Bøtker, Hans Erik

Jensen, Lisette O

Jensen, Svend E

Kristensen, Steen D

Lip, Gregory Y H

Maeng, Michael

Nielsen, Jens C

Olesen, Kevin K W

Steensig, Kamilla

Thim, Troels

English

    Aalborg UniversitetCAD is an independent risk factor for stroke among patients with atrial fibrillationSteensig, Kamilla; Olesen, Kevin K W; Thim, Troels; Nielsen, Jens C; Jensen, Svend E;Jensen, Lisette O; Kristensen, Steen D; Bøtker, Hans Erik; Lip, Gregory Y H; Maeng, MichaelPublished in:Journal of the American College of CardiologyDOI (link to publication from Publisher):10.1016/j.jacc.2018.08.1046Creative Commons LicenseCC BY-NC-ND 4.0Publication date:2018Document VersionAccepted author manuscript, peer reviewed versionLink to publication from Aalborg UniversityCitation for published version (APA):Steensig, K., Olesen, K. K. W., Thim, T., Nielsen, J. C., Jensen, S. E., Jensen, L. O., Kristensen, S. D., Bøtker,H. E., Lip, G. Y. H., & Maeng, M. (2018). CAD is an independent risk factor for stroke among patients with atrialfibrillation. Journal of the American College of Cardiology, 72(20), 2540-2542.https://doi.org/10.1016/j.jacc.2018.08.1046General rightsCopyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright ownersand it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights.            ? Users may download and print one copy of any publication from the public portal for the purpose of private study or research.            ? You may not further distribute the material or use it for any profit-making activity or commercial gain            ? You may freely distribute the URL identifying the publication in the public portal ?Take down policyIf you believe that this document breaches copyright please contact us at vbn@aub.aau.dk providing details, and we will remove access tothe work immediately and investigate your claim.Downloaded from vbn.aau.dk on: December 27, 2020Accepted ManuscriptCoronary artery disease is independent risk factor for stroke among patients withatrial fibrillationKamilla Steensig, BSc, Kevin K.W. Olesen, MD, Troels Thim, MD PhD, Jens C.Nielsen, MD PhD DMSc, Svend E. Jensen, MD PhD, Lisette O. Jensen, MD PhDDMSc, Steen D. Kristensen, MD DMSc, Hans Erik Bøtker, MD PhD DMSc, GregoryY.H. Lip, MD, Michael Maeng, MD PhDPII: S0735-1097(18)36961-4DOI: 10.1016/j.jacc.2018.08.1046Reference: JAC 25303To appear in: Journal of the American College of CardiologyReceived Date: 5 July 2018Revised Date: 14 August 2018Accepted Date: 16 August 2018Please cite this article as: Steensig K, Olesen KKW, Thim T, Nielsen JC, Jensen SE, Jensen LO,Kristensen SD, Bøtker HE, Lip GYH, Maeng M, Coronary artery disease is independent risk factor forstroke among patients with atrial fibrillation, Journal of the American College of Cardiology (2018), doi:10.1016/j.jacc.2018.08.1046.This is a PDF file of an unedited manuscript that has been accepted for publication. As a service toour customers we are providing this early version of the manuscript. The manuscript will undergocopyediting, typesetting, and review of the resulting proof before it is published in its final form. Pleasenote that during the production process errors may be discovered which could affect the content, and alllegal disclaimers that apply to the journal pertain.MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTCoronary artery disease is independent risk factor for stroke among patients with atrial fibrillation  Kamilla Steensig BSca, Kevin K.W. Olesen MDa,b, Troels Thim MD PhDa, Jens C. Nielsen MD PhD DMSca, Svend E. Jensen MD PhDc, Lisette O. Jensen MD PhD DMScd, Steen D. Kristensen MD DMSca, Hans Erik Bøtker MD PhD DMSca, Gregory Y. H. Lip MDe, and Michael Maeng MD PhDa  a) Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark  b) Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark  c) Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark d) Department of Cardiology, Odense University Hospital, Odense, Denmark e) Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, England  Funding: Funded by the Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. Disclosures: KKWO has received speaking honoraria from Bayer A/S. JCN is supported by the Novo Nordisk Foundation (NNF16OC0018658). SDK has received lecture fees from Aspen, AstraZeneca, Bayer, BMS/Pfizer and Boehringer-Ingelheim. GYHL is consultant for Bayer/Janssen, BMS/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo. Speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are directly received personally. MM has received lecture fees and consulting honoraria from Novo, Bayer, AstraZeneca, Boehringer-Ingelheim, and institutional grants from Volcano (now Philips), Boston Scientific, and Biosen ors.   Abbreviations AF: Atrial fibrillation  CAD: Coronary artery disease  CI: Confidence interval  IRR: Incidence rate ratios  TIA: Transient ischemic attack   Corresponding author: Michael Maeng, MD, PhD Department of Cardiology Aarhus University Hospital Palle Juul-Jensens Boulevard 99 8200 Aarhus N, Denmark Telephone: +45 26703237 Fax: +45 78452260 E-mail: michael.maeng@ki.au.dk Twitter: @AUHdk | @AarhusUni   MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTPatients with atrial fibrillation (AF) have an increased risk of ischemic stroke, transient ischemic attack (TIA), and systemic embolism compared to patients without AF (1). In patients with AF, several risk factors are well documented an included in risk scores used for risk stratification. These include advancing age, diabetes mellitus, hypertension, congestive heart disease, peripheral artery disease, and previous stroke/TIA, among others. Coronary artery disease (CAD) and ischemic stroke share several common risk factors, but whether CAD is an independent risk factor for ischemic stroke among patients with AF has not yet been examined. The aim of this study was to investigate whether th presence of CAD provided independent prognostic information of the risk of future ischemic stroke and thromboembolism in patients with AF.  The association between CAD and ischemic stroke ris was examined in a large prospectively collected dataset of consecutive patients with AF who underwent coronary angiography in Western Denmark between July 1, 2004 and December 1, 2012. All patients’ angiographic findings are registered in the Western De mark Heart Registry (2) by use of each patient’s unique 10-digit personal identifier, whic is a personal number assigned to each Danish resident upon birth or after immigration. This personal identifier is used throughout every regional and national registry, where it ensures accurate cross linkage of healthcare information and minimizes loss to follow-up. Patient data from the Western Denmark Heart Registry concerning the patients’ angiographic findings were cross linked with information from the Danish National Patient Registry,(3) which records all hospital-based inpatient and outpatient diagnoses, and the Danish National Database of Reimbursed Prescriptions (3), which contains data on all reimbursed prescriptions at Danish pharmacies. MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTThe total study cohort was divided into two groups; atients with CAD and patients without CAD. CAD was defined as obstructive (≥50%) coronary stenosis in ≥1 coronary vessel, or non-obstructive coronary stenoses in ≥2 coronary vessels. The primary endpoint was a composite of ischemic stroke, TIA, and systemic embolism obtained from the Danish National Patient Registry. Follow-up began 30 days after the ind x coronary angiography, and continued until endpoint event, death, emigration, or end of follow-up, whichever came first. The risk of ischemic stroke, TIA, and systemic embolism was estimated separately for both groups, and incidence rate ratios (IRR) were calculated with modified Poisson regression using patients without CAD as reference. We adjusted for age, gender, diabetes mellitus, hypertension, congestive heart disease, previous stroke/TIA, vascul r disease (previous myocardial infarction and/or peripheral artery disease/aortic plaque), antipl telet treatment, oral anticoagulant treatment, and statin treatment. Out of 96,430 patients undergoing coronary angiography between 2004-2012, a total of 12,690 patients had a diagnosis of AF, were 18 years or above and had a follow-up time of >30 days. Among these patients 7,533 patients (59.4%) had CAD and 5,157 patients (40.6%) had no CAD. Maximal follow-up was 8.4 years, and median follow-up was 3 years (IQR 1.3-5.2). Baseline characteristics are shown in Table 1. The rate of ischemic stroke/TIA/thromboembolism was 2.62 (95% confidence interval (CI) 2.42-2.84) per 100 person-years for patients with CAD and 1.61 (95% CI 1.43-1.81) per 100 person-years for patients without CAD. Crude IRR was 1.62 (95% CI 1.41-1.87). The impact of presence of CAD remained significant after adjustment and suggested a 29% increased risk of ischemic stroke/TIA/thromboembolism (adjusted IRR 1.29, 95% CI 1.08-1.53). MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTOur study suggests that CAD is an independent risk factor for ischemic stroke among patients with AF. The association between CAD and ischemic stroke has also been indicated in a previous study analyzing our entire cohort, i.e. prima ily including patients without AF.(3) Patients with AF, however, have a greater risk of ischemic stroke than patients without AF. Moreover, prophylactic oral anticoagulant therapy is well-documented in patients with AF but not in non-AF patients. There are several risk scores recommended for risk stratification of AF patients into those with a low risk of thromboembolic events (no indication for oral anticoagulation) and those with a high risk (indication for oral anticoagulation) of thromboembolic events including ischemic stroke. According to the current study, CAD is an independent risk factor for thromboembolic events icluding ischemic stroke in AF patients. Consequently, we suggest that CAD should be considered as a potential additional risk factor in the risk scores used for stratification of AF patients.    MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTReferences 1. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. J Am Coll Cardiol 2014;64(21):e1–76. 2. Schmidt M, Maeng M, Madsen M, Sørensen HT, Jensen LO, Jakobsen C-J. The Western Denmark Heart Registry: Its Influence on Cardiovascular Patient Care. J Am Coll Cardiol 2018;71(11):1259–72. 3. Olesen KKW, Madsen M, Lip GYH, et al. Coronary atery disease and risk of adverse cardiac events and stroke. Eur J Clin Invest 2017;47(11):819–28.    MANUSCRIPT ACCEPTEDACCEPTED MANUSCRIPTTable 1. Baseline characteristics of 12,690 patients with atrial fibrillation undergoing coronary angiography   No CAD*  Any CAD Total   (n=5,157) (n=7,533) (n=12,690)     n (%) n (%) n (%) Age    <65 years 2,050 (39.8) 1,478 (19.6) 3,528 (27.8)  65-74 years 1,764 (34.2) 2,801 (37.2) 4,565 (36.0)  ≥75 years 1,343 (26.0) 3,254 (43.2) 4,597 (36.2) Gender     Male 3,081 (59.7) 5,363 (71.2) 8,444 (66.5)  Female 2,076 (40.3) 2,170 (28.8) 4,246 (33.5) Smoking status   Never/former 3,632 (70.4) 5,105 (67.8) 8,737 (68.8)  Active 835 (16.2) 1,501 (19.9) 2,336 (18.4)  Missing 690 (13.4) 927 (12.3) 1,617 (12.7) Comorbidities   Diabetes mellitus 735 (14.3) 1,664 (22.1) 2,399 (18.9)  Hypertension 3,033 (58.8) 5,420 (72.0) 8,453 (66.6)  Congestive heart failure 1,933 (37.5) 2,991 (39.7) 4,924 (38.8)  Stroke/TIA† 564 (10.9) 1,116 (14.8) 1,680 (13.2)  Vascular disease‡ 733 (15.0) 3,752 (49.8) 4,525 (35.7)  PAD§/aortic plaque 282 (5.5) 1,087 (14.4) 1,369 (10.8)  Previous myocardial infarction 536 (10.4) 3,171 (42.1) 3,707 (29.2) Medical treatment   Vitamin K antagonists 3,390 (65.7) 4,125 (54.8) 7,515 (59.2)  NOAC// 97 (1.9) 119 (1.6) 216 (1.7)  Aspirin 2,608 (50.6) 5,919 (78.6) 8,527 (67.2)  Statin 2,226 (43.2) 5,915 (78.5) 8,141 (64.2)  * CAD: Coronary artery disease † TIA: Transient ischemic attack ‡ Vascular disease: Presence of previous myocardial infarction and/or peripheral artery disease/aortic plaque. § PAD: Peripheral artery disease // NOAC: Non-vitamin K antagonist anticoagulant treatment  

CAD is an independent risk factor for stroke among patients with atrial fibrillation

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CAD is an independent risk factor for stroke among patients with atrial fibrillation

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