Magnitude of Soluble ST2 as a Novel Biomarker for Acute Aortic Dissection

Wang, Yuan; Tan, Xin; Gao, Hai; Yuan, Hui; Hu, Rong; Jia, Lixin; Zhu, Jun; Sun, Li‐Zhong; Zhang, Hongjia; Huang, Lianjun; Zhao, Dong; Gao, Pei; Du, Jie

doi:10.1161/circulationaha.117.030469

Cited by 98 publications

(84 citation statements)

References 38 publications

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“…The present study post-dated the study by Wang et al reporting high sensitivity and specificity of plasma sST2 for AASs and indicating potential superiority of sST2 to D-dimer 21 . Several issues may cause the discrepancy between current and previous data.…”

Section: Discussionsupporting

confidence: 83%

“…The role of sST2 within vascular tissues and in the context of aortic disease is largely unknown 20 . However, Wang et al recently reported that plasma sST2, measured with a research-grade assay, showed striking diagnostic accuracy for AASs and outperformed D-dimer, in a Chinese patient cohort 21 . Since plasma sST2 levels can be measured with a clinical-grade assay already approved for patient use, we sought to further evaluate it as a diagnostic biomarker for AASs in an independent prospective cohort of acute patients from a European ED.…”

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confidence: 98%

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Prospective diagnostic accuracy study of plasma soluble ST2 for diagnosis of acute aortic syndromes

Morello

Bartalucci

Bironzo

et al. 2020

Sci Rep

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Acute aortic syndromes (AASs) are difficult to diagnose emergencies. Plasma soluble ST2 (sST2), a prognostic biomarker for heart failure, has been proposed as a diagnostic biomarker of AASs outperforming D-dimer, the current diagnostic standard. We performed a prospective diagnostic accuracy study of sST2 for AASs in the Emergency Department (ED). In 2017-2018, patients were enrolled if they had ≥1 red-flag symptoms (chest/abdominal/back pain, syncope, perfusion deficit) and a clinical suspicion of AAS. sST2 was detected with the Presage ® assay. Adjudication was based on computed tomography angiography (CTA) or on diagnostic outcome inclusive of 30-day follow-up. 297 patients were enrolled, including 88 with AASs. The median age was 67 years. In 162 patients with CTA, the median sST2 level was 41.7 ng/mL (IQR 29.4-103.2) in AASs and 34.6 ng/mL (IQR 21.4-51.5) in alternative diagnoses (P = 0.005). In ROC analysis, the AUC of sST2 was 0.63, as compared to 0.82 of D-dimer (P < 0.001). Sensitivity and specificity values of sST2 associated with different cutoffs were: 95.5% and 10.8% (≥12 ng/mL), 84.1% and 29.7% (≥23.7 ng/mL), 35.2% and 85.1% (≥66.5 ng/mL). Results were similar in the full cohort. In conclusion, in patients from a European ED, plasma sST2 provided modest accuracy for diagnosis of AASs.Acute aortic syndromes (AASs), which include acute aortic dissection (AAD), intramural aortic hematoma (IMH), penetrating aortic ulcer (PAU) and spontaneous aortic rupture (SAR), are severe cardiovascular emergencies affecting 5-10 per 100.000 individuals a year 1 . A conclusive diagnosis of AASs requires advanced aortic imaging, typically computed tomography angiography (CTA), which uses ionizing radiations and may cause contrast-induced nephropathy and anaphylaxis. However, selection of the right patient to image with CTA is cumbersome, because AASs present with unspecific symptoms such as truncal pain, syncope, neurological deficits and hindlimb ischemia. These are leading causes of Emergency Department (ED) visits worldwide, and most patients with these symptoms are affected by more common conditions, such as acute coronary syndromes, gastrointestinal diseases and muscle-skeletal pain. Hence, the misdiagnosis rate of AASs is high, affecting clinical outcomes 2-4 . Increasing use of CTA in EDs has led to a high number of CTA exams requested for suspected AAS turning out negative, but has not substantially changed misdiagnosis rates, indicating that pre-test patient selection remains a key node 5-7 . Development of reliable diagnostic biomarkers discriminating AASs could positively impact on their diagnostic workup, as for other cardiovascular emergencies such as acute coronary syndromes and pulmonary embolism 8,9 . So far, potential biomarkers of AASs have been searched for within aortic layers (e.g. smooth muscle myosin, soluble elastin fragments, calponin, CD40 ligand), within inflammation/remodeling pathways (e.g. matrix metalloproteinases) and within coagulation processes mobilized by blood exposure to non-endo...

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Section: Discussionsupporting

confidence: 83%

mentioning

confidence: 98%

Prospective diagnostic accuracy study of plasma soluble ST2 for diagnosis of acute aortic syndromes

Morello

Bartalucci

Bironzo

et al. 2020

Sci Rep

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“…Venous blood was immediately sent to the clinical laboratory center of the Anzhen hospital. Plasma PT, APTT, FDP, and D-dimer were measured using the commercially available automated latex immunoturbidimetric assay (Werfen ACL TOP 700, United States) (Di Nisio et al, 2007;Wang et al, 2018). Routine blood tests and some biochemical indicators were determined by standard quantitative assay techniques, according to the manufacturers' instructions.…”

Section: D-dimer Measurementmentioning

confidence: 99%

Association Between D-dimer and Early Adverse Events in Patients With Acute Type A Aortic Dissection Undergoing Arch Replacement and the Frozen Elephant Trunk Implantation: A Retrospective Cohort Study

et al. 2020

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In the present study, we investigated the associations between D-dimer levels at admission and early adverse events in patients with acute type A aortic dissection undergoing arch replacement and the frozen elephant trunk (FET). Methods: We retrospectively analyzed data of patients with acute type A aortic dissection undergoing aortic arch surgery and FET from July 2017 to December 2018 at Beijing Anzhen Hospital. D-dimer levels were evaluated within 24 h of admission. Multivariate Cox regression analysis was used to determine independent predictors of early postoperative adverse events. Results: A total of 347 patients were included in the study. The average age of the patients was 48.07 ± 10.56 years, with male predominance (79.25%). The incidence of 90-day postoperative adverse events was 18.7%, consisting of 14.7% mortality and 4.0% permanent neurological dysfunction (PND). The median D-dimer level was 1.95 ug/ml (interquartile range, 0.77-3.16 ug/ml). Multivariable Cox regression analysis revealed that D-dimer level was independently associated with 90-day postoperative adverse events after adjustment for confounding factors (hazard ratio = 1.19 per 10 ug/ml increase in D-dimer, 95% confidence interval: 1.01-1.41; P = 0.039). Kaplan-Meier analysis revealed that the highest tertile (median 6.27 ug/ml) had more 90-day postoperative adverse events compared with the median and lowest tertiles (P = 0.0014). Sub-analysis found that the association remained unchanged.

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“…Previous studies have reported that sST2 can be used as a prognostic biomarker for the development of systemic and highly inflammatory diseases, such as aortic dissection, sepsis, and heart failure as well as mortality in patients with these diseases. [36][37][38] This hypothesis is reinforced by the finding that plasma sST2 concentrations could predict poor prognosis in patients with acute-on-chronic hepatitis B liver failure. 39 The present study further revealed its prognostic .…”

Section: Discussionmentioning

confidence: 99%

Plasma levels of soluble ST2, but not IL‐33, correlate with the severity of alcoholic liver disease

Sun

Chang

Huang

et al. 2018

J Cellular Molecular Medi

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Alcoholic liver disease (ALD) is a complication that is a burden on global health and economy. Interleukin‐33 (IL‐33) is a newly identified member of the IL‐1 cytokine family and is released as an “alarmin” during inflammation. Soluble suppression of tumourigenicity 2 (sST2), an IL‐33 decoy receptor, has been reported as a new biomarker for the severity of systemic and highly inflammatory diseases. Here, we found the levels of plasma sST2, increased with the disease severity from mild to severe ALD. Importantly, the plasma sST2 levels in ALD patients not only correlated with scores for prognostic models (Maddrey's discriminant function, model for end‐stage liver disease and Child‐Pugh scores) and indexes for liver function (total bilirubin, international normalized ratio, albumin, and cholinesterase) but also correlated with neutrophil‐associated factors as well as some proinflammatory cytokines. In vitro, lipopolysaccharide‐activated monocytes down‐regulated transmembrane ST2 receptor but up‐regulated sST2 mRNA and protein expression and produced higher levels of tumour necrosis factor‐α (TNF‐α). By contrast, monocytes pretreated with recombinant sST2 showed decreased TNF‐α production. In addition, although plasma IL‐33 levels were comparable between healthy controls and ALD patients, we found the IL‐33 expression in liver tissues from ALD patients was down‐regulated at both RNA and protein levels. Immunohistochemical staining further showed that the decreased of IL‐33‐positive cells were mainly located in liver lobule area. These results suggested that sST2, but not IL‐33, is closely related to the severity of ALD. Consequently, sST2 could be used as a potential biomarker for predicting the prognosis of ALD.

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Magnitude of Soluble ST2 as a Novel Biomarker for Acute Aortic Dissection

Abstract: Among patients with suspected aortic dissection in the emergency department, sST2 showed superior overall diagnostic performance to D-dimer or cardiac troponin I. Additional study is needed to determine whether sST2 might be a useful rule-out marker for AAD in the emergency room.

Cited by 98 publications

References 38 publications

Prospective diagnostic accuracy study of plasma soluble ST2 for diagnosis of acute aortic syndromes

Prospective diagnostic accuracy study of plasma soluble ST2 for diagnosis of acute aortic syndromes

Association Between D-dimer and Early Adverse Events in Patients With Acute Type A Aortic Dissection Undergoing Arch Replacement and the Frozen Elephant Trunk Implantation: A Retrospective Cohort Study

Plasma levels of soluble ST2, but not IL‐33, correlate with the severity of alcoholic liver disease

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