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Aulin, Julia
Publications (4 of 4) Show all publications
Sandhu, R. K., Ezekowitz, J. A., Hijazi, Z., Westerbergh, J., Aulin, J., Alexander, J. H., . . . Wallentin, L. (2018). Obesity paradox on outcome in atrial fibrillation maintained even considering the prognostic influence of biomarkers: insights from the ARISTOTLE trial. Open heart, 5(2), Article ID UNSP e000908.
Open this publication in new window or tab >>Obesity paradox on outcome in atrial fibrillation maintained even considering the prognostic influence of biomarkers: insights from the ARISTOTLE trial
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2018 (English)In: Open heart, E-ISSN 2053-3624, Vol. 5, no 2, article id UNSP e000908Article in journal (Refereed) Published
Abstract [en]

Objective

We investigated the association between obesity and biomarkers indicating cardiac or renal dysfunction or inflammation and their interaction with obesity and outcomes.

Methods

A total of 14 753 patients in the Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial provided plasma samples at randomisation to apixaban or warfarin. Median follow-up was 1.9 years. Body Mass Index (BMI) was measured at baseline and categorised as normal, 18.5-25 kg/m(2); overweight, >25 to <30 kg/m(2); and obese, >= 30 kg/m(2). We analysed the biomarkers high-sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), growth differentiation factor-15 (GDF-15), troponin T and N-terminal B-type natriuretic peptide (NT-pro-BNP). Outcomes included stroke/systemic embolism (SE), myocardial infarction (MI), composite (stroke/SE, MI, or all-cause mortality), all-cause and cardiac mortality, and major bleeding.

Results

Compared with normal BMI, obese patients had significantly higher levels of hs-CRP and IL-6 and lower levels of GDF-15, troponin T and NT-pro-BNP. In multivariable analyses, higher compared with normal BMI was associated with a lower risk of all-cause mortality (overweight: HR 0.73 (95% CI 0.63 to 0.86); obese: 0.67 (0.56 to 0.80), p<0.0001), cardiac death (overweight: HR 0.74 (95% CI 0.60 to 0.93); obese: 0.71 (0.56 to 0.92), p=0.01) and composite endpoint (overweight: 0.80 (0.70 to 0.92); obese: 0.72 (0.62 to 0.84), p<0.0001).

Conclusions

Regardless of biomarkers indicating inflammation or cardiac or renal dysfunction, obesity was independently associated with an improved survival in anticoagulated patients with AF.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-376413 (URN)10.1136/openhrt-2018-000908 (DOI)000455601300059 ()30487982 (PubMedID)
Available from: 2019-02-04 Created: 2019-02-04 Last updated: 2019-02-04Bibliographically approved
Hijazi, Z., Aulin, J., Andersson, U., Alexander, J. H., Gersh, B., Granger, C. B., . . . Wallentin, L. (2016). Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation. Heart, 102(7), 508-517
Open this publication in new window or tab >>Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation
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2016 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 7, p. 508-517Article in journal (Refereed) Published
Abstract [en]

Objective: Atrial fibrillation (AF) is a risk factor for stroke and mortality and the prothrombotic state has been linked to inflammation. In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

Methods: The ARISTOTLE trial randomised 18 201 patients with AF to apixaban or warfarin. Interleukin 6 (IL-6) and C reactive protein (CRP) were analysed in plasma obtained at randomisation from 14 954 participants, and median follow-up was 1.9 years. Association between quartile groups of IL-6 and CRP and outcomes were analysed by Cox regression adjusted for clinical risk factors and other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).

Results: The IL-6 median level was 2.3 ng/L (IQR 1.5-3.9), median CRP level was 2.2 mg/L (1.0-4.8). IL-6 and CRP were significantly associated with all-cause mortality independent of clinical risk factors and other biomarkers (HR (95% CI) 1.93 (1.57 to 2.37) and 1.49 (1.24 to 1.79), respectively, Q4 vs Q1). IL-6 was associated with myocardial infarction, cardiovascular mortality, and major bleeding beyond clinical risk factors but not in the presence of cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Neither inflammatory biomarker was associated with stroke/systemic embolism. Risk prediction for stroke, death and major bleeding was not improved by IL-6 or CRP when added to clinical risk factors and the other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).

Conclusions: In patients with AF on anticoagulation, after accounting for clinical risk factors and other biomarkers, biomarkers of inflammation were significantly associated with an increased risk of mortality. However, there were no associations with the risk of stroke or major bleeding.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-293014 (URN)10.1136/heartjnl-2015-308887 (DOI)000373308500006 ()26839066 (PubMedID)
Available from: 2016-05-12 Created: 2016-05-11 Last updated: 2017-11-30Bibliographically approved
Aulin, J., Siegbahn, A., Hijazi, Z., Ezekowitz, M. D., Andersson, U., Connolly, S. J., . . . Oldgren, J. (2015). Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation. American Heart Journal, 170(6), 1151-1160
Open this publication in new window or tab >>Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation
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2015 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 170, no 6, p. 1151-1160Article in journal (Refereed) Published
Abstract [en]

Background Inflammation has been associated with cardiovascular disease and the burden of atrial fibrillation (AF). In this study we evaluate inflammatory biomarkers and future cardiovascular events in AF patients in the RE-LY study. Methods Interleukin-6 (IL-6), C-reactive protein (CRP) (n = 6,187), and fibrinogen (n = 4,893) were analyzed at randomization; outcomes were evaluated by Cox models and C-statistics. Results Adjusted for clinical risk factors IL-6 was independently associated with stroke or systemic embolism (P =.0041), major bleedings (P =.0001), vascular death (P<.0001), and a composite thromboembolic outcome (ischemic stroke, systemic embolism, myocardial infarction, pulmonary embolism and vascular death) (P<.0001). CRP was independently related to myocardial infarction (P =.0047), vascular death (P =.0004), and the composite thromboembolic outcome (P =.0001). When further adjusted for cardiac (troponin andN-terminal fragment B-type natriuretic peptide [NT-proBNP]) and renal (cystatin-C) biomarkers on top of clinical risk factors IL-6 remained significantly related to vascular death (P<.0001), major bleeding (P<.0170) and the composite thromboembolic outcome (P<.0001), and CRP to myocardial infarction (.0104). Fibrinogen was not associated with any outcome. C-index for stroke or systemic embolism increased from 0.615 to 0.642 (P =.0017) when adding IL-6 to the clinically used CHA(2)DS(2)-VASc risk score with net reclassification improvement of 28%. Conclusion In patients with AF, IL-6 is related to higher risk of stroke and major bleeding, and both markers are related to higher risk of vascular death and the composite of thromboembolic events independent of clinical risk factors. Adjustment for cardiovascular biomarkers attenuated the prognostic value, although IL-6 remained related to mortality, the composite of thromboembolic events, and major bleeding, and CRP to myocardial infarction.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:uu:diva-276878 (URN)10.1016/j.ahj.2015.09.018 (DOI)000368255700012 ()
Funder
AstraZenecaGlaxoSmithKline (GSK)
Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2017-11-30Bibliographically approved
Aulin, J., Hijazi, Z., Andersson, U., Gersh, B. J., Hanna, M., Horowitz, J. D., . . . Wallentin, L. (2014). Interleukin-6 and C-reactive protein and risk for cardiovascular events and death in anticoagulated patients with atrial fibrillation. Paper presented at Congress of the European-Society-of-Cardiology (ESC), AUG 30-SEP 03, 2014, Barcelona, SPAIN. European Heart Journal, 35, 1115-1116
Open this publication in new window or tab >>Interleukin-6 and C-reactive protein and risk for cardiovascular events and death in anticoagulated patients with atrial fibrillation
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2014 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 1115-1116Article in journal, Meeting abstract (Refereed) Published
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-240799 (URN)000343001306553 ()
Conference
Congress of the European-Society-of-Cardiology (ESC), AUG 30-SEP 03, 2014, Barcelona, SPAIN
Available from: 2015-01-08 Created: 2015-01-08 Last updated: 2017-12-05Bibliographically approved
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