Abstract
Background
Atrial fibrillation (AF) is a common arrhythmia that affects over 2 million people in the United States. We sought to determine whether the risk of incident AF among patients treated for hypertension differs by the degree of blood pressure control.
Methods
A population based, case-control study of 433 patients with verified incident AF and 899 controls was conducted to investigate the relationship between average achieved systolic (SBP) and diastolic (DBP) blood pressure and risk of AF. All patients were members of an integrated health care delivery system and were pharmacologically treated for hypertension. Medical records were reviewed to confirm the diagnosis of new onset AF and to collect information on medical conditions, health behaviors, and measured blood pressures. Average achieved SBP and DBP were calculated from the three most recent outpatient blood pressure measurements.
Results
Compared with the reference level of 120-129 mm Hg, for categories of average achieved SBP of <120, 130-139, 140-149, 150-159, 160-169 and ≥170 mm Hg, the odds ratios (95% confidence interval) for incident AF were 1.99 (1.10, 3.62), 1.19 (0.78, 1.81), 1.40 (0.93, 2.09), 2.02 (1.30, 3.15), 2.27 (1.31, 3.93) and 1.84 (0.89, 3.80), respectively. Based on the population attributable fraction (PAF), we estimated that, among patients with treated hypertension, 17.2% (95% CI 4.3%, 28.3%) of incident AF was attributable to an average achieved SBP ≥140 mmHg.
Conclusion
Among patients treated for hypertension, uncontrolled elevated SBP and SBP <120 mm Hg were associated with an increased risk of incident AF.
INTRODUCTION
Atrial fibrillation (AF) is a common arrhythmia that affects over 2 million people in the US1. AF is independently associated with an increased risk of stroke and death2,3. The incidence of AF doubles with each successive age decade beyond 50 years4, and the number of patients with AF is likely to increase 2.5 fold during the next 50 years5.
Prior studies have reported an association between hypertension and AF6. According to the National Health and Nutrition Examination Survey (NHANES) III, hypertension affects at least 50 million Americans7,8. Data from NHANES III indicate that only about half of all persons treated with anti-hypertensive medication achieve target blood pressure levels7. Given the established relationship between hypertension and AF, the degree to which blood pressure is controlled may be an important prognostic indicator of incident AF. We hypothesized that among patients treated for hypertension, uncontrolled compared with controlled blood pressure would be associated with a higher risk of new-onset AF.
MATERIALS AND METHODS
Study Setting and Design
This case-control study was conducted at Group Health (GH), a health care delivery system based in Washington State with more than 500,000 members9. The GH Human Subjects Review Committee approved the study procedures.
Study Subjects
We identified all GH members with an International Classification of Diseases, Ninth Revision (ICD-9) code for atrial fibrillation or flutter (427.31, 427.32) at any inpatient or outpatient visit between October 1, 2001 and September 30, 2003, who had never before been assigned an AF code during their enrollment at GH. Abstractors reviewed outpatient and inpatient medical records to confirm the diagnosis of incident AF and to determine eligibility. Cases were considered eligible if the medical record documented a first diagnosis of AF by 12-lead electrocardiogram and clinical recognition of the diagnosis by a physician. Cases with perioperative AF were considered eligible only if the AF persisted to the time of hospital discharge (n=2). Cases in whom AF occurred as part of a terminal hospitalized illness were not eligible.
Control patients were shared between this study and companion case-control studies of myocardial infarction (MI), stroke and venous thrombosis10,11. Controls were randomly sampled from the GH enrollment lists, and were frequency-matched to the largest case group, MI cases, on age, sex, and calendar year of presentation.
For cases, the index date was defined as the date AF was first clinically recognized, and for controls, it was randomly assigned within the range of cases’ index dates. Patients were 30 to 84 years of age at the index date. Cases and controls were required to have at least four visits to a GH provider before the index date and to have treated hypertension at the index date, defined as a physician diagnosis of hypertension and treatment with an anti-hypertensive medication for at least 30 days before the index date. We excluded controls with a pacemaker inserted before the index date (n = 6), to match the exclusion criteria for the AF cases, and controls with a prior history of AF. AF cases and controls (n = 157) with a history of clinically recognized congestive heart failure before the index date were excluded.
Data Collection
Outpatient and inpatient medical records covering a median of 20 years of enrollment were reviewed identically for cases and controls. Trained abstractors gathered information on demographic and clinical characteristics and medical history assessed prior to the index date: age, sex, height, weight, blood pressures, hypertension, diabetes, valvular heart disease, coronary disease, stroke, serum creatinine and hyperlipidemia. Telephone interviews were used to collect additional demographic and health behavior information including self-reported race (White, Black, Asian, Pacific Islander, American Indian, other), smoking status, and alcohol consumption prior to index date. If a telephone interview was not completed, these data were obtained from the medical record. Information on anti-hypertensive medication use at the index date was obtained from the GH automated pharmacy database.
Blood pressure measurement
For all patients, we recorded the three most recent outpatient blood pressure measurements before the index date and from these, calculated the average achieved SBP and DBP before the index date. For patients whose hypertension was first diagnosed and treated during GH enrollment, we recorded the three outpatient blood pressure measurements just before anti-hypertensive treatment was begun and from these, calculated the average pre-treatment SBP and DBP.
Atrial fibrillation classification
Incident AF was classified based on the duration and persistence of AF over the first 6 months after AF onset using a classification scheme based on the American College of Cardiology/American Heart Association/European Society of Cardiology (ACC/AHA/ESC) guidelines12. Some modification was required because we were evaluating AF pattern over 6 months rather than at a single time point. AF was classified as transitory if the initial episode of AF lasted ≤7 days without recognized recurrence over the next 6 months; persistent/intermittent if the AF lasted >7days or if AF recurred, but sinus rhythm was also documented in next 6 months (similar to the ACC/AHA/ESC categories of persistent and paroxysmal); or sustained if the patient was continuously in AF over the 6 months following onset (similar to the ACC/AHA/ESC category of permanent). An AF classification could not be determined for 4 cases.
Covariates
Anti-hypertensive medication use at the index date was obtained from the GH automated pharmacy database. Among patients in this age group, 96% of GH members report filling all or almost all prescriptions through GH pharmacies13. The medication fill for each anti-hypertensive medication immediately before the index date was identified to determine whether the quantity dispensed would last until the index date at 80% compliance. If so, and if the patient was also a user 30 days prior to index date, the patient was classified as a current user of that medication. Diabetes, hyperlipidemia, valvular heart disease, MI, and stroke were considered present if there was a physician diagnosis in the medical record prior to the index date. Hyperthyroidism was defined as a physician diagnosis of hyperthyroidism during the evaluation for new-onset AF or receipt of a medicaiton used to treat hyperthyroidism before the index date. Kidney function was estimated using the most recent serum creatinine measurements before the index date. The glomerular filtration rate (GFR) was calculated using the Cockcroft-Gault equation in order to correct for age, sex and weight14. Severe kidney disease was defined as a GFR of < 30 ml/min/1.73 m2 15.
Data Analyses
Average achieved blood pressure before the index date was modeled in categories and as a continuous variable. Increments of one standard deviation of average achieved SBP and DBP were used in analyses with a continuous blood pressure variable. Body mass index (BMI) was calculated as weight in kilograms divided by the square of height in meters. Descriptive analyses were performed to examine characteristics associated with AF and with average achieved SBP or DBP. Multivariate logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for the relationship between average achieved blood pressure and incident AF. All models were adjusted for the matching variables of age (as a continuous variable, measured in terms of days), sex and index year. Statistical models were adjusted for additional patient characteristics if their inclusion materially changed the estimated coefficients for blood pressure. We did not adjust for history of MI or stroke, as these conditions may be caused in part by elevated blood pressure and could be in the causal pathway between elevated blood pressure and AF. The PAF was calculated to estimate the AF disease burden in the population that might be explained by uncontrolled blood pressure16. A p-value of ≤ 0.05 was considered as statistically significant. All analyses were performed using Stata 8.2 (StataCorp LP, College Station, Texas).
RESULTS
A total of 515 eligible AF cases and 1,003 eligible controls with treated hypertension were identified during the study period. We excluded 82 AF cases and 114 controls that were not sufficiently compliant with their anti-hypertensive medication to be considered treated on the index date, leaving 433 AF cases and 889 controls.
As compared to controls, AF cases were more likely to be older, female and white (Table 1). Diabetes mellitus, history of stroke, MI, and valvular heart disease were more common among AF cases than controls as was use of thiazide or loop diuretics. Controls were more likely to be using ACE inhibitors. Duration of treated hypertension was available for 85% of cases and 84% of controls. The average duration of treated hypertension was 12 and 11 years, respectively for cases and controls, and only 4% of cases and 3% of controls had treated hypertension for less than 6 months before the index date. For both cases and controls, 90% of all blood pressures used to compute average achieved blood pressure were measured within 2 years before the index date. The average intervals between the AF event and the three most recent blood pressure measurements were 3, 6, and 13 months, and the corresponding average intervals for controls were 5, 9 and 12 months. Cases had complete records on each blood pressure measurement, and records for controls were 99.8% complete. Cases were more likely to have an average achieved SBP ≥150 mm Hg, while the distribution of average achieved DBP was similar between cases and controls. An average pre-treatment blood pressure measurement was available for 74% of cases and 72% of controls. The distribution of average pre-treatment SBP and DBP was similar between cases and controls.
Table 1.
Characteristics of atrial fibrillation cases and controls
| Cases | Controls | p -value | |
|---|---|---|---|
| Characteristics a | n = 433 | n = 889 | |
| Age, mean (SD), y | 72 (9) | 67 (10) | § |
| Female (%) | 232 (53.6) | 380 (42.7) | § |
| White race (%) | 400 (93.0) | 769 (87.4) | < 0.01 |
| Duration of GH enrollment, mean (SD), y | 22 (12) | 20 (12) | 0.08 |
| Body mass index, mean (SD), kg/m2 | 31 (8) | 30 (6) | 0.36 |
| Alcohol (%) | 0.10 | ||
| Never or former | 180 (42.9) | 319 (37.6) | |
| Occasional | 179 (42.6) | 414 (48.9) | |
| Heavy | 61 (14.5) | 114 (13.5) | |
| Smoking (%) | 0.22 | ||
| Never or former | 403 (93.1) | 810 (91.1) | |
| Current | 30 (6.9) | 79 (8.9) | |
| Glomerular Filtration Rate (ml/min/1.73 m2) | < 0.01 | ||
| Stage 1 (normal) ≥ 90 | 119 (27.6) | 355 (40.2) | |
| Stage 2 (mild reduction) 60-89 | 165 (38.4) | 319 (36.2) | |
| Stage 3 (moderate reduction) 30-59 | 127 (29.5) | 191 (21.7) | |
| Stage 4 (severe reduction) 15-29 | 9 (2.1) | 12 (1.4) | |
| Stage 5 (kidney failure) <15 | 10 (2.3) | 5 (0.6) | |
| Diabetes mellitus (%) | 79 (18.2) | 132 (14.9) | 0.11 |
| Myocardial infarction (%) | 44 (10.2) | 68 (7.7) | 0.12 |
| Stroke (%) | 37 (8.6) | 46 (5.2) | 0.02 |
| Hyperlipidemia (%) | 99 (22.9) | 215 (24.2) | 0.60 |
| Valvular heart disease (%) | 18 (4.2) | 24 (2.7) | 0.16 |
| Anti-hypertensive medication (%) b | |||
| Thiazide or loop diuretic | 183 (42.3) | 321 (36.1) | 0.03 |
| Potassium-sparing diuretic | 55 (12.7) | 91 (10.2) | 0.18 |
| ACE inhibitor | 132 (30.5) | 345 (38.8) | < 0.01 |
| Beta blocker | 187 (43.2) | 360 (40.5) | 0.35 |
| Calcium channel blocker | 52 (12.0) | 108 (12.2) | 0.94 |
| Other | 16 (3.7) | 27 (3.0) | 0.53 |
| Serum potassium, mean (SD), mEq/L | 4.3 (0.5) | 4.3 (0.5) | 0.86 |
|
Duration of treated hypertension, mean (SD), y |
13 (9) | 12 (10) | 0.01 |
|
Average achieved systolic blood pressure, mean (SD), mm Hg |
144 (15) | 140 (14) | < 0.01 c |
| <120 (%) | 27 (6.2) | 50 (5.6) | < 0.01 d |
| 120-129 (%) | 46 (10.6) | 150 (16.9) | |
| 130-139 (%) | 91 (21.0) | 237 (26.7) | |
| 140-149 (%) | 124 (28.6) | 256 (28.8) | |
| 150-159 (%) | 88 (20.3) | 124 (14.0) | |
| 160-169 (%) | 40 (9.2) | 48 (5.4) | |
| ≥ 170 (%) | 17 (3.9) | 24 (2.7) | |
|
Average achieved diastolic blood pressure, mean (SD), mm Hg |
79 (10) | 80 (9) | 0.10 c |
| <65 (%) | 30 (6.9) | 39 (4.4) | 0.25 d |
| 65-69 (%) | 40 (9.2) | 71 (8.0) | |
| 70-74 (%) | 68 (15.7) | 134 (15.1) | |
| 75-79 (%) | 90 (20.8) | 189 (21.3) | |
| 80-84 (%) | 96 (22.2) | 195 (22.9) | |
| 85-89 (%) | 60 (13.9) | 162 (18.2) | |
| 90-94 (%) | 26 (6.0) | 63 (7.1) | |
| ≥ 95 (%) | 23 (5.3) | 36 (4.1) | |
|
Average pre-treatment systolic blood pressure, mean (SD), mm Hg |
158 (16) | 156 (15) | 0.08 c |
| <120 (%) | 1 (0.3) | 0 (0.0) | 0.13 d |
| 120-129 (%) | 5 (1.6) | 6 (1.0) | |
| 130-139 (%) | 29 (9.1) | 62 (9.7) | |
| 140-149 (%) | 61 (19.1) | 165 (25.7) | |
| 150-159 (%) | 88 (27.6) | 169 (26.4) | |
| 160-169 (%) | 67 (21.0) | 134 (20.9) | |
| ≥170 (%) | 68 (21.3) | 105 (16.4) | |
|
Average pre-treatment diastolic blood pressure, mean (SD), mm Hg |
93 (9) | 94 (9) | 0.02 c |
| <65 (%) | 0 (0.0) | 1 (0.2) | 0.09 d |
| 65-69 (%) | 2 (0.6) | 3 (0.5) | |
| 70-74 (%) | 6 (1.9) | 5 (0.8) | |
| 75-79 (%) | 18 (5.6) | 19 (3.0) | |
| 80-84 (%) | 29 (9.1) | 38 (5.9) | |
| 85-89 (%) | 48 (15.1) | 115 (17.9) | |
| 90-94 (%) | 78 (24.5) | 148 (23.1) | |
| ≥95 (%) | 139 (43.3) | 312 (48.7) |
Cases and controls were frequency matched on age and sex
BMI was missing in 2 cases and 9 controls; alcohol use in 13 cases and 42 controls; race in 3 cases and 9 controls; duration of GH enrollment in 2 cases and 5 controls; glomerular filtration rate in 3 cases and 7 controls; potassium level in 6 cases and 13 controls; duration of hypertension in 65 cases and 146 controls; average pre-treatment systolic and diastolic blood pressure in 114 cases and 248 controls
Anti-hypertensive medication categories are not mutually exclusive; patients could be on more than one anti-hypertensive medication
P value given for a difference in blood pressure means
P value given for differences in blood pressure categories
Among controls, patient characteristics were generally similar across categories of average achieved SBP and DBP (not shown). The exceptions were that controls with higher average achieved SBP were more likely to be older and female, and controls with higher average achieved DBP were more likely to be younger.
In categorical analyses, both very low and high levels of average achieved SBP were associated with increased odds of incident AF, after adjustment for age, sex, and index year (Figure 1). Compared with the reference level of 120-129 mm Hg, for categories of average achieved SBP of <120, 130-139, 140-149, 150-159, 160-169 and ≥170 mm Hg, the odds ratios (95% CI) for incident AF were 1.99 (1.10, 3.62), 1.19 (0.78, 1.81), 1.40 (0.93, 2.09), 2.02 (1.30, 3.15), 2.27 (1.31, 3.93) and 1.84 (0.89, 3.80), respectively. Overall, a significant trend of higher AF risk across categories of average achieved SBP was observed (p = .001). Among patients with an average achieved SBP ≥120 mm Hg, an increment of one standard deviation in average achieved SBP (14 mm Hg) was associated with a 33% higher AF risk (OR 1.33, 95% CI 1.16, 1.52), after adjustment for age, sex, and index year. Using the formula for PAF, we estimated that 16.3% (95% CI -7.8%, 35.0%), 17.2% (95% CI 4.3%, 28.3%) and 13.6% (95% CI 6.5%, 20.2%) of incident AF was attributable to an average achieved SBP ≥ 130 mm Hg, ≥140 mmHg and ≥150 mm Hg, respectively, among patients with treated hypertension.
Figure 1.
Odds ratios of incident atrial fibrillation associated with average achieved systolic blood pressure
Adjusted for age (continuous), sex, and index year. P — values vs. SBP = 120-129 mm Hg: SBP = <120 mm Hg, p = .02; 130-139 mm Hg, p = .42; 140-149 mm Hg, p = .11; 150-159 mm Hg, p < .01; 160-169 mm Hg, p < .01; ≥170 mm Hg, p = .10
DBP was associated with increased AF risk only at the highest level (Figure 2), after adjustment for age, sex, and index year. An average achieved DBP of≥95 mm Hg was associated with a doubling of the AF risk compared with the reference level of 65-69 mm Hg (OR 2.14, 95% CI 1.07, 4.28). An increment of one standard deviation in average achieved DBP (9 mm Hg) was associated with a 13% higher AF risk (OR 1.13, 95% CI 0.98, 1.30), after adjustment for age, sex, and index year. Estimates associated with both average achieved SBP and DBP did not change materially after further adjustment for race, diabetes status, body mass index, alcohol use, smoking, diuretic use, ACE inhibitor use, pre-treatment blood pressure, duration of hypertension, potassium level, or hyperthyroidism. Exclusion of patients with valvular heart disease (n = 42), a GFR < 30 (n = 36) or perioperative AF (n=2) did not substantially affect the estimated odds ratios. Among patients with an average achieved SBP ≥120 mm Hg, addition of average achieved DBP to a model with average achieved SBP did not materially change the estimated odds ratio for average achieved SBP, nor was DBP significantly associated with AF risk (χ2 = 0.00; P = 0.96). A model using average achieved pulse pressure (PP) as the predictor of interest produced similar results to the model with SBP. Among patients with an average achieved SBP ≥120 mm Hg, an increase of one standard deviation in average achieved PP (14 mm Hg) was associated with a 26% higher AF risk (OR 1.26, 95% CI 1.10, 1.44), after adjusting for age, sex, and index year.
Figure 2.
Odds ratios of incident atrial fibrillation associated with average achieved diastolic blood pressure
Adjusted for age (continuous), sex, and index year. P — values vs. DBP = 65-69 mm Hg: DBP = <65 mm Hg, p = .46; 70-74 mm Hg, p = .90; 75-79 mm Hg, p = .76; 80-84 mm Hg, p = .53; 85-89 mm Hg, p = .66; 90-95 mm Hg, p = .38; ≥95 mm Hg, p = .03
There were more female patients who had either transitory or persistent/intermittent AF and more male patients with sustained AF. A history of MI was more common among transitory AF cases. Use of ACE inhibitors and calcium channel blockers were more common among transitory AF cases, while diuretic use was more common among persistent/intermittent AF cases. Average achieved SBP was progressively higher across the categories from transitory to persistent/intermittent to sustained AF. The association between average achieved SBP and incident AF varied by AF classification (Table 2). Among patients with an average achieved SBP ≥120 mmHg, a one standard deviation increase was associated with a 24% higher risk of transitory AF (OR 1.24, 95% CI 1.02, 1.50), a 39% higher risk of persistent/intermittent AF (OR 1.39, 1.16, 1.67), and a 39% higher risk of sustained AF (OR 1.39, 95% CI 1.07, 1.80), after adjustment for age, sex, and index year (P for heterogeneity of risks <0.01). Among patients with an average achieved DBP ≥65 mm Hg, a one standard deviation increase was associated with a 1.00 (0.81, 1.22), 1.14 (0.94, 1.38) and 1.40 (1.04, 1.87) fold increase in the odds of incident transitory, persistent/intermittent and sustained AF, respectively (P for heterogeneity of risks 0.10).
Table 2.
Odds ratios of incident transitory, persistent/intermittent and sustained AF associated with achieved systolic/diastolic blood pressure
| Controls | Transitory AF |
Persistent/ Intermittent AF |
Sustained AF |
p-value for heterogeneity of odds ratios |
|
|---|---|---|---|---|---|
|
Average achieved systolic blood pressure, per 14 mm Hg a |
|||||
| n | 838 | 159 | 173 | 70 | |
| Odds Ratio, vs. controls | 1.24 | 1.39 | 1.39 | < 0.01 | |
| (95% CI) c | (1.02, 1.50) | (1.16, 1.67) | (1.07, 1.80) | ||
|
Average achieved diastolic blood pressure, per 9 mm Hg b |
|||||
| n | 845 | 156 | 173 | 66 | |
| Odds Ratio, vs. controls | 1.00 | 1.14 | 1.40 | 0.10 | |
| (95% CI) c | (0.81, 1.22) | (0.94, 1.38) | (1.04, 1.87) |
Restricted to patients with average achieved systolic blood pressure ≥ 120 mm Hg
Restricted to patients with average achieved diastolic blood pressure ≥ 65 mm Hg
Adjusted for age (continuous), sex, and index year
DISCUSSION
In this population based case-control study of treated hypertensive patients, higher average achieved SBP and SBP < 120 mm Hg were associated with increased odds of incident AF. Based on the PAF, we estimated that 17.2% of incident AF was attributable to an average achieved SBP ≥140 mm Hg.
We observed a J-shaped relationship for the association between average achieved SBP and AF. Volko et al found a J-shaped relationship between blood pressure and stroke risk in patients treated for hypertension17. In a meta-analysis, Boutitie et al found a J-shaped relationship between blood pressure and cardiovascular mortality in treated and untreated hypertensives18. Both studies hypothesized that low blood pressure may have been a marker for poor health conditions like advanced atherosclerosis17 or coronary heart disease and history of MI18, though neither found a difference in their results after adjustment for these factors. In the current analyses, we have adjusted for cardiovascular conditions that may underlie the association between average achieved SBP <120 mm Hg and AF, however there may be additional unmeasured confounders that may account for this association. Upon exclusion of patients with average achieved SBP <120 mm Hg, the observed association between average achieved SBP and AF was approximately linear.
In previous reports from a population treated for hypertension, uncontrolled compared to controlled blood pressure was associated with a higher risk of incident MI19 and stroke20. In contrast to our results, these studies did not report an increased risk associated with low SBP. However, low SBP was defined in those reports as <140 mm Hg in contrast to the definition used in this analysis (<120 mm Hg).
A study by Mitchell et al in a general population found that the association of SBP with AF was slightly weaker than the association of pulse pressure with AF, and concluded that SBP and DBP should be considered together when assessing the association between blood pressure and AF21. In our study of patients treated for hypertension, addition of average achieved DBP to a model with average achieved SBP did not significantly improve the model. In addition, we did not observe a substantial difference in odds ratios associated with a standard deviation change in SBP or pulse pressure as the main predictors of AF.
The association between average achieved SBP and AF was stronger for persistent/intermittent and sustained AF as opposed to transitory AF. Among those with SBP ≥120 mm Hg, a one standard deviation increase in average achieved SBP was associated with a 39% increase in the odds of persistent/intermittent or sustained AF, but only a 24% higher risk of transitory AF. Prolonged levels of elevated blood pressure may help maintain AF once it has been initiated.
Strengths of our study include the use of a population-based design where controls were drawn from the same population as the AF cases, the use of medical records to validate diagnoses and covariates, and the assessment of average blood pressure within 2 years before the index date for most patients. Confounding was addressed using adjustment and restriction.
Our study has several limitations. We cannot rule out residual confounding by unmeasured covariates. Approximately 30% of patients were missing pre-treatment blood pressure measurements and 16% were missing data on duration of treated hypertension. We cannot assume that values were missing at random. Our results may not be applicable to other populations given that this population was primarily white and as an insured population, of higher socioeconomic status than the general population. Blood pressure measurements were not made using a standardized protocol, which may have led to non-differential misclassification and an attenuation of estimated odds ratios. Because AF cases were identified in clinical settings, additional asymptomatic or transitory cases may have been missed.
Our findings suggest that among patients treated for hypertension, elevated SBP and SBP < 120 mm Hg are associated with higher risk of AF, particularly AF that is persistent/intermittent or sustained. Strategies to improve blood pressure control might remove a substantial amount of the AF disease burden in this population.
ACKNOWLEDGEMENTS
This research was funded by grants HL 68986, HL 43201, and HL 73410 and Matthew Thomas was supported by cardiovascular epidemiology training grant T32 HL007902, all from the National Heart, Lung, and Blood Institute.
Footnotes
DISCLOSURES All authors report no conflict of interest in the submission of this manuscript.
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