Atrial fibrillation (AF) occurs frequently in patients with chronic obstructive pulmonary disease. Epidemiologic studies have found inconsistent associations between lung function and AF, and none have studied pulmonary emphysema, which overlaps only partially with chronic obstructive pulmonary disease in the general population. The aim of this study was to assess the relation among lung function measured by spirometry, the percentage of emphysema-like lung on computed tomography, and incident AF. The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study following 6,814 subjects free of clinical cardiovascular disease, including AF, at baseline. Spirometry was performed in a subset of 3,965 participants. Percentage emphysema was defined on baseline computed tomographic scans as lung regions <950 Hounsfield units. Incident AF was identified from hospital discharge diagnosis and Medicare claims data. Cox proportional hazards models were used to assess independent associations of lung volumes and percentage emphysema with AF. A total of 3,811 participants with valid spirometric results were included in this study. The mean age was 64.5 ± 9.8 years, and 49.4% were men. AF developed in 149 subjects (3.8%) over a mean follow-up period of 4.1 years after spirometry. Lower levels of forced expiratory volume at 1 second and forced vital capacity were associated with a higher risk for AF (hazard ratios 1.21 and 1.19 per 500 ml, respectively, p <0.001) after adjustment for demographic and cardiovascular risk factors. Percentage emphysema was not significantly related to AF. In conclusion, in a multiethnic community-based sample of subjects free of cardiovascular disease at baseline, functional airflow limitation was related to a higher risk for AF.
Data from multiple epidemiologic studies have identified risk factors for the development of atrial fibrillation (AF), including hypertension, smoking, obesity, diabetes, ischemic heart disease, congestive heart disease, and valvular heart disease. Atrial arrhythmias occur in increased frequency in patients with chronic obstructive pulmonary disease (COPD). Results from previous cohort studies have shown inconsistent relations between lung function indexes and incident AF. Furthermore, the numbers of AF events were relatively small, and participants were of limited age groups, were ethnically homogenous, and had prevalent cardiac disease at study onset. COPD overlaps partially with emphysema, which is characterized by the destruction of alveolar walls and permanent enlargement of air spaces distal to the terminal bronchioles. In this post hoc analysis, we aimed to examine the relation among lung function and the percentage of emphysema-like lung (hereafter referred to as percentage emphysema) on computed tomographic (CT) imaging and incident AF in a multiethnic population sample free of cardiovascular disease at baseline.
Methods
The Multi-Ethnic Study of Atherosclerosis (MESA) is a multicenter cohort study designed to investigate the prevalence, correlates, and progression of subclinical cardiovascular disease in subjects without previous clinical cardiovascular disease. The details of the study design have been previously described. The participants of MESA were 6,814 men and women aged 45 to 84 years who were white, African-American, Hispanic, or Chinese. Exclusion criteria included clinical cardiovascular disease, current AF, pregnancy, active cancer treatment, weight >300 lb, any cardiovascular procedure, or any serious medical condition that precluded long-term participation. The MESA-Lung Study enrolled 3,965 participants who were sampled randomly from MESA participants who consented to genetic analyses, underwent baseline measures of endothelial function, and attended examinations during MESA-Lung recruitment from 2004 to 2006. The protocols of all studies described herein were approved by the institutional review boards of all collaborating institutions and the National Heart, Lung and Blood Institute, and all participants provided informed consent.
The MESA-Lung Study quantitatively assessed percentage emphysema on the lung fields of all baseline MESA cardiac computed tomographic scans (2000 to 2002), which included approximately 70% of the lung volume from the carina to the lung bases. Percentage emphysema was reported as the percentage of the total voxels in the imaged lung, as well as in the upper and lower lung, with radiodensity <950 Hounsfield units. Spirometry was conducted from 2004 to 2006 in accordance with American Thoracic Society and European Respiratory Society recommended guidelines.
For the purpose of this study, except spirometric data that were collected from 2004 to 2006, all covariates, including CT parameters, were derived from the MESA baseline examinations from 2000 to 2002. Standard questionnaires were used to ascertain smoking. Height was measured to the nearest 0.1 cm with the subject in stocking feet. Weight was measured to the nearest pound with the subject in light clothing using a balanced scale. Blood pressure at rest was measured using the Dinamap Monitor PRO 100 (Critikon, Tampa, Florida) automated oscillometric device. Serum glucose and total and high-density lipoprotein cholesterol were measured from blood samples after a 12-hour fast, which were frozen at the time of processing and sent in weekly shipments for assay. The diagnosis of diabetes mellitus was based on the use of insulin or oral hypoglycemic medication or fasting glucose ≥126 mg/dl. Impaired fasting glucose was considered present if fasting glucose ranged from 100 to 125 mg/dl. Low-density lipoprotein cholesterol was calculated with the Friedewald equation. Participants were reexamined at 4 subsequent clinic visits after the baseline examination. In addition, a telephone interviewer contacted each participant every 9 to 12 months to inquire about all interim hospital admissions and cardiovascular outpatient diagnoses. Inpatient medical records were requested for hospitalizations with cardiovascular diagnoses, including AF. In the present study, we defined AF by the presence of a hospital discharge International Classification of Diseases, Ninth Revision, diagnosis code for AF or atrial flutter (427.31 and 427.32, respectively) in any position. In addition, for subjects >65 years of age and enrolled in fee-for-service Medicare, we classified AF as present if the Medicare inpatient claims data included an International Classification of Diseases, Ninth Revision, code for AF or atrial flutter in any position. The date of incident AF was assumed to be the date of the earliest hospital admission with an AF or atrial flutter diagnosis.
Participant characteristics were summarized using percentage for discrete variables and means and SDs for continuous variables ( Table 1 ). Pearson chi-square and 2-sample Student’s t test p values were obtained separately for each of these covariates. Cox proportional hazards models were used to estimate hazard ratios for the association of risk factors with time to heart failure, with death and loss to follow-up being treated as censored. Lung function and log-transformed percentage emphysema were assessed in models adjusted for demographic and cardiovascular risk factors. Because lung CT studies were performed earlier than spirometric examinations, the follow-up times used in analyses were different. The mean follow-up time from lung CT examinations was 7.9 years and from spirometric measures was 4.1 years. Model 1 was adjusted for age, gender, ethnicity, height, and weight. Model 2 was further adjusted for cigarette smoking status, systolic blood pressure, diabetes status, total and high-density lipoprotein cholesterol, heart rate, alcohol use, and exercise. Natural log transformations were applied to percentage emphysema measure because of skewed distribution. We also looked at risk for AF and severity of reduction in percent predicted forced expiratory volume in 1 second (FEV 1 ; mild [FEV 1 ≥80%], moderate [FEV 1 50% to <80%], or severe [FEV 1 <50%]) on the basis of the severity classification by the Global Initiative for Chronic Obstructive Lung Disease.
| Variable | Atrial Fibrillation | |
|---|---|---|
| Yes (149) | No (3662) | |
| Age (years) | 72.6±10.0 ∗ | 64.4±8.0 |
| Male | 62.2% ∗ | 46.6% |
| Race/Ethnicity | ||
| White | 56.8% ∗ | 39.0% |
| African-American | 20.1% | 27.5% |
| Hispanic | 16.2% | 21.5% |
| Asian | 6.9% | 12.0% |
| Height (cm) | 168.2±10.0 ∗ | 166.0±9.9 |
| Weight (lbs) | 178.3±37.8 β | 172.4±38.3 |
| Body mass index (kg/m 2 ) | 28.6±5.4 | 28.3±5.5 |
| Systolic blood pressure (mm per Hg) | 127.0±21.2 ∗ | 123.1±20.6 |
| Diastolic blood pressure (mm per Hg) | 68.5±9.9 † | 70.0±10.0 |
| Any hypertension medicine | 50.8% ∗ | 33.7% |
| Heart rate (beats/minute) | 61.1±10.2 | 62.9±9.2 |
| Diabetes mellitus | 16.1% | 15.0% |
| Impaired fasting glucose | 19.2% | 15.5% |
| Fasting glucose (mg/dl) | 101.2±35.6 | 98.3±26.3 |
| Total cholesterol (mg/dl) | 173.5±34.9 ∗ | 194.3±34.8 |
| Low density lipoprotein cholesterol (mg/dl) | 99.4±28.6 ∗ | 112.0±31.8 |
| High density lipoprotein cholesterol (mg/dl) | 49.8±16.0 ∗ | 51.8±15.0 |
| Triglycerides (mg/dl) | 128.3±122.7 | 128.0±85.5 |
| Any lipid lowering medicine | 19.2% ∗ | 15.3% |
| FEV1 (ml) | 2212.3±748.9 β | 2389.5±730.0 |
| FEV6 (ml) | 2887.9±904.4 | 3020.2±890.3 |
| FVC (ml) | 3099.2±925.4 | 3191.6±956.2 |
| FEV1 percent predicted | 88.2±21.2 ∗ | 94.0±18.0 |
| FEV6 percent predicted | 89.9±18.0 ∗ | 94.7±16.3 |
| FVC percent predicted | 91.3±17.4 ∗ | 95.6±16.2 |
| FEV1/FVC | 0.72±0.1 ∗ | 0.75±0.09 |
| FEV1/FVC percent predicted | 96.7±13.6 † | 98.5±10.8 |
| FEF 2575 (ml) | 1640.4±970.0 ∗ | 2042.6±1026.2 |
| PEF (ml) | 6455.6±2286.3 ∗ | 7004.0±2147.4 |
| Restrictive defect | 5.7% | 3.8% |
| Percent emphysema | 4.74±4.95 | 4.27±4.41 |
| Ever smoker | 62.5.% ∗ | 54.3% |
| Pack years (in current smokers) | 32.6±34.0 ∗ | 22.9±24.2 |
| Current alcohol use | 61.7% | 55.6% |
| Exercise (MET-mins/week) | 1397.05±1830.78 | 1582.79±2406.92 |
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