Methods

The Atherosclerosis Risk in Communities (ARIC) study is a community based cohort study that began recruitment in 1987. At baseline, 15,792 participants aged 45 to 64 years were randomly recruited at 4 field centers in the United States (Forsyth County, North Carolina; suburban Minneapolis, Minnesota; Washington County, Maryland; and Jackson, Mississippi). The details of the recruitment and baseline characteristics have been published previously. During the visit-5 examination that was conducted from 2011 to 2013, echocardiography was performed by certified technicians, and LA volume was measured. Thus, this study only includes participants who survived until the fifth examination. For the present analysis, we used the data from 5,496 patients who underwent 2-dimensiontional echocardiography at the field centers during visit 5. Race was dichotomized into white and nonwhite categories for easier interpretation as there were only 15 patients who were nonwhite and nonblack who were added to blacks.

Two-dimensional echocardiography was performed and echocardiographic parameters were measured at the core laboratory for ARIC. LA volume index was measured by Simpson’s method according to established protocol of the American Society of Echocardiography. We defined LA volume index of ≥29 mm ³ /m ² as atrial enlargement. Prevalent AF was defined as presence of AF during any of ARIC visits 1 to 5 by either study scheduled electrocardiography or by hospital discharge International Classification of Diseases -9 codes 427.3, 427.31, and 427.32 that were obtained by active surveillance of ARIC community hospitals until 2010. Random zero sphygmomanometers were used to measure systolic and diastolic blood pressures with participants in the sitting position after 5 minutes of rest. The average of 2 readings was recorded and hypertension was defined as systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or antihypertensive medication use. Height and weight were measured in light clothing without shoes. Body mass index was calculated as weight in kilograms by the square of height in meters. Diabetes mellitus was defined as fasting blood glucose level ≥7.0 mmol/L, nonfasting blood glucose ≥11.0 mmol/L, or use of diabetic medication. Alcohol use and smoking status were determined by self-report. Physical activity was defined as frequency of exercise in days per week when exercise was at least 20 minutes of aerobic workout. Coronary artery disease was defined by adjudicated myocardial infarction and coronary heart disease events. Heart failure was identified by hospital discharge International Classification of Diseases 9 and 10 codes 428.0, 428.1, 428.2, 428.3, 428.4, and 428.9 and death certificates code I50.0. The coronary artery disease and heart failure events were available until 2010. Blood glucose and uric acid were determined by standard protocols.

Descriptive statistics were used to summarize the data. Continuous variables are expressed in mean ± SD and categorical variables are given as percentages. For examining the differences, the Student t test was used for continuous variables and the chi-square test was used for categorical variables, wherever appropriate. We assessed association of traditional risk factors such as age, gender, race, height, weight, hypertension, diabetes, current smoking, current alcohol use, moderate to vigorous exercise (>1 time perweek), coronary artery disease, and heart failure with AF stratified by dilated or normal-sized LA in a multivariate logistic regression model. We used interaction terms of dilated LA × traditional risk factor after adjusting for covariates previously mentioned, 1 at a time to assess association with AF to determine significant interactions. All p values were 2 sided and p <0.05 is considered significant. Because the analysis was used for only screening for interactions and not testing a hypothesized interaction, we used an interaction p value of 0.20, which gives power of 90% to detect interaction.

Results

Of the 5,496 participants (mean age 75 ± 5 years, women 58%), there were 665 patients (12%) with prevalent AF. There were 1,230 (22%) patients with dilated LA diagnosed by echocardiography. AF occurred in 477 (11%) of patients with normal-sized LA and in 188 (15%) of patients with dilated LA. Patients with AF were more likely to be older, exercise <1 time per week, and had heart failure. Patients with AF with dilated LA were more likely to be of white race and consume alcohol, whereas patients with AF with normal LA were more likely to be men, taller, hypertensive, and have coronary artery disease ( Table 1 ). When risk factors for all participants with AF were evaluated in a multivariate logistic regression model, we found age >75 years, race, height, hypertension, coronary artery disease, and heart failure were directly associated with risk of AF and exercise >1 times per week was inversely associated with risk of AF ( Table 2 ). Female gender, alcohol use, and weight were stronger risk factors for AF in dilated LA group than normal-sized LA group, whereas age >75 years and heart failure (p for interaction <0.20) were stronger risk factors for AF in normal-sized LA group than dilated LA group. Figure 1 shows the prevalence of AF by demographic variables among patients with dilated and normal-sized LA. Prevalence of AF among groups of risk factors stratified by American Society of Echocardiography based classification of LA volume index is given in the appendix ( Supplementary Figures 1 and 2 ).

Table 2

Differential association of risk factors of atrial fibrillation in individuals with dilated and normal-sized left atrial cavity

Risk Factors	All Participants ∗ OR (95% CI)	Left Atrial Cavity Size		Interaction-p
		Increased OR (95% CI)	Normal OR (95% CI)
Number of patients	5496	1230	4266
Age >75 years	1.74 (1.43–2.11)	1.36 (0.93–1.97)	1.87 (1.49–2.35)	0.12
Women	1.20 (0.92–1.57)	1.67 (1.01–2.77)	1.06 (0.77–1.46)	0.09
White race	1.44 (1.13–1.84)	1.37 (0.84–2.23)	1.48 (1.12–1.97)	0.72
Height, per 10 cm	1.27 (1.11–1.46)	1.44 (1.18–1.77)	1.24 (1.05–1.46)	0.48
Weight, per 20 kg	1.09 (0.97–1.23)	1.32 (1.02–1.71)	1.12 (0.98–1.29)	0.19
Hypertension	1.32 (1.08–1.61)	1.31 (0.87–1.98)	1.31 (1.04–1.65)	0.64
Diabetes mellitus	0.97 (0.78–1.20)	1.15 (0.76–1.72)	0.99 (0.77–1.26)	0.20
Alcohol use	0.96 (0.79–1.16)	1.61 (1.08–2.41)	0.81 (0.64–1.01)	0.004
Smoking	1.21 (0.82–1.77)	1.54 (0.75–3.16)	1.13 (0.71–1.78)	0.30
Exercise >1 day/week	0.83 (0.69–1.00)	0.81 (0.56–1.16)	0.82 (0.66–1.02)	0.86
Coronary artery disease	2.17 (1.40–3.37)	1.82 (0.74–4.51)	2.38 (1.44–3.94)	0.35
Heart failure	4.76 (3.51–6.49)	3.62 (2.03–4.50)	5.43 (3.77–7.87)	0.10

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