Obesity is associated with new-onset atrial fibrillation (AF). However, the effect of obesity on AF recurrence or burden has not been studied. The aim of this study was to investigate the relation between AF recurrence, AF burden, and body mass index (BMI). A limited-access data set from the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial provided by the National Heart, Lung, and Blood Institute was used. Statistical analysis was done with a generalized linear mixed model. In 2,518 patients who had BMIs recorded, higher BMI was associated with a higher number of cardioversions (odds ratio [OR] 1.017, 95% confidence interval [CI] 1.005 to 1.029 for a BMI increase of 1 kg/m 2 ; OR 1.088, 95% CI 1.024 to 1.155 for a BMI increase of 5 kg/m 2 ; OR 1.183, 95% CI 1.049 to 1.334 for a BMI increase of 10 kg/m 2 ; p = 0.006 for each). Increased BMI was also associated with a higher likelihood of being in AF on follow-up (OR 1.020, 95% CI 1.002 to 1.038 per 1 kg/m 2 increased BMI, p = 0.0283; OR 1.104, 95% CI 1.011 to 1.205 per 5 kg/m 2 increased BMI, p = 0.0283; OR 1.218, 95% CI 1.021 to 1.452 per 10 kg/m 2 increased BMI, p = 0.0283). In a multivariate analysis, left atrial size but not BMI was an independent predictor of AF recurrence and AF burden. Because left atrial size was correlated with BMI, the effect of BMI on AF can be likely explained by greater left atrial size in subjects with higher BMIs. In conclusion, obesity is associated with a higher incidence of recurrence of AF and greater AF burden.
Obesity is a risk factor for the development of new-onset atrial fibrillation (AF). Multiple studies have documented a strong and independent association between body mass index (BMI) and the incidence of AF. In the Framingham Heart Study, obese participants had a 45% to 50% increased risk for incident AF compared to participants with normal BMI, independent of other cardiovascular risk factors. In a Danish study, overweight subjects were also at increased risk for incident AF. In addition to increasing the susceptibility of developing AF, a recent longitudinal cohort study over 21 years suggested that obesity was an independent predictor of progression from paroxysmal to permanent AF. However, the association between obesity and total AF burden or recurrence rate has not been studied.
Methods
To evaluate the relation of obesity with recurrence of AF or burden of AF, we used a limited access data set from the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial, provided by the National Heart, Lung, and Blood Institute (Bethesda, Maryland). Detailed selection criteria for the study population, their baseline characteristics, and randomization into rate-control versus rhythm-control arms was previously explained.
Our main independent variable was BMI. We used BMI (calculated as weight in kilograms divided by height in meters squared) entered in the data set by the AFFIRM investigators as a surrogate measure of obesity. It was analyzed as a continuous and a categorical variable.
Two outcome measures were AF recurrence and AF burden. We used the number of cardioversions done throughout the follow-up period (electrical as well as pharmacological) as a surrogate marker of AF recurrence, and the number of follow-up visits when patients were in AF as a surrogate marker of AF burden. All the data were analyzed with a generalized linear mixed model using SAS (SAS Institute Inc., Cary, North Carolina). A univariate analysis was done first to identify variables linked to the recurrence rate and total burden of AF. The connection between BMI as our main variable of interest and the 2 outcomes was then examined in detail, for the whole AFFIRM population and for the rate- and rhythm-control arms separately.
The following variables were also checked for association with AF recurrence rate or AF burden: age, use of angiotensinogen-converting enzyme inhibitors, use of β blockers, systolic blood pressure, history of hypertension, history of coronary artery disease, history of coronary artery bypass surgery, history of congestive heart failure, history of diabetes, history of cardiomyopathy, history of myocardial infarction, New York Heart Association class at baseline, the left ventricular ejection fraction, and left atrial size. Variables found to be significantly associated with the outcomes were then put in a multivariate model. Because left ventricular ejection fractions were missing in >50% of the cases, we calculated fractional shortening on the basis of left ventricular systolic and diastolic dimensions (fractional shortening = [left ventricular diastolic dimension − left ventricular systolic dimension]/left ventricular diastolic dimension) and used it for the final analysis. A p value of <0.05 was considered statistically significant.
Results
In the AFFIRM study, 4,060 patients were enrolled at baseline. We excluded 1,542 patients who did not have baseline BMI information. Of the remaining 2,518 patients, 1,255 were assigned to the rate-control arm and 1,263 to the rhythm-control arm; the mean BMIs were 29.0 and 28.8 kg/m 2 , respectively. These 2,518 patients had 22,753 follow-up visits and a total of 1,094 cardioversions, either pharmacologic or electrical: 888 in the rhythm-control arm and 206 in the rate-control arm.
In a univariate analysis, BMI, left atrial size, age, and history of hypertension were independently associated with a higher AF recurrence rate ( Table 1 ).
| Variable | Number of Cardioversions | Number of Follow-Up Visits in AF | ||||
|---|---|---|---|---|---|---|
| OR | 95% CI | p Value | OR | 95% CI | p Value | |
| BMI | 1.016 | 1.004–1.029 | 0.0086 | 1.01 | 0.99–1.02 | 0.4233 |
| Age | 0.99 | 0.981–0.999 | 0.0244 | 1.02 | 0.82–1.26 | 0.857 |
| Hypertension ⁎ | 1.236 | 1.064–1.50 | 0.0075 | 0.99 | 0.98–1.00 | 0.1403 |
| Left atrial size | 1.345 | 1.158–1.561 | 0.0001 | 1.32 | 1.14–1.54 | 0.0003 |
In the study population as a whole (n = 2,518), higher BMI was associated with a greater number of cardioversions. The odds ratios (OR) of receiving cardioversion were 1.017 (95% confidence interval [CI] 1.005 to 1.029, p = 0.006) for a BMI increase of 1 kg/m 2 , 1.088 (95% CI 1.024 to 1.155, p = 0.006) for a BMI increases of 5 kg/m 2 , and 1.183 (95% CI 1.049 to 1.334, p = 0.006) for a BMI increase of 10 kg/m 2 .
In the rhythm-control arm (n = 1,263), in which a higher rate of cardioversions was expected, the ORs for cardioversion were 1.015 (95% CI 1.003 to 1.028), 1.079 (95% CI 1.013 to 1.148), and 1.164 (95% CI 1.027 to 1.319) for BMI increases of 1, 5, and 10 kg/m 2 , respectively (p = 0.0178 for each). In the rate-control arm, in which there was a lower rate of cardioversions, the association between BMI and number of cardioversions was not significant ( Table 2 ).
| BMI Increase (kg/m 2 ) | Study Arm | Cardioversions | ||
|---|---|---|---|---|
| OR | 95% CI | p Value | ||
| 1 | Rate control | 1.023 | 0.99–1.058 | 0.1788 |
| Rhythm control | 1.015 | 1.003–1.028 | 0.0178 | |
| 5 | Rate control | 1.121 | 0.949–1.323 | 0.1788 |
| Rhythm control | 1.079 | 1.013–1.148 | 0.0178 | |
| 10 | Rate control | 1.256 | 0.901–1.751 | 0.1788 |
| Rhythm control | 1.164 | 1.027–1.319 | 0.0178 | |
When patients were classified into underweight (BMI <18.5 kg/m 2 ), normal weight (BMI 18.5 to 24.9 kg/m 2 ), overweight (BMI 25 to 29.9 kg/m 2 ), and obese (BMI ≥30 kg/m 2 ), obese patients were more likely to undergo cardioversion (OR 1.268, p = 0.0194; Table 3 ), with normal-weight patients used as a reference. We did not find a significant association between obesity and the number of cardioversions in the rate-control arm. However, in the rhythm-control arm, the OR of requiring cardioversion in obese subjects was 1.291 (p = 0.0173), with normal weight used as a reference.
| Study Arm | BMI (kg/m 2 ) | Number of Cardioversions | OR | 95% CI | p Value |
|---|---|---|---|---|---|
| Total | <18.5 | 10 (6.2%) | 1.518 | 0.68–3.391 | 0.3086 |
| 18.5–24.9 | 231 (4.2%) | Reference | |||
| 25–29.9 | 401 (4.5%) | 1.056 | 0.863–1.291 | 0.5987 | |
| ≥30 | 452 (5.4%) | 1.268 | 1.039–1.548 | 0.0194 | |
| Rate control | <18.5 | 1 (2.1%) | 1.511 | 0.138–16.513 | 0.7353 |
| 18.5–24.9 | 39 (1.5%) | Reference | |||
| 25–29.9 | 87 (1.9%) | 1.164 | 0.733–1.849 | 0.5194 | |
| ≥30 | 79 (2.0%) | 1.236 | 0.773–1.977 | 0.3755 | |
| Rhythm control | <18.5 | 9 (7.8%) | 1.176 | 0.533–2.594 | 0.6875 |
| 18.5–24.9 | 192 (6.8%) | Reference | |||
| 25–29.9 | 314 (7.5%) | 1.107 | 0.892–1.372 | 0.3562 | |
| ≥30 | 373 (8.7%) | 1.291 | 1.046–1.593 | 0.0173 | |
During each follow-up visit, the current rhythm was recorded as AF versus no AF (presumed sinus rhythm). Of 22,374 follow-up visits, patients were found to be in AF or atrial flutter on 8,686 visits: 6,289 in the rate-control group and 2,397 in the rhythm-control arm. Using a linear mixed model, the ORs of a patient being in AF or atrial flutter were 1.020 (95% CI 1.002 to 1.038) per 1 kg/m 2 BMI increase, 1.104 (95% CI 1.011 to 1.205) per 5 kg/m 2 BMI increase, and 1.218 (95% CI 1.021 to 1.452) per 10 kg/m 2 BMI increase (p = 0.0283 for each).
In the rate-control arm, obese (BMI ≥30 kg/m 2 ) patients had an OR of 1.55 (p = 0.0484) of being in AF on a follow-up visit, when normal weight (BMI 18.5 to 24.9 kg/m 2 ) was used as a reference ( Table 4 ). No significant association between BMI and the likelihood of being in AF was found in the rhythm-control arm.
