6. Detection and Management of Modifiable Risk Factors

Modifiable cardiovascular risk factors are well recognized contributors to the development and progression of AF.^{[29],[65],[66]} These established, emerging, and potential risk factors for AF have been summarized in section 3, and Tables 1 and 2. The risk of developing AF increases with the severity and number of modifiable cardiovascular risk factors (such as hypertension, diabetes mellitus, and obesity). In many cases this risk increase is linear within and between risk factors and might be apparent even within the established “normal range.” For example, a systolic BP in the prehypertensive range (130-139 mm Hg) has been associated with a 28% higher adjusted risk of developing AF compared with a systolic BP < 120 mm Hg.^[119] Similarly, although the corrected AF incidence increases approximately 5% for each unit increase in body mass index (BMI),^[120] weight gain has been associated with incident AF independent of BMI (34% increased AF with a 16%-35% weight gain, and 61% increased AF with a > 35% weight gain).^[121] In light of the breadth of data supporting an association between these modifiable cardiovascular risk factors and AF incidence, it has been suggested that the implementation of lifestyle modification and risk factor intervention could significantly decrease the incidence of AF. Unfortunately, the evidence to support targeted risk factor modification to prevent incident AF is limited, in part because of the observation that the absolute risk increase of incident AF from any individual risk factor is low. As such, two complementary approaches have been proposed. The first is to target preventive intervention in individuals who are at highest risk for AF occurrence. Identification of these individuals could be accomplished through the use of risk prediction models or, potentially, with artificial intelligence-enabled screening algorithms.^{[122]–[124]} When identified, these high-risk populations could be targeted for comprehensive risk factor modification. However, it is important to recognize that a focus on only those identified as at highest risk of developing AF would miss the opportunity to prevent most incident cases of AF because these occur in the large segment of the population typically considered to be at “lower risk.” As such, decreasing the population effect of AF will require broad implementation of lifestyle modification strategies (eg, a focus on physical activity, and avoidance of alcohol and tobacco consumption) in addition to targeted intervention of traditional cardiovascular risk factors (including hypertension, HF, diabetes, OSA, and obesity) in those at highest risk of AF development. In patients with established AF, the relationship between risk factor intervention and AF outcomes is well recognized. Several studies have shown that continuous positive airway pressure usage in patients with OSA is associated with a lower risk of AF recurrence compared with nonusage, with rates of recurrent AF comparable with those in patients without OSA.^{[125]–[127]} Many studies have shown that targeted weight loss interventions significantly reduce AF burden (number and cumulative duration of AF episodes)and AF symptom severity scores.^{[128]–[130]} The Long-Term Effect of Goal-Directed Weight Management on Atrial Fibrillation Cohort: A Long-Term Follow-Up Study (LEGACY) cohort study showed that patients with a weight loss of > 10% was associated with a sixfold increase in the likelihood of being arrhythmia-free over a 5-year follow-up compared with those with lesser degrees of weight loss.^[129] Abed et al. showed that weight reduction with intensive risk factor management resulted in a significant improvement in AF-related QOL, AF symptom scores, and AF burden.^[128] The Impact of Cardiorespiratory Fitness on Arrhythmia Recurrence in Obese Individuals with Atrial Fibrillation (CARDIO-FIT) study showed that a > 2 Metabolic Equivalents (METs) improvement in cardiorespiratory fitness was associated with a significantly reduced AF burden compared with a gain of < 2 METs over longterm follow-up.^[131] AF burden reduction was proportional to the increase in cardiorespiratory fitness, with an adjusted reduction in AF recurrence of 10% for each MET gained (hazard ratio [HR], 0.90; 95% CI, 0.83-1.00).^[131] Rienstra et al. showed improved maintenance of sinus rhythm at 1 year with a strategy of cardiac rehabilitation, HF medication optimization, and aggressive BP control (75% maintenance of sinus rhythm on a 7-day Holter vs 63% in the control group; OR, 1.77, P ¼ 0.042).^[132] The Aggressive Risk Factor Reduction Study for Atrial Fibrillation and Implications for the Outcome of Ablation (ARREST-AF) single-centre cohort study showed that patients who chose to undergo aggressive risk factor modification had better QOL and symptom control, a significant reduction in AF burden, and greater arrhythmia-free survival after catheter ablation compared with those who did not (OR, 4.8; 95% CI, 2.04-11.4; P < 0.001).^[65] Taken together, these data suggest that outcomes might be improved by using a comprehensive management strategy that includes suppression of triggers (targeted by risk factor modification, antiarrhythmic drugs, and/or catheter ablation) and amelioration of arrhythmogenic substrate (risk factor modification). Treatment targets for modifiable risk factor intervention are presented in Figure 6.