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The Reply

  • Antonios Vitalis
    Affiliations
    Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, United Kingdom

    Institute of Cardiovascular Sciences, University of Birmingham, United Kingdom
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  • Alena Shantsila
    Affiliations
    Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, United Kingdom
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  • Gregory Y.H. Lip
    Correspondence
    Requests for reprints should be addressed to Gregory Y.H. Lip, MD, FRCP, Price-Evans Professor of Cardiovascular Medicine, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7.
    Affiliations
    Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart & Chest Hospital, United Kingdom

    Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Denmark
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      We are grateful to Kawada for the interest in our paper.
      • Vitalis A
      • Shantsila A
      • Proietti M
      • et al.
      Peripheral arterial disease in patients with atrial fibrillation: the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study.
      Peripheral arterial disease is an independent risk factor for the development of atrial fibrillation.
      • Lin L-Y
      • Lee C-H
      • Yu C-C
      • et al.
      Risk factors and incidence of ischemic stroke in Taiwanese with nonvalvular atrial fibrillation—A nation wide database analysis.
      • Rasmussen LH
      • Larsen TB
      • Due KM
      • Tjønneland A
      • Overvad K
      • Lip GYH.
      Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet, Cancer and Health Cohort study.
      • O'Neal WT
      • Efird JT
      • Nazarian S
      • Alonso A
      • Heckbert SR
      • Soliman EZ.
      Peripheral arterial disease and risk of atrial fibrillation and stroke: the Multi-Ethnic Study of Atherosclerosis.
      The coexistence of peripheral arterial disease and atrial fibrillation have significant additive effects on the increased risk of mortality, cardiac, and cerebrovascular complications.
      • Lin L-Y
      • Lee C-H
      • Yu C-C
      • et al.
      Risk factors and incidence of ischemic stroke in Taiwanese with nonvalvular atrial fibrillation—A nation wide database analysis.
      The exact mechanisms underlying this association merits further investigation. Indeed, atrial fibrillation and peripheral arterial disease share several common risk factors such as hypertension, diabetes, and coronary artery disease. Various studies (including ours), have shown that despite controlling for those risk factors the impact of peripheral arterial disease on atrial fibrillation patients remains significant.
      • Heeringa J
      • Van Der Kuip DAM
      • Hofman A
      • et al.
      Subclinical atherosclerosis and risk of atrial fibrillation: the Rotterdam study.
      As pointed out by Kawada, an increased burden of peripheral arterial disease, indicated by lower ankle-brachial pressure index readings parallels a higher incidence of atrial fibrillation. This accords with previous reports that prevalent atrial fibrillation is linked to the presence of systemic atherosclerosis and burden of atherosclerotic disease.
      • Heeringa J
      • Van Der Kuip DAM
      • Hofman A
      • et al.
      Subclinical atherosclerosis and risk of atrial fibrillation: the Rotterdam study.
      ,
      • Proietti M
      • Calvieri C
      • Malatino L
      • et al.
      Relationship between carotid intima-media thickness and non valvular atrial fibrillation type.
      Both atrial fibrillation and peripheral arterial disease are characterized by endothelial dysfunction, hypercoagulability, and chronic inflammation.
      • Proietti M
      • Farcomeni A.
      Association between peripheral artery disease and incident risk of atrial fibrillation: strong evidence coming from population-based cohort studies.
      We would like to thank Kawada for emphasizing the need for meticulous risk factor modification, including smoking cessation, in patients with atrial fibrillation. We agree that it is important to follow a systematic and holistic approach to the management of atrial fibrillation patients, as it is not only a factor associated with peripheral arterial disease but also a major cause of thromboembolism, a potentially disabling or even life-threatening complication of peripheral arterial disease.
      In order to effectively carry out this holistic approach, healthcare providers should follow the ABC (Atrial fibrillation Better Care) pathway (ie, Anticoagulation/Avoid stroke, Better symptom control, Cardiovascular risk factors and Concomitant diseases),
      • Hindricks G
      • Potpara T
      • Dagres N
      • et al.
      2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC.
      ,
      • Lip GYH
      The ABC pathway: an integrated approach to improve AF management.
      the adherence of which has been associated with improved clinical outcomes.

      Romiti GF, Pastori D, Rivera-Caravaca JM, et al. Adherence to the “Atrial Fibrillation Better Care” (ABC) pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients [e-pub ahead of print]. Thromb Haemost. doi:10.1055/a-1515-9630

      ,
      • Yoon M
      • Yang P-S
      • Jang E
      • et al.
      Improved population-based clinical outcomes of patients with atrial fibrillation by compliance with the simple ABC (Atrial Fibrillation Better Care) pathway for integrated care management: a nationwide cohort study.
      Given that atrial fibrillation is also commonly asymptomatic, appropriate screening should be considered in peripheral arterial disease patients, given the worse outcomes with such patients.

      Sun W, Freedman B, Martinez C, Wallenhorst C, Yan BP. Atrial fibrillation detected by single time-point handheld electrocardiogram screening and the risk of ischemic stroke [e-pub ahead of print]. Thromb Haemost. doi:10.1055/a-1588-8867

      ,

      Wallenhorst C, Martinez C, Freedman B. Risk of ischemic stroke in asymptomatic atrial fibrillation incidentally detected in primary care compared with other clinical presentations [e-pub ahead of print]. Thromb Haemost. doi:10.1055/a-1541-3885

      Indeed, symptoms suggestive of peripheral arterial disease in atrial fibrillation patients clearly merit further evaluation. Our study highlights the need for assessment for coexisting peripheral arterial disease and adequate risk factor modification in atrial fibrillation patients.

      References

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        • Shantsila A
        • Proietti M
        • et al.
        Peripheral arterial disease in patients with atrial fibrillation: the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) study.
        Am J Med. 2021;134:514-518;
        • Lin L-Y
        • Lee C-H
        • Yu C-C
        • et al.
        Risk factors and incidence of ischemic stroke in Taiwanese with nonvalvular atrial fibrillation—A nation wide database analysis.
        Atherosclerosis. 2011; 217: 292-295
        • Rasmussen LH
        • Larsen TB
        • Due KM
        • Tjønneland A
        • Overvad K
        • Lip GYH.
        Impact of vascular disease in predicting stroke and death in patients with atrial fibrillation: the Danish Diet, Cancer and Health Cohort study.
        J Thromb Haemost. 2011; 9: 1301-1307
        • O'Neal WT
        • Efird JT
        • Nazarian S
        • Alonso A
        • Heckbert SR
        • Soliman EZ.
        Peripheral arterial disease and risk of atrial fibrillation and stroke: the Multi-Ethnic Study of Atherosclerosis.
        J Am Heart Assoc. 2014; 3 (e001270-e001270)
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        • Van Der Kuip DAM
        • Hofman A
        • et al.
        Subclinical atherosclerosis and risk of atrial fibrillation: the Rotterdam study.
        Arch Intern Med. 2007; 167: 382-387
        • Proietti M
        • Calvieri C
        • Malatino L
        • et al.
        Relationship between carotid intima-media thickness and non valvular atrial fibrillation type.
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        • Proietti M
        • Farcomeni A.
        Association between peripheral artery disease and incident risk of atrial fibrillation: strong evidence coming from population-based cohort studies.
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        • Hindricks G
        • Potpara T
        • Dagres N
        • et al.
        2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC.
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        The ABC pathway: an integrated approach to improve AF management.
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      1. Romiti GF, Pastori D, Rivera-Caravaca JM, et al. Adherence to the “Atrial Fibrillation Better Care” (ABC) pathway in patients with atrial fibrillation: impact on clinical outcomes-a systematic review and meta-analysis of 285,000 patients [e-pub ahead of print]. Thromb Haemost. doi:10.1055/a-1515-9630

        • Yoon M
        • Yang P-S
        • Jang E
        • et al.
        Improved population-based clinical outcomes of patients with atrial fibrillation by compliance with the simple ABC (Atrial Fibrillation Better Care) pathway for integrated care management: a nationwide cohort study.
        Thromb Haemost. 2019; 119: 1695-1703
      2. Sun W, Freedman B, Martinez C, Wallenhorst C, Yan BP. Atrial fibrillation detected by single time-point handheld electrocardiogram screening and the risk of ischemic stroke [e-pub ahead of print]. Thromb Haemost. doi:10.1055/a-1588-8867

      3. Wallenhorst C, Martinez C, Freedman B. Risk of ischemic stroke in asymptomatic atrial fibrillation incidentally detected in primary care compared with other clinical presentations [e-pub ahead of print]. Thromb Haemost. doi:10.1055/a-1541-3885