REVIEW URRENT C OPINION
Smoking, atrial fibrillation, and ischemic stroke: a confluence of epidemics Ida Ehlers Albertsen a, Thure Filskov Overvad b, Gregory Y.H. Lip b,c, and Torben Bjerregaard Larsen a,c
Purpose of review Smoking and atrial fibrillation are major contemporary health concerns. They commonly coexist and are frequent causes of ischemic stroke. The purpose of this article is to describe recent scientific investigations about smoking, atrial fibrillation, and ischemic stroke, with a primary focus on prevention. Recent findings Smoking predisposes to atrial fibrillation and is useful for the prediction of future atrial fibrillation. Several recent risk prediction models for adverse events associated with atrial fibrillation include smoking as a component. Smoking status identifies patients at high risk of incident atrial fibrillation, adverse events in an emergency ward after admission with atrial fibrillation, thromboembolic events following a diagnosis of atrial fibrillation, and potentially poor control of vitamin K antagonist treatment. Summary From multiple perspectives of atrial fibrillation, patients who smoke represent a high-risk population. Appropriate preventive measures targeting this endangered population are paramount. These include smoking cessation, appropriate care in the emergency ward, and careful selection of the optimal antithrombotic strategy to reduce the major burden of ischemic stroke attributed to the confluence of the epidemics of smoking and atrial fibrillation. Keywords atrial fibrillation, prevention, smoking, stroke
INTRODUCTION Atrial fibrillation is the most common cardiac arrhythmia and a frequent and devastating cause of morbidity and mortality from cardioembolic stroke [1,2]. The prevalence of atrial fibrillation has taken a daunting rise. It is expected to reach pandemic proportions due to the continued aging of the general population [3 ]. Atrial fibrillation may be prevalent in up to 1/3 of all patients with incident ischemic stroke [4 ]. One potential factor involved in the pathogenesis of atrial fibrillation is smoking [5–8]. Smoking causes a broad range of oncogenic [9], cardiovascular [10], cerebrovascular [10], and respiratory disease. Unfortunately, smoking continues to be a dominant health hazard worldwide and responsible for major healthcare costs [11]. The purpose of the current article is to describe recent scientific investigations linking the epidemics of smoking, atrial fibrillation, and ischemic stroke, with a primary focus on prevention strategies. &&
SMOKING AND PRECIPITATION OF ATRIAL FIBRILLATION Smoking predisposes to atrial fibrillation [6,12–14] in a dose–response manner [15 ]. Possible mediators include diabetes mellitus [16 ], chronic obstructive pulmonary disease/impaired lung function [17 ,18], hypertension, and heart failure – all diseases that are likely to be caused by smoking [19 ], and which in turn can induce atrial fibrillation [15 ]. In addition, &&
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www.co-cardiology.com
a
Department of Cardiology, Aalborg Atrial Fibrillation Study Group, Aalborg University Hospital, bThrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark and cUniversity of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK. Correspondence to Torben Bjerregaard Larsen, MD, PhD, FESC, Department of Cardiology, Aalborg Atrial Fibrillation Study Group, Aalborg University Hospital, Forskningens Hus, Søndre Skovvej 15, DK9100 Aalborg, Denmark. Tel: +45 99 32 81 00; fax: +45 99 32 80 99; e-mail: [email protected] Curr Opin Cardiol 2015, 30:512–517 DOI:10.1097/HCO.0000000000000205 Volume 30 Number 5 September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Smoking, atrial fibrillation, and ischemic stroke Albertsen et al.
KEY POINTS Smoking and atrial fibrillation are two worldwide epidemics that converge as smoking precipitates atrial fibrillation. Patients who smoke represent a high-risk population from many perspectives related to the growing epidemic of atrial fibrillation, including the risk of a thromboembolic event following a diagnosis of atrial fibrillation. Smoking is included as a major component in several risk prediction models concerning atrial fibrillation. Preventive approaches targeting this high-risk population are paramount. Smoking cessation services and individualized antithrombotic treatment should be provided in every cardiovascular clinical setting.
smoking also causes structural remodeling of the myocardium, which has direct toxic effects on the conductive properties and may lead to atrial fibrillation [15 ,20]. Continued tobacco use is also associated with atrial fibrillation after catheter ablation [15 ]. &&
&&
SMOKING STATUS AND PREDICTION OF INCIDENT ATRIAL FIBRILLATION Smoking status has also proven valuable for the prediction of future atrial fibrillation. Among five other variables, smoking status is included in the Women’s Health Study Atrial Fibrillation risk prediction algorithm identifying women at higher risk for incident atrial fibrillation [21] (see Table 1 for risk prediction models covered in this article). In the Cohorts for Heart and Aging Research in Genomic Epidemiology - Atrial Fibrillation model for the prediction of incident atrial fibrillation, current smoking status is included as a component adding predictive ability independent of other traditional cardiovascular-risk predictors such as age, race, height, weight, systolic and diastolic blood pressure, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure [22 ,23]. In summary, smoking not only causes atrial fibrillation, but smoking status also aids in the identification of people at high risk of future incident atrial fibrillation. &&
REDUCING THE BURDEN How can we reduce the combined burden caused by the confluence of smoking and atrial fibrillation? Two approaches are immediately evident. First, as
smoking predisposes to atrial fibrillation, primary prevention of atrial fibrillation is partly achieved through smoking cessation. Secondly, improving the identification of patients with established atrial fibrillation who stand to gain most from anticoagulant treatment is essential. This is currently provided through the use of risk stratification models used for the prediction of thromboembolic events and anticoagulant-related bleeding in patients with incident atrial fibrillation. The stratification models used for the prediction of thromboembolic events will be briefly introduced in the following section.
ATRIAL FIBRILLATION, STROKE-RISK STRATIFICATION, AND ANTITHROMBOTIC STRATEGIES: WHAT IS KNOWN ALREADY? Anticoagulant therapy, when used appropriately, has a dramatic effect on the prevention of thromboembolic events – preventing approximately twothirds of all atrial fibrillation-related strokes [24]. Although anticoagulant treatment is highly preventive, not all patients stand to gain. Despite the overall advantage in reducing the risk of stroke, anticoagulant therapy is a double-edged sword, with an inherent risk of potentially fatal bleeding.
RISK STRATIFICATION TOOLS FOR STROKE RISK IN ATRIAL FIBRILLATION The risk of thromboembolic events is not homogeneous, but varies according to the presence or absence of various lifestyle and clinical-risk factors. These risk factors have formed the basis for stroke-risk stratification schemes and clinical practice guidelines for stroke prevention in patients with atrial fibrillation. The purpose of these schemes is to identify patients who could benefit from oral anticoagulation. In recent international guidelines [25,26], the CHA2DS2-VASc score [Cardiac failure or dysfunction, Hypertension, Age 75 (doubled), Diabetes, Stroke (doubled)-Vascular disease, Age 65–74 and Sex category (Female)] score [27] is recommended as a risk stratification tool for all patients with atrial fibrillation. It is advocated that all patients with a single risk factor from the CHA2DS2-VASc score (except women with female sex as their only risk factor) should be considered for preventive anticoagulant treatment. Despite these clear guideline recommendations, many atrial fibrillation patients do not receive oral anticoagulation as often as is clinically indicated [4 ,28 ]. It has been suggested that physicians may overestimate bleeding risk from oral anticoagulation and underestimate its benefits in stroke prevention [29].
0268-4705 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
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www.co-cardiology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
513
514
www.co-cardiology.com Age 65–74 years
Ethnicity
Cholesterol:HDL ratio BMI
Myocardial infarction
Left ventricular hypertrophy by electrocardiogram PR interval (199 versus 120 to 199)
Race (nonwhite)
Tobacco use within 2 years
Medical history (more than two comorbidities including hypertension, diabetes, coronary heart disease/myocardial infarction, peripheral arterial disease, congestive heart failure, previous stroke, pulmonary disease and hepatic or renal disease) Treatment (interacting drugs, e.g., amiodarone for rhythm control)
Age (2 drinks per day Ever smoking status
Systolic blood pressure (20 mm Hg increment) Diastolic blood pressure (10 mm Hg increment) Smoking (current)
Type 1 or 2 diabetes
Age >75 years
Heart failure
Systolic blood pressure
Weight (15 kg increment)
Treated hypertension
Hypertension
Congestive heart failure
Female sex
Height
Height (10 cm increment)
Sex
Age
Diet, Cancer and Healthd
Deprivation score
Weight
QStrokec
Antihypertensive medication use Diabetes
Age
Race (white)
WHS-AFb
Age (5 year increment)
CHARGE-AFa
Table 1. Components of various risk prediction models for use in patients with atrial fibrillation that include information on smoking habits
Prevention
Volume 30 Number 5 September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Smoking, atrial fibrillation, and ischemic stroke Albertsen et al.
When oral anticoagulation with adjusted-dose vitamin K antagonists is used, the quality of anticoagulation control, as reflected by the time in therapeutic range of the international normalized ratio (INR), is an important determinant of risk of thromboembolism and bleeding [30,31]. The Sex [female], Age
Smoking, atrial fibrillation, and ischemic stroke: a confluence of epidemics Ida Ehlers Albertsen a, Thure Filskov Overvad b, Gregory Y.H. Lip b,c, and Torben Bjerregaard Larsen a,c
Purpose of review Smoking and atrial fibrillation are major contemporary health concerns. They commonly coexist and are frequent causes of ischemic stroke. The purpose of this article is to describe recent scientific investigations about smoking, atrial fibrillation, and ischemic stroke, with a primary focus on prevention. Recent findings Smoking predisposes to atrial fibrillation and is useful for the prediction of future atrial fibrillation. Several recent risk prediction models for adverse events associated with atrial fibrillation include smoking as a component. Smoking status identifies patients at high risk of incident atrial fibrillation, adverse events in an emergency ward after admission with atrial fibrillation, thromboembolic events following a diagnosis of atrial fibrillation, and potentially poor control of vitamin K antagonist treatment. Summary From multiple perspectives of atrial fibrillation, patients who smoke represent a high-risk population. Appropriate preventive measures targeting this endangered population are paramount. These include smoking cessation, appropriate care in the emergency ward, and careful selection of the optimal antithrombotic strategy to reduce the major burden of ischemic stroke attributed to the confluence of the epidemics of smoking and atrial fibrillation. Keywords atrial fibrillation, prevention, smoking, stroke
INTRODUCTION Atrial fibrillation is the most common cardiac arrhythmia and a frequent and devastating cause of morbidity and mortality from cardioembolic stroke [1,2]. The prevalence of atrial fibrillation has taken a daunting rise. It is expected to reach pandemic proportions due to the continued aging of the general population [3 ]. Atrial fibrillation may be prevalent in up to 1/3 of all patients with incident ischemic stroke [4 ]. One potential factor involved in the pathogenesis of atrial fibrillation is smoking [5–8]. Smoking causes a broad range of oncogenic [9], cardiovascular [10], cerebrovascular [10], and respiratory disease. Unfortunately, smoking continues to be a dominant health hazard worldwide and responsible for major healthcare costs [11]. The purpose of the current article is to describe recent scientific investigations linking the epidemics of smoking, atrial fibrillation, and ischemic stroke, with a primary focus on prevention strategies. &&
SMOKING AND PRECIPITATION OF ATRIAL FIBRILLATION Smoking predisposes to atrial fibrillation [6,12–14] in a dose–response manner [15 ]. Possible mediators include diabetes mellitus [16 ], chronic obstructive pulmonary disease/impaired lung function [17 ,18], hypertension, and heart failure – all diseases that are likely to be caused by smoking [19 ], and which in turn can induce atrial fibrillation [15 ]. In addition, &&
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&
www.co-cardiology.com
a
Department of Cardiology, Aalborg Atrial Fibrillation Study Group, Aalborg University Hospital, bThrombosis Research Unit, Department of Clinical Medicine, Faculty of Health, Aalborg University, Aalborg, Denmark and cUniversity of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, UK. Correspondence to Torben Bjerregaard Larsen, MD, PhD, FESC, Department of Cardiology, Aalborg Atrial Fibrillation Study Group, Aalborg University Hospital, Forskningens Hus, Søndre Skovvej 15, DK9100 Aalborg, Denmark. Tel: +45 99 32 81 00; fax: +45 99 32 80 99; e-mail: [email protected] Curr Opin Cardiol 2015, 30:512–517 DOI:10.1097/HCO.0000000000000205 Volume 30 Number 5 September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Smoking, atrial fibrillation, and ischemic stroke Albertsen et al.
KEY POINTS Smoking and atrial fibrillation are two worldwide epidemics that converge as smoking precipitates atrial fibrillation. Patients who smoke represent a high-risk population from many perspectives related to the growing epidemic of atrial fibrillation, including the risk of a thromboembolic event following a diagnosis of atrial fibrillation. Smoking is included as a major component in several risk prediction models concerning atrial fibrillation. Preventive approaches targeting this high-risk population are paramount. Smoking cessation services and individualized antithrombotic treatment should be provided in every cardiovascular clinical setting.
smoking also causes structural remodeling of the myocardium, which has direct toxic effects on the conductive properties and may lead to atrial fibrillation [15 ,20]. Continued tobacco use is also associated with atrial fibrillation after catheter ablation [15 ]. &&
&&
SMOKING STATUS AND PREDICTION OF INCIDENT ATRIAL FIBRILLATION Smoking status has also proven valuable for the prediction of future atrial fibrillation. Among five other variables, smoking status is included in the Women’s Health Study Atrial Fibrillation risk prediction algorithm identifying women at higher risk for incident atrial fibrillation [21] (see Table 1 for risk prediction models covered in this article). In the Cohorts for Heart and Aging Research in Genomic Epidemiology - Atrial Fibrillation model for the prediction of incident atrial fibrillation, current smoking status is included as a component adding predictive ability independent of other traditional cardiovascular-risk predictors such as age, race, height, weight, systolic and diastolic blood pressure, use of antihypertensive medication, diabetes, and history of myocardial infarction and heart failure [22 ,23]. In summary, smoking not only causes atrial fibrillation, but smoking status also aids in the identification of people at high risk of future incident atrial fibrillation. &&
REDUCING THE BURDEN How can we reduce the combined burden caused by the confluence of smoking and atrial fibrillation? Two approaches are immediately evident. First, as
smoking predisposes to atrial fibrillation, primary prevention of atrial fibrillation is partly achieved through smoking cessation. Secondly, improving the identification of patients with established atrial fibrillation who stand to gain most from anticoagulant treatment is essential. This is currently provided through the use of risk stratification models used for the prediction of thromboembolic events and anticoagulant-related bleeding in patients with incident atrial fibrillation. The stratification models used for the prediction of thromboembolic events will be briefly introduced in the following section.
ATRIAL FIBRILLATION, STROKE-RISK STRATIFICATION, AND ANTITHROMBOTIC STRATEGIES: WHAT IS KNOWN ALREADY? Anticoagulant therapy, when used appropriately, has a dramatic effect on the prevention of thromboembolic events – preventing approximately twothirds of all atrial fibrillation-related strokes [24]. Although anticoagulant treatment is highly preventive, not all patients stand to gain. Despite the overall advantage in reducing the risk of stroke, anticoagulant therapy is a double-edged sword, with an inherent risk of potentially fatal bleeding.
RISK STRATIFICATION TOOLS FOR STROKE RISK IN ATRIAL FIBRILLATION The risk of thromboembolic events is not homogeneous, but varies according to the presence or absence of various lifestyle and clinical-risk factors. These risk factors have formed the basis for stroke-risk stratification schemes and clinical practice guidelines for stroke prevention in patients with atrial fibrillation. The purpose of these schemes is to identify patients who could benefit from oral anticoagulation. In recent international guidelines [25,26], the CHA2DS2-VASc score [Cardiac failure or dysfunction, Hypertension, Age 75 (doubled), Diabetes, Stroke (doubled)-Vascular disease, Age 65–74 and Sex category (Female)] score [27] is recommended as a risk stratification tool for all patients with atrial fibrillation. It is advocated that all patients with a single risk factor from the CHA2DS2-VASc score (except women with female sex as their only risk factor) should be considered for preventive anticoagulant treatment. Despite these clear guideline recommendations, many atrial fibrillation patients do not receive oral anticoagulation as often as is clinically indicated [4 ,28 ]. It has been suggested that physicians may overestimate bleeding risk from oral anticoagulation and underestimate its benefits in stroke prevention [29].
0268-4705 Copyright ß 2015 Wolters Kluwer Health, Inc. All rights reserved.
&
&
www.co-cardiology.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
513
514
www.co-cardiology.com Age 65–74 years
Ethnicity
Cholesterol:HDL ratio BMI
Myocardial infarction
Left ventricular hypertrophy by electrocardiogram PR interval (199 versus 120 to 199)
Race (nonwhite)
Tobacco use within 2 years
Medical history (more than two comorbidities including hypertension, diabetes, coronary heart disease/myocardial infarction, peripheral arterial disease, congestive heart failure, previous stroke, pulmonary disease and hepatic or renal disease) Treatment (interacting drugs, e.g., amiodarone for rhythm control)
Age (2 drinks per day Ever smoking status
Systolic blood pressure (20 mm Hg increment) Diastolic blood pressure (10 mm Hg increment) Smoking (current)
Type 1 or 2 diabetes
Age >75 years
Heart failure
Systolic blood pressure
Weight (15 kg increment)
Treated hypertension
Hypertension
Congestive heart failure
Female sex
Height
Height (10 cm increment)
Sex
Age
Diet, Cancer and Healthd
Deprivation score
Weight
QStrokec
Antihypertensive medication use Diabetes
Age
Race (white)
WHS-AFb
Age (5 year increment)
CHARGE-AFa
Table 1. Components of various risk prediction models for use in patients with atrial fibrillation that include information on smoking habits
Prevention
Volume 30 Number 5 September 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Smoking, atrial fibrillation, and ischemic stroke Albertsen et al.
When oral anticoagulation with adjusted-dose vitamin K antagonists is used, the quality of anticoagulation control, as reflected by the time in therapeutic range of the international normalized ratio (INR), is an important determinant of risk of thromboembolism and bleeding [30,31]. The Sex [female], Age
