Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in the general population.1)2)3) AF increases the risk of mortality and morbidity resulting from stroke, congestive heart failure, dementia, and impaired quality of life, which explains its enormous socioeconomic and healthcare implications.3)4) The prevalence of AF progressively increased by 2.10-fold from 0.73% in 2006 to 1.53% in 2015 in Korea. The prevalence of AF in the Korean population is expected to reach 5.81% (2,290,591 patients with AF) by 2060.3)

The incidence of AF has been shown to be positively correlated with age, male sex, diabetes, hypertension, congestive heart failure, valve disease, and myocardial infarction (MI).3)5)6) The management of risk factors or comorbidities, including lifestyle factors, is an important component of an integrated AF management.3)7) An integrated approach to AF management is the basis of consistent guideline-based treatment of AF, and such guideline adherence helps improve patient outcomes.

Hypertension is highly prevalent in the adult population with AF, especially among persons older than 60 years, and affects approximately 1 billion adults worldwide.1)2)8) According to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure guidelines, 62.2% of Korean patients with AF had hypertension.9) After applying the 2017 American College of Cardiology/American Heart Association guidelines for hypertension, 79.4% had hypertension, adding 17.2% cases as newly re-defined hypertension (130–139/80–89 mmHg). The Korean population with hypertension (hazard ratio [HR], 1.80; 95% confidence interval [CI], 1.62–1.99; p<0.001) had an increased risk of new-onset AF (Table 1).5) Hypertension and pre-hypertension are independently associated with AF.10)11) Indeed, AF can be considered a manifestation of target organ damage due to hypertension.

Diabetes and AF frequently coexist because of their associations with other risk factors. Diabetes is a risk factor for stroke and other complications in AF.2)14) In patients with AF, a longer duration of diabetes seems to confer a higher risk of thrombo-embolism, albeit without a greater risk of oral anticoagulant (OAC)-related bleeding.15)

An impaired fasting glucose (IFG) is a prior stage to diabetes, which is a well-known risk factor for AF. Because IFG is common worldwide and is considered clinically normal, treatments for this condition are rare. Lee et al.11) reported that in healthy Asian populations without comorbidities, IFG and pre-hypertension were important risk factors for AF. Subjects with IFG (HR, 1.16) had a higher risk of AF, and diastolic blood pressure (HR, 1.11) was a stronger indicator for the occurrence of AF than systolic blood pressure. As the risks IFG, pre-hypertension, and body mass index (BMI) ≥25 kg/m² increased, the risk of AF also increased. Even in a healthy population, subjects with all 3 risks had a much higher AF risk (HR, 1.50) than those without. IFG related to AF was more prominent in subjects with BMI <25 kg/m² (HR, 1.18) than in those with BMI ≥25 kg/m², and subjects with both IFG and pre-hypertension had a greater AF risk (HR, 1.27) than those without (Figure 5).11) The BMI-dependent effects of pre-hypertension and IFG also showed a similar pattern for AF-related stroke, HF, and mortality in a healthy population.11)

Obesity is linked to AF and is considered a conventional risk factor for adverse cardiovascular events.16)17)18)19) Large epidemiological studies have observed strong associations between obesity and the incidence of AF and AF-related complications.16)17)18)19) Obesity is associated with an increased left atrial size and a decreased left ventricular diastolic function, which, in turn, leads to an increased left atrial pressure.18) In addition, dynamic changes in left atrial size and pressure likely affect both the atrial substrate and the triggers for AF.17) In the Korean population, a high BMI (≥25 kg/m²; HR, 1.24; 95% CI, 1.10–1.41) was associated with a greater AF risk compared with a BMI of 20–22.5 kg/m² (Table 1).5)

Waist circumference and waist-to-hip circumference ratio are also associated with a higher risk of AF.20) Visceral adiposity is associated with incident cardiovascular disease after adjustment for clinical risk factors and generalized adiposity.21) The prevalence of overweight and obesity is much lower in Asian populations than in Western populations.1)19)

Baek et al.19) showed that abdominal obesity is an important, potentially modifiable risk factor for AF in non-obese Asians. After multivariable adjustment, each 1 standard deviation (3.7 kg/m² and 9.4 cm) increase in BMI or waist circumference was associated with an increase of 8% (p<0.001) and 12% (p<0.001), respectively. Spline curves between BMI and waist circumference, and the HR of new-onset AF are presented in Figure 6. A non-linear J-shaped association was found between continuous BMI variables and AF risk. AF risk positively increased with the increase of waist circumference. Interestingly, the overall J-shaped and linear patterns in the association seem to be mainly driven by the patterns for men. Abdominal obesity was associated with new-onset AF in the underweight (p<0.001), normal (p<0.001), and overweight (p<0.001) groups, but not in the obese group (p=0.894). These data suggest that interventions to decrease abdominal obesity may reduce the population burden of AF.19)

The use of baseline weight or BMI measurements alone cannot capture the dynamic BMI changes that may influence the incidence of AF.17) Patients in the normal or underweight BMI category may experience undesired weight loss due to other medical problems, which may affect the incidence of AF in the general population.22) The Atherosclerosis Risk in Communities study found that a weight loss or gain of >5% of the initial body weight was positively associated with AF.22) In addition, the LEGACY study reported incremental increases in AF burden with weight fluctuations.23)

In the underweight and normal Asian population, BMI variability, especially weight gain, increased the risk of incident AF and MI but not the risk of stroke.5) Figure 7 shows the incidence of new-onset AF, MI, ischemic stroke, and cardiovascular death per 1,000 person-years according to BMI variability. In initially underweight and normal individuals (initial BMI <25 kg/m²), the highest BMI variability (Q4) was associated with a significantly higher incidence of AF than a stable BMI variability (Q1). Furthermore, the highest BMI variability, especially weight gain, was related to higher systolic and diastolic blood pressure, fasting blood glucose level, and total cholesterol level than those with a more stable BMI variability. The Korean population with dyslipidemia (HR, 1.12; 95% CI, 1.02–1.24; p=0.01) had an increased risk of new-onset AF (Table 1).5) This finding suggests that avoiding weight fluctuation, especially weight gain, is important to prevent AF and to decrease the risk of MI in the underweight and normal Asian populations.5)

AF is a common arrhythmia of acute MI (AMI) that has been shown to be related to increased in-hospital and long-term mortality rates.24) Various pathologic mechanisms including elevated left ventricular end-diastolic pressure, increased atrial pressures, acute deterioration of left ventricular function, left atrial enlargement, atrial ischemia, or infarction can contribute to the development of AF in the AMI setting.24) Inflammatory markers, mainly C-reactive protein, have been reported to be related to future AF development.25)26) Accordingly, Hwang et al.27) reported that C-reactive protein could be strongly related to early AF in patients with AMI, especially in those with a less dilated left atrium.

In addition to being an established complicating factor for MI, recent studies have revealed that AF increased the risk of MI.28) Lee et al.29) reported that AF was associated with a 3-fold increased risk of MI (HR, 3.1; 95% CI, 2.22–4.37) in both men (HR, 2.91; 95% CI, 1.91–4.45) and women (HR, 3.52; 95% CI, 2.01–6.17) (Figure 8). The risk of AF-associated MI was higher in patients free of hypertension, diabetes, ischemic stroke, and dyslipidemia at baseline. The cumulative incidence of AF-associated MI was lower in patients under anticoagulant and statin treatments. This finding suggests that that AF complications beyond stroke should extend to total mortality to include MI.29)

Epidemiological studies have suggested that exposure to elevated levels of ambient particulate matter (PM) <2.5 μm (PM_2.5) or <10 μm (PM₁₀) in aerodynamic diameter is consistently associated with adverse cardiac events.30)31)32)33) Although many studies for these adverse cardiovascular outcomes have been performed, the correlations between short-term exposures to PM_2.5 and incident AF were uncertain.34) However, these studies were performed in the European countries and United States, where the air pollution levels are much lower than in Asian countries. Therefore, the effect sizes could be low in those studies.

Kim et al.35) reported that long-term exposure to PM_2.5 (HR 1.18 for 10 μg/m³ increments, p<0.001) and PM₁₀ (HR 1.03 for 10 μg/m³ increments, p<0.001) is associated with an increased incidence of new-onset AF in the Asian general population (Figure 9). It is more profound in obese male subjects older than 60 years and in those with a history of hypertension or previous MI.35)

Stroke prevention is the principal management priority in patients with AF, given its association with a 5-fold increase in stroke risk.3)15)36) The CHA₂DS₂-VASc score is now used in most guidelines for stroke prevention in patients with AF.3)15) The adjusted incidence rates (per 100 person-years) of ischemic stroke were 3.79 in Korea, being 0.26 in low-risk patients (CHA₂DS₂-VASc score 0 [men] or 1 [female]), 1.18 in intermediate-risk patients (CHA₂DS₂-VASc score 1 [men]), and 5.30 in high-risk patients (CHA₂DS₂-VASc ≥2).2) The more recent focus of stroke prevention in patients with non-valvular AF has shifted away from predicting “high-risk” patients toward initially identifying patients at a “truly low-risk” of ischemic stroke in whom OAC has no net clinical benefit.8) Korean patients who were categorized as “low-risk” by the CHA₂DS₂-VASc score (i.e., score of 0 point in men or 1 point in female) consistently had an event rate of <1%/year.2)

Stroke risk as assessed by the CHA₂DS₂-VASc score is dynamic and changes over time. The rates of ischemic stroke increased when patients accumulated risk factors and were re-classified into higher CHA₂DS₂-VASc score categories. Assessment of stroke risk is needed at every patient contact, as accumulation of risk factors with increasing CHA₂DS₂-VASc score translates to greater stroke risks over time (Figure 10).14)

The management of diseases (obesity, hypertension, heart failure, diabetes mellitus, sleep apnea) related to AF should be provided continuously, whereas lifestyle factors such as smoking and drinking should be monitored in an integrated manner.3) However, in lean Asian populations, strict blood pressure control and management of IFG should be emphasized. Avoiding abdominal obesity and weight fluctuation, as well as controlling the exposure to air pollution might reduce the development of AF. Finally, female sex is not a risk factor for stroke in Asian populations. Lowering the current age threshold (age ≥65 years) in the CHA₂DS₂-VASc score to age ≥55 years might be appropriate in Asian patients with AF. Knowledge of these factors and their management will enable optimal management and can improve the outcome of patients with AF.