Association of Soluble Suppression of Tumorigenesis-2 (ST2) with Endothelial Function in Patients with Ischemic Heart Failure

Dimitropoulos, Stathis; Mystakidi, Vasiliki Chara; Oikonomou, Evangelos; Siasos, Gerasimos; Tsigkou, Vasiliki; Athanasiou, Dimitris; Gouliopoulos, Nikolaos; Bletsa, Evanthia; Kalampogias, Aimilios; Charalambous, Georgios; Tsioufis, Costas; Vavuranakis, Manolis; Tousoulis, Dimitris

doi:10.3390/ijms21249385

Cited by 18 publications

(11 citation statements)

References 42 publications

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“…Endothelial dysfunction could also contribute to rising levels of sST2 [21] . This could explain another finding in this study, in which sST2 levels were observed to be significantly higher in the third trimester of pregnancy with preeclampsia compared with normal pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Differences in maternal soluble ST2 levels in the third trimester of normal pregnancy versus preeclampsia

Prameswari

Khalid

Anggraeni

et al. 2022

European Journal of Obstetrics & Gynecology and Reproductiv

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Background Preeclampsia is associated with intense inflammatory response in pregnancy, and soluble ST2 (sST2) is pathologically increased in this condition. No data exist regarding maternal sST2 levels in normal pregnancy versus preeclampsia in areas of southeast Asia with an ethnic Malay predominance. Materials and Methods Patients were sorted into normal pregnancy or preeclampsia. Patients with a history of allergic, inflammatory, or malignant disease were excluded. One sample was taken per patient; all samples were taken during the third trimester of pregnancy. Thirty samples from each group were enrolled in the study, totaling 60 samples. Soluble ST2 levels in maternal plasma were measured using the Presage® ST2 Assay according to manufacturer instructions, and data was analyzed using SPSS 23. Results Patients in the preeclampsia group were significantly older than those in the normal pregnancy group (p = 0.01). Most patients with preeclampsia presented as early-onset (n = 23). Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were significantly higher (p < 0.001) in the preeclampsia group. Mean sST2 level in the preeclampsia group (85.89 ng/ml) was significantly higher than the normal pregnancy group mean (38.3 ng/ml) during the third trimester (p < 0.001). This study also found a correlation between sST2 and preeclampsia (p < 0.001, r = 0.480), SBP (p < 0.001, r = 0.407), and DBP (p = 0.007, r = 0.342), while preeclampsia was found to be the best explanatory variable of sST2 levels (r = 0.468, p < 0.001). sST2 level> 63.66 ng/ml has sensitivity 50% and specificity 93.3%, with AUC of 0.78 [95% CI 0.66 – 0.90], p < 0.001. The sST2 > 63.66 ng/ml has an OR of 14.0 [95% CI 2.82 – 69.6], p < 0.001 for preeclampsia. The dose-response relationship between sST2 level and preeclampsia was linear. Conclusion Soluble ST2 levels were increased in both normal pregnancy and preeclampsia but were significantly higher in patients with preeclampsia. Preeclampsia was also found to be the best explanatory variable for the increase of sST2 levels in ethnic Malay predominance.

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Section: Discussionmentioning

confidence: 99%

Differences in maternal soluble ST2 levels in the third trimester of normal pregnancy versus preeclampsia

Prameswari

Khalid

Anggraeni

et al. 2022

European Journal of Obstetrics & Gynecology and Reproductiv

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“…Serum ST2 is a biomarker of cardiovascular injury and risk of mortality. 50,51 Furthermore, ST2 levels were found to be associated with increased 6-month NRM post-alloSCT. 52 We show here that ST2 levels were lower in statin-treated patients.…”

Section: Discussionmentioning

confidence: 96%

“…Another serum marker that differed in the statin group was the soluble IL33 receptor ST2. Serum ST2 is a biomarker of cardiovascular injury and risk of mortality 50,51 . Furthermore, ST2 levels were found to be associated with increased 6‐month NRM post‐alloSCT 52 .…”

Section: Discussionmentioning

confidence: 99%

Statin‐based endothelial prophylaxis and outcome after allogeneic stem cell transplantation

Pabst

Schreck

Benner

et al. 2022

Eur J Clin Investigation

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Background Allogeneic haematopoietic stem cell transplantation (alloSCT) often remains the only curative therapy for hematologic malignancies. Although the management of transplant‐associated adverse events considerably improved over the last decades, nonrelapse mortality (NRM) remains a challenge, and endothelial dysfunction was identified as a major contributor to NRM. Methods Statin‐based endothelial prophylaxis (SEP) has been implemented in the standard of care in our transplant centre to reduce NRM caused by endothelial injury. Here, we retrospectively analysed the impact of SEP on clinical outcome in a cohort of 347 alloSCT patients. Results SEP (n = 209) was associated with significantly reduced NRM (hazard ratio 0.61, 95% CI 0.38–0.96) and better overall survival (OS) after acute graft‐versus‐host disease (HR 0.59, 95% CI 0.37–0.93). Subgroup analyses showed that the NRM benefit was mainly found in patients with an intermediate endothelial activation and stress index (EASIX), while relapse risk was not affected. On day 100 post‐alloSCT, patients receiving SEP had significantly higher levels of the rate‐limiting enzyme of tryptophan metabolism, indoleamine 2,3‐dioxygenase (IDO), higher kynurenine to tryptophan ratios as a proxy of IDO activity and tended to have lower levels of the endothelial injury marker ST2 (p = .055). No significant differences in interferon‐gamma or IL18 levels were observed. These biomarker signatures suggest that the beneficial effects of SEP might be mediated by both endothelial protection and immunomodulation. Conclusions Together, these data suggest that SEP improves NRM and OS post‐alloSCT in particular in patients with intermediate endothelial risk and provide first mechanistic clues about its potential mode of action.

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“…Therefore, the biomarker MIF has an advantage over CRP as an earlier predictor of adverse events. Several studies have shown that higher levels of sST2 were associated with a large risk of mortality and the development of heart failure [31,32]. However, this biomarker has been yet insufficiently studied in STEMI, while its diagnostic and predictive values in heart failure patients appear to be interested [33,34].…”

Section: Discussionmentioning

confidence: 99%

Prediction of one-year adverse clinical outcomes by macrophage migration inhibitory factor in stemi patients

et al. 2022

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Biomarkers have taken one of the first places as diagnostic and prognostic tools in ST-segment elevation myocardial infarction (STEMI) and are consequently widely used as predictors of short-term and long-term prognosis. One of the promising biomarkers for early cardiovascular outcomes prediction is the pro-inflammatory cytokine macrophage migration inhibitory factor (MIF). The aim of the study was to elucidate a plausible predictive value of the MIF levels for one-year clinical outcomes in STEMI patients who underwent primary percutaneous coronary intervention (PCI). Materials and methods. 134 STEMI patients were enrolled in the study after receiving voluntary informed consent. All patients underwent conventional investigations, and additionally, the MIF levels were determined at baseline, directly before and after PCI. During 1-year follow-up, 37 % of patients reached the endpoint, which was composite and included all-cause mortality, non-fatal myocardial infarction, non-fatal stroke, hospitalization for unstable angina, heart failure decompensation, and urgent revascularization. Results. We have found that pre-PCI MIF levels > 3934 pg/mL (AUC=0.7; 95 % CI 0.578 to 0.753; Youden index=0.31; p=0.008) might be an independent predictor of composite endpoints with sensitivity 54 % and specificity 82 %. A positive correlation between MIF and inflammatory biomarkers was revealed (WBC count r=0.33, p=0.0001; CRP r=0.19, p=0.032). Adverse outcomes associated with higher pre- and post-PCI MIF levels (OR 1.0, 95 % CI 1.0001–1.0008; p=0.013 and OR 1.0, 95 % CI 1.0001–1.0009; p=0.019) and CRP that determined during the first week after the event (OR 1.0, 95 % CI 1.005–1.2, p=0.03). Kaplan-Meier analysis has shown a substantially lower long-term survival rate in patients with a MIF level > 3493 pg/ml compared to a MIF level ≤ 3493 pg/ml (Log rank=0.00025). Conclusions. The MIF levels exceeding 3934 ng/ml were associated with a higher risk of one-year adverse clinical outcomes in STEMI patients who underwent primary PCI.

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Association of Soluble Suppression of Tumorigenesis-2 (ST2) with Endothelial Function in Patients with Ischemic Heart Failure

Cited by 18 publications

References 42 publications

Differences in maternal soluble ST2 levels in the third trimester of normal pregnancy versus preeclampsia

Differences in maternal soluble ST2 levels in the third trimester of normal pregnancy versus preeclampsia

Statin‐based endothelial prophylaxis and outcome after allogeneic stem cell transplantation

Prediction of one-year adverse clinical outcomes by macrophage migration inhibitory factor in stemi patients

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