Marina Cardellini1,2, Stefano Rizza1,2, Viviana Casagrande1, Iris Cardolini1, Marta Ballanti1, Francesca Davato1, Ottavia Porzio3,4, Maria Paola Canale1, Jacopo Maria Legramante1, Maria Mavilio1, Rossella Menghini1, Eugenio Martelli5, Alessio Farcomeni6, Massimo Federici7,8. 1. Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. 2. Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy. 3. Department of Experimental Medicine and Surgery, University of Rome Tor Vergata, Rome, Italy. 4. Medical Laboratory Unit, Bambino Gesù Children's Hospital and Research Institute, IRCCS, Rome, Italy. 5. Division of Vascular Surgery, Department of Experimental, Surgery and Clinical Medicine, University of Sassari, Sassari, Italy. 6. Department of Public Health and Infectious Diseases, University of Rome La Sapienza, Rome, Italy. 7. Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133, Rome, Italy. federicm@uniroma2.it. 8. Center for Atherosclerosis, Policlinico Tor Vergata, Rome, Italy. federicm@uniroma2.it.
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.
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-tolerantpatients 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.
Authors: Pietro Scicchitano; Andrea Marzullo; Annarita Santoro; Annapaola Zito; Francesca Cortese; Cristina Galeandro; Andrea Sebastiano Ciccone; Domenico Angiletta; Fabio Manca; Raffaele Pulli; Eliano Pio Navarese; Paul A Gurbel; Marco Matteo Ciccone Journal: J Clin Med Date: 2022-05-31 Impact factor: 4.964