| 1. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Predicting outcome in acute myocardial infarction : an analysis investigating 175 circulating biomarkers
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 10:7, s. 806-812
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Tidskriftsartikel (refereegranskat)abstract
- Aims There is a paucity of studies comprehensively comparing the prognostic value of larger arrays of biomarkers indicative of different pathobiological axes in acute myocardial infarction (MI).Methods and results In this explorative investigation, we simultaneously analysed 175 circulating biomarkers reflecting different inflammatory traits, coagulation activity, endothelial dysfunction, atherogenesis, myocardial dysfunction and damage, apoptosis, kidney function, glucose-, and lipid metabolism. Measurements were performed in samples from 1099 MI patients (SWEDEHEART registry) applying two newer multimarker panels [Proximity Extension Assay (Olink Bioscience), Multiple Reaction Monitoring mass spectrometry]. The prognostic value of biomarkers regarding all-cause mortality, recurrent MI, and heart failure hospitalizations (median follow-up <= 6.6years) was studied using Lasso analysis, a penalized logistic regression model that considers all biomarkers simultaneously while minimizing the risk for spurious findings. Tumour necrosis factor-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), ovarian cancer-related tumour marker CA 125 (CA-125), and fibroblast growth factor 23 (FGF-23) consistently predicted all-cause mortality in crude and age/sex-adjusted analyses. Growth-differentiation factor 15 (GDF-15) was strongly predictive in the crude model. TRAIL-R2 and B-type natriuretic peptide (BNP) consistently predicted heart failure hospitalizations. No biomarker predicted recurrent MI. The prognostic value of all biomarkers was abrogated following additional adjustment for clinical variables owing to our rigorous statistical approach.Conclusion Apart from biomarkers with established prognostic value (i.e. BNP and to some extent GDF-15), several 'novel' biomarkers (i.e. TRAIL-R2, CA-125, FGF-23) emerged as risk predictors in patients with MI. Our data warrant further investigation regarding the utility of these biomarkers for clinical decision-making in acute MI.
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| 2. |
- Eggers, Kai M., 1962-, et al.
(författare)
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Sex-differences in circulating biomarkers during acute myocardial infarction : An analysis from the SWEDEHEART registry
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
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Tidskriftsartikel (refereegranskat)abstract
- Background Sex-differences in the pathobiology of myocardial infarction are well established but incompletely understood. Improved knowledge on this topic may help clinicians to improve management of men and women with myocardial infarction. Methods In this registry-based cohort study (SWEDEHEART), we analyzed 175 circulating biomarkers reflecting various pathobiological axes in 856 men and 243 women admitted to Swedish coronary care units because of myocardial infarction. Two multimarker panels were applied (Proximity Extension Assay [Olink Bioscience], Multiple Reaction Monitoring mass spectrometry). Lasso analysis (penalized logistic regression), multiple testing-corrected Mann- Whitney tests and Cox regressions were used to assess sex-differences in the concentrations of these biomarkers and their implications on all-cause mortality and major adverse events (median follow-up up to 6.6 years). Results Biomarkers provided a very high discrimination between both sexes, when considered simultaneously (c-statistics 0.972). Compared to women, men had higher concentrations of six biomarkers with the most pronounced differences seen for those reflecting atherogenesis, myocardial necrosis and metabolism. Women had higher concentrations of 14 biomarkers with the most pronounced differences seen for those reflecting activation of the reninangiotensin- aldosterone axis, inflammation and for adipokines. There were no major variations between sexes in the associations of these biomarkers with outcome. Conclusions Severable sex-differences exist in the expression of biomarkers in patients with myocardial infarction. While these differences had no impact on outcome, our data suggest the presence of various sex-related pathways involved in the development of coronary atherosclerosis, the progression to plaque rupture and acute myocardial damage, with a greater heterogeneity in women.
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| 3. |
- Hjort, Marcus, et al.
(författare)
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Differences in biomarker concentrations and predictions of long-term outcome in patients with ST-elevation and non-ST-elevation myocardial infarction
- 2021
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 42, s. 1268-1268
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Tidskriftsartikel (refereegranskat)abstract
- Background: Differences in biomarkers reflective of pathobiology and prognosis between ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) are incompletely understood and may offer insights for tailoring of treatment. Methods: This registry-based study included 538 STEMI and 544 NSTEMI patients admitted 2008–2014. Blood samples were collected day 1–3 after admission and 175 biomarkers were analyzed using Proximity Extension Assay and Multiple Reaction Monitoring mass spectrometry. Adjusted Lasso analysis (penalized logistic regression model) was used to select biomarkers that discriminated STEMI from NSTEMI patients. Biomarkers identified by the Lasso analysis were then evaluated in adjusted Cox regressions for associations with death or major adverse cardiovascular events. Results: Biomarkers strongly discriminated STEMI and NSTEMI when considered simultaneously in adjusted Lasso analysis (c-statistic 0.764). Eleven biomarkers independently discriminated STEMI and NSTEMI; seven showing higher concentrations in STEMI: myoglobin, N-terminal pro-B-type natriuretic peptide, serum amyloid A-1 and A-2 protein, ST2 protein, interleukin-6 and chitinase-3-like protein 1; and four showing higher concentrations in NSTEMI: fibroblast growth factor 23, membrane-bound aminopeptidase P, tumor necrosis factor-related activation-induced cytokine and apolipoprotein C-I. During up to 6.6 years of prognostic follow-up, none of these biomarkers exhibited different associations with adverse outcome between STEMI and NSTEMI. Conclusions: In the acute setting, biomarkers indicated greater myocardial dysfunction and inflammation in STEMI, whereas they displayed a more diverse pathophysiologic pattern in NSTEMI patients. These biomarkers were similarly prognostic in STEMI and NSTEMI patients. The results do not support treating STEMI and NSTEMI patients differently based on the concentrations of these biomarkers.
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| 4. |
- Mörtberg, Josefin, et al.
(författare)
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Prognostic importance of biomarkers associated with haemostatic, vascular and endothelial disturbances in acute coronary syndrome patients in relation to kidney function
- 2023
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 373, s. 64-71
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.METHODS: Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 ml/min/1.73 m 2 was tested. RESULTS: Tissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 ml/min/ 1.73 m 2. CONCLUSIONS: Adrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.
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| 5. |
- Rezeli, Melinda, et al.
(författare)
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Quantitation of 87 Proteins by nLC-MRM/MS in Human Plasma : Workflow for Large-Scale Analysis of Biobank Samples
- 2017
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Ingår i: Journal of Proteome Research. - : AMER CHEMICAL SOC. - 1535-3893 .- 1535-3907. ; 16:9, s. 3242-3254
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Tidskriftsartikel (refereegranskat)abstract
- A multiple reaction monitoring (MRM) assay was developed for precise quantitation of 87 plasma proteins including the three isoforms of apolipoprotein E (APOE) associated with cardiovascular diseases using nanoscale liquid chromatography separation and stable isotope dilution strategy. The analytical performance of the assay was evaluated and we found an average technical variation of 4.7% in 4-5 orders of magnitude dynamic range (approximate to 0.2 mg/L to 4.5 g/L) from whole plasma digest. Here, we report a complete workflow, including sample processing adapted to 96-well plate format and normalization strategy for large-scale studies. To further investigate the MS-based quantitation the amount of six selected proteins was measured by routinely used clinical chemistry assays as well and the two methods showed excellent correlation with high significance (p-value < 10e-5) for the six proteins, in addition for the cardiovascular predictor factor, APOB: APOA1 ratio (r = 0.969, p-value < 10e-5). Moreover, we utilized the developed assay for screening of biobank samples from patients with myocardial infarction and performed the comparative analysis of patient groups with STEMI (ST- segment elevation myocardial infarction), NSTEMI (non ST- segment elevation myocardial infarction) and type-2 AMI (type-2 myocardial infarction) patients.
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