Atrial fibrillation and stroke: chicken or egg? Does it really matter?

This editorial refers to ‘Temporal relations between atrial fibrillation and ischemic stroke and their prognostic impact on mortality’, by S. Camen et al., on pages 522--529. Atrial fibrillation (AF) is the most common sustained arrhythmia1 and its prevalence is projected to double over the next 30 years, due to an ageing population and increased prevalence of AF risk factors.2 Atrial fibrillation is associated with a 3- to 5-fold increased risk of stroke,3 and AF-related strokes are typically severe, causing significant long-term physical and cognitive disability, high mortality, and healthcare costs.2 Fortunately, the risk of AF-related stroke can be mitigated with the use of oral anticoagulation (OAC) therapy.4 Among patients who have already suffered an ischaemic stroke, it is particularly important to search for AF to prevent recurrent stroke. It remains unclear if the risk of stroke is particularly high in the time around the occurrence of AF. A better understanding of the temporal relationship between AF and stroke would help guide AF management and AF screening. In this issue of Europace, Camen et al.5 report on the results of a large, prospective observational study evaluating the temporal relationship between ischaemic stroke and AF, and the subsequent risk on mortality using harmonized data from five prospective European community cohorts. The population-based samples (median age 46 years; 48% men) were recruited between 1982 and 2010, and follow-up occurred for a median of 16 years, using hospital, ambulatory, and death registries to capture cardiovascular outcomes and mortality. There are three key findings from this report. First, the temporal relationship between ischaemic stroke and AF appears bi-directional. Second, among individuals with either AF or stroke, both conditions occur within 30 days of each other in about a quarter. Finally, the presence of both stroke and AF confers a higher risk of subsequent stroke than either condition alone irrespective of which event occurs first. The ability to pool patient-level data from representative populations from different countries with long-term follow-up is impressive. In over 100 000 individuals, complete information was available for stroke, AF, mortality, and baseline cardiovascular risk factors including total cholesterol, body mass index, systolic blood pressure, anti-hypertensive treatment, daily smoking, and prevalent myocardial infarction. In addition, prevalent heart failure and peripheral vascular disease were also available in selected populations, although it is unclear how many patients had these two conditions, as data were not reported. As with most observational research, there is a trade-off between study power and the availability of data, which is likely why the authors did not analyse other potentially important factors, such as alcohol consumption, valvular heart disease, left ventricular dysfunction, sleep apnoea, and kidney disease. Such factors may have been common in both AF and stroke. In addition, information regarding the specific type of anti-hypertensive and other cardiovascular medications was not reported and may have influenced prognosis. How do the study results improve our understanding of the relationship between AF and stroke and aid clinicians with management of the two conditions? First, there does not appear to be a close temporal relationship between AF and stroke. This was a consistent finding in studies among individuals with pacemakers and implanted cardioverter-defibrillators who had subclinical AF (SCAF) and stroke. In these individuals, cardiac monitoring for AF was continuous, giving a precise understanding of the timing of stroke in relation to any prior AF. Fewer than half of the patients in the TRENDS,6 ASSERT,7 and IMPACT AF8 studies had any SCAF prior to a stroke event, and the majority of patients (73–94%) had no SCAF in the 30 days prior to stroke. Thus, it appears that whether AF is clinical or subclinical, a temporal relationship with stroke events exists in only a minority of individuals. This work helps frame stroke prevention strategies for three groups of individuals. For individuals with stroke after a prior diagnosis of AF, these data again remind us of the failure to implement AF anticoagulation guidelines. Despite abundant data showing the safety and efficacy of OAC to prevent stroke in patients with AF, and with simple risk stratification tools and clinical practice guidelines, under-utilization or inappropriate use of OAC is still a problem and addressing this care gap needs to be a priority.9 For individuals with AF and stroke occurring within 30 days of each other, this work highlights the importance of early AF detection following stroke; particularly since randomized trials failed to show a reduction in recurrent stroke with empiric OAC therapy in patients with embolic stroke of undetermined source.11,12 Clinical practice dictates the need for at least 24 h of electrocardiogram monitoring after stroke to detect AF; however, the yield is extremely low. This study and previous work10 suggest in selected patients with stroke of undetermined source for which AF is suspected, additional ambulatory monitoring beyond 24 h should be pursued; perhaps as long as 30 days. Finally, this work shows that for some individuals suffering stroke, AF can occur many years following stroke, making it to the cause of the prior stroke, but likely related to shared risk factors for both conditions, and still warranting OAC therapy. This stresses the importance of aggressive diagnosis and treatment of common risk factors, such as hypertension, as an additional method of preventing stroke. One might also consider longer-term surveillance for AF in patients with stroke, particularly those in whom stroke is felt to be embolic. The use of implantable cardiac monitors has recently been shown to increase the incidence of AF detection and OAC initiation and reduce recurrent stroke.13 However, the feasibility and cost-effectiveness of such strategies are still the subject of active study, at a time of rapid advancement in cardiac monitoring technologies. Camen et al.5 provide a nice contribution to an ongoing discussion regarding the relationship between AF and stroke, and the impact on prognosis. Whether AF occurs before stroke or after stroke may not be that important. We should manage individuals with AF according to guidelines before stroke occurs. Similarly, we should aggressively search for AF in individuals following stroke, to help reduce the risk of recurrent stroke; particularly given the availability of modern tools for AF detection. Finally, we should recognize that both AF and stroke share many risk factors, whose treatment could lead to improvements in prognosis, not only limited to stroke prevention, but the prevention of heart failure and cardiovascular death. Conflict of interest: R.K.S. has a research grant from Servier Alberta Innovation in Health Fund. J.S.H. has received research grants and speaking fees from BMS/Pfizer, Medtronic, Boston Scientific, and Servier. The opinions expressed in this article are not necessarily those of the Editors of Europace or of the European Society of Cardiology.

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