Table 5. Newer Modifiable and Non-Modifiable Risk Factors: Description of the Novel Risk Factors and their Implications in AF.

	Novel risk factors	Important characteristics
1	Genetic	Details are discussed below in section “Genetic Basis of Familial AF”.
2	Ethnicity	African Americans appear to be at lower risk of AF than Caucasians. Risk of AF was 25% lower in blacks than Caucasians (HR 0.75, 95% CI=0.64-0.87). [73]
3	Sleep apnea syndrome	Sleep Apnea Syndrome is associated with obesity, which in turn increases AF risk .[70]
4	Pericardial Fat	Increased epicardial fat is linked with increased AF persistence independent of other risk factors.[74]
5	Blood Pressure in Non-hypertensive Range.	Data regarding the risk of AF at lower blood pressure levels are sparse. An analysis of 34,221 women participating in the Women's Health Study showed that blood pressure was strongly associated with incident AF, and systolic blood pressure was more strongly related to AF incidence than diastolic blood pressure.[75]
6	Subclinical Coronary Artery Disease	Nucifora et al.[76] however, used multislice computed tomography to detect asymptomatic coronary artery disease. Eighteen percent of patients with AF were classified as having no coronary artery disease, whereas 41% showed non-obstructive coronary artery disease, and the remaining 41% had obstructive coronary artery disease compared with patients without AF (P=0.01).[76]
7	Physical Activity	Physical activity is associated with a 3 to 5 mm Hg reduction in systolic blood pressure, [77] a reduction in body weight and body mass index, [78] and the prevention of coronary heart disease, suggesting that exercise may reduce the incidence of AF.
8	Chronic Kidney Disease	Patients with chronic kidney disease are at higher risk for coronary heart disease and heart failure.[79] Alonso et al.[80] sought to examine the risk between chronic kidney disease and AF in 10,328 men and women from the Atherosclerosis Risk in Communities study. They found that impaired kidney function and presence of albuminuria were strongly associated with the incidence of AF.
9	EKG-base parameters	EKG-based parameters such as long (within the normal range) or prolonged PR interval clearly relate to AF in the population, and possibly relate to atrial structural remodeling and delayed intra-atrial conduction[81]
10	Left Ventricular Diastolic Dysfunction	Atrial fibrillation and left ventricular diastolic dysfunction share multiple risk factors, including aging and hypertension.[82] Because diastolic dysfunction causes atrial pressure and volume overload, atrial structural remodeling is common among patients with abnormal diastolic parameters. More recently, investigators of the Cardiovascular Health Study examined echocardiographic parameters of diastolic function in 4,480 older adults and reported that Doppler peak E-wave velocity and left atrial diameter were positively and nonlinearly associated. Doppler A-wave velocity time integral displayed a U-shaped relationship with the risk of AF.[83]
11	Biochemical and structural association	A. Serum biomarkers: Biomarkers can be potentially used as novel instruments to enhance AF risk prediction and to provide insights into the pathophysiology of the disease, and may help to identify novel targets for therapy. B-type natriuretic peptide (BNP) Even though BNP is traditionally investigated as a biomarker for heart failure, elevated levels have been reported in patients with incident AF.[84,85]In the Cardiovascular Health Study, a community-based population of 5,445 older adults, N-terminal proBNP was a strong predictor of incident AF, adjusting for other risk factors (adjusted HR, 4.0; 95% CI, 3.2–5.0; P<0.001). [86] Blood lipids: are established risk factors for coronary artery disease, which may precede incident AF. B. Functional imaging: Echocardiographic estimators of left atrial size is ‘integral’ to measure the degree of left atrial structural changes over time, and thereby relate to incident AF or to AF-related complications, including death. Left atrial size or volume and left ventricular mass may predict AF and AF-related mortality.