Dataset Information

The Association Between S100A8/A9 and the Development of Very Late Stent Thrombosis in Patients With Acute Myocardial Infarction.

ABSTRACT: Very late stent thrombosis (VLST) is a rare but serious complication following percutaneous coronary intervention (PCI). S100A8/A9 plays an important role in thrombosis through modulating the inflammatory response. This observational study aimed to reveal the association between S100A8/A9 and VLST. Continuous blood samples were collected from patients at both the time of index PCI for acute myocardial infarction (AMI) and the time of PCI for VLST (VLST group) or follow-up coronary angiography (AMI group). In all, 56 patients were selected in each group from a cohort of 8476 patients and other 112 individuals who underwent health checkups (normal control [NC] group) were selected as controls. Serum levels of S100A8/A9 and high sensitivity C-reactive protein (hs-CRP) were tested and compared. The mean level of S100A8/A9 was 3754.4 ± 1688.9 ng/mL during index PCI and increased to 5517.8 ± 2650.9 ng/mL at the time of VLST; in the AMI group, S100A8/A9 level was 2434.9 ± 1243.4 ng/mL during index PCI and decreased to 1568.2 ± 772.1 ng/mL during follow-up, similar to that detected in the NC group (1618.2 ± 641.4 ng/mL). Of note, S100A8/A9 levels showed significant increases during VLST when compared to its own levels during index PCI, which was different from the changes of hs-CRP. Higher serum levels of S100A8/A9 are associated with the development of VLST.

SUBMITTER: Wang X

PROVIDER: S-EPMC7401045 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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The Association Between S100A8/A9 and the Development of Very Late Stent Thrombosis in Patients With Acute Myocardial Infarction.

Wang Xiang X Guan Meng M Zhang Xiuhang X Ma Taiyuan T Wu Muli M Li Yulin Y Chen Xinxin X Zheng Yang Y

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20200101

Very late stent thrombosis (VLST) is a rare but serious complication following percutaneous coronary intervention (PCI). S100A8/A9 plays an important role in thrombosis through modulating the inflammatory response. This observational study aimed to reveal the association between S100A8/A9 and VLST. Continuous blood samples were collected from patients at both the time of index PCI for acute myocardial infarction (AMI) and the time of PCI for VLST (VLST group) or follow-up coronary angiography (A ...[more]

PMID: 32734774

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Project description:BackgroundMyocardial infarction (MI) triggers myelopoiesis, resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear.MethodsUsing a mouse model of the permanent ligation of the left anterior descending artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of the acute inflammatory response and the underlying signaling pathways. Using a combination of genetic and pharmacological strategies, we identified the sequelae of events that led to MI-induced myelopoiesis. Cardiac function was assessed by echocardiography. The association of early indexes of neutrophilia with major adverse cardiovascular events was studied in a cohort of patients with acute MI.ResultsInduction of MI results in rapid recruitment of neutrophils to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins bind to the Toll-like receptor 4 and prime the nod-like receptor family pyrin domain-containing 3 inflammasome in naïve neutrophils and promote interleukin-1β secretion. The released interleukin-1β interacts with its receptor (interleukin 1 receptor type 1) on hematopoietic stem and progenitor cells in the bone marrow and stimulates granulopoiesis in a cell-autonomous manner. Genetic or pharmacological strategies aimed at disruption of S100A8/A9 and their downstream signaling cascade suppress MI-induced granulopoiesis and improve cardiac function. Furthermore, in patients with acute coronary syndrome, higher neutrophil count on admission and after revascularization correlates positively with major adverse cardiovascular disease outcomes.ConclusionsOur study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response after myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or their downstream mediators (eg, nod-like receptor family pyrin domain-containing 3 inflammasome, interleukin-1β) in neutrophils suppress granulopoiesis and may improve cardiac function in patients with acute coronary syndrome.

Project description:BackgroundStent thrombosis (ST) is an uncommon but serious complication of stent implantation. This study aimed to explore factors associated with early, late, and very late ST to help guide risk assessment and clinical decision-making on ST.MethodsThe analysis included patients who received stent placement for the index acute coronary syndrome (ACS). Cumulative incidence of ST was assessed at 30 days (early ST), 31-360 days (late ST), 361-720 days (very late ST), and up to 720 days. Cox proportional hazards models were used to assess associations between ST and various factors, including patient characteristics [i.e., age, sex, ACS presentation, history of hypertension, smoking, diabetes, prior myocardial infarction (MI), heart failure, prior ischemic stroke, and cancer], laboratory tests [i.e., positive cardiac biomarker, hemoglobin, platelet count, white blood cell (WBC) count], and treatment [i.e., drug-eluting stent (DES) vs. bare-metal stent (BMS) and anticoagulant with rivaroxaban vs. placebo].ResultsAmong the 8,741 stented patients, 155 ST events (2.25%) occurred by Day 720. The cumulative incidences of early, late, and very late ST were 0.80%, 0.81%, and 0.77%, respectively. After multivariable adjustment, age ≥ 75 [hazard ratio (HR) = 2.13 (95% confidence interval, CI: 1.26-3.60)], a history of prior MI [HR = 1.81 (95% CI: 1.22-2.68)], low hemoglobin level [HR = 2.34 (95% CI: 1.59-3.44)], and high WBC count [HR = 1.58 (95% CI: 1.02-2.46)] were associated with a greater risk of overall ST, whereas DES [HR = 0.56 (95% CI: 0.38-0.83)] and rivaroxaban therapy [HR = 0.63 (95% CI: 0.44-0.88)] were associated with a lower risk of overall ST up to 720 days. Low hemoglobin level and high WBC count were associated with early ST (low hemoglobin: HR = 2.35 [95% CI: 1.34-4.12]; high WBC count: HR = 2.11 [95% CI: 1.17-3.81]). Low hemoglobin level and prior MI were associated with a greater risk of late ST (low hemoglobin: HR = 2.32 [95% CI: 1.26-4.27]; prior MI: HR = 2.98 [95% CI: 1.67-5.31]), whereas DES was associated with a lower risk of late ST [HR = 0.33 (95% CI: 0.16-0.67)]. Age ≥75 years was associated with very late ST.ConclusionThe study identified positive and negative associations with early, late, and very late ST. These variables may be useful in constructing risk assessment models for ST.Clinical trial registrationhttp://www.clinicaltrials.gov, identifier NCT00809965.

Dataset Information

The Association Between S100A8/A9 and the Development of Very Late Stent Thrombosis in Patients With Acute Myocardial Infarction.

Publications

The Association Between S100A8/A9 and the Development of Very Late Stent Thrombosis in Patients With Acute Myocardial Infarction.

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