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Hijazi, Ziad
Publications (10 of 61) Show all publications
Lopes, R. D., Heizer, G., Aronson, R., Vora, A. N., Massaro, T., Mehran, R., . . . Alexander, J. H. (2019). Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation. New England Journal of Medicine, 380(16), 1509-1524
Open this publication in new window or tab >>Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation
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2019 (English)In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 380, no 16, p. 1509-1524Article in journal (Refereed) Published
Abstract [en]

Background Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. Methods In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y(12) inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. Results Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P=0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. Conclusions In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y(12) inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both.

Place, publisher, year, edition, pages
MASSACHUSETTS MEDICAL SOC, 2019
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-383192 (URN)10.1056/NEJMoa1817083 (DOI)000465144100012 ()30883055 (PubMedID)
Available from: 2019-07-24 Created: 2019-07-24 Last updated: 2019-07-24Bibliographically approved
Hijazi, Z., Verdecchia, P., Oldgren, J., Andersson, U., Reboldi, G., Di Pasquale, G., . . . Wallentin, L. (2019). Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the RE-LY Trial. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 8(2), Article ID e010107.
Open this publication in new window or tab >>Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the RE-LY Trial
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2019 (English)In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 2, article id e010107Article in journal (Refereed) Published
Abstract [en]

Background

Cardiac biomarkers and left ventricular hypertrophy (LVH) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes.

Methods and Results

Plasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE‐LY (Randomized Evaluation of Long‐Term Anticoagulation Therapy) trial. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor‐15 were determined using high‐sensitivity (hs) assays. LVH was defined by ECG. Cox models were adjusted for baseline characteristics, LVH, and biomarkers. LVH was present in 1257 patients. During a median follow‐up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly (P<0.0001) associated with higher levels of all biomarkers in linear regression analyses adjusting for baseline characteristics. Geometric mean ratios (95% CIs) were as follows: NT‐proBNP, 1.32 (1.25–1.38); hs cardiac troponin I, 1.67 (1.57–1.78); hs troponin T, 1.38 (1.32–1.44); and growth differentiation factor‐15, 1.09 (1.05–1.12). For stroke, the hazard ratios (95% CIs) per 50% increase were as follows: NT‐proBNP, 1.09 (1.00–1.19); hs cardiac troponin I, 1.09 (1.03–1.15); hs troponin T, 1.14 (1.06–1.24); and growth differentiation factor‐15, 1.22 (1.08–1.38) (all P<0.05). For death, hazard ratios (95% CIs) were as follows: NT‐proBNP, 1.24 (1.17–1.31); hs cardiac troponin I, 1.13 (1.10–1.17); hs troponin T, 1.28 (1.23–1.34); and growth differentiation factor‐15, 1.31 (1.22–1.42) (all P<0.0001). LVH was not significantly associated with stroke or death after adjustment for biomarkers.

Conclusions

Cardiac biomarkers are significantly associated with LVH. The prognostic value of biomarkers for stroke and death is not affected by LVH. The prognostic information of LVH is attenuated in the presence of cardiac biomarkers.

Keywords
atrial fibrillation, biomarker, left ventricular hypertrophy, risk prediction
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-379402 (URN)10.1161/JAHA.118.010107 (DOI)000460105800004 ()30651032 (PubMedID)
Available from: 2019-03-15 Created: 2019-03-15 Last updated: 2019-03-15Bibliographically approved
Hohnloser, S. H., Fudim, M., Alexander, J. H., Wojdyla, D. M., Ezekowitz, J. A., Hanna, M., . . . Lopes, R. D. (2019). Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight: Insights From the ARISTOTLE Trial. Circulation, 139(20), 2292-2300
Open this publication in new window or tab >>Efficacy and Safety of Apixaban Versus Warfarin in Patients With Atrial Fibrillation and Extremes in Body Weight: Insights From the ARISTOTLE Trial
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2019 (English)In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 139, no 20, p. 2292-2300Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Guidelines caution against the use of non-vitamin K antagonist oral anticoagulants in patients with extremely high (> 120 kg) or low (= 60 kg) body weight because of a lack of data in these populations.

METHODS: In a post hoc analysis of ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation; n= 18 201), a randomized trial comparing apixaban with warfarin for the prevention of stroke in patients with atrial fibrillation, we estimated the randomized treatment effect (apixaban versus warfarin) stratified by body weight (= 60, > 60-120, > 120 kg) using a Cox regression model and tested the interaction between body weight and randomized treatment. The primary efficacy and safety outcomes were stroke or systemic embolism and major bleeding.

RESULTS: Of the 18 139 patients with available weight and outcomes data, 1985 (10.9%) were in the low-weight group (= 60 kg), 15 172 (83.6%) were in the midrange weight group (> 60-120 kg), and 982 (5.4%) were in the high-weight group (> 120 kg). The treatment effect of apixaban versus warfarin for the efficacy outcomes of stroke/systemic embolism, all-cause death, or myocardial infarction was consistent across the weight spectrum (interaction P value> 0.05). For major bleeding, apixaban had a better safety profile than warfarin in all weight categories and even showed a greater relative risk reduction in patients in the low (= 60 kg; HR, 0.55; 95% CI, 0.36-0.82) and midrange (> 60-120 kg) weight groups (HR, 0.71; 95% CI, 0.61-0.83; interaction P value= 0.016).

CONCLUSIONS: Our findings provide evidence that apixaban is efficacious and safe across the spectrum of weight, including in low-(= 60 kg) and highweight patients (> 120 kg). The superiority on efficacy and safety outcomes of apixaban compared with warfarin persists across weight groups, with even greater reductions in major bleeding in patients with atrial fibrillation with low to normal weight as compared with high weight. The superiority of apixaban over warfarin in regard to efficacy and safety for stroke prevention seems to be similar in patients with atrial fibrillation across the spectrum of weight, including in low-and very high-weight patients. Thus, apixaban appears to be appropriate for patients with atrial fibrillation irrespective of body weight.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
atrial fibrillation, bleeding, non-vitamin K antagonist oral anticoagulants, stroke, warfarin
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-386162 (URN)10.1161/CIRCULATIONAHA.118.037955 (DOI)000468397500007 ()30773022 (PubMedID)
Available from: 2019-06-20 Created: 2019-06-20 Last updated: 2019-06-20Bibliographically approved
Guimaraes, P. O., Lopes, R. D., Alexander, J. H., Thomas, L., Hellkamp, A. S., Hijazi, Z., . . . Granger, C. B. (2019). International normalized ratio control and subsequent clinical outcomes in patients with atrial fibrillation using warfarin. Journal of Thrombosis and Thrombolysis, 48(1), 27-34
Open this publication in new window or tab >>International normalized ratio control and subsequent clinical outcomes in patients with atrial fibrillation using warfarin
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2019 (English)In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 48, no 1, p. 27-34Article in journal (Refereed) Published
Abstract [en]

We explored associations between INR measures and clinical outcomes in patients with AF using warfarin, and whether INR history predicted future INR measurements. We included patients in ARISTOTLE who were randomized to and received warfarin. Among patients who had events, we included those with ≥ 3 INR values in the 180 days prior to the event, with the most recent ≤ 60 days prior to the event, who were on warfarin at the time of event (n = 545). Non-event patients were included in the control group if they had ≥ 180 days of warfarin exposure with ≥ 3 INR measurements (n = 7259). The median (25th, 75th) number of INR values per patient was 29 (21, 38) over a median follow-up of 1.8 years. A total of 87% had at least one INR value < 1.5; 49% had at least one value > 4.0. The last INRs before events (median 14 [24, 7] days) were < 3.0 for at least 75% of patients with major bleeding and > 2.0 for half of patients with ischemic stroke. Historic time in therapeutic range (TTR) was weakly associated with future TTR (R2 = 0.212). Historic TTR ≥ 80% had limited predictive ability to discriminate future TTR ≥ 80% (C index 0.61). In patients with AF receiving warfarin, most bleeding events may not have been preventable despite careful INR control. Our findings suggest that INRs collected through routine management are not sufficiently predictive to provide reassurance about future time in therapeutic range or to prevent subsequent outcomes, and might be over-interpreted in clinical practice.

Keywords
International normalized ratio, Clinical outcomes, Warfarin, Atrial fibrillation
National Category
Hematology Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-388767 (URN)10.1007/s11239-019-01858-1 (DOI)000470789500004 ()30972712 (PubMedID)
Available from: 2019-07-05 Created: 2019-07-05 Last updated: 2019-07-05Bibliographically approved
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: 2019-01-23Bibliographically 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: 2019-01-23Bibliographically 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
Hijazi, Z. & Wallentin, L. (2018). Natriuretic peptide should be used as a routine tool for evaluation of patients with atrial fibrillation. Heart, 105(5), 353-354
Open this publication in new window or tab >>Natriuretic peptide should be used as a routine tool for evaluation of patients with atrial fibrillation
2018 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 105, no 5, p. 353-354Article in journal, Editorial material (Other academic) Published
Keywords
atrial fibrillation, cardiac risk factors and prevention
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:uu:diva-374975 (URN)10.1136/heartjnl-2018-314040 (DOI)000471065600003 ()30314973 (PubMedID)
Available from: 2019-01-24 Created: 2019-01-24 Last updated: 2019-06-28Bibliographically 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
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