Author + information
- Published online November 12, 2018.
- Kamilla 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, PhD, DMSc,
- Steen D. Kristensen, MD, DMSc,
- Hans Erik Bøtker, MD, PhD, DMSc,
- Gregory Y.H. Lip, MD‡ and
- Michael Maeng, MD, PhD‡∗ (, )@AUHdk@AarhusUni
- ↵∗Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark
Patients with atrial fibrillation (AF) have an increased risk of ischemic stroke, transient ischemic attack (TIA), and systemic embolism compared with patients without AF (1). In patients with AF, several risk factors are well documented and 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 the 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 risk 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 Denmark Heart Registry (2) by use of each patient’s unique 10-digit personal identifier, which 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 health care 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.
The total study cohort was divided into 2 groups: patients with and patients without CAD. CAD was defined as obstructive (≥50%) coronary stenosis in ≥1 coronary vessel, or nonobstructive 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 index 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 (IRRs) were calculated with modified Poisson regression using patients without CAD as reference. We adjusted for age, sex, diabetes mellitus, hypertension, congestive heart disease, previous stroke/TIA, vascular disease (previous myocardial infarction and/or peripheral artery disease/aortic plaque), antiplatelet treatment, oral anticoagulant treatment, and statin treatment.
Of 96,430 patients undergoing coronary angiography between 2004 and 2012, a total of 12,690 patients had a diagnosis of AF, were aged 18 years or older, and had a follow-up time >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 (interquartile range: 1.3 to 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 to 2.84) per 100 person-years for patients with CAD and 1.61 (95% CI: 1.43 to 1.81) per 100 person-years for patients without CAD. Crude IRR was 1.62 (95% CI: 1.41 to 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 to 1.53).
Our 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, that is, primarily 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 of thromboembolic events (indication for oral anticoagulation) including ischemic stroke. According to the current study, CAD is an independent risk factor for thromboembolic events including 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.
↵† Ms. Steensig and Dr. Olesen contributed equally to this work.
↵‡ Drs. Lip and Maeng are joint senior authors.
Please note: This work was funded by the Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark. Dr. Olesen has received speaking honoraria from Bayer A/S. Dr. Nielsen is supported by the Novo Nordisk Foundation (NNF16OC0018658). Dr. Kristensen has received lecture fees from Aspen, AstraZeneca, Bayer, Bristol-Myers Squibb/Pfizer, and Boehringer Ingelheim. Dr. Lip is consultant for Bayer/Janssen, Bristol-Myers Squibb/Pfizer, Biotronik, Medtronic, Boehringer Ingelheim, Novartis, Verseon, and Daiichi-Sankyo; and has served as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo; no fees are directly received personally. Dr. Maeng has received lecture fees and consulting honoraria from Novo, Bayer, AstraZeneca, and Boehringer Ingelheim; and institutional grants from Volcano (now Philips), Boston Scientific, and Biosensors. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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