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

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.

Alterations in Rev-ERBα/BMAL1 ratio and glycated hemoglobin in rotating shift workers: the EuRhythDia study

“…Univariate ANOVA was used to compare each of the reported variables in the a-NSW, f-NSW and control groups as described [ 16 ]. The Mann–Whitney test was used for variables with non-normal distribution.…”

<p>Soluble Suppression of Tumorigenicity 2 is Directly Correlated with Glycated Hemoglobin in Individuals with an Average glycemia in the Normal/Prediabetes Range</p>

“…13 Importantly, studies have shown that sST2 is elevated in individuals with T2D, [14][15][16] post-transplant diabetes mellitus, 17,18 and CVD. 19,20 Moreover, sST2 is associated with markers of metabolic dysfunction in atherosclerotic disease, 21 and with increased CVD mortality. 21,22 It has also been shown to be elevated in other inflammatory conditions such as inflammatory bowel disease, 23 gut mucosal damage, 3 and sepsis.…”

“…Therefore, identification of early biomarkers that may be associated with the onset of cardiometabolic disease is of considerable importance. Since elevated levels of sST2 are associated with both CVD [19][20][21][22] and T2D, [14][15][16] we hypothesized that sST2 may serve as a novel biomarker to detect subclinical CVD risk in the earliest stages of metabolic disease development. Therefore, we conducted a preliminary study to determine whether sST2 is correlated with glycated haemoglobin (HbA1c) in individuals with glycemia in the normal/prediabetes range.…”

“…19 , 20 Moreover, sST2 is associated with markers of metabolic dysfunction in atherosclerotic disease, 21 and with increased CVD mortality. 21 , 22 It has also been shown to be elevated in other inflammatory conditions such as inflammatory bowel disease, 23 gut mucosal damage, 3 and sepsis. 24 However, the source of sST2 is unclear but it is thought to be secreted as a result of tissue damage and/or be secondary to an unregulated ongoing inflammatory process.…”

The Risk of Carotid Plaque Instability in Patients with Metabolic Syndrome: It is Higher in Women with Hypertriglyceridemia

“…Many studies have demonstrated that Metabolic Syndrome (MetS), defined as a cluster of interconnected metabolic risk factors (including abdominal obesity, elevated fasting glucose, hypertriglyceridemia, hypertension, and low High-Density Lipoprotein (HDL) cholesterol levels), increases the risk for atherosclerosis and cardiovascular disease [1][2][3][4][5][6]. In addition, the recent interest of the scientific community has focused on the possible involvement of insulin resistance as a linking factor [7][8][9][10].…”