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Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction.

ABSTRACT: Plasma concentrations of many cardiovascular and inflammatory proteins are altered after ST-elevation myocardial infarction (STEMI) and may provide prognostic information. We conducted a large-scale proteomic analysis in patients with STEMI, correlating protein levels to infarct size and left ventricular ejection fraction (LVEF) determined with cardiac magnetic resonance imaging. We analysed 131 cardiovascular and inflammatory proteins using a multiplex proximity extension assay and blood samples obtained at baseline, 6, 24, and 96 h from the randomised clinical trial CHILL-MI. Cardiac magnetic resonance imaging data at 4?±?2 days and 6 months were available as per trial protocol. Using a linear regression model with bootstrap resampling and false discovery rate adjustment we identified five proteins (ST2, interleukin-6, pentraxin-3, interleukin-10, renin, and myoglobin) with elevated values corresponding to larger infarct size or worse LVEF and four proteins (TNF-related apoptosis-inducing ligand, TNF-related activation induced cytokine, interleukin-16, and cystatin B) with values inversely related to LVEF and infarct size, concluding that among 131 circulating inflammatory and cardiovascular proteins in the acute and sub-acute phase of STEMI, nine showed a relationship with infarct size and LVEF post-STEMI, with IL-6 and ST2 exhibiting the strongest association.

SUBMITTER: Mohammad MA

PROVIDER: S-EPMC7596042 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction.

Mohammad Moman A MA Koul Sasha S Egerstedt Anna A Smith J Gustav JG Noc Marko M Lang Irene I Holzer Michael M Clemmensen Peter P Gidlöf Olof O Metzler Bernhard B Engstrøm Thomas T Erlinge David D

Scientific reports 20201029 1

Plasma concentrations of many cardiovascular and inflammatory proteins are altered after ST-elevation myocardial infarction (STEMI) and may provide prognostic information. We conducted a large-scale proteomic analysis in patients with STEMI, correlating protein levels to infarct size and left ventricular ejection fraction (LVEF) determined with cardiac magnetic resonance imaging. We analysed 131 cardiovascular and inflammatory proteins using a multiplex proximity extension assay and blood sample ...[more]

PMID: 33122738

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Project description:There are conflicting data on the relationship between the time of symptom onset during the 24-hour cycle (circadian dependence) and infarct size in ST-elevation myocardial infarction (STEMI). Moreover, the impact of this circadian pattern of infarct size on clinical outcomes is unknown. We sought to study the circadian dependence of infarct size and its impact on clinical outcomes in STEMI.We studied 6,710 consecutive patients hospitalized for STEMI from 2006 to 2009 in a tropical climate with non-varying day-night cycles. We categorized the time of symptom onset into four 6-hour intervals: midnight-6:00 A.M., 6:00 A.M.-noon, noon-6:00 P.M. and 6:00 P.M.-midnight. We used peak creatine kinase as a surrogate marker of infarct size.Midnight-6:00 A.M patients had the highest prevalence of diabetes mellitus (P = 0.03), more commonly presented with anterior MI (P = 0.03) and received percutaneous coronary intervention less frequently, as compared with other time intervals (P = 0.03). Adjusted mean peak creatine kinase was highest among midnight-6:00 A.M. patients and lowest among 6:00 A.M.-noon patients (2,590.8±2,839.1 IU/L and 2,336.3±2,386.6 IU/L, respectively, P = 0.04). Midnight-6:00 A.M patients were at greatest risk of acute heart failure (P<0.001), 30-day mortality (P = 0.03) and 1-year mortality (P = 0.03), while the converse was observed in 6:00 A.M.-noon patients. After adjusting for diabetes, infarct location and performance of percutaneous coronary intervention, circadian variations in acute heart failure incidence remained strongly significant (P = 0.001).We observed a circadian peak and nadir in infarct size during STEMI onset from midnight-6:00A.M and 6:00A.M.-noon respectively. The peak and nadir incidence of acute heart failure paralleled this circadian pattern. Differences in diabetes prevalence, infarct location and mechanical reperfusion may account partly for the observed circadian pattern of infarct size and acute heart failure.

Project description:Preinfarction angina may act as a clinical surrogate of ischemic preconditioning that may reduce infarct size and improve mortality in the setting of thrombolytic therapy for ST-elevation myocardial infarction. However, the benefits of preinfarction angina in the setting of primary percutaneous coronary intervention with stenting is inconclusive because of the greater achievement of infarct artery patency and speed of reperfusion.To identify a homogeneous population, we performed a retrospective analysis of 1031 patients admitted with a first ST-elevation myocardial infarction with ischemic times between 1 and 6 hours who received primary percutaneous coronary intervention. We identified 245 patients who had occluded arteries on presentation, of which 79 patients had documented preinfarction angina defined as chest pain within 24 hours of infarction. Infarct size was measured as the peak creatine kinase level, a metric supported in a subgroup by late enhancement on cardiac magnetic resonance imaging. Patients with preinfarction angina (n=79) had a 50% reduction in infarct size compared with those patients without preinfarction angina (n=166) by both peak creatine kinase (1094±75 IU/L versus 2270±102 IU/L; P<0.0001) and creatine kinase area under curve (18 420±18 941 versus 36 810±21 741 IU/h per liter; P<0.0001) despite having identical ischemic times (185±8 minutes versus 181±5 minutes; P=0.67) and angiographic area at risk (24.1±1.2% versus 25.3±0.9%; P=0.43). There was an absolute 4% improvement in left ventricular ejection fraction before discharge in those patients with preinfarction angina (P<0.02).The occurrence of preinfarction angina is associated with significant myocardial protection in the setting of primary percutaneous coronary intervention with stenting during ST-elevation myocardial infarction. Because preinfarction angina is relatively common, it is important that these patients be identified in clinical trials investigating therapies designed to reduce reperfusion injury and infarct size.

Dataset Information

Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction.

Publications

Using proximity extension proteomics assay to identify biomarkers associated with infarct size and ejection fraction after ST-elevation myocardial infarction.

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