Physical Activity and Incidence of Atrial Fibrillation - Systematic Review and Meta-Analysis

Abstract

Background:

The relationship between exercise and atrial fibrillation (AF) is controversial.

Objectives:

To analyze the effects of physical activity on the incidence of atrial fibrillation using systematic review and meta-analysis.

Methods:

Systematic review and meta-analysis of studies that relate physical exercise and atrial fibrillation. The following databases were searched: PubMed, BVS Saúde and Cochrane. The following descriptors were used: "atrial fibrillation", "exercise", "physical activity" and "exercise therapy". All prospective, retrospective, cross-sectional and cohort studies were investigated. All statistical analyzes were provided using Review Manager 5.3 to provide the mean difference (MD) and relative risk (RR) ratio with 95% confidence intervals (95% CI). The statistical method of heterogeneity index was used to assess heterogeneity. Level of significance was 5%.

Results:

Combined analysis of 11 studies totaling 276,323 participants aged between 12 and 90 years did not suggest a significant increase in AF in individuals submitted to physical exercise (RR = 0.914, 95% CI = 0.833-1.003, heterogeneity: p < 0.001).

Conclusions:

Physical exercise, lato sensu, without stratification by intensity, sex or age does not seem to be associated with an increase of atrial fibrillation.

Keywords:
Exercise; Atrial Fibrillation; Asthma; Exercise Therapy; Cardiorespiratory Fitness; Review; Meta-Analysis as Topic

Introduction

Atrial fibrillation (AF) is the most frequent arrhythmia occurring in 0.1% - 4.0% of the population and the prevalence increased to 7.2% in patients aged ≥ 65, with an annual increase of 1.6% in patients aged ≥ 75. Characterized by loss of atrial contraction capacity (loss of atrial systole), AF is responsible for almost one-third of hospitalizations for heart rhythm disturbances. It may present high morbidity and mortality due to hemodynamic involvement, cardiomyopathy due to tachycardia and thromboembolic phenomena.

Risk factors for the development of AF include cardiac and non-cardiac factors such as age, structural heart disease, hypertension, diabetes mellitus and hyperthyroidism.¹ The change in cardiac function is associated with increased mortality and risk of infarction, decreased quality of life, decreased exercise capacity and impaired left ventricular function.²

It is known that physical activity is an effective adjunct in the treatment of various types of cardiovascular diseases. However, patients with AF present decreased tolerance to exercise, dyspnea and palpitations.³ Some studies report a J or U curve between the correlation of intensity of physical activity and AF.^4-10 On the other hand, some studies show a linear correlation between the amount of physical activity and the development of AF.^11-14

Considering the regular practice of physical activity as a cardiovascular benefit and literature inconsistency about its potential arrhythmogenic effect, the objective of this study was to analyze the effects of physical activity on the incidence of AF.

Methods

Data source and search

In order to ensure a review of studies on the effects of physical exercise on the development of atrial fibrillation, we searched the following databases: PubMed, BVS Health and Cochrane. The following descriptors were used: “atrial fibrillation”, “exercise”, “physical activity” and “exercise therapy”. The search was limited to articles published in English whose full texts were reviewed. We used prospective, retrospective, cross-sectional and cohort studies. Data collection took place between September and October 2017 and data analysis was performed between October and December 2017. References in all articles included were examined for other relevant publications.

Participants were patients without AF who underwent physical exercise and were followed up. Figure 1 shows the flowchart of the meta-analysis selection process according to the Jadad quality scale.

Figure 1
Selection process of studies.

Criteria for data inclusion and extraction

The inclusion criteria were as follows: (1) study design: all cohort studies, prospective, cross-sectional, observational and randomized clinical trials with patients who performed physical exercises and the development of AF. The studies were excluded from the analysis if: (1) they included patients with previous atrial fibrillation, (2) they included athletes and/or patients submitted to vigorous physical exercise (3) they could not extract concrete data from published results, such as comments, letters, cases, abstracts, reviews, experimental studies and animal studies, (4) the results were not clearly reported. Screening, selection, data extraction and risk of bias evaluation were performed independently and duplicated by two researchers and, ultimately, the potential of disagreement and disagreement was resolved by the corresponding author.

Quality assessment

The quality assessments were evaluated by the composite scale of Jadad, a numerical score of zero meaning the weakest to seven meaning the strongest. The scale contains the following points: (1) generation of random sequence (0-2), (2) concealment of allocation (0-2), (3) blinding double (0-2), (4) description of withdrawals and drop-outs (0-1). The total score of 4-7 indicates high quality.

Methods of data synthesis and risk of bias in individual studies

All statistical analyses were provided using Review Manager 5.3 to provide the mean difference (MD) and the relative risk (RR) ratio with 95% confidence intervals (95% CI). The statistical method of heterogeneity index was used to assess heterogeneity. The level of significance was 5%.

Results

Search on the chosen databases resulted in 731 articles. After reviewing the titles, abstracts and articles repeated, a total of 11 studies were included in this systematic review.

Study and characteristics of patients

In the 11 studies included in the meta-analysis, there were 276,323 participants and, in the studies, the number of participants ranged from 2,014 to 81,317, with ages varying between 12 and 90 years. The characteristics of the studies and the patients are presented in Table 1.

Table 1
Characteristics of the studies included in the meta-analysis

Study	Design	Date	Sample size	Average age	p value adopted	Inclusion of participants
Aizer et al.4	Post-Hoc Analysis of a Randomized Clinical Trial	Randomization in 1982 with follow-up until 2001	22.071	40 to 84 years	0.01	Participants from the Physicians' Health Study aged 40-82 years in 1982 and randomized to aspirin and/or beta-carotene
Azarbal et al.5	Prospective Observational	Data from medical centers collected between 1994 and 1998	81.317	50 to 79 years	0.01	Participants from the Multi-Ethnic Study of Atherosclerosis
Bapat et al.6	Prospective Cohort	The database is from 2000 to 2002	5.793	45 to 84 years	0.05	Participants from the MESA database
Grundvold et al.7	Prospective Cohort	The database is from 1972 to 1975	2.014	40 to 59 years	0.05	Five government institutions in Oslo
Mokhayeri et al.8	Prospective Cohort	Patients followed from the years 2000 to 2011	6.487	45 to 84 years	0.05	Participants from the Multi-Ethnic Study of Atherosclerosis
Morseth et al.9	Prospective Cohort	The database is from 1986/7	4.791	12 to 67 years	0.05	Tromsø Study participants
Mozaffarian et al.10	Prospective Cohort	The database is from 1999 to 2001	5.446	≥ 65 years	0,05	Participants from the Cardiovascular Health Study
Myrstad et al.11	Transversal	The database is for 2009	2.277	65 to 90 years	0.001	Elderly men undergoing long-term sports
Qureshi et al.12	Observational	The database is from 1991 to 2009	64.561	Extracts of ages (< 40, 40-49, 50-59, ≥ 60)	0.05	Participants from the Henry Ford Exercise Testing (FIT) Project
Everett et al.13	Post-Hoc analysis of a prospective study	Beginning in 1993 and randomization in 2004	34.759	≥ 45 years	0.05	Women participating in the Women's Health Study
Williams et al.14	Cohort	Partial reevaluation of 2006 from the National Health Study of Corridors II and the National Walkers' Health Study	46.807	33 to 72 years	0.05	Participants from the national study of runners and walkers for health

Four studies were prospective (Bapat et al.,⁶ Grundvold et al.,⁷ Mokhayeri et al.,⁸ Morseth et al.,⁹ and Mozaffarian et al.,¹⁰) with mean follow-up periods of 7.7, 35, 11, 20 and 12 years, respectively; a cohort study (Williams et al.,¹⁴) with mean follow-up period of 6.2 years; a Post-Hoc analysis of a prospective study (Everett et al.,¹³), a cross-sectional study (Myrstad et al.,¹¹) and an observational study (Qureshi et al.,¹²). In addition to these, one was a Post-Hoc analysis of a Randomized Clinical Trial (Aizer et al.,⁴) with follow-up period of 12 years, and a prospective observational study (Azarbal et al.,⁵) with follow-up period of 11.5 years. From the analyzed studies, no data were identified regarding patient hospitalization.

Study of the effect of exercise on the population analyzed

Figure 2 shows the results of the meta-analysis considering the selected studies.

Figure 2
Risk of incidence of atrial fibrillation in individuals submitted to physical exercises.

The combined analysis of the studies did not suggest a significant increase in AF in subjects submitted to exercise (RR = 0.914, 95% CI = 0.833 - 1.003, heterogeneity: p < 0.001).

Discussion

Although the benefits of physical exercise on cardiovascular diseases are well described, the same does not occur in relation to AF. In this sense, the results of this meta-analysis, based on the studies analyzed, indicate that individuals who exercise are less likely to have AF.

Mozaffarian et al.,¹⁰ suggest that mild and moderate activities, especially leisure activities such as walking, are associated with a significantly lower incidence of AF. On the other hand, Drca et al.,¹⁵ observed an increased risk of the development of AF in men under 30 years of age submitted to high levels of exercise, and this does not occur at older ages. In this sense, Larsson et al.,¹⁶ suggest that maintaining a body mass index (BMI) of less than 25 kg/m², doing more than 20 minutes of exercise daily, not consuming or consuming alcohol in a mild to moderate manner (≤ 2 drinks/day for men and ≤ 1 drink/day for women) and not smoking reduce the risk of developing AF by half.

Bapat et al.,⁶ from the Multiethnic Atherosclerosis Study (MESA), associated physical activity and AF in a diverse population without clinically recognized cardiovascular disease. The results showed that neither vigorous physical activity nor total intentional exercise were independently related to AF, when adjusted for some covariates. It has even been shown that the greater the relationship of the individual with vigorous activities, the lower the risk of AF. Also, Ofman et al.,¹⁷ after meta-analysis involving 95,526 individuals, did not identify a statistically significant association between regular physical activity and increased incidence of AF. In this sense, the guidelines recommend performing at least 150 minutes of moderate physical activity or 75 minutes of intense physical activity per week.¹⁸

Patients with AF report symptoms such as decreased exercise tolerance, dyspnea, palpitations and fatigue, which directly affect the quality of life. However, physical exercise and training decrease these symptoms, and may have antiarrhythmic effects in individuals with paroxysmal AF, as well as protect against the development of AF.¹⁹ In this sense, in order to verify the effects of training on the functional capacity of individuals with AF, Luo et al.,²⁰ submitted patients with AF and patients after myocardial infarction with reduced ejection fraction to supervised training with aerobic exercises, three times a week for 36 sessions, then moving on to a home program for another two years. The training was efficient, resulting in increased cardiorespiratory capacity and peak VO₂ in both groups, but no significant differences were identified between the groups.

The international guidelines recommend the practice of physical activity in patients with AF in order to reduce their comorbidities.²¹ When Malmo et al.,²² submitted 26 AF patients to interval aerobic training, demonstrated that 12 weeks were enough to decrease arrhythmic load, besides causing a decrease in the symptoms related to AF. In addition, improvement in maximum work capacity, atrial and left ventricular function, lipid levels and quality of life were identified. For Osbak et al.,³ patients with heart disease lose muscle mass and strength due to inactivity and local hemodynamic changes. This way, developing strategies that allow the increase of muscle strength in these patients becomes important in order to increase mobility, posture and balance.

In an observational study of 20,000 adults, Proietti et al.²³ observed lower all-cause mortality in AF patients who reported being involved with regular physical activity. Still, Hegbom et al.,²⁴ and Plisiene et al.,²⁵ demonstrated improvements promoted by physical exercise in quality of life, in addition to the reduction of symptoms in patients with AF.

According to Anderson and Taylor,²⁶ physical capacity is the main clinical outcome of cardiac rehabilitation, regardless of diagnosis. For each increase of 1 Metabolic Equivalent (MET) in physical capacity, mortality rate decreases by 17% in men and 14% in women. Thus, physical exercise seems safe for patients with AF besides triggering several benefits.²⁷

Another important factor is the strong relationship between obesity and AF. According to Pathak et al.,²⁸ electrical factors and structural remodeling caused by obesity lead to the genesis and perpetuation of AF. In this sense, physical exercise, in addition to assisting in weight loss and consequent reduction in AF recurrence,^5,29 may protect against AF even in the presence of obesity.³⁰

The study by Pathack et al.,³¹ showed that an increase in cardiorespiratory fitness around 2 METs was associated with reduced density of AF. According to Abed et al.,³² decrease in AF density due to exercise can be explained by increased cardiorespiratory capacity and weight loss. Increase in each metabolic equivalent (MET) results in a 20% decrease in the risk of recurrence of AF.³² Skielboe et al.,³³ in order to verify if high-intensity exercises were more effective in decreasing AF density than low-intensity exercises, did not identify differences. However, it has been shown that high-intensity exercises do not increase risk and that patients tolerate exercises of this type.

Regular practice of physical activity has been reported to increase vagal tonus due to physiological adaptations resulting from increased cardiac work,³⁴ inducing electrical stability of the heart and maintenance of homeostasis. In this sense, low resting HR tends to represent a good health picture.³⁵ Thus, well-trained or physically conditioned individuals have lower resting HR, which suggests greater parasympathetic activity³⁶ or less sympathetic activity.³⁷ Still, Uusitalo et al.,³⁸ and Bonaduce et al.,³⁹ doing studies with longitudinal characteristics, observed a reduction in resting HR, although significant abnormalities in the autonomic indicators were not identified. Thus, Catai et al.,⁴⁰ suggest that exercise-induced bradycardia may result from intrinsic sinus node adaptations.

Like any systematic review, this study also presents limitations, since the results demonstrated here are limited by the quality of the studies available. This way, trying to make a complete literature review, all studies available, on the proposed theme, were included, and were evaluated, however, with a robust quality meta-analysis technique. In addition, the data analyzed were not stratified by type of exertion, gender or age.

Conclusion

It is concluded, therefore, that physical exercise, lato sensu, without stratification by intensity, sex or age, does not seem to be associated with an increase in the occurrence of atrial fibrillation.

• Sources of Funding
  There were no external funding sources for this study.
• Study Association
  This article is part of the thesis of postgraduate submitted by Daniel Carlos Garlipp, from Instituto de Cardiologia / Fundação Universitária de Cardiologia do Rio Grande do Sul.
• Ethics approval and consent to participate
  This study was approved by the Ethics Committee of the IC/FUC under the protocol number 1797.204. All the procedures in this study were in accordance with the 1975 Helsinki Declaration, updated in 2013. Informed consent was obtained from all participants included in the study.

Acknowledge

The postgraduate team of the Institute of Cardiology of Porto Alegre.

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Publication Dates

• Publication in this collection
  12 Aug 2019
• Date of issue
  Jul-Aug 2019

History

• Received
  18 July 2018
• Reviewed
  10 Apr 2019
• Accepted
  04 May 2019