highest birth weight category (<2.5 [5.5], 2.5 [5.5] to 3.2 [7.1], 3.2 [7.1] to 3.9 [8.6], 3.9 [8.6] to 4.5, and >4.5 [9.9] kg [pounds]), during a median follow-up of 14.5 years. Inflammation and infection Inflammatory processes may play a role in the genesis of AF. Measurement of serum C-reactive protein (CRP), an acute phase reactant, has been used to assess the relationship between AF and inflammation. Observational studies have reported elevated serum levels of CRP in patient populations with any of the following characteristics: later (after known high CRP) development of AF [97], history of atrial arrhythmias [98], failed cardioversion [99], recurrence of AF after cardioversion [100], and development of AF after cardiac surgery. (See "Atrial fibrillation and flutter after cardiac surgery".) However, inflammation is more likely a marker for other conditions associated with AF, as opposed to being a direct cause or a perpetuating agent. The strongest evidence against a direct causal role for inflammation, as detected by an elevation in CRP, comes from a Mendelian randomization study that evaluated nearly 47,000 individuals in two cohorts from Copenhagen, Demark [101]. (See "Mendelian randomization".) The following observations were made: After multifactorial adjustment, a CRP level in the upper versus lower quintile was associated with a significantly increased risk of the development of AF (hazard ratio 1.77, 95% CI 1.22-2.55). Genotype combinations of four CRP polymorphisms were significantly associated with up to a 63 percent increase in plasma CRP levels, but not with an increased risk of the development of AF. https://www.uptodate.com/contents/epidemiology-risk-factors-and-prevention-of-atrial-fibrillation/print 12/33 7/5/23, 9:30 AM Epidemiology, risk factors, and prevention of atrial fibrillation - UpToDate Thus, inflammation, as determined by CRP, is not likely to be causative of AF. In addition to inflammation as detected by serum CRP, new onset AF and other acute cardiac events have been associated with pneumococcal pneumonia [102]. (See "Pneumococcal pneumonia in patients requiring hospitalization", section on 'Cardiac events and other noninfectious complications'.) The risk of AF increases after infection with the influenza virus [103]. Pericardial (epicardial) fat Pericardial fat, also referred to as epicardial fat, is the fat depot within the pericardial sac, which is in between the visceral and parietal pericardium. It has inflammatory properties: both obesity and inflammation are risk factors for AF [104,105]. In a study of 126 patients with AF and 76 controls, those with AF had a significantly higher pericardial fat volume (102 versus 76 ml) [104]. This was true for patients with either paroxysmal or persistent AF, and was independent of other traditional predictors of AF, including left atrial enlargement. Autonomic dysfunction The autonomic nervous system may be involved in the initiation and maintenance of AF. It may be particularly important in patients with paroxysmal AF, as both heightened vagal and sympathetic tone can promote AF. Vagal tone is predominant in normal hearts, which may explain why vagally-mediated AF is often seen in athletic young men without apparent heart disease who have slow heart rates during rest or sleep; such patients may also have an electrocardiogram (ECG) pattern of typical atrial flutter alternating with AF [106,107]. In comparison, AF induced by increased sympathetic tone may be observed in patients with underlying heart disease or during exercise or other activity [107]. (See "Paroxysmal atrial fibrillation", section on 'Pathogenesis'.) Findings on the electrocardiogram Abnormal QT or P-wave duration are associated with an increased risk of AF: Corrected QT interval Individuals with either congenital long QT syndrome or short QT syndrome have an increased risk of AF [108,109]. (See "Congenital long QT syndrome: Epidemiology and clinical manifestations" and "Short QT syndrome".) The issue of whether there is an association between the corrected QT interval (QTc) and the risk of AF in the general population was addressed in a study of 281,277 individuals without baseline AF in the greater Copenhagen region who were followed for a median st period of 5.7 years after a first ECG [110]. Individuals with a QTc <372 ms (1 percentile) or th 419 ms (60 percentile) had an increased risk (adjusted hazard ratios [HRs] 1.45 up to 1.44, respectively) compared with the reference group (411 to 419 ms). The risk increased in a dose-dependent manner above 419 ms and was strongest among individuals with lone AF. https://www.uptodate.com/contents/epidemiology-risk-factors-and-prevention-of-atrial-fibrillation/print 13/33 7/5/23, 9:30 AM Epidemiology, risk factors, and prevention of atrial fibrillation - UpToDate P-wave duration The relationship between P-wave duration and the risk of AF was evaluated in a study of nearly 285,933 individuals, of whom 9550 developed AF during a median follow-up period of 6.7 years [111]. Compared with the reference group (100 to 105 milliseconds [ms]), individuals with very short ( 89 ms; HR 1.6), intermediate (112 to 119 ms; HR 1.22), long (120 to 129; HR 1.5), and very long P wave duration ( 130 ms; HR 2.06) had an increased risk. Premature atrial complex PAC is important as a trigger of PAF (see 'Pathogenesis' above). The issue of whether they are predictor of incident AF was evaluated in a study of 1260 adults without prevalent AF who underwent 24-hour ambulatory ECG (Holter) monitoring at baseline [112]. During a median follow-up of 13.0 years, 27 percent developed incident AF. After adjusting for other known predictors of AF, PAC count (by quartile) was significantly associated with incident AF; the adjusted HRs comparing quartile 2, 3, and 4 with quartile 1 were 2.17, 2.79, and 4.92, respectively. Other supraventricular tachyarrhythmias Spontaneous transition between typical atrial flutter and AF has been observed, although little is known about the mechanism of this conversion [113,114]. In addition, AF is, in some patients, associated with paroxysmal supraventricular tachycardia (PSVT) [115-117]. The most common causes of PSVT are atrioventricular nodal re-entrant tachycardia and atrioventricular reentrant tachycardia, which occurs in patients with the Wolff-Parkinson-White syndrome or concealed accessory pathways. (See "Atrioventricular nodal reentrant tachycardia" and "Atrioventricular reentrant tachycardia (AVRT) associated with an accessory pathway".) The association between AF and PSVT was illustrated in a report that evaluated 169 patients who presented with PSVT and were followed by clinic visits and transtelephonic ECG monitoring during symptomatic episodes [115]. Nineteen percent had an episode of AF during a mean follow-up of 31 months. Neither the mechanism nor the rate of the PSVT was associated with the time to occurrence of AF. Enhanced vagal tone, as determined by baroreflex sensitivity, or an increase in dispersion of right atrial refractory periods may contribute to the development of AF associated with PSVT [118]. Alternatively, an atrial premature beat can cause stable PSVT to degenerate into AF. Among patients with Wolff-Parkinson-White syndrome, the mechanism of AF may be retrograde conduction via the accessory pathway of a premature beat, stimulating the atrial myocardium during its vulnerable period [119]. Ablation of the accessory pathway reduces the incidence of subsequent AF [119,120]. https://www.uptodate.com/contents/epidemiology-risk-factors-and-prevention-of-atrial-fibrillation/print 14/33 7/5/23, 9:30 AM Epidemiology, risk factors, and prevention of atrial fibrillation - UpToDate Low serum magnesium In an observational study of over 3500 participants in the Framingham Offspring Study, individuals in the lower quartile of serum magnesium were approximately 50 percent more likely to develop AF compared with those in the upper quartiles after multivariable adjustment [121]. Alcohol Alcohol is both a chronic risk factor for the development of new AF and also an acute trigger for AF episodes. AF occurs in up to 60 percent of binge drinkers with or without an underlying alcoholic cardiomyopathy [122]. Most cases occur during and following weekends or holidays when alcohol intake is increased, a phenomenon that has been termed "the holiday heart syndrome." However, even modest amounts of alcohol (one to two drinks) can trigger AF in some patients [123]. In a case-crossover study, 100 individuals free of alcohol dependence and with AF wore transdermal ethanol sensors and continuous ECG monitors for four weeks. Among the 56 persons who had an AF episode during this time period, having had one alcoholic drink doubled the odds of having AF (odds ratio [OR] 2.02 [95% CI 1.38-3.17]) and having two or more alcohol drinks tripled the odds of having an AF episode (OR 3.58 [CI 1.63-7.89]) in the next four hours. This study demonstrated a probable dose-response relationship between the amount of alcohol consumed and the likelihood of triggering an AF episode. The evidence is mixed for long-term alcohol consumption being a risk factor for developing new AF. Moderate, long-term alcohol consumption was not shown to be a risk factor for AF in relatively small studies [56,124,125]. However, a positive association was found in a 2014 study of 79,019 men and women free from AF at baseline [126]. Compared with current drinkers of <1 drink per week, the multivariable risk ratios of AF were 1.01 (95% CI 0.94-1.09) for one to six drinks per week, 1.07 (95% CI 0.98-1.17) for 7 to 14 drinks per week, 1.14 (95% CI 1.01-1.28) for 15 to 21 drinks per week, and 1.39 (95% CI 1.22-1.58) for >21 drinks per week. Heavy alcohol consumption is associated with a greater increase in incidence of AF. Two large cohort studies found an increased incidence among men with heavy alcohol consumption (HR 1.45 in both) [127,128]. Neither study found a correlation between heavy alcohol use and AF in women, but the ability to detect such a correlation was limited by the small numbers of women with alcohol consumption in this range. Another study of 1055 cases of AF occurring during long-term follow-up found an increased risk (relative risk 1.34, 95% CI 1.01-1.78) with consumption of more than 36 grams per day (approximately >3 drinks/day) [125]. Caffeine There is a widespread belief that caffeine, particularly at high doses, is associated with palpitations and a number of arrhythmias, including AF and supraventricular and ventricular ectopy. However, despite the theoretical relationship between caffeine and arrhythmogenesis, there is no evidence in humans that ingestion of caffeine in doses typically https://www.uptodate.com/contents/epidemiology-risk-factors-and-prevention-of-atrial-fibrillation/print 15/33 7/5/23, 9:30 AM Epidemiology, risk factors, and prevention of atrial fibrillation - UpToDate consumed can provoke AF or any other spontaneous arrhythmia [129]. (See "Cardiovascular effects of caffeine and caffeinated beverages", section on 'Arrhythmias'.) Fish and fish oil supplements Observational data has suggested that dietary fish intake or fish oil supplements, particularly those rich in long-chain n-3 fatty acids, may reduce the incidence of arrhythmias, although evidence is mixed with regard to both atrial and ventricular arrhythmias. (See "Overview of sudden cardiac arrest and sudden cardiac death", section on 'Fish intake and fish oil'.) With regard to dietary fish intake and incident AF, three cohort studies (approximately 45,000, 48,000, and 5000 individuals) found no relationship [130-132], while one (approximately 5000 individuals) suggested a reduction in AF burden [133]. Medications Certain medications can cause or contribute to the development of AF [134]. These include theophylline [135], adenosine [136], and, since increased vagal tone can induce AF [107], drugs that enhance vagal tone, such as digitalis. (See 'Autonomic dysfunction' above.) Bisphosphonates (eg, alendronate, risedronate, etidronate) are widely used in the treatment of osteoporosis, and concern has been raised that these drugs can cause AF. The weight of evidence suggests that the risk of AF from oral bisphosphonates is small, if it exists at all. (See "Risks of bisphosphonate therapy in patients with osteoporosis", section on 'Atrial fibrillation'.) Case-control studies have suggested a modest increased risk for the development of AF in patients taking nonsteroidal anti-inflammatory drugs [137-140]. However, the absence of an accepted biologic mechanism and the susceptibility of case-control studies to unmeasured confounders makes us cautious about the strength of this association [141]. Certain antiarrhythmic drugs may increase the risk of AF. A 2020 scientific statement from the American Heart Association details drugs associated with AF [142]. While exhaustive, this statement includes many medications for which the association with AF is likely relatively weak. Ivabradine, a selective blocker of the I channel that slows the sinus rate, has been associated f with a higher incidence of AF [143]. A meta-analysis of 11 studies suggests a 15 percent excess of AF in patients treated with ivabradine [144]. Regular physical activity The relationship between physical activity and the development of AF is uncertain. Some [145-147], but not all [148-150], studies have suggested that regular physical activity is associated with a risk of AF in the general population. In a 2013 meta-analysis of four prospective cohorts (n = 43,672), and after dividing subjects into four or five groups on the basis of cumulative physical activity per week, there was no difference in the risk of AF https://www.uptodate.com/contents/epidemiology-risk-factors-and-prevention-of-atrial-fibrillation/print 16/33 7/5/23, 9:30 AM Epidemiology, risk factors, and prevention of atrial fibrillation - UpToDate comparing patients in the maximum and minimal groups (odds ratio 1.08, 95% CI 0.97-1.21) [151]. Air pollution Air pollution, and specifically fine particulate matter, is associated with increased cardiovascular disease mortality. (See "Overview of possible risk factors for cardiovascular disease", section on 'Air pollution'.) Whether air pollution is associated with episodes of AF was evaluated in a study of 176 patients with dual chamber implantable cardioverter-defibrillators that were capable of detecting episodes of AF. After follow-up of nearly two years, there were 328 episodes of AF lasting 30 seconds or more found in 49 patients [152]. The potential impact of multiple parameters of air pollution, (measured hourly) on the development of AF was examined. The odds of AF increased significantly as the concentration of particulate matter increased in the two hours prior to the event. Night shift work Data from The United Kingdom Biobank study showed that both current and lifetime night shift exposures were associated with increased AF risk, regardless of genetic AF risk [153]. This cohort had 283,657 participants with 5777 incident AF events over an approximately 10-year follow-up. Usual or permanent night shift workers (4 percent), compared with day workers (83 percent), had higher risks of AF (HR 1.16, 95% CI 1.02-1.32). Workers with a >10-year duration of night shifts (2.4 percent) had a higher AF risk compared with day workers (HR 1.18, 95% CI 0.99-1.40). Workers with three to eight night shifts per month but not <3 per month or >8 per month had an increased risk of developing AF (HR 1.22, 95% CI 1.02-1.45; HR 0.88, 95% CI 0.64 1.21; HR 1.05, 95% CI 0.86-12.8, respectively). A potential limitation of this study is the inability to fully account for underlying socioeconomic factors. A limitation of this sub-analysis was relatively low AF event rates in the group with <3 and >8 shifts per month. Whether decreasing or stopping shift work protects against later AF is uncertain. RISK PREDICTION MODELS Models that attempt to predict the risk of development of atrial fibrillation (AF) have been developed but are not widely employed. Using the Framingham Heart Study population, age, sex, systolic blood pressure, treatment for hypertension, PR interval, clinically significant cardiac murmur, body mass index, and heart failure were incorporated into a risk prediction model that predicts an individual's absolute risk over 10 years [154]. This model has been validated in two geographically and racially diverse cohorts in the age range of 45 to 95 years and predicted the five-year incidence of AF with https://www.uptodate.com/contents/epidemiology-risk-factors-and-prevention-of-atrial-fibrillation/print 17/33 7/5/23, 9:30 AM Epidemiology, risk factors, and prevention of atrial fibrillation - UpToDate moderate accuracy (C statistic 0.66 to 0.68) [155]. Other models have been studied, including one in a racially diverse population [156]. However, the benefit of using risk prediction models in this setting has not been established. There are no studies linking this with improved outcomes. PREVENTION For many risk factors of AF, preventive strategies that significantly reduce risk of incident AF have not been identified. The following are possible preventive strategies: Healthy fats There is weak evidence that dietary modifications such as extra virgin olive oil or n-3 polyunsaturated fatty acids in fish oil lower the risk of the development of AF [157,158]. Mediterranean diet The PREDIMED primary prevention trial found that a Mediterranean diet enriched with either extra virgin olive oil or mixed nuts reduces the incidence of stroke, MI, and cardiovascular mortality [159] (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention) or at very high risk", section on 'Diet'.) In a post-hoc analysis of PREDIMED, the group that received the Mediterranean diet supplemented with extra virgin olive oil had a lower risk of development of AF compared with the control group (hazard ratio [HR] 0.62; 95% CI 0.45-0.85) [160]. Blood pressure lowering Among patients with hypertension, a study suggests that lowering blood pressure reduced the risk of the development of AF. In the SPRINT trial, intensive compared with standard blood pressure lowering was associated with a lower risk of developing new AF (HR 0.74, 95% CI 0.56-0.98) [161]. (See "Goal blood pressure in adults with hypertension".) Cardiac pacing The role of pacing for the prevention of AF is discussed separately. (See "The role of pacemakers in the prevention of atrial fibrillation".) Although cardiac resynchronization therapy (CRT) improves some potential risk factors for AF. such as atrial size and left ventricular systolic function, CRT has not been shown to decrease the incidence of new or recurrent AF. This is discussed in detail separately. (See "Cardiac resynchronization therapy in atrial fibrillation".) https://www.uptodate.com/contents/epidemiology-risk-factors-and-prevention-of-atrial-fibrillation/print 18/33 7/5/23, 9:30 AM Epidemiology, risk factors, and prevention of atrial fibrillation - UpToDate SUMMARY Epidemiology The incidence and prevalence of atrial fibrillation (AF) depends upon the population studied and the intensity of monitoring. Both increase significantly with increasing age. (See 'Epidemiology' above.) Chronic disease associations Hypertensive heart disease and coronary heart disease are the most common chronic disease associations in patients with AF in developed countries. Other frequent causes include alcohol excess, heart failure, valvular heart disease including both regurgitant and stenotic lesions, and hyperthyroidism. (See 'Chronic disease associations' above.) AF occurs in relation to a variety of different types of surgery; the incidence is greatest in patients undergoing coronary artery bypass graft or cardiac valve surgery. (See 'Chronic disease associations' above.) Chronic, heavy alcohol use does increase the risk of AF in men, while the impact of heavy alcohol use in women is less clear. Chronic moderate alcohol use does not appear to increase the incidence of AF in men or women. (See 'Chronic disease associations' above.) Genetic factors The heritability of AF is complex. For the majority of patients, genetic susceptibility, if present, is probably a polygenic phenomenon, meaning that it is due to the combined effects of a number of genes. (See 'Genetic factors' above.) Risk Prediction Models to predict the risk of subsequent AF have been developed. However, a benefit from using such models has not been established. (See 'Risk prediction models' above.) Prevention There is some evidence that dietary intake of healthy fats, a Mediterranean diet, and blood pressure lowering can prevent the onset of AF. (See 'Prevention' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Leonard Ganz, MD, FHRS, FACC, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES https://www.uptodate.com/contents/epidemiology-risk-factors-and-prevention-of-atrial-fibrillation/print 19/33 7/5/23, 9:30 AM Epidemiology, risk factors, and prevention of atrial fibrillation - UpToDate 1. Benjamin EJ, Wolf PA, D'Agostino RB, et al. Impact of atrial fibrillation on the risk of death: the Framingham Heart Study. Circulation 1998; 98:946. 2. Chugh SS, Blackshear JL, Shen WK, et al. Epidemiology and natural history of atrial fibrillation: clinical implications. J Am Coll Cardiol 2001; 37:371. 3. Patel NJ, Deshmukh A, Pant S, et al. 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