Risk Factor Modification Reduces Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia, with approximately 5 million new cases diagnosed worldwide each year. The rising incidence of atrial fibrillation is related to the increasing prevalence of risk factors such as obesity, physical inactivity, sleep apnea, diabetes mellitus, and hypertension. Recent studies have shown that targeting these risk factors has a positive impact on reducing AF burden. The AHA Scientific Statement entitled “Lifestyle and Risk Factor Modification for Reduction of Atrial Fibrillation” reviews the current data regarding potential effects of risk factor intervention on primary (AF risk or incidence reduction) and secondary (AF burden reduction) prevention of AF.

Obesity

Prior studies have demonstrated strong associations between AF and obesity (BMI≥30 kg/m2). Data from the Framingham Heart Study showed a 1.5-fold increase in AF burden in obese patients.¹ Animal studies have shown that obese animals have larger atrial sizes, increased intra-atrial pressure, and conduction slowing. Obesity has also been shown to increase pericardial and epicardial fat, creating a cardiac substrate at increased risk for AF.²

Given this potential causal relationship between obesity and AF, several studies have investigated weight loss as a treatment for reducing AF burden. The LEGACY trial showed that in patients with AF, sustained weight loss of ≥10% was associated with a 6-fold greater freedom from atrial arrhythmias when compared to patients with less weight loss or weight gain.³ Weight fluctuation (either weight gain followed by weight loss, or weight loss followed by weight gain) >5% was independently associated with AF recurrence.

A sub-group analysis of LEGACY entitled REVERSE-AF showed that patients with the least percent of body weight lost had the highest progression to persistent AF (48%).⁴ Furthermore, in a subgroup of patients with ≥10% weight loss and pre-existing persistent AF, 88% regressed to paroxysmal or no AF. The ARREST AF study targeted risk factor reduction in patients with BMI >27 following AF ablation and showed achieving a BMI <27 or >10% weight loss was associated with longer arrhythmia-free survival.⁵

Studies investigating whether weight loss is effective in reducing the incidence of new cases of AF have reported conflicting results. The Look AHEAD trial showed no difference in incident AF in obese patients with high percent weight loss versus lower percent weight loss or weight gain.⁶ However, the SOS trial showed weight loss after bariatric surgery was associated with a 29% reduction in incident AF.⁷

The statement acknowledges that further mechanistic and clinical studies are necessary to better understand how to best target obesity in AF prevention. It also notes the paradoxically increased risk of AF in patients with very low body weight, which is somewhat analogous to the worse prognosis of patients with heart failure who have low or low normal BMI as compared to those patients with heart failure who are overweight.⁸ The AHA Statement concludes that optimal weight management is an important component of AF management, with goals of a 10% reduction in weight and a BMI <27 kg/m².

Physical Activity

Physical inactivity is also thought to be an independent risk factor. Additionally, improved cardiorespiratory fitness reduces AF burden, and partially offsets the increased AF risk associated with obesity.⁹ The CARDIO-FIT study showed obese patients with AF who improved their exercise tolerance by ≥2 METS had a significant decrease in AF burden.¹⁰ Other studies have demonstrated regular moderate intensity training improved quality of life, exercise capacity, and symptoms in persistent AF patients.

The AHA Statement acknowledges that regular exercise can be difficult to achieve, less 10% of patients are able to meet the physical activity benchmarks recommended by the 2018 Physical Activity Guidelines Advisory Committee Report. While many patients are unable to reach the recommended exercise dose, there is concern that endurance athletes who greatly exceed these recommendations are at increased risk of AF. One meta-analysis showed a 5-fold increase in AF risk in athletes, this data is observational and limited by a lack of controls.¹¹

More novel forms of exercise, such as high intensity interval training (HIIT) are also explored by the statement. The potential benefits of HIIT include improved cardiorespiratory fitness at comparable energy expenditure as traditional moderate intensity continuous training, while also being less time intensive. While initial studies show that a short duration (12 weeks) of HIIT was associated with reduction in AF burden¹², these results are inconsistent. It is unclear if durations longer than 12 weeks remain beneficial, or whether they paradoxically induce the increased AF burden seen in endurance athletes.

Finally, the statement touches on the impact of mind-body exercise on AF burden. As exercises such as yoga, tai chi, and qigong affect cardiac autonomic function, these exercises could be useful in AF management. While the YOGA My Heart Study shows that 3 months of yoga did reduce AF burden, further studies will be necessary to clarify this effect.¹³

Sleep Disordered Breathing

Untreated sleep disordered breathing (SDB) has long been associated with an increase in cardiovascular mortality, this risk extends to AF with a recent meta-analysis demonstrating a two-fold increase in AF risk amongst patients with SDB.¹⁴ The severity of SDB is related with AF incidence, burden, and response to treatment. Patients with severe SDB have higher risks of AF incidence, and are less likely to respond to antiarrhythmic therapy than those with milder SDB.¹⁵

Treatment of SDB in AF patients improves cardiovascular outcomes. It is important to screen patients with AF for SDB, initially via history, with referral to polysomnography or home apnea testing as necessary. The ORBIT-AF cohort demonstrated patients with AF and SDB using CPAP had lower rates of progression to more permanent AF.¹⁶

In some studies, CPAP has also been shown to improve freedom from AF recurrence in patients undergoing cardioversion or ablation.¹⁷ These data come primarily from observational studies, the recent SAVE trial showed CPAP versus usual care did not cause a reduction of cardiovascular events, including incident AF, in patients with SDB and cardiovascular disease.¹⁸ More randomized trials are needed to support stronger recommendations for SDB identification and treatment in AF patients.

Diabetes Mellitus

Several large population based studies have shown associations between diabetes mellitus (DM) and AF^19,20, though this association may be over-estimated due to confounding. While prolonged duration of DM and poor glycemic control are associated with increased risk of AF²¹, the exact mechanism by which glycemic damage promotes AF is unclear. Patients with DM typically have greater stroke volume, pulse pressure, and LV and wall thickness/mass, which may lead to atrial remodeling and increased arrhythmogenicity.²² The end products of glycosylation contribute to atrial fibrosis, further worsening the atrial substrate for AF.²³

Aggressive glycemic control via oral diabetes medications is associated with reduced risk of AF development and recurrence.^24,25 Conversely, another study showed patients undergoing ablation with higher A1c levels had increased risk of AF recurrence.²⁶ Importantly, the AHA Scientific Statement notes that most of this data is retrospective. While diabetic control is important in AF management, there is no data supporting unique treatment targets in patients with AF apart from the current diabetes guidelines. Further research is needed to assess whether aggressive glycemic control may help reduce AF incidence and recurrence.

Hypertension

Uncontrolled blood pressure provides the highest attributable risk for the development of AF. In the Atherosclerosis Risk in Communities (ARIC) study, the population attributable risk for AF was 21.6% for elevated BP.²⁷ Comparatively, the attributable risk from obesity, smoking, DM, and prior cardiac disease were 12.7%, 7.5%, 8.8%, and 5.4%, respectively. The available data supports targeting blood pressure at the guideline directed levels for general cardiovascular health in order to lower incident AF risk, sustained exposure to even pre-hypertension blood pressures is associated with increase in AF risk.

Elevated levels of angiotensin II and aldosterone can increase AF risk via inflammation, fibrosis, and anisotropic conduction.²⁸ While mineralocorticoid receptor antagonist treatment was associated with reduced risk of AF recurrence²⁹, the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers has questionable benefit in primary prevention of AF.³⁰ The AHA Statement recommends managing HTN through a combination of lifestyle management and pharmacotherapy to improve AF risk.

Other modifiable risk factors

Several other risk factors have been associated with AF incidence and prevalence, including tobacco use, alcohol use, coronary artery disease, heart failure, and dyslipidemia. While the direct impact of these risk factors on AF have not been as thoroughly studied, the statement notes that a comprehensive AF management program should address these factors.

Implications for Clinical Practice and Implementation Strategies

The lifestyle risk factors discussed above should be targeted as chronic diseases requiring multi-disciplinary interventions. Initial goals of a 10% weight loss and a 2 MET increase in fitness can decrease AF burden. These goals should progress over time to target BMI ≤25 kg/m and 200 minutes per week of moderate-intensity activity. Tobacco and alcohol cessation should also be pursued and several attempts may be necessary.

The prevalence of wearable devices and smart phones can help make these goals achievable, setting a step goal measured by a pedometer can help sustain physical activity over time, and dietary apps can help patients track caloric intake and weight loss. Comprehensive weight management programs can be useful for sustained weight loss. Bariatric surgery should also be considered for certain morbidly obese patients, as this has been shown to decrease AF incidence, as well as recurrence after ablation.

Regarding SDB therapy, it is important to inquire about barriers to CPAP adherence, and trial different CPAP delivery devices if necessary. A referral to specialty sleep clinic can be beneficial.

Due to the high number of risk factors that increase AF burden, it can be difficult to optimally manage each risk factor in the busy clinic setting. Integrated multi-disciplinary clinics that focus on protocol-driven, guideline directed therapy have been shown to be effective in reducing morbidity and mortality from both AF and overall cardiovascular disease.³¹

Conclusion

Improvements in many modifiable risk factors such as obesity, physical fitness, disordered sleep breathing, diabetes, and blood pressure, can greatly reduce AF burden. Moreover, these lifestyle interventions can improve the benefits of disease-directed therapies, such as catheter ablation. While there remains a need for additional evidence through randomized trials, the AHA Scientific Statement concludes that AF management should begin with aggressive risk factor modification through patient-focused, multi-disciplinary programs.