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      Association between exercise habits and stroke, heart failure, and mortality in Korean patients with incident atrial fibrillation: A nationwide population-based cohort study

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          Abstract

          Background

          There is a paucity of information about cardiovascular outcomes related to exercise habit change after a new diagnosis of atrial fibrillation (AF). We investigated the association between exercise habits after a new AF diagnosis and ischemic stroke, heart failure (HF), and all-cause death.

          Methods and findings

          This is a nationwide population-based cohort study using data from the Korea National Health Insurance Service. A retrospective analysis was performed for 66,692 patients with newly diagnosed AF between 2010 and 2016 who underwent 2 serial health examinations within 2 years before and after their AF diagnosis. Individuals were divided into 4 categories according to performance of regular exercise, which was investigated by a self-reported questionnaire in each health examination, before and after their AF diagnosis: persistent non-exercisers (30.5%), new exercisers (17.8%), exercise dropouts (17.4%), and exercise maintainers (34.2%). The primary outcomes were incidence of ischemic stroke, HF, and all-cause death. Differences in baseline characteristics among groups were balanced considering demographics, comorbidities, medications, lifestyle behaviors, and income status. The risks of the outcomes were computed by weighted Cox proportional hazards models with inverse probability of treatment weighting (IPTW) during a mean follow-up of 3.4 ± 2.0 years. The new exerciser and exercise maintainer groups were associated with a lower risk of HF compared to the persistent non-exerciser group: the hazard ratios (HRs) (95% CIs) were 0.95 (0.90–0.99) and 0.92 (0.88–0.96), respectively ( p < 0.001). Also, performing exercise any time before or after AF diagnosis was associated with a lower risk of mortality compared to persistent non-exercising: the HR (95% CI) was 0.82 (0.73–0.91) for new exercisers, 0.83 (0.74–0.93) for exercise dropouts, and 0.61 (0.55–0.67) for exercise maintainers ( p < 0.001). For ischemic stroke, the estimates of HRs were 10%–14% lower in patients of the exercise groups, yet differences were statistically insignificant ( p = 0.057). Energy expenditure of 1,000–1,499 MET-min/wk (regular moderate exercise 170–240 min/wk) was consistently associated with a lower risk of each outcome based on a subgroup analysis of the new exerciser group. Study limitations include recall bias introduced due to the nature of the self-reported questionnaire and restricted external generalizability to other ethnic groups.

          Conclusions

          Initiating or continuing regular exercise after AF diagnosis was associated with lower risks of HF and mortality. The promotion of exercise might reduce the future risk of adverse outcomes in patients with AF.

          Abstract

          Using a population-based cohort study, Dr. Choi and colleagues studied patients with atrial fibrillation to determine whether their exercise habits were associated with occurrence of ischemic stroke, heart failure, and all-cause mortality.

          Author summary

          Why was this study done?
          • Atrial fibrillation (AF) is associated with an increased risk of stroke, heart failure, and death. As AF and its related healthcare burden are expected to surge, integrated management of AF is advocated as part of holistic care.

          • Exercise has been established to benefit AF-related outcomes, including symptoms, incidence, recurrence, burden, and quality of life. However, there are no current data providing the association between exercise and cardiovascular morbidities in patients with AF.

          What did the researchers do and find?
          • We performed a retrospective analysis of 66,692 patients with newly diagnosed AF who underwent 2 serial health examinations before and after their AF diagnosis from 2010 to 2016 using data from the Korea National Health Insurance Service.

          • Individuals self-reported exercise status by a questionnaire included in each health examination and were categorized into 4 groups according to their change of exercise status from before to after their AF diagnosis. We investigated and compared the incidences of ischemic stroke, heart failure, and all-cause death across the groups.

          • Initiating or continuing regular exercise after a diagnosis of AF was associated with a 5%–8% lower risk of HF and 17%–39% lower risk of mortality than being a persistent non-exerciser. For ischemic stroke, the estimated hazard ratios were 10%–14% lower in patients in the exercise group, yet statistical significance was undetermined.

          What do these findings mean?
          • We suggest the potential benefits of exercise as a lifestyle intervention for cardiovascular outcomes in AF patients by demonstrating the association. The promotion of exercise might reduce the future risk of adverse outcomes in patients with AF.

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          Most cited references61

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            Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples

            The propensity score is a subject's probability of treatment, conditional on observed baseline covariates. Conditional on the true propensity score, treated and untreated subjects have similar distributions of observed baseline covariates. Propensity-score matching is a popular method of using the propensity score in the medical literature. Using this approach, matched sets of treated and untreated subjects with similar values of the propensity score are formed. Inferences about treatment effect made using propensity-score matching are valid only if, in the matched sample, treated and untreated subjects have similar distributions of measured baseline covariates. In this paper we discuss the following methods for assessing whether the propensity score model has been correctly specified: comparing means and prevalences of baseline characteristics using standardized differences; ratios comparing the variance of continuous covariates between treated and untreated subjects; comparison of higher order moments and interactions; five-number summaries; and graphical methods such as quantile–quantile plots, side-by-side boxplots, and non-parametric density plots for comparing the distribution of baseline covariates between treatment groups. We describe methods to determine the sampling distribution of the standardized difference when the true standardized difference is equal to zero, thereby allowing one to determine the range of standardized differences that are plausible with the propensity score model having been correctly specified. We highlight the limitations of some previously used methods for assessing the adequacy of the specification of the propensity-score model. In particular, methods based on comparing the distribution of the estimated propensity score between treated and untreated subjects are uninformative. Copyright © 2009 John Wiley & Sons, Ltd.
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              Worldwide epidemiology of atrial fibrillation: a Global Burden of Disease 2010 Study.

              The global burden of atrial fibrillation (AF) is unknown. We systematically reviewed population-based studies of AF published from 1980 to 2010 from the 21 Global Burden of Disease regions to estimate global/regional prevalence, incidence, and morbidity and mortality related to AF (DisModMR software). Of 377 potential studies identified, 184 met prespecified eligibility criteria. The estimated number of individuals with AF globally in 2010 was 33.5 million (20.9 million men [95% uncertainty interval (UI), 19.5-22.2 million] and 12.6 million women [95% UI, 12.0-13.7 million]). Burden associated with AF, measured as disability-adjusted life-years, increased by 18.8% (95% UI, 15.8-19.3) in men and 18.9% (95% UI, 15.8-23.5) in women from 1990 to 2010. In 1990, the estimated age-adjusted prevalence rates of AF (per 100 000 population) were 569.5 in men (95% UI, 532.8-612.7) and 359.9 in women (95% UI, 334.7-392.6); the estimated age-adjusted incidence rates were 60.7 per 100 000 person-years in men (95% UI, 49.2-78.5) and 43.8 in women (95% UI, 35.9-55.0). In 2010, the prevalence rates increased to 596.2 (95% UI, 558.4-636.7) in men and 373.1 (95% UI, 347.9-402.2) in women; the incidence rates increased to 77.5 (95% UI, 65.2-95.4) in men and 59.5 (95% UI, 49.9-74.9) in women. Mortality associated with AF was higher in women and increased by 2-fold (95% UI, 2.0-2.2) and 1.9-fold (95% UI, 1.8-2.0) in men and women, respectively, from 1990 to 2010. There was evidence of significant regional heterogeneity in AF estimations and availability of population-based data. These findings provide evidence of progressive increases in overall burden, incidence, prevalence, and AF-associated mortality between 1990 and 2010, with significant public health implications. Systematic, regional surveillance of AF is required to better direct prevention and treatment strategies.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: SoftwareRole: Validation
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Validation
                Role: ConceptualizationRole: Formal analysisRole: Methodology
                Role: ConceptualizationRole: Formal analysisRole: Methodology
                Role: ConceptualizationRole: Formal analysisRole: Methodology
                Role: SupervisionRole: ValidationRole: Writing – review & editing
                Role: ConceptualizationRole: SupervisionRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                8 June 2021
                June 2021
                : 18
                : 6
                : e1003659
                Affiliations
                [1 ] Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
                [2 ] Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
                [3 ] Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea
                [4 ] Department of Medical Statistics, College of Medicine, Catholic University of Korea, Seoul, Republic of Korea
                [5 ] Liverpool Centre for Cardiovascular Science, University of Liverpool and Liverpool Heart and Chest Hospital, Liverpool, United Kingdom
                [6 ] Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
                University of Oxford, UNITED KINGDOM
                Author notes

                I have read the journal’s policy and the authors of this manuscript have the following competing interests: HJA, SRL, KDH, JHJ, JHL, JPY, SK, SO: None to disclose. EKC: Research grants from Bayer, BMS/Pfzer, Biosense Webster, Chong Kun Dang, Daiichi-Sankyo, Samjinpharm, Sanof-Aventis, Seers Technology, Skylabs, and Yuhan. GYHL: Consultant for Bayer/Janssen, BMS/Pfzer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo. Speaker for Bayer, BMS/Pfzer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo. No fees are received personally. The external funders and sponsors of the study had no role in study design and conduct of the study; in the collection, analysis, and interpretation of the data; in the preparation, review, or approval of the manuscript; or in the decision to submit the manuscript for publication.

                Author information
                https://orcid.org/0000-0003-3590-0378
                https://orcid.org/0000-0002-0411-6372
                https://orcid.org/0000-0002-6096-1263
                https://orcid.org/0000-0002-8920-8777
                https://orcid.org/0000-0002-9450-5653
                https://orcid.org/0000-0002-4791-6855
                https://orcid.org/0000-0002-2504-9615
                https://orcid.org/0000-0002-7566-1626
                Article
                PMEDICINE-D-20-03103
                10.1371/journal.pmed.1003659
                8219164
                34101730
                a932bf03-2231-4c3b-b0c1-7a42937577b8
                © 2021 Ahn et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 June 2020
                : 18 May 2021
                Page count
                Figures: 3, Tables: 2, Pages: 19
                Funding
                Funded by: Korea Medical Device Development Fund
                Award ID: Project Number: HI20C1662
                Funded by: Korea National Research Foundation
                Award ID: Grant 2020R1F1A106740
                This work and EKC, as a representative of all authors (HJA, SRL, KDH, JHJ, JHL, JPY, SK, SO, and GYHL), was supported by the Korea Medical Device Development Fund grant funded by the Korea government (the Ministry of Science and ICT, the Ministry of Trade, Industry and Energy, the Ministry of Health & Welfare, Republic of Korea, the Ministry of Food and Drug Safety) (Project Number: HI20C1662), and by the Korea National Research Foundation funded by the Ministry of Education, Science and Technology (Grant 2020R1F1A106740). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Public and Occupational Health
                Physical Activity
                Physical Fitness
                Exercise
                Medicine and Health Sciences
                Sports and Exercise Medicine
                Exercise
                Biology and Life Sciences
                Sports Science
                Sports and Exercise Medicine
                Exercise
                Medicine and Health Sciences
                Cardiology
                Arrhythmia
                Atrial Fibrillation
                Medicine and Health Sciences
                Medical Conditions
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Medicine and Health Sciences
                Cardiology
                Cardiovascular Medicine
                Cardiovascular Diseases
                Cardiovascular Disease Risk
                Medicine and Health Sciences
                Medical Conditions
                Cerebrovascular Diseases
                Stroke
                Ischemic Stroke
                Medicine and Health Sciences
                Neurology
                Cerebrovascular Diseases
                Stroke
                Ischemic Stroke
                Medicine and Health Sciences
                Vascular Medicine
                Stroke
                Ischemic Stroke
                Medicine and Health Sciences
                Cardiology
                Heart Failure
                Medicine and Health Sciences
                Cardiology
                Myocardial Infarction
                Medicine and Health Sciences
                Pulmonology
                Chronic Obstructive Pulmonary Disease
                Biology and Life Sciences
                Biochemistry
                Bioenergetics
                Custom metadata
                vor-update-to-uncorrected-proof
                2021-06-22
                All relevant data are within the manuscript and its Supporting Information files.

                Medicine
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