Health Ricerca Finalizzata RF-2011-02349921, Fondazione Roma call for Non-Communicable Diseases NCD 2014 Call; M.C: is funded by University of Tor Vergata Mission Sustainability program no. E81I18000390005.

Author information

Authors and Affiliations

  1. Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy

    Marina Cardellini, Stefano Rizza, Viviana Casagrande, Iris Cardolini, Marta Ballanti, Francesca Davato, Maria Paola Canale, Jacopo Maria Legramante, Maria Mavilio, Rossella Menghini & Massimo Federici

  2. Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy

    Marina Cardellini, Stefano Rizza & Massimo Federici

  3. Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy

    Ottavia Porzio

  4. Medical Laboratory Unit, Bambino Gesù Children’s Hospital and Research Institute, IRCCS, Rome, Italy

    Ottavia Porzio

  5. Division of Vascular Surgery, Department of Experimental, Surgery and Clinical Medicine, University of Sassari, Sassari, Italy

    Eugenio Martelli

  6. Department of Public Health and Infectious Diseases, University of Rome La Sapienza, Rome, Italy

    Alessio Farcomeni

Authors
  1. Marina Cardellini
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  2. Stefano Rizza
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  3. Viviana Casagrande
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  4. Iris Cardolini
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  5. Marta Ballanti
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  6. Francesca Davato
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  7. Ottavia Porzio
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  8. Maria Paola Canale
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  9. Jacopo Maria Legramante
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  10. Maria Mavilio
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  11. Rossella Menghini
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  12. Eugenio Martelli
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  13. Alessio Farcomeni
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  14. Massimo Federici
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Contributions

MC and AF performed statistical analysis, interpreted results and generated figures and tables. MF, MC and AF wrote the manuscript. MB, MM, FD, IC, GG, SR, VG, OP, CP, RM, and AI performed experiments. All authors discussed the data and commented on the manuscript before submission.

Corresponding author

Correspondence to Massimo Federici.

Ethics declarations

Conflict of interest

All authors declare that they have no conflict of interest.

Ethics approval

The study was approved by the ethics committee of the Policlinico Tor Vergata in Rome, Italy. All the procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the principles of the Declaration of Helsinki as revised in 2000.

Informed consent

An informed written consent was obtained from all participants.

Availability of data and material

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Managed by Massimo Porta.

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Cardellini, M., Rizza, S., Casagrande, V. et al. Soluble ST2 is a biomarker for cardiovascular mortality related to abnormal glucose metabolism in high-risk subjects. Acta Diabetol 56, 273–280 (2019). https://doi.org/10.1007/s00592-018-1230-z

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  • DOI: https://doi.org/10.1007/s00592-018-1230-z

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