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Siegbahn, Agneta
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Publications (10 of 232) Show all publications
Hijazi, Z., Oldgren, J., Lindbäck, J., Alexander, J. H., Connolly, S. J., Eikelboom, J. W., . . . Wallentin, L. (2018). A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score. European Heart Journal, 39(6), 477-485
Open this publication in new window or tab >>A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score
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2018 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 6, p. 477-485Article in journal (Refereed) Published
Abstract [en]

Aims: In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers.

Methods and results: The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score.

Conclusion: A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
Atrial fibrillation, Biomarkers, Mortality, NOAC, Oral anticoagulation, Risk score
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-348121 (URN)10.1093/eurheartj/ehx584 (DOI)000424876100015 ()29069359 (PubMedID)
Funder
Swedish Foundation for Strategic Research , RB13-0197Swedish Heart Lung Foundation, 20090183
Available from: 2018-04-11 Created: 2018-04-11 Last updated: 2018-04-11Bibliographically approved
Åberg, M., Edén, D. & Siegbahn, A. (2018). Activation of beta1-integrins and caveolin-1 by TF/FVIIa promotes cell survival. Paper presented at 5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, APR 20-22, 2018, Vienna, AUSTRIA. Cardiovascular Research, 114, S88-S88
Open this publication in new window or tab >>Activation of beta1-integrins and caveolin-1 by TF/FVIIa promotes cell survival
2018 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 114, p. S88-S88Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357489 (URN)000430678500252 ()
Conference
5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, APR 20-22, 2018, Vienna, AUSTRIA
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-08-23Bibliographically approved
Edén, D., Mokhtari, D., Eriksson, J. W., Åberg, M. & Siegbahn, A. (2018). Adipocytes are coagulant active in a TF/FVIIa dependent manner but lipolysis is unaffected by TF/FVIIa. Paper presented at 5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, APR 20-22, 2018, Vienna, AUSTRIA. Cardiovascular Research, 114, S131-S131
Open this publication in new window or tab >>Adipocytes are coagulant active in a TF/FVIIa dependent manner but lipolysis is unaffected by TF/FVIIa
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2018 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 114, p. S131-S131Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357491 (URN)000430678500386 ()
Conference
5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, APR 20-22, 2018, Vienna, AUSTRIA
Available from: 2018-08-23 Created: 2018-08-23 Last updated: 2018-08-23Bibliographically approved
Rocca, B., Fox, K. A. A., Ajjan, R. A., Andreotti, F., Baigent, C., Collet, J.-P., . . . Storey, R. F. (2018). Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis. European Heart Journal, 39(19), 1672-1686
Open this publication in new window or tab >>Antithrombotic therapy and body mass: an expert position paper of the ESC Working Group on Thrombosis
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2018 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 19, p. 1672-1686Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Oxford University Press, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357008 (URN)10.1093/eurheartj/ehy066 (DOI)000432687200007 ()29509886 (PubMedID)
Available from: 2018-08-13 Created: 2018-08-13 Last updated: 2018-08-13Bibliographically approved
Sumaya, W., Wallentin, L., James, S. K., Siegbahn, A., Gabrysch, K., Bertilsson, M., . . . Storey, R. F. (2018). Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy. European Heart Journal, 39(13), 1078-1085
Open this publication in new window or tab >>Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy
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2018 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 13, p. 1078-1085Article in journal, Editorial material (Other academic) Published
Abstract [en]

Aims To determine whether fibrin clot properties are associated with clinical outcomes following acute coronary syndrome (ACS). Methods and results Plasma samples were collected at hospital discharge from 4354 ACS patients randomized to clopidogrel or ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. A validated turbidimetric assay was employed to study plasma clot lysis time and maximum turbidity (a measure of clot density). One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were estimated using Cox proportional hazards models. After adjusting for CV risk factors, each 50% increase in lysis time was associated with CV death/spontaneous MI [HR 1.17, 95% confidence interval (CI) 1.05-1.31; P < 0.01] and CV death alone (HR 1.36, 95% CI 1.17-1.59; P < 0.001). Similarly, each 50% increase in maximum turbidity was associated with increased risk of CV death (HR 1.24, 95% CI 1.03-1.50; P = 0.024). After adjustment for other prognostic biomarkers (leukocyte count, high-sensitivity C-reactive protein, high-sensitivity troponin T, cystatin C, N-terminal pro B-type natriuretic peptide, and growth differentiation factor15), the association with CV death remained significant for lysis time (HR 1.2, 95% CI 1.01-1.42; P = 0.042) but not for maximum turbidity. These associations were consistent regardless of randomized antiplatelet treatment (all interaction P > 0.05). Neither lysis time nor maximum turbidity was associated with major bleeding events. Conclusion Fibrin clots that are resistant to lysis independently predict adverse outcome in ACS patients. Novel therapies targeting fibrin clot properties might be a new avenue for improving prognosis in patients with ACS.

Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
Keywords
Acute coronary syndrome, Fibrin clot, Lysis time, Biomarker
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357171 (URN)10.1093/eurheartj/ehy013 (DOI)000429350500010 ()29390064 (PubMedID)
Available from: 2018-08-14 Created: 2018-08-14 Last updated: 2018-08-14Bibliographically approved
Lind, L., Ingelsson, E., Sundström, J., Siegbahn, A. & Lampa, E. (2018). Methylation-based estimated biological age and cardiovascular disease.. European Journal of Clinical Investigation, 48(2), Article ID e12872.
Open this publication in new window or tab >>Methylation-based estimated biological age and cardiovascular disease.
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2018 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 48, no 2, article id e12872Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: DNA methylation changes over life at specific sites in the genome, which can be used to estimate "biological age." The aim of this population-based longitudinal cohort study was to investigate the association between estimated biological age and incident cardiovascular disease (CVD).

MATERIALS AND METHODS: Based on formulas published by Hannum et al and Horvath et al, "biological age" was calculated using data from the Illumina 450k Bead Methylation chip in 832 participants free from cardiovascular disease in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between estimated biological and chronological age was calculated (DiffAge).

RESULTS: During 10 years of follow-up, 153 incident cases of cardiovascular disease occurred. In the sex-adjusted analyses, the Horvath estimation of DiffAge was significantly related to incident cardiovascular disease (HR 1.040, 95% CI 1.010-1.071, P = .0079). Thus, for each year of increased biological age, a 4% increased risk of future cardiovascular disease was observed. This relationship was still significant following adjustment for the traditional risk factors sex, BMI, diabetes, HDL and LDL-cholesterol, systolic blood pressure and smoking (HR 1.033, 95% CI 1.004-1.063, P = .024). No such significant association was found using the Hannum formula.

CONCLUSIONS: DNA methylation-based estimation of "biological age" per Horvath was associated with incident cardiovascular disease.

Keywords
DNA, age, cardiovascular diseases, methylation, risk factors
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-343485 (URN)10.1111/eci.12872 (DOI)000423370500006 ()29231988 (PubMedID)
Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-03-07Bibliographically approved
Pol, T., Hijazi, Z., Lindbäck, J., Oldgren, J., Alexander, J., Granger, C., . . . Wallentin, L. (2018). New Biomarkers Associated With Cardiovascular Death In Patients With Atrial Fibrillation Using Multimarker Screening: Insights From The Aristotle Trial. Paper presented at 67th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 10-12, 2018, Orlando, FL, USA. Journal of the American College of Cardiology, 71(11), 330-330
Open this publication in new window or tab >>New Biomarkers Associated With Cardiovascular Death In Patients With Atrial Fibrillation Using Multimarker Screening: Insights From The Aristotle Trial
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2018 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 71, no 11, p. 330-330Article in journal, Meeting abstract (Other academic) Published
Abstract [en]

Background

Atrial fibrillation (AF) is associated with significant mortality. Biomarkers have shown to add predictive value and could facilitate the understanding of key pathophysiologic mechanisms in AF. Using proximity extension assay (PEA), a new multiplex analytic technique enabling analysis of hundreds of plasma biomarkers, we explored the association between 255 cardiovascular and inflammatory biomarkers with cardiovascular death in patients with AF on oral anticoagulation.

Methods

From the ARISTOTLE trial of patients with AF, 517 cases of cardiovascular death and 4057 randomly selected controls were included in an unstratified case-control cohort study. Plasma obtained at randomization was analyzed with conventional immunoassays or the OLINK PEA- panels CVDII, CVDIII, and inflammation panel. Median follow-up time was 1.8 years. The association between biomarkers and cardiovascular death was evaluated using Random Forest and individual Cox-regression analyses adjusted for clinical characteristics, renal function, and cardiac biomarkers (NT-proBNP and cTnT-hs), with adjustment for multiple testing.

Results

Of the 255 studied biomarkers, NT-proBNP, cTnT-hs, interleukin-6 (IL-6), transferrin receptor protein 1 (TfR1) and fibroblast growth factor 23 (FGF-23) remained statistically significantly associated with cardiovascular death according to both the Random Forest and the adjusted Cox-regression analysis. In the adjusted Cox analysis, the hazard ratio (95% confidence intervals) per interquartile range was 1.58 (1.38 - 1.83) for NT-proBNP, 1.56 (1.40 -1.75) for cTnT-hs, 1.28 (1.14 - 1.44) for IL-6, 1.27 (1.14 - 1.41) for TfR1 and 1.18 (1.09 -1.28) for FGF-23.

Conclusion

Among a vast number of biomarkers, NT-proBNP, cTnT-hs, IL-6, TfR1 and FGF-23 had an independent association with cardiovascular death in patients with AF. The associations of TfR1 and FGF-23 with cardiovascular death in AF are novel and the role of iron regulation (TfR1), and phosphate metabolism (FGF-23), warrants further investigation.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357329 (URN)10.1016/S0735-1097(18)30871-4 (DOI)000429659701180 ()
Conference
67th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 10-12, 2018, Orlando, FL, USA
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Hijazi, Z., Pol, T., Oldgren, J., Lindbäck, J., Alexander, J., Granger, C., . . . Siegbahn, A. (2018). Novel Prognostic Biomarkers For Ischemic Stroke In Patients With Atrial Fibrillation Using Multimarker Screening: Insights From The Aristotle Trial. Paper presented at 67th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 10-12, 2018, Orlando, FL, USA. Journal of the American College of Cardiology, 71(11), 506-506
Open this publication in new window or tab >>Novel Prognostic Biomarkers For Ischemic Stroke In Patients With Atrial Fibrillation Using Multimarker Screening: Insights From The Aristotle Trial
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2018 (English)In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 71, no 11, p. 506-506Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
ELSEVIER SCIENCE INC, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357330 (URN)000429659701356 ()
Conference
67th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), MAR 10-12, 2018, Orlando, FL, USA
Available from: 2018-08-16 Created: 2018-08-16 Last updated: 2018-08-16Bibliographically approved
Ueland, T., Åkerblom, A., Ghukasyan, T., Michelsen, A. E., Aukrust, P., Becker, R. C., . . . Wallentin, L. (2018). Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(2), Article ID e007009.
Open this publication in new window or tab >>Osteoprotegerin Is Associated With Major Bleeding But Not With Cardiovascular Outcomes in Patients With Acute Coronary Syndromes: Insights From the PLATO (Platelet Inhibition and Patient Outcomes) Trial
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2018 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 2, article id e007009Article in journal (Refereed) Published
Abstract [en]

Background-Elevated levels of osteoprotegerin, a secreted tumor necrosis factor-related molecule, might be associated with adverse outcomes in patients with coronary artery disease. We measured plasma osteoprotegerin concentrations on hospital admission, at discharge, and at 1 and 6months after discharge in a predefined subset (n=5135) of patients with acute coronary syndromes in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Methods and Results-The associations between osteoprotegerin and the composite end point of cardiovascular death, nonprocedural spontaneous myocardial infarction or stroke, and non-coronary artery bypass grafting major bleeding during 1year of follow-up were assessed by Cox proportional hazards models. Event rates of the composite end point per increasing quartile groups at baseline were 5.2%, 7.5%, 9.2%, and 11.9%. A 50% increase in osteoprotegerin level was associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI], 1.21-1.42) for the composite end point but was not significant in adjusted analysis (ie, clinical characteristics and levels of C-reactive protein, troponin T, NT-proBNP [N-terminal pro-B-type natriuretic peptide], and growth differentiation factor-15). The corresponding rates of non-coronary artery bypass grafting major bleeding were 2.4%, 2.2%, 3.8%, and 7.2%, with an unadjusted HR of 1.52 (95% CI, 1.36-1.69), and a fully adjusted HR of 1.26 (95% CI, 1.09-1.46). The multivariable association between the osteoprotegerin concentrations and the primary end point after 1month resulted in an HR of 1.09 (95% CI, 0.89-1.33); for major bleeding after 1month, the HR was 1.33 (95% CI, 0.91-1.96). Conclusions-In patients with acute coronary syndrome treated with dual antiplatelet therapy, osteoprotegerin was an independent marker of major bleeding but not of ischemic cardiovascular events. Thus, high osteoprotegerin levels may be useful in increasing awareness of increased bleeding risk in patients with acute coronary syndrome receiving antithrombotic therapy.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
acute coronary syndrome, bleeding, osteoprotegerin, prognosis
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-352997 (URN)10.1161/JAHA.117.007009 (DOI)000426642400005 ()29330256 (PubMedID)
Funder
AstraZenecaSwedish Foundation for Strategic Research
Available from: 2018-07-16 Created: 2018-07-16 Last updated: 2018-07-16Bibliographically approved
Kask, L., Hörnaeus, K., Åberg, M., Jorsback, A., Bergquist, J. & Siegbahn, A. (2018). Proteomic, functional and receptor studies of growth differentiation factor 15, GDF-15. Paper presented at 5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, APR 20-22, 2018, Vienna, AUSTRIA. Cardiovascular Research, 114, S76-S76
Open this publication in new window or tab >>Proteomic, functional and receptor studies of growth differentiation factor 15, GDF-15
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2018 (English)In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 114, p. S76-S76Article in journal, Meeting abstract (Other academic) Published
Place, publisher, year, edition, pages
OXFORD UNIV PRESS, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-357492 (URN)000430678500211 ()
Conference
5th Congress of the ESC-Council-on-Basic-Cardiovascular-Science on Frontiers in Cardio Vascular Biology, APR 20-22, 2018, Vienna, AUSTRIA
Available from: 2018-08-17 Created: 2018-08-17 Last updated: 2018-08-17Bibliographically approved
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