| 1. |
- Christersson, Christina, et al.
(författare)
-
Screening for Biomarkers Associated with Left Ventricular Function During Follow-up After Acute Coronary Syndrome
- 2023
-
Ingår i: Journal of Cardiovascular Translational Research. - : Springer Nature. - 1937-5387 .- 1937-5395. ; 16:1, s. 244-254
-
Tidskriftsartikel (refereegranskat)abstract
- A proportion of patients with the acute coronary syndrome (ACS) will suffer progressive remodeling of the left ventricular (LV). The aim was to screen for important biomarkers from a large-scale protein profiling in 420 ACS patients and define biomarkers associated with reduced LV function early and 1 year after the ACS. Transferrin receptor protein 1 and NT-proBNP were associated with LV function early and after 1 year, whereas osteopontin and soluble ST2 were associated with LV function in the early phase and, tissue-type plasminogen activator after 1 year. Fatty-acid-binding protein and galectin 3 were related to worse GLS but not to LVEF 1 year after the ACS. Proteins involved in remodeling and iron transport in cardiomyocytes were related to worse LV function after ACS. Biomarkers for energy metabolism and fibrosis were exclusively related to worse LV function by GLS. Studies on the functions of these proteins might add knowledge to the biological processes involved in heart failure in long term after ACS.
|
|
| 2. |
- Batra, Gorav, et al.
(författare)
-
Atrial fibrillation in patients undergoing coronary artery surgery is associated with adverse outcome
- 2019
-
Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; :1, s. 70-77
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The aim was to determine the association between atrial fibrillation (AF) and outcome in patients undergoing coronary artery bypass grafting (CABG).METHODS: All patients undergoing CABG between January 2010 and June 2013 were identified in the Swedish Heart Surgery Registry. Outcomes studied were all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, ischemic stroke, and recurrent AF. Patients with history of AF prior to surgery (preoperative AF) and patients without history of AF but with AF episodes post-surgery (postoperative AF) were compared to patients with no AF using adjusted Cox regression models.RESULTS: Among 9,107 identified patients, 8.1% (n = 737) had preoperative AF, and 25.1% (n = 2,290) had postoperative AF. Median follow-up was 2.2 years. Compared to no AF, preoperative AF was associated with higher risk of all-cause mortality, adjusted hazard ratio with 95% confidence interval (HR) 1.76 (1.33-2.33); cardiovascular mortality, HR 2.43 (1.68-3.50); and congestive heart failure, HR 2.21 (1.72-2.84). Postoperative AF was associated with risk of all-cause mortality, HR 1.27 (1.01-1.60); cardiovascular mortality, HR 1.52 (1.10-2.11); congestive heart failure, HR 1.47 (1.18-1.83); and recurrent AF, HR 4.38 (2.46-7.78). No significant association was observed between pre- or postoperative AF and risk for myocardial infarction and ischemic stroke.CONCLUSIONS: Approximately 1 in 3 patients undergoing CABG had pre- or postoperative AF. Patients with pre- or postoperative AF were at higher risk of all-cause mortality, cardiovascular mortality, and congestive heart failure, but not of myocardial infarction or ischemic stroke. Postoperative AF was associated with higher risk of recurrent AF.
|
|
| 3. |
- Edfors, R., et al.
(författare)
-
Use of proteomics to identify biomarkers associated with chronic kidney disease and long-term outcomes in patients with myocardial infarction
- 2020
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:5, s. 581-592
-
Tidskriftsartikel (refereegranskat)abstract
- Background Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. Methods A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. Results A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min(-1)/1.73 m(2)were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. Conclusion In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD.
|
|
| 4. |
|
|
| 5. |
- Eggers, Kai M., 1962-, et al.
(författare)
-
Predicting outcome in acute myocardial infarction : an analysis investigating 175 circulating biomarkers
- 2021
-
Ingår i: European Heart Journal. - : Oxford University Press. - 2048-8726 .- 2048-8734. ; 10:7, s. 806-812
-
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.
|
|
| 6. |
- Eggers, Kai M., 1962-, et al.
(författare)
-
Sex-differences in circulating biomarkers during acute myocardial infarction : An analysis from the SWEDEHEART registry
- 2021
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:4 April
-
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.
|
|
| 7. |
- Hjort, Marcus, et al.
(författare)
-
Differences in biomarker concentrations and predictions of long-term outcome in patients with ST-elevation and non-ST-elevation myocardial infarction
- 2021
-
Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 42, s. 1268-1268
-
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.
|
|
| 8. |
- Hjort, Marcus, et al.
(författare)
-
Increased Inflammatory Activity in Patients 3 Months after Myocardial Infarction with Nonobstructive Coronary Arteries
- 2019
-
Ingår i: Clinical Chemistry. - : AMER ASSOC CLINICAL CHEMISTRY. - 0009-9147 .- 1530-8561. ; 65:8, s. 1023-1030
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Around 5%-10% of patients with myocardial infarction (MI) present with nonobstructive coronary arteries (MINOCA). We aimed to assess pathophysiological mechanisms in MINOCA by extensively evaluating cardiovascular biomarkers in the stable phase after an event, comparing MINOCA patients with cardiovascular healthy controls and MI patients with obstructive coronary artery disease (MI-CAD).METHODS: Ninety-one biomarkers were measured with a proximity extension assay 3 months after MI in 97 MINOCA patients, 97 age-and sex-matched MI-CAD patients, and 98 controls. Lasso analyses (penalized logistic regression models) and adjusted multiple linear regression models were used for statistical analyses.RESULTS: In the Lasso analysis (MINOCA vs MI-CAD), 8 biomarkers provided discriminatory value: P-selectin glycoprotein ligand 1, C-X-C motif chemokine 1, TNF-related activation-induced cytokine, and pappalysin-1 (PAPPA) with increasing probabilities of MINOCA, and tissue-type plasminogen activator, B-type natriuretic peptide, myeloperoxidase, and interleukin-1 receptor antagonist protein with increasing probabilities of MI-CAD. Comparing MINOCA vs controls, 7 biomarkers provided discriminatory value: N-terminal pro-B-type natriuretic peptide, renin, NF-kappa-B essential modulator, PAPPA, interleukin-6, and soluble urokinase plasminogen activator surface receptor with increasing probabilities of MINOCA, and agouti-related protein with increasing probabilities of controls. Adjusted multiple linear regression analyses showed that group affiliation was associated with the concentrations of 7 of the 8 biomarkers in the comparison MINOCA vs MI-CAD and 5 of the 7 biomarkers in MINOCA vs controls.CONCLUSIONS: Three months after the MI, the biomarker concentrations indicated greater inflammatory activity in MINOCA patients than in both MI-CAD patients and healthy controls, and a varying degree of myocardial dysfunction among the 3 cohorts.
|
|
| 9. |
- Jönelid, Birgitta, et al.
(författare)
-
Biochemical biomarkers associated with peripheral artery disease contribute to prediction of outcome during long-term follow up after myocardial infarction
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- AbstractBackground: Few studies have investigated biomarkers and their association to cardiovascular (CV) outcomes in patients with myocardial infarction (MI) and peripheral artery disease (PAD). Tumor necrosis factor receptor 1(TNFR-1), tumor necrosis factor receptor 2(TNFR-2) and growth differentiation factor 15 (GDF-15) are inflammatory biomarkers found to predict PAD.Aim: To evaluate whether pathological ankle brachial index (ABI) and the group of biomarkers TNFR-1, TNFR-2 and GDF-15 analyzed early after a MI, were associated with all-cause mortality and the risk of new cardiovascular events during long-term follow up. Method: 388 patients with MI included in the REBUS (Relevance of Biomarkers for future risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined with ABI to diagnose PAD (defined as an ABI score <0.9 or > 1.4 on at least one side). TNFR-1, -2 and GDF-15 was measured using the Proseek Multiplex CVD III ⁹⁶˟⁹⁶ proximity extension assay (www.olink.com/products/cvd-i and iii-panel). The composite results for these 3 biomarkers were dichotomized into two groups (i.e high and low values) We evaluated pathological ABI and the group with higher biomarkers values with the association to long-term outcome, and if the group of biomarkers for inflammation could further improve prediction of recurrence of cardiovascular events (mortality, new acute coronary syndrome (ACS) and the composite of mortality, new ACS, stroke/TIA and PAD) after an MI. Results: The mean follow-up time was 5.5 years. After adjustment for established CV risk factors, pathological ABI was associated with a higher risk of new ACS, HR 1.97, 95 % CI 1.12-3.49, p = 0.019, and the composite endpoint; HR 1.97, 95 % CI 1.29-3.01, p=0.002, compared to patients with normal ABI. The group with the higher biomarker value was associated with a higher risk for all-cause mortality; HR 1.84, 95 % CI 1.00-3.38, p=0.049 and the composite endpoint; HR 1.62, 95 % CI 1.03-2.53, p=0.035. In the ROC analyses pathological ABI added to established CV risk factors improved the AUC for a new ACS from 0.753 (95% C.I. 0.684-0.822, p<0.001) to 0.763 (95% C.I. 0.697-0.830, p<0.001). When the group with higher biomarker values was added to established CV risk factors AUC for all-cause mortality increased from 0.789 (95% C-I. 0.729-0.849, p<0.001) to 0.805 (95% C.I. 0.746-0.863, p<0.001).Conclusion: Despite a high proportion of revascularization and guideline-recommended secondary medical treatment, both pathological ABI and the group with higher values of the inflammatory biomarkers (TNFR-1, TNFR-2, GDF-15) predictive for PAD were associated with the risk of new CV events and mortality in patients with a recent MI. The group of inflammatory biomarkers provide additional information to established risk factors in prediction of CV outcome in this cohort with recent MI.
|
|
| 10. |
- Jönelid, Birgitta, et al.
(författare)
-
Biomarkers in addition to clinical characteristics for prediction of peripheral artery disease in patients with recent myocardial infarction
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- AbstractBackground Few studies have examined biomarkers in CAD and peripheral artery disease (PAD), their association and the ability to predict PAD.Methods: Two prospectively observational studies including unselected patients with recent myocardial infarction were used for the analyses. PAD was defined as an abnormal ankle brachial index (ABI) score (<0.9 or > 1.4) on at least one side. The proximity extension assay (PEA) technique was used to simultaneously analyze 92 biomarkers with association to cardiovascular disease in samples early after an acute MI. Random forest was used to identify the biomarkers with a higher association to PAD. The additional discriminatory accuracy of adding biomarkers to clinical characteristics were analyzed by the c-statistics.Results: Six biomarkers were identified associated with prediction of PAD in the REBUS cohort. Three of these could be validated in the VaMIS cohort; Tumor necrosis factor receptor (TNFR-1), Tumor necrosis factor receptor 2 (TNFR-2) and Growth Differentiation Factor 15 (GDF-15) with an increase in c-statistics; Tnfr1:0.709 (95% CI 0.640, 0.779) and 0.746 (95% CI 0.706,0.787), Tnfr2: 0.703 (95% CI 0.633, 0.773) and 0.745 (95% CI 0.704, 0.785), GDF-15: 0.710 (95% CI 0.640, 0.781) and 0.752 (95% CI 0.711, 0.792) in the REBUS and VaMIS cohort respectively. Adding a group of biomarkers to clinical characteristics further increased the c-statistics compared to a single biomarker.Conclusions: Three biomarkers out of a panel of 92; TNFR-1, TNFR-2 and GDF-15 were identified associated with PAD in MI patients and could improve prediction of PAD in addition to clinical characteristics.
|
|
