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

Marina Cardellini, Stefano Rizza, Viviana Casagrande, Iris Cardolini, Marta Ballanti, Francesca Davato, Ottavia Porzio, Maria Paola Canale, Jacopo Maria Legramante, Maria Mavilio, Rossella Menghini, Eugenio Martelli, Alessio Farcomeni, Massimo Federici

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)273-280
Number of pages8
JournalActa Diabetologica
Volume56
Issue number3
DOIs
Publication statusPublished - Mar 2019

Keywords

  • Aged
  • Aged, 80 and over
  • Atherosclerosis/blood
  • Biomarkers/blood
  • Blood Glucose/drug effects
  • Cardiovascular Diseases/blood
  • Cause of Death
  • Cohort Studies
  • Diabetes Mellitus, Type 2/blood
  • Diabetic Angiopathies/blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glucose Metabolism Disorders/blood
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein/blood
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors

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    Cardellini, M., Rizza, S., Casagrande, V., Cardolini, I., Ballanti, M., Davato, F., Porzio, O., Canale, M. P., Legramante, J. M., Mavilio, M., Menghini, R., Martelli, E., Farcomeni, A., & Federici, M. (2019). Soluble ST2 is a biomarker for cardiovascular mortality related to abnormal glucose metabolism in high-risk subjects. Acta Diabetologica, 56(3), 273-280. https://doi.org/10.1007/s00592-018-1230-z