Obesity is associated with an increased likelihood for the development of atrial fibrillation (AF) and with worsened AF symptom severity. However, other factors that are correlated with obesity may confound or mediate the relation of obesity with AF symptom severity. The purpose of this study was to determine if depression and physical inactivity may confound the association of obesity and AF symptom severity. Health status and demographic data were captured by questionnaire for 332 outpatients with documented AF. Weight/height was measured and body mass index (kg/m 2 ) calculated. Recent depression symptom severity was assessed using the Patient Health Questionnaire-9 questionnaire. Physical activity during the last month was assessed by questionnaire. AF symptom severity was assessed using the University of Toronto AF Severity scale. Multivariate linear regression was used to evaluate which factors were associated with AF symptom severity. Obesity in patients with AF is associated with increased depression severity. In bivariate analysis, increasing body mass index (p = 0.001), lower levels of physical activity (p <0.001), and more severe depression (p <0.001) were associated with worsened AF symptom severity. In multivariate analysis, only physical activity and depression persisted as significant predictors of AF symptom severity. In conclusion, although obesity likely contributes to the substrate predisposing to the development of AF, other factors may contribute to or mediate the worsened AF symptoms associated with obesity. Depression symptoms and physical inactivity, factors closely correlated with obesity, may exacerbate symptoms in patients with AF.
Recent studies have established a correlation between obesity and worsened atrial fibrillation (AF) symptom burden and symptom severity. Poor physical activity, which is associated with obesity, is also associated with increased AF symptom severity. Symptom severity is particularly important for managing AF, as it drives patient and provider desire to address AF with interventional treatments such as ablation. Prospective studies have evaluated the change in AF symptom severity after implementation of targeted measures to reduce body mass index (BMI) and increase physical activity, finding that decreases in body mass and increases in exercise levels lead to lower AF symptom severity and decreased likelihood of AF recurrence with or without therapy including antiarrhythmic drugs or catheter ablation. Factors that may be associated with obesity, including depression and anxiety, have been associated with increased AF symptom severity. Although evidence suggests that there is a strong association of BMI and exercise levels with AF symptom severity, no studies have incorporated psychiatric co-morbidities, which may confound the relations of obesity and physical activity with AF symptoms. Depression and anxiety are common co-morbidities in patients with AF with approximate rates of 38% in patients with AF. To understand if psychological co-morbidities may affect the relation between obesity and physical fitness with AF symptom severity, we analyzed the effect of obesity, physical fitness, and depression separately and in combined models in a single-center registry of patients with AF.
Methods
The Symptom Mitigation in Atrial Fibrillation study is a single-center (University of North Carolina) prospective cohort study of AF health outcomes and symptoms in stable outpatients with documented AF. Eligible participants had at least one documented episode of AF by electrocardiogram or continuous heart monitor without a reversible cause. Vulnerable patient populations including minors and prisoners were excluded from the study. Appropriate institutional review board approval was garnered, and written informed consent was obtained from all participants.
Participants were enrolled through University of North Carolina electrophysiology outpatient clinics on referral for AF management. At the time of study enrollment, participants completed baseline questionnaires of demographic and health status information. This study included 332 patients who were enrolled from September 2009 to January 2012.
Patient height and weight was collected at the time of enrollment and used to calculate BMI. Obesity was classified using the National Heart Lung and Blood Institute guidelines; subjects with a BMI ≥30 were deemed obese. We further classified BMI into 6 categories, according to National Heart Lung and Blood Institute guidelines: underweight (BMI <18), healthy weight (18< BMI <25), overweight (25< BMI <30), mildly obese (30< BMI <35), moderately obese (35< BMI <40), and extremely obese (BMI >40). Physical activity was measured by survey. Participants were asked how much exercise they engaged in the last month. Exercise was defined as 15 to 20 minutes of brisk walking, swimming, general conditioning, or recreational sports. Participants answered with Likert scale responses categorized as: not at all active, a little active (1 to 2 times a month), fairly active (3 to 4 times a month), quite active (1 to 2 times a week), very active (3 to 4 times a week), or extremely active (5 or more times a week). Depression severity was obtained from the Patient Health Questionnaire (PHQ)-9, consisting of 9 questions, scored from 0 to 3, each correlated to one of the Diagnostic and Statistical Manual of Mental Disorders-IV criteria. Studies have documented the validity and high internal consistency of the PHQ-9 questionnaire. Depression severity was stratified into 5 categories based on score: minimal depression (0 to 4), mild depression (5 to 9), moderate depression (10 to 14), moderately severe depression (15 to 19), and severe depression (20 to 27). Obesity, physical activity, and depression were analyzed as categorical variables (as described previously) as well as continuous variables.
The 7-item AF symptom severity subscale of the widely validated, 19-question University of Toronto AF Severity Scale (AFSS) was used to calculate an AF symptom severity score, which we used as our outcome measurement. The symptom severity subscale of the AFSS questionnaire assesses symptoms attributed to AF, including: palpitations, shortness of breath at rest, exercise intolerance, tiredness at rest, lightheadedness/dizziness, and chest pain or pressure. Participants were asked how bothered they had been by the aforementioned symptoms (if at all) in the past 4 weeks. Responses were scored on a 5-point Likert scale, with higher scores on the 0 to 35 scale representative of higher AF symptom severity levels.
Patient demographic information and co-morbidities were assessed by chart review and baseline questionnaires. Co-morbidities assessed included: hypertension, heart failure, diabetes, a cerebral vascular accident or transient ischemic attack, coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty or percutaneous coronary intervention, and myocardial infraction.
We first used univariate statistics to evaluate frequency distributions for categorical variables and means, SDs, and shapes of distributions for continuous variables. Bivariate statistics were used to compare obese and nonobese patients based on demographic and medical history. To do this, we used Student t tests for continuous variables and chi-squared analyses for categorical variables.
We then used bivariate and multivariate linear regression to evaluate the relation of BMI, depression severity, and physical activity independently and in several combined models with AF symptom severity as the outcome. Predictors were included in the model as categorical or continuous variables. All statistical analyses were completed using STATA, version 11 (StataCorp LP, College Station, Texas). Statistical tests were 2-tailed, with p <0.05 considered significant.
Results
Table 1 depicts demographic data specific to all patients, stratified by obesity as a dichotomous variable (< or ≥30 kg/m 2 ). Patients in our study population were majority men. Co-morbidities of the study cohort included hypertension, congestive heart failure, diabetes, previous cerebral vascular accident or transient ischemic attack, a history of myocardial infraction, CABG, and percutaneous transluminal coronary angioplasty or percutaneous coronary intervention. Of the patient population, nearly half indicated that they were not at all active or only a little active (classified as 15 to 20 minutes of exercise once or twice a month). The mean PHQ-9 score of patients indicated a mild severity of depression. The mean BMI of our study population was 32.3 ± 8.2. The mean AFSS symptom severity subscale score was 13.1 ± 8.2. Obese patients were significantly younger, more likely to have diabetes, and less likely to have undergone a CABG procedure. In addition, obese patients had significantly greater depression severity scores.
| Variable | Overall (n= 332) | BMI<30 (n= 237) | BMI>/=30 (n= 95) | P-Value |
|---|---|---|---|---|
| Age, mean (years) | 60.1 ± 15.8 | 61.9 ± 16.5 | 55.7 ± 12.7 | 0.0012 † |
| Male | 237 (71.4%) | 163 (68.8%) | 61 (64%) | 0.422 |
| Myocardial Infraction | 234 (71.1%) | 19 (8.1%) | 7 (7%) | 0.819 |
| Hypertension | 199 (59.9%) | 140 (59.1%) | 59 (62%) | 0.610 |
| Congestive Heart Failure | 46 (13.9%) | 28 (11.9%) | 18 (19%) | 0.085 |
| Diabetes | 67 (20.1%) | 41 (17.3%) | 26 (27%) | 0.039 ∗ |
| CVA/TIA | 30 (9.1%) | 21 (9.0%) | 9 (10%) | 0.869 |
| CABG | 13 (4.0%) | 13 (5.6%) | 0 (0%) | 0.02 ∗ |
| PCTA/PCI | 27 (8.3%) | 21 (9.1%) | 6 (7%) | 0.443 |
| Depression (PHQ9), mean | 5.3 ± 5.1 | 4.8 ± 4.7 | 6.4 ± 5.7 | 0.011 ∗ |
| Exercise Last Mo | 0.063 | |||
| Not at all active | 93 (28.0%) | 60 (25.3%) | 33 (35%) | |
| A little active (1 to 2 times a month) | 67 (20.2%) | 44 (18.6%) | 23 (24%) | |
| Fairly active (3 to 4 times a month) | 43 (13.0%) | 30 (12.7%) | 13 (14%) | |
| Quite active (1 to 2 times a week) | 46 (13.9%) | 35 (14.8%) | 11 (12%) | |
| Very active (3 to 4 times a week) | 50 (15.1%) | 38 (16.0%) | 12 (13%) | |
| Extremely Active (>/= 5 times a week) | 33 (9.9%) | 176 (12.7%) | 3 (3%) | |
Increased depression symptom severity as a categorical variable was associated with increased AF symptom severity ( Figure 1 ). Increased physical activity as a categorical variable was associated with decreased AF symptom severity ( Figure 2 ). Increased BMI as a categorical variable was also associated with increased AF symptom severity ( Figure 3 )
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