Characteristics of Hospitalized Patients with Atrial Fibrillation in Taiwan: A Nationwide Observation

The American Journal of Medicine (2007) 120, 819.e1-819.e7 CLINICAL RESEARCH STUDY Characteristics of Hospitalized Patients with Atrial Fibrillation in Taiwan: A Nationwide Observation Cheng-Han Lee, MD, a,b Ping-Yen Liu, MD, PhD, a Liang-Miin Tsai, MD, a Wei-Chuan Tsai, MD, a,b Ming-Tsung Ho, c Jyh-Hong Chen, MD, PhD, a Li-Jen Lin, MD a a Department of Internal Medicine, National Cheng Kung University Hospital, Tainan; b Department of Internal Medicine, National Cheng Kung University Hospital Dou-Liou Branch, Yun-Lin; c Department of Health Care Administration, Chung Hwa College of Medical Technology, Tainan, Taiwan. ABSTRACT PURPOSE: The aim of the study is to describe the nationwide epidemiological data for hospitalized patients with atrial fibrillation in Taiwan. METHODS: We collected information on hospitalized patients with discharge-diagnosed atrial fibrillation from 1997 through 2002 from the Taiwan National Health Insurance database. Patients were examined for temporal trends in the frequency of the disease, clinical characteristics, and in-hospital mortality. RESULTS: Of 162,340 patients (mean age, 73.8 years), 55.3% were men and 38.6% had a primary diagnosis of atrial fibrillation. The mean annual frequency of diagnosed atrial fibrillation was 127 per 100,000 persons. The frequency of atrial fibrillation rose from 91 (1997) to 150 (2002) per 100,000 persons (P.001); it significantly increased directly with age from 4 per 100,000 in patients 50 years to 1571 per 100,000 in patients 80 years. The frequency was significantly higher in men than in women (137 vs 116 per 100,000; P.001). The average in-hospital mortality rate was 9.3%. In-hospital mortality rate showed a decreasing trend (9.9% vs 7.6%; P.003). Comorbidities of ischemic heart disease, valvular heart disease, hypertension, ischemic stroke, and congestive heart failure were predictors of higher mortality. CONCLUSIONS: This Taiwanese study showed a 1.65-fold increase in the frequency of diagnosed atrial fibrillation during the study period. The in-hospital mortality rate, however, declined. The frequency of atrial fibrillation was higher in men and the elderly. We should be more concerned about negative outcomes in hospitalized patients with atrial fibrillation and other coexisting cardiovascular conditions. 2007 Elsevier Inc. All rights reserved. KEYWORDS: Atrial fibrillation; Epidemiology; Incidence; In-hospital mortality Atrial fibrillation, the most common cardiac arrhythmia, is responsible for significant morbidity and mortality. Most available knowledge of atrial fibrillation comes from Western databases. Studies in Western countries show that the number of hospitalizations for and the prevalence of atrial fibrillation increased markedly with age in elderly adults, from 1% in adults younger than 55 years to about 9% in Requests for reprints should be addressed to Li-Jen Lin, MD, Associate Professor of Internal Medicine, Department of Internal Medicine, National Cheng Kung University Hospital, 138 Sheng-Li Road, Tainan 70428, Taiwan. E-mail address: linl@mail.ncku.edu.tw those older than 80 years. 1-4 Gender and ethnicity also influenced the occurrence: Atrial fibrillation is more frequent in men (1.5 times higher than in women) and Caucasian populations. 1,2 Gender differences also influenced clinical characteristics and outcomes. 5-7 Although the epidemiology of atrial fibrillation has not been well-evaluated in non-western countries, the conventional wisdom is that the prevalence of atrial fibrillation is lower in Asian populations. 8-10 Since the implementation of National Health Insurance (NHI) in Taiwan in 1995, the vast majority of Taiwan s population has received health care coverage from this system. The NHI database, which contains information on 0002-9343/$ -see front matter 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.amjmed.2006.10.014

819.e2 The American Journal of Medicine, Vol 120, No 9, September 2007 NHI-covered patients given inpatient care since 1995, makes an epidemiologic analysis of atrial fibrillation possible. Using NHI data, we analyzed the epidemiologic characteristics of atrial fibrillation in hospitalized patients, coexisting conditions, gender differences in the clinical features of atrial fibrillation, and changes in the frequency of and in-hospital mortality rates for atrial fibrillation from 1997 through 2002. CLINICAL SIGNIFICANCE METHODS Study Population and Study Design Some detailed disease information on the NHI database, for example, the epidemiology of aortic dissection and Kawasaki disease, have been published. 11,12 Hospitalization health care records from 1997 through 2002 were collected from NHI databases, which contained health care data from 96.3% of all the hospitals in Taiwan. To identify hospitalized patients who met the criteria listed for atrial fibrillation, we searched an NHI clinical database containing diagnoses from all ambulatory visits for primary or secondary diagnoses of atrial fibrillation (code 427.31 from the International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]). Several proven diseases predisposing patients to atrial fibrillation were selected based on ICD-9-CM codes (Appendix Table 1). We analyzed data from hospitalized patients with atrial fibrillation by age group, gender, primary or secondary discharge diagnosis of atrial fibrillation, comorbidity, length of hospital stay, and in-hospital mortality. We also analyzed the data for annual trends in age at hospitalization, the frequency of atrial fibrillation, comorbidity, and in-hospital mortality rate. During the 6 years from 1997 through 2002, the population of Taiwan was about 22.2 million. The annual frequency of atrial fibrillation was calculated by dividing the number of hospitalized patients with atrial fibrillation by the general population of the same age reported between 1997 and 2002, according to the Taiwan census data. The annual frequency of atrial fibrillation is expressed as the number of hospitalizations per 100,000 inhabitants of Taiwan. Definitions The disease categories we used to analyze comorbid conditions in these patients are based on the ICD-9-CM classification (Appendix Table 1). Congestive heart failure includes unspecified, left heart, systolic, and diastolic types. Valvular heart disease includes diseases of the mitral valve, the aortic valve, both valves, and other endocardial structures. Systemic hypertension includes malignant, benign, The hospitalization-based frequency of atrial fibrillation in Taiwan was not lower than that reported in Western countries. The frequency of atrial fibrillation was higher in men and in the elderly. There was an upward trend in the frequency of atrial fibrillation. However, the in-hospital mortality rate decreased over time in men and women. Existing cardiovascular comorbidities were predictors of higher mortality. and unspecified types. Ischemic heart disease includes acute myocardial infarction, old myocardial infarction, and other forms of acute and chronic coronary artery disease. Cardiomyopathy encompasses primary and secondary cardiomyopathies. Pulmonary heart disease consists of acute cor pulmonale, pulmonary embolism and infarction, and primary and secondary pulmonary hypertension. Statistical Analysis The estimates of Taiwan s civilian resident population from Taiwan Department of Statistics for the years 1997 through 2002 were used to calculate the age- and gender-specific frequency of hospitalization for atrial fibrillation per 100,000 habitants of the population. NHI uses a systematic sampling method to randomly sample a representative database from the entire database. The size of the subset for each month is determined by the ratio of the amount of data in each month to that of the entire year. Then systematic sampling is performed for each month to randomly choose a representative subset. This sampling database is obtained by combining the subsets from 12 months. The sampling database is 5% of the entire database. We analyzed the data using commercial software (SPSS v. 10.0; SPSS Institute, Chicago, Ill). Data are expressed as means ( standard deviation) or percentages. Univariate analysis was done using Student s t test for continuous variables and the chi-square test for categorical variables. A Poisson regression model was used to examine the temporal trends in the annual frequency of hospitalized patients with atrial fibrillation, with categorical year variables. Trends in continuous variables and categorical data by calendar period were evaluated using Spearman nonparametric correlation analysis. Finally, multivariate analysis using a binary logistic regression test with a stepwise forward selection was used to determine the independent predictors of in-hospital mortality. Statistical significance was set at P.05. RESULTS Overall Patient Demographics There were 162,340 hospitalized patients with a discharge diagnosis of primary (38.6%; n 62,663) or secondary (61.4%; n 99,677) atrial fibrillation in Taiwan from 1997 through 2002. Their mean age was 73.8 years, 81% (n 131,495) were older than 65 years, and 55.3% (n 89,780) were men. The common comorbidities were congestive heart failure (23.8%), ischemic heart disease (21.4%), diabetes mellitus (16.3%), ischemic stroke (15.2%), valvular

Lee et al Atrial Fibrillation in Taiwan 819.e3 Table 1 Overall Clinical Characteristics of 162,340 Hospitalized Patients with Atrial Fibrillation Primary AF* Secondary AF Characteristics Males Females P Males Females P Clinical features Mean age, years 71.5 73.7.001 73.8 75.6.001 Heart failure, % 19.3 23.6.004 24.2 26.6.051 Ischemic heart disease, % 20.1 21.0.53 23.0 20.7.051 Ischemic stroke, % 12.1 14.7.024 15.2 17.6.008 Diabetes mellitus, % 11.5 17.4.001 14.8 21.2.001 Valvular heart disease, % 11.9 17.9.001 12.5 18.1.001 Hypertension, % 13.7 14.7.29 15.2 16.6.35 Cardiomyopathy, % 3.5 1.9.008 5.9 3.4.001 Pulmonary heart disease, % 1.0 1.4.11 2.9 2.7.61 Renal insufficiency, % 1.6 1.4.66 1.6 1.0.11 Thyrotoxicosis, % 0.01 0.01 1 0.2 0.1.49 Clinical outcome In-hospital mortality, % 6.8 7.4.52 10.4 11.0.49 Mean hospital stay, days 7.9 8.3.42 11.8 12.0.75 Need to transfer, % 1.6 1.3.48 4.6 3.9.21 AF atrial fibrillation. *Defined as having a primary discharge diagnosis of atrial fibrillation. Defined as having a secondary discharge diagnosis of atrial fibrillation. P-value compared with male and female groups using an unpaired Student s t-test or 2 test. heart disease (14.8%), and systemic hypertension (14.8%). Patients with a primary discharge diagnosis of atrial fibrillation were significantly younger than those with a secondary discharge diagnosis of atrial fibrillation (72.5 years vs 74.6 years) and had a lower frequency of coexisting congestive heart failure (21.3% vs 25.3%), diabetes mellitus (14.1% vs 17.6%), cardiomyopathy (2.7% vs 4.8%), and pulmonary heart disease (1.1% vs 2.8%). Furthermore, clinical outcomes, including mean length of hospital stay (8 days vs 12 days) and in-hospital mortality rate (7.0% vs 10.7%), were better in patients with atrial fibrillation as a primary discharge diagnosis. Gender Differences On average, the women with a primary or secondary discharge diagnosis of atrial fibrillation were older than the men were and had a higher frequency of congestive heart failure, diabetes, and valvular heart disease. Conversely, the women had a lower incidence of coexisting cardiomyopathy (Table 1). There was no statistically significant difference in the gender distribution (54.8% vs 55.6%) between patients with a primary or secondary discharge diagnosis of atrial fibrillation. Furthermore, the clinical outcomes, including mean length of hospital stay, and in-hospital mortality rate, were insignificant between men and women with a primary or secondary discharge diagnosis of atrial fibrillation (Table 1). The Frequency of Atrial Fibrillation From 1997 through 2002, the average overall annual frequency of hospitalized patients with diagnosed atrial fibrillation was 127 per 100,000 persons (Figure 1). The overall annual frequency of atrial fibrillation was higher in men than in women (137 per 100,000 vs 116 per 100,000) for every calendar year and all the age groups except the 80- year-old group (Figure 2). In women, the frequency drastically increased from 3 per 100,000 persons younger than 50 years to 1631 per 100,000 persons 80 years old or older. We found a similar trend in men, for whom the frequency increased from 4 per 100,000 persons in those younger than 50 years to 1510 per 100,000 in those 80 years old or older (Figure 2). From 1997 through 2002, the average overall annual frequency of patients with a primary discharge diagnosis of atrial fibrillation was 48 per 100,000 persons (Figure 3). The overall annual frequency of atrial fibrillation in those with a primary discharge diagnosis of atrial fibrillation also was Figure 1 Temporal trends in the annual frequency of overall patients with any diagnostic atrial fibrillation in Taiwan from 1997 through 2002.

819.e4 The American Journal of Medicine, Vol 120, No 9, September 2007 Figure 2 Annual frequency of overall patients with any diagnostic atrial fibrillation in Taiwan in different age and gender groups. higher in men in all the age groups except the 80-year-old group (Figure 4). Temporal Trends of Clinical Characteristics We found a statistically significant upward linear trend in the annual frequency of patients with diagnosed atrial fibrillation: The frequency increased from 91 per 100,000 persons in 1997 to 150 per 100,000 in 2002 (Figure 1). We also found a similar increasing linear trend in the annual frequency of patients with a primary discharge diagnosis of atrial fibrillation: The frequency increased from 39 per 100,000 persons in 1997 to 52 per 100,000 in 2002 (Figure 3). During the 6-year study period, more men than women had a discharge diagnosis of atrial fibrillation; there was an upward linear trend in the mean age for hospitalization, congestive heart failure, and systemic hypertension in both men and women; and the rate of a primary discharge diagnosis of atrial fibrillation declined in both men and women (Table 2). Conversely, there was a downward linear trend in the frequency of valvular heart disease and cardiomyopathy in men only. Although there was an upward linear trend in the frequency of ischemic heart disease in men only, there Figure 4 Annual frequency of patients with a primary discharge diagnosis of atrial fibrillation in Taiwan in different age and gender groups. were no differences in the linear trends in thyrotoxicosis, pulmonary heart disease, and renal insufficiency in men and women. In-hospital Outcomes The overall in-hospital mortality for patients with atrial fibrillation was 9.3%. There was no gender difference in mortality (Table 1). From 1997 through 2002, the rate of in-hospital mortality significantly declined in all patients with atrial fibrillation and in those with a secondary diagnosis of atrial fibrillation, but not in patients with a primary diagnosis of atrial fibrillation (Table 3). Using multivariate logistic regression analysis, determinants of in-hospital death in patients with a primary discharge diagnosis of atrial fibrillation included ischemic stroke (odds ratio (OR), 2.17 95% confidence interval (CI), 1.52-3.11), hypertension (OR 2.45 95% CI, 1.49-4.03), and valvular heart disease (OR 2.48, 95% CI, 1.45-4.03). Predictors of in-hospital death in patients with a secondary discharge diagnosis of atrial fibrillation included congestive heart failure, hypertension, older age, valvular heart disease, and ischemic heart disease (Table 4). DISCUSSION The clinical and epidemiological characteristics of a discharge diagnosis of atrial fibrillation have not been well documented in Asian countries despite its importance in public health. This is the first nationwide study to demonstrate the temporal trend in epidemiological features of hospitalized patients with atrial fibrillation in an Asian country. Figure 3 Temporal trends in the annual frequency of patients with a primary discharge diagnosis of atrial fibrillation in Taiwan from 1997 through 2002. Frequency of Atrial Fibrillation The hospitalization-based frequency of atrial fibrillation should not be assumed as the true incidence of atrial fibrillation in the general population of Taiwan because the authors did not include both initial and recurrent cases of atrial fibrillation in their study sample. However, the trend

Lee et al Atrial Fibrillation in Taiwan 819.e5 Table 2 Temporal Trends in Characteristics of Hospitalized Patients with Atrial Fibrillation from 1997 through 2002 Linear Features Year (n) 1997 (18,960) 1998 (23,460) 1999 (25,380) 2000 (29,800) 2001 (32,300) 2002 (32,440) P for Trend* Mean age, years Men 71.3 71.9 72.2 73.4 73.7 73.9.001 Women 73.8 74.7 74.1 74.8 75.6 75.8.001 Gender, % Men 52 57 53 55 55 58.044 Primary atrial fibrillation, % Men 44.3 38.2 39.7 36.4 35.1 34.2.001 Women 42.4 42.6 40.1 39.7 32.3 35.0.001 Congestive heart failure, % Men 15.1 24.1 22.1 22.0 24.3 23.8.007 Women 15.1 23.6 26.1 25.9 29.2 28.9.001 Hypertension, % Men 9.7 9.9 13.9 15.6 16.7 16.5.001 Women 10.2 11.9 14.3 17.4 17.0 18.7.001 Valvular heart disease, % Men 12.5 13.3 13.5 13.7 11.2 10.0 0.035 Women 20.4 17.0 18.2 19.2 17.1 16.9 0.25 Diabetes mellitus, % Men 12.9 13.6 13.0 13.3 13.8 14.2 0.47 Women 17.5 17.2 20.4 21.9 20.0 20.3 0.15 Ischemic heart disease, % Men 19.5 20.1 21.2 21.5 24.0 23.3 0.018 Women 21.3 21.2 21.2 21.7 20.1 19.7 0.40 Cardiomyopathy, % Men 5.6 6.3 6.2 4.6 3.9 4.3 0.02 Women 2.4 3.0 3.9 3.6 1.9 2.3 0.28 *Continuous variables and categorical data in the different year groups were compared for linear trends. Defined as having a primary discharge diagnosis of atrial fibrillation. in the frequency of atrial fibrillation found is informative of the epidemiology of atrial fibrillation over the time period examined. Because patients with atrial fibrillation who were not hospitalized were not enrolled in this NHI database, the frequency of atrial fibrillation in hospitalized patients could be lower than the actual prevalence of atrial fibrillation in Taiwan. Our results did show, however, that the frequency of atrial fibrillation increased both over time and with increasing age trends similar to those shown in other studies. 2,4,9,13-16 Irrespective of whether atrial fibrillation was a primary or secondary discharge diagnosis, the overall hospitalization rate associated with this condition increased 1.65-fold between 1997 and 2002. The frequency of hospitalization associated with a primary diagnosis of atrial fibrillation increased 1.33-fold during the same period. Stewart et al 15 reported a nearly 3-fold increase in hospitalization associated with atrial fibrillation and principal atrial fibrillation. In addition, the annual frequency of atrial fibrillation in Taiwanese patients ranged from 4 per 100,000 for patients younger than 50 years old to 1571 per 100,000 for patients more than 80 years old. In Khairallah et al, 16 the annual frequency was 14 per 100,000 for patients between 15 and 44 years old to 1141 per 100,000 for patients 85 years old. Gender-related Differences Few studies have touched on gender differences in arrhythmias. 17 We found that women who presented with atrial fibrillation were approximately 2 years older than men who presented with the condition. The frequency of atrial fibrillation was lower in hospitalized women than in hospitalized men 80 years old, but the frequency was higher in hospitalized women than in hospitalized men 80 years old. We also found that women had a higher burden of congestive heart failure, valvular heart disease, and diabetes mellitus. Khairallah et al 16 proposed that the frequency of atrial fibrillation was higher in men than in age-matched women, but that for hospitalized patients 65 years old, the frequency was higher in women. In the Canadian Registry of Atrial Fibrillation, men had a higher ratio of ischemic heart

819.e6 The American Journal of Medicine, Vol 120, No 9, September 2007 Table 3 Temporal Trends in In-hospital Mortality of Hospitalized Patients with Atrial Fibrillation from 1997 through 2002 Linear Features Year (n) 1997 (18,960) 1998 (23,460) 1999 (25,380) 2000 (29,800) 2001 (32,300) 2002 (32,440) All atrial fibrillation, % Overall 9.9 11.1 10.2 9.0 9.0 7.6.003 Men 10.3 10.5 9.2 9.0 8.7 7.8.04 Women 9.5 11.9 11.4 9.0 9.5 7.3.03 Primary atrial fibrillation, % Overall 7.3 7.9 7.6 7.1 7.1 5.7.28 Men 7.3 5.1 7.1 7.4 7.4 6.3.87 Women 7.3 10.7 8.0 6.8 6.8 5.0.08 Secondary atrial fibrillation, % Overall 11.9 13.3 12.2 10.2 10.1 8.6.001 Men 12.6 13.8 10.6 9.9 9.3 8.6.004 Women 11.2 12.8 13.8 10.4 10.8 8.5.07 *Continuous variables and categorical data in the different year groups were compared for linear trends. Defined as having a primary discharge diagnosis of atrial fibrillation. Defined as having a secondary discharge diagnosis of atrial fibrillation. P for Trend* disease, but women had a higher prevalence of hypertension and a history of thyroid dysfunction. 6 The Framingham study suggested that women had a higher burden of congestive heart failure, valvular heart disease, and diabetes mellitus. 5 Gender differences in atrial fibrillation-related mortality are controversial. We did not identify gender differences for in-hospital mortality in patients with a primary or secondary diagnosis of atrial fibrillation. Although women have a lower frequency of atrial fibrillation, some studies have demonstrated a worse outcome. 5,6 Conversely, Khairallah et al 16 reported a slightly better hospital outcome in women. Table 4 Multivariate Model of Risk Factors Associated with In-hospital Mortality in Hospitalized Patients with a Primary or Secondary Discharge Diagnosis of Atrial Fibrillation Parameters Primary Atrial Fibrillation* Odds Ratio (95% CI) Secondary Atrial Fibrillation Odds Ratio (95% CI) Hypertension 2.45 (1.49-4.03) 1.68 (1.25-2.26) Valvular heart disease 2.48 (1.45-4.03) 1.69 (1.24-2.30) Congestive heart failure NS 1.35 (1.07-1.68) Older age ( 65 years) NS 1.73 (1.29-2.33) Ischemic heart disease NS 2.51 (1.89-3.32) Ischemic stroke 2.17 (1.52-3.11) NS CI confidence interval; NS not significant. *Defined as having had a primary discharge diagnosis of atrial fibrillation. Defined as having had a secondary discharge diagnosis of atrial fibrillation. In-hospital Outcome In the current study, we found that older age ( 65 years), ischemic heart disease, valvular heart disease, systemic hypertension, congestive heart failure, and ischemic stroke were positive predictors of in-hospital mortality, and that a primary discharge diagnosis of atrial fibrillation was a negative predictor of in-hospital mortality. In Khairallah et al, 16 independent predictors of in-hospital mortality for atrial fibrillation included older age, male gender, black race, and heart, renal, and respiratory failure. Essential hypertension, diabetes mellitus, valvular heart disease, and myocardial infarction, however, were associated with lower in-hospital mortality. Our data showed that the in-hospital mortality rate declined from 11.9% in 1997 to 8.6% in 2002 in patients with a secondary discharge diagnosis of atrial fibrillation, and from 7.3% to 5.7% in patients with a primary discharge diagnosis of atrial fibrillation. Frost et al 13 reported that from 1980 through 1999, mortality decreased by 20% in men and 18% in women (adjusted for the 10-year age group, comorbidity, and the mortality trend in the general population). Stewart et al 15 proposed that the in-hospital mortality rate fell from 2.9% in 1986 to 1.8% in 1996 in patients with a primary diagnosis of atrial fibrillation, and from 13.0% to 7.8% in patients with a secondary diagnosis of atrial fibrillation. In women, the in-hospital mortality rate associated with a primary diagnosis of atrial fibrillation fell from 5.2% in 1986 to 3.4% in 1996; in women with a secondary diagnosis of atrial fibrillation, it fell from 19.2% to 11.8%. Khairallah et al, 16 however, found no significant trend in in-hospital mortality, but they did find low in-hospital mortality (0.5%-1.0%) in patients with a primary discharge diagnosis of atrial fibrillation. Limitations First, the present study was based on diagnostic coding by site-hospital accounting departments; therefore, that coding may be incomplete and imprecise. In addition, the diagnoses of comorbid diseases may be invalid because of errors of

Lee et al Atrial Fibrillation in Taiwan 819.e7 omission as well as commission. Because we were concerned about the possibility of misdiagnosis, we carefully chose those diseases that need no difficult diagnostic methods or tools. Second, detailed accounts of treatment that each patient received were not available. Finally, there were no follow-up data for the present study; therefore, the subsequent clinical course and readmission rate of patients in the registry, after discharge from the index hospitalization, was unknown. CONCLUSIONS This first nationwide study of atrial fibrillation in an Asian country demonstrated temporal trends in the epidemiological features and determinants of the in-hospital outcomes of hospitalized patients with the condition. The frequency of atrial fibrillation in Taiwan was no lower than that in Western countries. Men and the elderly had higher frequency of atrial fibrillation. During the 6-year study period, there was a 1.65-fold increase in the frequency of hospital-diagnosed atrial fibrillation. However, in-hospital mortality rate decreased over time. We should be more concerned about negative outcomes in hospitalized patients with atrial fibrillation and other coexisting cardiovascular conditions. ACKNOWLEDGMENTS We are grateful for the generosity of the Taiwan Bureau of National Health Insurance, Department of Health, the Taiwan National Health Research Institutes, and the Taiwan Department of Statistics, Ministry of the Interior, for giving us access to the National Health Insurance Research Database. The interpretations and conclusions in the present study are those of the authors and not those of the Bureau of National Health Insurance, Department of Health, or National Health Research Institutes. The authors also thank Miss Shu-Nu Han for her technical assistance in analyzing data. References 1. Benjamin EJ, Wolf PA, D Agostino RB, et al. Impact of atrial fibrillation on the risk of death: The Framingham Heart Study. Circulation. 1998;98:946-952. 2. Feinberg WM, Blackshear JL, Laupacis A, et al. Prevalence, age distribution, and gender of patients with atrial fibrillation: analysis and implication. Arch Intern Med. 1995;155:469-473. 3. Go AS, Hylek EM, Philips KA, et al. Prevalence of diagnosed atrial fibrillation in adults: national implications for rhythm management and stroke prevention. The AnTicoagulation and Risk Factors in Atrial Fibrillation (ATRIA) Study. JAMA. 2001;285:2370-2375. 4. Furberg CD, Psaty BM, Manolio TA, et al. Prevalence of atrial fibrillation in elderly subjects. Am J Cardiol. 1994;74:236-241. 5. Benjamin EJ, Levy D, Vaziri S, et al. Independent risk factors for atrial fibrillation in a population-based cohort: the Framingham Heart Study. JAMA. 1994;271:2455-2458. 6. Humphries KH, Kerr CR, Connolly SJ, et al. New-onset atrial fibrillation: sex differences in presentation, treatment and outcome. Circulation. 2001;103:2365-2570. 7. Suttorp MJ, Kingma JH, Koomen EM, et al. Recurrence of paroxysmal atrial fibrillation or flutter after successful cardioversion in patients with normal left ventricular function. Am J Cardiol. 1993; 71:710-713. 8. Krahn AD, Manfreda J, Tate RB, et al. The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study. Am J Med. 1995;98:476-484. 9. Lip GYH, Bawden L, Hodson R, et al. Atrial fibrillation amongst the indo-asian general practice population: The West Birminggham Atrial Fibrillation Project. Int J Cardiol. 1998;65:187-192. 10. Kiatchoosakan S, Pachirat O, Chirawatkul A, et al. Prevalence of cardiac arrhythmia in Thai Community. J Med Assoc Thailand. 1999; 82(7):727-733. 11. Yu HY, Chen YS, Huang SC, et al. Late outcome of patients with aortic dissection: study of a national database. Eur J Cardiothorac Surg. 2004;25(5):683-690. 12. Chang LY, Chang IS, Lu CY, et al. 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Appendix Table 1 World Health Organization International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) Code Numbers Used for Present Analysis Disease Category ICD-9-CM Number Atrial fibrillation 427.31 Diseases of mitral valve 394.0-394.9, 424.0 Diseases of aortic valve 395.0-395.9, 424.1 Diseases of mitral and 396.0-396.9 aortic valves Diseases of other 397.0-397.9, 424.2-3 endocardial structures Hypertension (malignant, 401.0-405.9 benign, unspecified) Heart failure (unspecified, 428.0-428.9 left heart, systolic, diastolic) Ischemic heart disease 410-414 Acute and chronic 415.0-416.9 pulmonary heart disease Diabetes mellitus 250.00-250.90 Thyrotoxicosis 242.0-242.9 Cardiomyopathy (primary 425.0-425.9 and secondary) Ischemic stroke 434.0-434.9, 436