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Hijazi, Ziad
Publications (10 of 52) 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
Proietti, M., Hijazi, Z., Andersson, U., Connolly, S. J., Eikelboom, J. W., Ezekowitz, M. D., . . . Wallentin, L. (2018). Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE-LY trial. Journal of Internal Medicine, 283(3), 282-292
Open this publication in new window or tab >>Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE-LY trial
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2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 3, p. 282-292Article in journal (Refereed) Published
Abstract [en]

Background: Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF.

Objectives: To compare the performance of contemporary clinical bleeding risk scores in 18113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE-LY trial.

Methods: HAS-BLED, ORBIT, ATRIA and HEMORR(2)HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated.

Results: There were 1182 (6.5%) major bleeding events during a median follow-up of 2.0 years. For all the four schemes, high-risk subgroups had higher risk of major bleeding (all P<0.001). The ORBIT score showed the best discrimination with c-indices of 0.66, 0.66 and 0.62, respectively, for major, life-threatening and intracranial bleeding, which were significantly better than for the HAS-BLED score (difference in c-indices: 0.050, 0.053 and 0.048, respectively, all P<0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P=0.0019), ATRIA (P<0.001) and HEMORR(2)HAGES (P<0.001) scores. HAS-BLED score showed a nonsignificant trend for interaction (P=0.0607).

Conclusions: Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
anticoagulation treatment, atrial fibrillation, bleeding risk scores, dabigatran, major bleeding
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-347538 (URN)10.1111/joim.12702 (DOI)000425521000005 ()29044861 (PubMedID)
Available from: 2018-04-04 Created: 2018-04-04 Last updated: 2018-04-04Bibliographically approved
Pol, T., Held, C., Westerbergh, J., Lindbäck, J., Alexander, J. H., Alings, M., . . . Hijazi, Z. (2018). Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) Trial. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 7(3), Article ID e007444.
Open this publication in new window or tab >>Dyslipidemia and Risk of Cardiovascular Events in Patients With Atrial Fibrillation Treated With Oral Anticoagulation Therapy: Insights From the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) 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 3, article id e007444Article in journal (Refereed) Published
Abstract [en]

BackgroundDyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillation receiving oral anticoagulation. Methods and ResultsUsing data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, ApoA1 and ApoB plasma levels were measured at baseline in 14884 atrial fibrillation patients. Median length of follow-up was 1.9years. Relationships between continuous levels of ApoA1 and ApoB and clinical outcomes were evaluated using Cox models adjusted for cardiovascular risk factors, medication including statins, and cardiovascular biomarkers. A composite ischemic outcome (ischemic stroke, systemic embolism, myocardial infarction, and cardiovascular death) was used as the primary end point. Median (25th, 75th) ApoA1 and ApoB levels were 1.10 (0.93, 1.30) and 0.70g/L (0.55, 0.85), respectively. In adjusted analyses, higher levels of ApoA1 were independently associated with a lower risk of the composite ischemic outcome (hazard ratio, 0.81; P<0.0001). Similar results were observed for the individual components of the composite outcome. ApoB was not significantly associated with the composite ischemic outcome (P=0.8240). Neither apolipoprotein was significantly associated with major bleeding. There was no interaction between lipoproteins and randomized treatment for the primary outcome (both P values 0.2448). ConclusionsIn patients with atrial fibrillation on oral anticoagulation, higher levels of ApoA1 were independently associated with lower risk of ischemic cardiovascular outcomes. Investigating therapies targeting dyslipidemia may thus be useful to improve cardiovascular outcomes in patients with atrial fibrillation. Clinical Trial RegistrationURL: . Unique identifier: NCT00412984.

Place, publisher, year, edition, pages
WILEY, 2018
Keywords
atrial fibrillation, biomarkers, cardiovascular disease, cerebrovascular disease, stroke
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-351017 (URN)10.1161/JAHA.117.007444 (DOI)000426643800035 ()
Funder
Swedish Heart Lung Foundation, 20090183
Available from: 2018-05-24 Created: 2018-05-24 Last updated: 2018-05-24Bibliographically approved
Hijazi, Z., Hohnloser, S. H., Oldgren, J., Andersson, U., Connolly, S. J., Eikelboom, J. W., . . . Wallentin, L. (2018). Efficacy and safety of dabigatran compared with warfarin in patients with atrial fibrillation in relation to renal function over time-A RE-LY trial analysis. American Heart Journal, 198, 169-177
Open this publication in new window or tab >>Efficacy and safety of dabigatran compared with warfarin in patients with atrial fibrillation in relation to renal function over time-A RE-LY trial analysis
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2018 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 198, p. 169-177Article in journal (Refereed) Published
Abstract [en]

Background: Renal function may decline over time, and the efficacy and safety of dabigatran in atrial fibrillation (AF) in relation to renal function changes are unknown.& para;& para;Methods: The RE-LY trial randomized 18,113 patients with AF to 2 doses of dabigatran or warfarin for stroke prevention. Serial creatinine measurements were available in 16,988 patients. The relations between treatment, outcomes, and renal function (Cockcroft-Gault) were investigated using Cox-regression (1) with renal function as a time-dependent covariate and (2) according to worsening renal function (WRF) during follow-up, predefined as a decline in estimated glomerular filtration rate >20% from baseline.& para;& para;Results: During a median follow-up of 1.8 years, 4,106 (24.2%) participants were observed to have WRF, and 12,882 (75.8%) had stable renal function. The risks of all-cause mortality and major bleeding were higher in patients with WRF versus those with stable renal function (hazard ratio [95% CI]: 2.17 [1.81-2.59] and 1.43 [1.19-1.71]. respectively; both P < .0005). The efficacy and safety of dabigatran versus warfarin were similar irrespective of renal function changes over time (interaction P values >= .13 in both models). Dabigatran 110 mg showed a greater relative risk reduction of major bleeding in patients with normal renal function (estimated glomerular filtration rate >80 mL/min) during follow-up (interaction P= .026).& para;& para;Conclusions: In AF, WRF was associated with a higher risk of death and major bleeding. The efficacy and safety profile of dabigatran compared with warfarin was similar irrespective of renal function changes over time. Dabigatran 110 mg showed a greater relative risk reduction of major bleeding in patients with normal renal function during follow-up.

Place, publisher, year, edition, pages
MOSBY-ELSEVIER, 2018
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-352697 (URN)10.1016/j.ahj.2017.10.015 (DOI)000430004300023 ()29653640 (PubMedID)
Funder
AstraZeneca
Available from: 2018-06-08 Created: 2018-06-08 Last updated: 2018-06-08Bibliographically 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
Hijazi, Z., Oldgren, J., Siegbahn, A. & Wallentin, L. (2017). Application of Biomarkers for Risk Stratification in Patients with Atrial Fibrillation. Clinical Chemistry, 63(11), 152-164
Open this publication in new window or tab >>Application of Biomarkers for Risk Stratification in Patients with Atrial Fibrillation
2017 (English)In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 63, no 11, p. 152-164Article, review/survey (Refereed) Published
Abstract [en]

BACKGROUND: Atrial fibrillation is the most common sustained arrhythmia and an important contributor to cardiovascular morbidity and mortality. Several strategies have been proposed for prediction of outcomes and individualization of treatments to better balance the benefits of stroke prevention and risks of bleeding during anticoagulation. CONTENT: The availability of analytically more specific and sensitive methods to measure circulating biomarkers of cellular and organ stress and dysfunction has led to testing of their utility in several cardiovascular conditions. In patients with atrial fibrillation, biomarkers of myocardial injury (troponin) and cardiovascular stress and dysfunction (natriuretic peptides, growth differentiation factor 15), myocardial fibrosis (galectin-3), renal dysfunction (creatinine, cystatin C), inflammation (C reactive protein, cytokines) and coagulation activity (D-dimer) have been found associated with underlying pathophysiology, clinical outcomes and effects of treatment. Measurements of these markers might therefore expand the understanding of the pathophysiology, improve risk assessment and optimize treatment in individual patients with atrial fibrillation. SUMMARY: Biomarkers for risk stratification have potential roles as tools for evaluation of patients with atrial fibrillation and for selection of the best treatment strategies to prevent stroke, major bleeding, and mortality.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-319170 (URN)10.1373/clinchem.2016.255182 (DOI)000395048800024 ()
Funder
AstraZenecaGlaxoSmithKline (GSK)
Available from: 2017-03-31 Created: 2017-03-31 Last updated: 2017-04-28Bibliographically approved
Hijazi, Z., Oldgren, J., Andersson, U., Connolly, S. J., Eikelboom, J. W., Ezekowitz, M. D., . . . Wallentin, L. (2017). Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial. American Heart Journal, 190, 94-103, Article ID S0002-8703(17)30172-2.
Open this publication in new window or tab >>Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial
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2017 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 190, p. 94-103, article id S0002-8703(17)30172-2Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial.

METHODS: GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1, <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment.

RESULTS: GDF-15 concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores.

CONCLUSIONS: In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-342941 (URN)10.1016/j.ahj.2017.06.001 (DOI)000407410800012 ()28760218 (PubMedID)
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-03-22Bibliographically approved
Svennberg, E., Henriksson, P., Engdahl, J., Hijazi, Z., Al-Khalili, F., Friberg, L. & Frykman, V. (2017). N-terminal pro B-type natriuretic peptide in systematic screening for atrial fibrillation. Heart, 103(16), 1271-1277
Open this publication in new window or tab >>N-terminal pro B-type natriuretic peptide in systematic screening for atrial fibrillation
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2017 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 16, p. 1271-1277Article in journal (Refereed) Published
Abstract [en]

Objective Screening for atrial fibrillation (AF) in individuals aged 65 and above is recommended by the European Society of Cardiology. Increased levels of the biomarker N-terminal pro B-type natriuretic peptide (NT-proBNP) has in cohort studies been associated with incident AF. The aim of this study was to assess whether NT-proBNP could be useful for AF detection in systematic screening.

Methods The Strokestop study entailed 7173 Swedish residents aged 75/76 that were screened for AF using twice daily intermittent ECG recordings during 2 weeks. In a substudy of 886 participants, the last 815 consecutive participants and 71 individuals with newly detected AF, levels of NT-proBNP were determined.

Results Participants with newly detected AF (n=96) had a median NT-proBNP of 330 ng/L (IQR 121; 634). In individuals without AF (n=742), median NT-proBNP was 171 ng/L (IQR 95; 283), p<0.001. The CHA2DS2-VASc parameters did not differ significantly between individuals with newly detected AF and without AF nor between newly detected AF in the NT-proBNP cohort compared with the cohort where NT-proBNP was not assessed. Using an NT-proBNP cut-off of >= 125 ng/L in a non-acute setting yielded a negative predictive value of 92%, meaning that 35% fewer participants would need to be screened when applied to systematic AF screening. Adding weight to NT-proBNP further reduced participants needed to be screened with a preserved sensitivity.

Conclusions NT-proBNP was increased in individuals with newly detected AF. Prospective studies could clarify if NT-proBNP can be used to correctly select individuals that benefit most from AF screening.

National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-332926 (URN)10.1136/heartjnl-2016-310236 (DOI)000406309300011 ()28255099 (PubMedID)
Funder
Stockholm County CouncilSwedish Heart Lung Foundation
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2017-11-16Bibliographically approved
Hijazi, Z., Lindahl, B., Oldgren, J., Andersson, U., Lindbäck, J., Granger, C. B., . . . Wallentin, L. (2017). Repeated Measurements of Cardiac Biomarkers in Atrial Fibrillation and Validation of the ABC Stroke Score Over Time. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 6(6), Article ID e004851.
Open this publication in new window or tab >>Repeated Measurements of Cardiac Biomarkers in Atrial Fibrillation and Validation of the ABC Stroke Score Over Time
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2017 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 6, article id e004851Article in journal (Refereed) Published
Abstract [en]

Background: Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker-based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short-term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short- term risk estimate.

Methods and Results: According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide were measured with high-sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small ( median change cardiac troponin T +2.8%, troponin I +2.0%, and N-terminal pro-B-type natriuretic peptide +13.5%) and within-subject correlation was high ( all >= 0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person-years of follow-up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65-0.76) as compared with 0.70 (95% CI, 0.65-0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes.

Conclusions: In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker- based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score remains consistent and well calibrated with similar good predictive performance if patients are retested after 2 months.

Clinical Trial Registration --URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Place, publisher, year, edition, pages
WILEY, 2017
Keywords
atrial fibrillation, cardiac biomarkers, natriuretic peptide, risk score, stroke, troponin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-330752 (URN)10.1161/JAHA.116.004851 (DOI)000404098700009 ()
Funder
Swedish Foundation for Strategic Research
Available from: 2017-10-03 Created: 2017-10-03 Last updated: 2017-11-29Bibliographically approved
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