Atrial fibrillation (AF) is a major global health issue and 1 of the leading preventable causes of stroke.
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Over the past 40 years, we have learned how to better estimate the risk of stroke resulting from AF and how to wisely use oral anticoagulant medications.2
However, this knowledge has been based in large part on research conducted in North America and western Europe. Researchers in other regions of the world have recently shown us that there are important regional differences in the risk factors and outcomes of patients with AF.3
, 4
, 5
These recent data suggest that more research must be done to understand the realities of AF in different regions of the world and to help design stroke prevention strategies that are adapted to local conditions.In this issue of the Canadian Journal of Cardiology, Chan et al.
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report on their observational study of nearly 1200 Chinese patients seen in a Hong Kong hospital for AF. Despite a low average CHADS-VASc (Congestive Heart Failure, Hypertension, Age [≥ 75 years], Diabetes, Stroke/Transient Ischemic Attack, Vascular Disease, Age [65-74 years], Sex [Female] score) of 1.8 ± 1.0, they observed an annual stroke rate of 6.6%, which is much higher than would be expected based on rates derived from other populations.7
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Although the selection bias of a hospital-based sample may have been a factor, the high observed stroke rate among these Chinese patients is consistent with a large recent study.7
This study suggests that regional differences in stroke risk may be mediated through differences in risk factors, the use of oral anticoagulants, and socioeconomic factors.7
Other large observational studies demonstrate that about 90% of the risk of stroke can be explained on the basis of modifiable stroke risk factors, which also differ substantially between regions.9
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These include not only patient-specific factors such as blood pressure or physical activity but also local environmental factors such as air pollution.9
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Thus, public health strategies to prevent stroke will need to be adapted to reflect local conditions.The second major finding of this work is that advancing age appears to be the key predictor of stroke risk in this group of patients, even for patients as young as 50 years. This observation is consistent with the evolution in opinion regarding age as a stroke risk factor in AF. The original CHADS2 (Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack) risk stratification scheme considered age > 75 years as a stroke risk factor, whereas the newer CHA2DS2-VASc scheme considers all patients > 65 years to have a sufficient stroke risk to justify anticoagulation. The Canadian Cardiovascular Society has proposed the CHADS-65 approach to the CHA2DS2-VASc scheme, which highlights the importance of age in decision-making regarding anticoagulation for patients with AF.
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In their work, Chan et al.
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suggest that among Chinese patients, stroke risk increases sharply at age 50 years. Although further corroboration of their findings is needed, they raise concern that in some populations it may make sense to recommend oral anticoagulation to prevent stroke in patients with AF as young as 50 years, even in the absence of other stroke risk factors. In addition to clinical stroke, we have also seen evidence that younger white patients with AF but no stroke risk factors appear to have an increased risk of cognitive decline and covert stroke.12
A clinical trial is under way (Blinded Randomized Trial of Anticoagulation to Prevent Ischemic Stroke and Neurocognitive Impairment in Atrial Fibrillation [BRAIN-AF]; NCT02387229) to determine if oral anticoagulation can prevent both of these outcomes in young patients without additional stroke risk factors.Why is age such an important predictor of stroke in patients with AF? Is age simply a marker for other age-dependent stroke risk factors such as hypertension and vascular disease, or are other factors at play? It is difficult to answer this question, because most studies report only the rate of age-specific ischemic stroke and do not further subclassify stoke into large-vessel, lacunar, cardioembolic, and other ischemic categories. Understanding what types of stroke are driving the increased incidence may help guide mechanistic research into understanding how age modulates stroke risk. Another consideration is that most existing studies focus on clinical stroke. We are beginning to appreciate that covert stroke is common in patients with AF, and multiple lesions are often seen on magnetic resonance imaging, even among younger individuals.
12
Patients with AF may simply accumulate more covert strokes over time, which eventually become manifested clinically.In the future, the age threshold for recommending oral anticoagulation for patients with AF may decrease. The observed safety of direct oral anticoagulants and their ease of use has led investigators to consider if these agents should be used in younger patients without traditional stroke risk factors.
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The work of Chan et al.6
demonstrates that in some populations, the risk of AF-related stroke may be elevated in patients as young as 50 years. Ongoing trials such as BRAIN-AF will determine if younger patients might derive benefits beyond stroke reduction, such as the prevention of cognitive decline. However, these potential benefits need to be demonstrated in prospective randomized trials before guidelines are changed.Funding Sources
Supported by a Heart and Stroke Foundation of Ontario Mid-Career Award (MC7450).
Disclosures
Dr Healey has received research grants from Boehringer-Ingelheim, Bayer, and Bristol-Meyers-Squib.
References
- Atrial fibrillation as an independent risk factor for stroke: the Framingham Study.Stroke. 1991; 22: 983-988
- Added predictive ability of the CHA2DS2VASc risk score for stroke and death in patients with atrial fibrillation: the prospective Danish Diet, Cancer and Health cohort study.Circ Cardiovasc Qual Outcomes. 2012; 5: 335-342
- Atrial fibrillation in Africa: clinical characteristics, prognosis and adherence to guidelines in Cameroon.Europace. 2010; 12: 482-484
- Management and 1-year outcomes of patients with atrial fibrillation in the Middle East: Gulf survey of atrial fibrillation events.Angioology. 2015; 66: 464-471
- Variations in cause and management of atrial fibrillation in a prospective registry of 15,400 emergency department patients in 46 countries: the RE-LY Atrial Fibrillation Registry.Circulation. 2014; 129: 1568-1576
- CHA2DS2-VASc recalibration with an additional age category (50-64 years) enhances stroke risk stratification in Chinese patients with atrial fibrillation.Can J Cardiol. 2016; 32: 1381-1387
- Occurrence of death and stroke in patients in 47 countries 1 year after presenting with atrial fibrillation: a cohort study.Lancet. 2016; 388: 1161-1169
- Apixaban in patients with atrial fibrillation.N Engl J Med. 2011; 364: 806-817
- Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.Lancet. 2016; 388: 761-765
- Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.Lancet Neurol. 2016; 15: 913-924
- 2014 Focused update of the Canadian Cardiovascular Society Guidelines for the management of atrial fibrillation.Can J Cardiol. 2014; 30: 1114-1130
- Prevalence of silent cerebral ischemia in paroxysmal atrial fibrillation and correlation with cognitive function.J Am Coll Cardiol. 2013; 62: 1990-1997
- Rates, management and outcome of rivaroxaban bleeding in daily care: results from the Dresden NOAC registry.Blood. 2014; 124: 955-962
Article info
Publication history
Published online: September 13, 2016
Accepted:
September 11,
2016
Received:
August 22,
2016
Footnotes
See article by Chan et al., pages 1381–1387 of this issue.
See page 1365 for disclosure information.
Identification
Copyright
© 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
