Markers of Thrombin Generation Are Associated With Long-Term Clinical Outcome in Patients With ST-Segment Elevation Myocardial Infarction

Hansen, Charlotte Holst; Ritschel, Vibeke N.; Andersen, Geir Øystein; Halvorsen, Sigrun; Eritsland, Jan; Arnesen, Harald; Seljeflot, Ingebjørg

doi:10.1177/1076029618764847

Cited by 11 publications

(12 citation statements)

References 28 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A "two-hit hypothesis", where both an inflammatory stimulus and activated platelets are required for NETosis in STEMI could explain the lack of association between the NETs-specific components and hypercoagulability markers peripherally 16 . We have previously shown that a prothrombotic state was predictive of death in this population, even after adjusting for the administration of prehospital thrombolysis 27 . Although fewer endpoints were recorded among patients receiving thrombolysis, the risk of death conferred by higher dsDNA levels was relatively unchanged when adjusting for both thrombolysis and D-dimer levels.…”

Section: Discussionmentioning

confidence: 84%

Double-Stranded DNA and NETs Components in Relation to Clinical Outcome After ST-Elevation Myocardial Infarction

Langseth

Helseth

Ritschel

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

Neutrophil extracellular traps (NETs) have been implicated in atherothrombosis; however, their potential role as markers of risk is unclear. We investigated whether circulating NETs-related components associated with clinical outcome and hypercoagulability in St-elevation myocardial infarction (STEMI). In this observational cohort study, STEMI patients admitted for PCI (n = 956) were followed for median 4.6 years, recording 190 events (reinfarction, unscheduled revascularization, stroke, heart failure hospitalization, or death). Serum drawn median 18 hours post-PCI was used to quantify double-stranded DNA (dsDNA) and the more specific NETs markers myeloperoxidase-DNA and citrullinated histone 3. Levels of the NETs markers did not differ significantly between groups with/without a primary composite endpoint. However, patients who died (n = 76) had higher dsDNA compared to survivors (p < 0.001). Above-median dsDNA was associated with an increased number of deaths (54 vs. 22, p < 0.001). dsDNA in the upper quartiles (Q) was associated with increased mortality (Q3 vs. Q1 + 2 adjusted HR: 1.89 [95% CI 1.03 to 3.49], p = 0.041 and Q4 vs. Q1 + 2 adjusted HR: 2.28 [95% CI 1.19 to 4.36], p = 0.013). dsDNA was weakly correlated with D-dimer (r s = 0.17, p < 0.001). dsDNA levels associated with increased all-cause mortality, yet weakly with hypercoagulability in STEMI patients. The prognostic significance of potentially NETs-related markers requires further exploration. Acute coronary syndrome (ACS) often results from erosion or rupture of atherosclerotic plaques followed by thrombosis, ischemia, and myocardial injury. It has been suggested that the risk-stratification of ACS patients should be expanded to include new soluble biomarkers, which may help individualize treatment 1. Potential candidates include components of the innate immune response, widely accepted to be important in the immediate aftermath of ACS, yet still not completely understood. Neutrophil extracellular traps (NETs) were first described in 2004 by Brinkmann and colleagues, who documented the expulsion of extracellular webbed structures comprising deoxyribonucleic acid (DNA) and histones, studded with neutrophil granule proteins 2. The process of NETs release, or NETosis, is initiated by granular proteins such as myeloperoxidase (MPO), neutrophil elastase, and peptidylarginine deiminase 4 3. The latter mediates the citrullination of histone 3, inducing chromatin decondensation before extracellular release 3. Circulating NETs-associated components may contribute to endothelial dysfunction and plaque instability 4 , as well as coronary thrombus formation 5 by activating platelets, triggering the coagulation cascade, and trapping thrombus constituents 6,7. Nevertheless, it is not yet clear how NETs per se are implicated in the fine balance between beneficial and deleterious effects of inflammation after revascularization.

show abstract

Section: Discussionmentioning

confidence: 84%

Double-Stranded DNA and NETs Components in Relation to Clinical Outcome After ST-Elevation Myocardial Infarction

Langseth

Helseth

Ritschel

et al. 2020

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…These eligible studies were published between 1999 and 2020. Four studies 8,9,17,24 were retrospective, and the others were prospective studies. The sample sizes of the included studies ranged from 165 to 8565, with a total of 25 600 patients with CAD.…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…Nine studies 8,9,16,18,20,21,[23][24][25] reported the association between D-dimer level and all-cause mortality. As shown in Figure 2, no significant heterogeneity was observed across these studies (I 2 ¼ 39.1%; P ¼ .107).…”

Section: All-cause Mortalitymentioning

confidence: 99%

“…However, the associations between elevated D-dimer level and adverse outcomes are not fully established in patients with CAD. [8][9][10] No previous meta-analysis has investigated the association of D-dimer level with adverse prognosis in patients with CAD. To address this knowledge gap, we performed a meta-analysis to evaluate the prognostic value of elevated D-dimer level at baseline among patients with CAD in terms of major adverse cardiovascular events (MACEs) and cardiovascular or allcause mortality.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic Value of Baseline d-Dimer Level in Patients With Coronary Artery Disease: A Meta-Analysis

et al. 2021

View full text Add to dashboard Cite

The prognostic significance of d-dimer level in patients with coronary artery disease (CAD) is not fully established. This meta-analysis aimed to examine the association between elevated d-dimer level at baseline and adverse outcomes in patients with CAD. Two independent authors comprehensively searched PubMed and Embase databases from their inception to December 31, 2020. All observational studies reporting the values of baseline d-dimer level in predicting the major adverse cardiovascular events (MACEs) or survival outcomes in patients with CAD were included. The prognostic values were calculated by pooling adjusted RR with 95% CI for the highest versus the lowest d-dimer level. Thirteen studies consisting of 25 600 patients with CAD were identified. Comparison between the highest and lowest d-dimer level showed that the pooled multivariable adjusted RR was 1.69 (95% CI, 1.53-1.86) for all-cause mortality, 2.37 (95% CI, 1.52-3.69) for cardiovascular mortality, and 1.44 (95% CI, 1.19-1.74) for MACEs, respectively. Elevated blood level of d-dimer at baseline was independently associated with higher risk of MACEs, cardiovascular death, and all-cause mortality in patients with CAD. The baseline d-dimer level may have important prognostic value in patients with CAD.

show abstract

“…Several prospective studies have found low ETP/peak thrombin in the acute phase of CVD to be associated with outcome. Gremmel et al found low levels of peak thrombin to be associated incident AMI, stroke, TIA, or CVD death in patients having gone through angioplasty due to peripheral artery disease 15 ; Hansen et al found low ETP in the acute phase of ST-elevation myocardial infarction to be associated with a composite outcome 16 and Christersson et al found low acute-phase ETP in patients with AMI to be associated with stroke of any type (but not AMI). 17 In the former two studies, consumption of coagulation factors was again the proposed explanation.…”

Section: Discussionmentioning

confidence: 99%

High Thrombin Generation after Acute Ischemic Stroke or Transient Ischemic Attack Is Associated with a Reduced Risk of Recurrence: An Observational Cohort Study

et al. 2020

View full text Add to dashboard Cite

Thrombin is increasingly recognized to be of importance for cardiovascular disease. The aim of this study was to investigate the prognostic value of thrombin generation variables in a cohort of patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). Thrombin generation potential measured by calibrated automated thrombogram (CAT) and prothrombin fragment F1 + 2 was determined in the acute and convalescent phases for a cohort of 190 patients with AIS/TIA. Microvesicle (MV)-induced thrombin generation potential was determined for a subset of patients using modified CAT. Primary outcome was a composite of fatal and nonfatal AIS or myocardial infarction as documented in Swedish registers during a total follow-up of 986 patient-years. Hazard ratios (HRs) were calculated using Cox regression based on variable median split. Peak thrombin and endogenous thrombin potential (ETP) above median in the acute phase were associated with a reduced risk of primary outcome after adjustment for cardiovascular risk factors, HR: 0.50 (0.27–0.92), p = 0.026 and HR: 0.53 (0.28–0.99), p = 0.048, respectively. F1 + 2 was lower in patients than in healthy controls but not associated with outcome. MV-induced peak thrombin above median in the acute phase was associated with recurrent AIS, unadjusted HR: 2.65 (1.03–6.44), p = 0.044. Contrary to expectation, high thrombin generation potential is associated with a reduced risk of recurrent ischemic event in patients with AIS/TIA. Low ETP/peak thrombin combined with high MV-induced peak thrombin can potentially identify patients at high risk of recurrence.

show abstract

Markers of Thrombin Generation Are Associated With Long-Term Clinical Outcome in Patients With ST-Segment Elevation Myocardial Infarction

Cited by 11 publications

References 28 publications

Double-Stranded DNA and NETs Components in Relation to Clinical Outcome After ST-Elevation Myocardial Infarction

Double-Stranded DNA and NETs Components in Relation to Clinical Outcome After ST-Elevation Myocardial Infarction

Prognostic Value of Baseline d-Dimer Level in Patients With Coronary Artery Disease: A Meta-Analysis

High Thrombin Generation after Acute Ischemic Stroke or Transient Ischemic Attack Is Associated with a Reduced Risk of Recurrence: An Observational Cohort Study

Contact Info

Product

Resources

About