Double-Stranded DNA and NETs Components in Relation to Clinical Outcome After ST-Elevation Myocardial Infarction.
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ABSTRACT:
SUBMITTER: Langseth MS
PROVIDER: S-EPMC7081350 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
Publications
Double-Stranded DNA and NETs Components in Relation to Clinical Outcome After ST-Elevation Myocardial Infarction.
Langseth Miriam Sjåstad MS Helseth Ragnhild R Ritschel Vibeke V Hansen Charlotte Holst CH Andersen Geir Øystein GØ Eritsland Jan J Halvorsen Sigrun S Fagerland Morten Wang MW Solheim Svein S Arnesen Harald H Seljeflot Ingebjørg I Opstad Trine Baur TB
Scientific reports 20200319 1
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 f ...[more]
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| S-EPMC4718183 | biostudies-literature
Project description:It is assumed that platelets in diseased conditions share similar properties to platelets in healthy conditions, although this has never been examined in detail for myocardial infarction (MI). We examined platelets from patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) compared with platelets from healthy volunteers to evaluate for differences in platelet phenotype and function. Platelet activation was examined and postreceptor signal transduction pathways were assessed. Platelet-derived plasma biomarkers were evaluated by receiver operator characteristic curve analysis. Maximum platelet activation through the thromboxane receptor was greater in STEMI than in NSTEMI but less through protease-activated receptor 1. Extracellular-signal related-kinase 5 activation, which can activate platelets, was increased in platelets from subjects with STEMI and especially in platelets from patients with NSTEMI. Matrix metalloproteinase 9 (MMP9) protein content and enzymatic activity were several-fold greater in platelets with MI than in control. Mean plasma MMP9 concentration in patients with MI distinguished between STEMI and NSTEMI (area under curve [AUC] 75% [confidence interval (CI) 60-91], P?=?0.006) which was superior to troponin T (AUC 66% [CI 48-85, P?=?0.08), predicting STEMI with 80% sensitivity (95% CI 56-94), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P?<?0.0001), and NSTEMI with 50% sensitivity (CI 27-70), 90% specificity (CI 68-99), 70% AUC (CI 54-86, P?=?0.03). Platelets from patients with STEMI and NSTEMI show differences in platelet surface receptor activation and postreceptor signal transduction, suggesting the healthy platelet phenotype in which antiplatelet agents are often evaluated in preclinical studies is different from platelets in patients with MI.
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Project description:ImportanceChallenges to improving ST-segment elevation myocardial infarction (STEMI) care are formidable in low- to middle-income countries because of several system-level factors.ObjectiveTo examine access to reperfusion and percutaneous coronary intervention (PCI) during STEMI using a hub-and-spoke model.Design, setting, and participantsThis multicenter, prospective, observational study of a quality improvement program studied 2420 patients 20 years or older with symptoms or signs consistent with STEMI at primary care clinics, small hospitals, and PCI hospitals in the southern state of Tamil Nadu in India. Data were collected from the 4 clusters before implementation of the program (preimplementation data). We required a minimum of 12 weeks for the preimplementation data with the period extending from August 7, 2012, through January 5, 2013. The program was then implemented in a sequential manner across the 4 clusters, and data were collected in the same manner (postimplementation data) from June 12, 2013, through June 24, 2014, for a mean 32-week period.ExposuresCreation of an integrated, regional quality improvement program that linked the 35 spoke health care centers to the 4 large PCI hub hospitals and leveraged recent developments in public health insurance schemes, emergency medical services, and health information technology.Main outcomes and measuresPrimary outcomes focused on the proportion of patients undergoing reperfusion, timely reperfusion, and postfibrinolysis angiography and PCI. Secondary outcomes were in-hospital and 1-year mortality.ResultsA total of 2420 patients with STEMI (2034 men [84.0%] and 386 women [16.0%]; mean [SD] age, 54.7 [12.2] years) (898 in the preimplementation phase and 1522 in the postimplementation phase) were enrolled, with 1053 patients (43.5%) from the spoke health care centers. Missing data were common for systolic blood pressure (213 [8.8%]), heart rate (223 [9.2%]), and anterior MI location (279 [11.5%]). Overall reperfusion use and times to reperfusion were similar (795 [88.5%] vs 1372 [90.1%]; P = .21). Coronary angiography (314 [35.0%] vs 925 [60.8%]; P < .001) and PCI (265 [29.5%] vs 707 [46.5%]; P < .001) were more commonly performed during the postimplementation phase. In-hospital mortality was not different (52 [5.8%] vs 85 [5.6%]; P = .83), but 1-year mortality was lower in the postimplementation phase (134 [17.6%] vs 179 [14.2%]; P = .04), and this difference remained consistent after multivariable adjustment (adjusted odds ratio, 0.76; 95% CI, 0.58-0.98; P = .04).Conclusions and relevanceA hub-and-spoke model in South India improved STEMI care through greater use of PCI and may improve 1-year mortality. This model may serve as an example for developing STEMI systems of care in other low- to middle-income countries.
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Project description:Aims. We sought for peripheral blood gene expression signatures at presentation that distinguish the ST elevation (STEMI) and non-ST elevation myocardial infarction (NSTEMI) conditions, to define a precise map of differentially regulated biological processes, unveil new distinctive traits, and help predict markers of outcome. Methods and results. Total RNA from whole blood of STEMI and NSTEMI patients was used to prepare poly(A)+ enriched libraries for paired-end RNA-Seq. Transcriptomes were reconstructed and, after adjustment for unwanted variation, we performed differential expression analysis. Enrichment analyses was performed to infer differentiating functional networks. We identified 153 differentially expressed genes, which stood correction for TnI levels at admission and included 32 putative novel genes (false discovery rate-adjusted P<0.05). We found a divergent modulation of inflammatory, immune-response, angiogenic, and mitochondrial dynamics pathways. Finally, we showed that specific gene expression patterns at admission predict troponin I (TnI) peak levels and/or GRACE risk score. Conclusions. RNA-Seq allowed identifying novel differentially expressed genes in STEMI vs. NSTEMI, which might uncover unappreciated mechanisms underlying acute MI. Overall, our results depicted a scenario characterizing different pathological traits of these two types of acute MI that could pave the way for the identification of novel, specific biomarkers for early diagnosis, risk stratification, and therapeutic decision-making.
2020-05-27 | GSE103182 | GEO
Project description:BackgroundDespite the high incidence and mortality of ST-segment elevation myocardial infarction (STEMI) among the very elderly, risk markers for this condition remain poorly defined. This study was designed to identify independent markers of STEMI among individuals carefully selected for being healthy or manifesting STEMI in < 24 h.MethodsWe enrolled participants aged 80 years or older of whom 50 were STEMI patients and 207 had never manifested cardiovascular diseases. Blood tests, medical and psychological evaluations were obtained at study admission. Odds Ratio (OR) and attributed risk (AR) were obtained by multivariate regression models using STEMI as dependent variable.ResultsLow glomerular filtration rate (GFR) [OR:4.41 (1.78-10.95); p = 0.001], reduced levels of HDL-C [OR:10.70 (3.88-29.46); p = 0.001], male gender [OR:12.08 (5.82-25.08); p = 0.001], moderate to severe depressive symptoms [OR:10.00 (2.82-35.50); p = 0.001], prior smoking [OR:2.00 (1.05-3.80); p = 0.034] and current smoking [OR:6.58 (1.99-21.70); p = 0.002] were significantly associated with STEMI. No association was found between STEMI and age, diabetes, hypertension, mild depressive symptoms, triglyceride or LDL-C.ConclusionsThis is the first case-control study carried out with very elderlies to assess STEMI risk. Our findings indicate that reduced HDL-C, GFR, male gender, smoking habits and moderate to severe depressive symptoms are markers of STEMI in this age group.General significanceIn Individuals aged 80 or more years, a greater attention must be paid to low HDL-C and GFR at the expense of conventional STEMI risk factors for younger adults such as diabetes mellitus, hypertension and high LDL-C or triglyceride.
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