185
Stroke, Systemic or Venous Thromboembolism
Atrial fibrillation associated with increased risk of venous thromboembolism A population-based cohort study Chun-Cheng Wang1,2; Cheng-Li Lin3,6; Guei-Jane Wang1,4,5; Chiz-Tzung Chang6,7; Fung-Chang Sung8; Chia-Hung Kao8,9* 1Graduate
of Clinical Medical Science, China Medical University, Taichung, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Taichung Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taichung, Taiwan; 3Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 4Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 5Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan; 6College of Medicine, China Medical University, Taichung, Taiwan; 7Division of Nephrology, China Medical University Hospital, Taichung, Taiwan; 8Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 9Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
Summary Whether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54–2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97–3.64), respectively. The baseline demographics indicated Correspondence to: Prof. Chia-Hung Kao, MD Graduate Institute of Clinical Medical Science and School of Medicine College of Medicine, China Medical University, No. 2 Yuh-Der Road, Taichung 404, Taiwan Tel.: +886 4 22052121×7412, Fax: +886 4 22336174 E-mail: [email protected]
Introduction Atrial fibrillation (AF) is the most common form of atrial arrhythmia, and frequently causes stroke, yielding substantial morbidity and mortality. However, whether AF is associated with venous thromboembolism (VTE) remains less understood. Previous studies have suggested that AF is both a contributing factor and consequence of pulmonary embolism (PE) (1). On the one hand, right atrial thrombi can be observed in patients with AF, leading to PE (2–4). On the other hand, the PE can cause pulmonary arterial hypertension, increased RV wall stress (strain), and right atrial pressure, ultimately leading to AF (5). The association between AF and PE remains controversial and unsettled. Gex et al. conducted a case-control study, concluding that in emergency patients presenting with dyspnea, the existence of AF cannot predict the occurrence of PE (6). Noel et al. proposed that AF is a risk factor for deep-vein thrombosis (DVT) and PE in stroke patients (7). However, both of these studies have focused on © Schattauer 2015
that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the nonAF group (adjusted HR = 1.74; 95 %CI = 1.36–2.24, adjusted HR = 2.18; 95 %CI = 1.51–3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p 75 years), comorbidities, and medication history of oestrogen were compared between the AF cohort and the non-AF cohorts; the categorical variables were examined using a Chi-square test and the continuous variables were examined using a t-test. The sex-, age-, and comorbidity-specific incidence densities of DVT and PE were measured among both cohorts. After accounting for the competing risks of death, we used the Fine and Gray model (13), (which extends the standard Cox proportional hazard regression model) to estimate the cumulative incidence of DVT and PE, after accounting for the competing risk of death. The identification of death events was based on hospital discharge because of death and withdrawal from the NHI as indicated in the LHID2000. Univariable and multivariable competing-risks regression models were used to estimate the subhazard ratios and 95 % confidence intervals (CIs) for DVT and PE among the AF patients in relation to the non-AF patients. The multivariable models were adjusted for age, sex, oestrogen, and the following comorbidities: hypertension, diabetes, hyperlipidaemia, CVA, heart failure, lower leg fracture or surgery, and cancer. In the multivariable Cox model, only heart failure attained significance. Further data analysis was performed to evaluate the interaction between AF and heart failure. Because oestrogen is presumably mostly for females, an interaction between atrial fibrillation and oestrogen in female patients should be considered. We further performed an analysis to evaluate the AF-estrogen interaction in female patients. Considering the potential effects of competing events of the other endpoint or other censoring events will lead to a biased estimate of the cumulative incidence, we compared the Kaplan-Meier analyses to competing risk cumulative incidence curves using the Aalen-Johansen estimator (14). We plotted a 12-year cumulative incidence of DVT and PE, using the cumulative risk method, which considers death events as the competing risk.
Men
25489(55.9)
6389(55.8)
≤ 65
12168(26.7)
3042(26.6)
66–75
12372(27.1)
3093(27.0)
21097(46.2)
5323(46.5)
70.5(13.2)
71.6(13.2)
Stroke, Systemic or Venous Thromboembolism
Atrial fibrillation associated with increased risk of venous thromboembolism A population-based cohort study Chun-Cheng Wang1,2; Cheng-Li Lin3,6; Guei-Jane Wang1,4,5; Chiz-Tzung Chang6,7; Fung-Chang Sung8; Chia-Hung Kao8,9* 1Graduate
of Clinical Medical Science, China Medical University, Taichung, Taiwan; 2Division of Cardiology, Department of Internal Medicine, Taichung Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, Taichung, Taiwan; 3Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan; 4Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; 5Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan; 6College of Medicine, China Medical University, Taichung, Taiwan; 7Division of Nephrology, China Medical University Hospital, Taichung, Taiwan; 8Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 9Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan
Summary Whether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54–2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97–3.64), respectively. The baseline demographics indicated Correspondence to: Prof. Chia-Hung Kao, MD Graduate Institute of Clinical Medical Science and School of Medicine College of Medicine, China Medical University, No. 2 Yuh-Der Road, Taichung 404, Taiwan Tel.: +886 4 22052121×7412, Fax: +886 4 22336174 E-mail: [email protected]
Introduction Atrial fibrillation (AF) is the most common form of atrial arrhythmia, and frequently causes stroke, yielding substantial morbidity and mortality. However, whether AF is associated with venous thromboembolism (VTE) remains less understood. Previous studies have suggested that AF is both a contributing factor and consequence of pulmonary embolism (PE) (1). On the one hand, right atrial thrombi can be observed in patients with AF, leading to PE (2–4). On the other hand, the PE can cause pulmonary arterial hypertension, increased RV wall stress (strain), and right atrial pressure, ultimately leading to AF (5). The association between AF and PE remains controversial and unsettled. Gex et al. conducted a case-control study, concluding that in emergency patients presenting with dyspnea, the existence of AF cannot predict the occurrence of PE (6). Noel et al. proposed that AF is a risk factor for deep-vein thrombosis (DVT) and PE in stroke patients (7). However, both of these studies have focused on © Schattauer 2015
that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the nonAF group (adjusted HR = 1.74; 95 %CI = 1.36–2.24, adjusted HR = 2.18; 95 %CI = 1.51–3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p 75 years), comorbidities, and medication history of oestrogen were compared between the AF cohort and the non-AF cohorts; the categorical variables were examined using a Chi-square test and the continuous variables were examined using a t-test. The sex-, age-, and comorbidity-specific incidence densities of DVT and PE were measured among both cohorts. After accounting for the competing risks of death, we used the Fine and Gray model (13), (which extends the standard Cox proportional hazard regression model) to estimate the cumulative incidence of DVT and PE, after accounting for the competing risk of death. The identification of death events was based on hospital discharge because of death and withdrawal from the NHI as indicated in the LHID2000. Univariable and multivariable competing-risks regression models were used to estimate the subhazard ratios and 95 % confidence intervals (CIs) for DVT and PE among the AF patients in relation to the non-AF patients. The multivariable models were adjusted for age, sex, oestrogen, and the following comorbidities: hypertension, diabetes, hyperlipidaemia, CVA, heart failure, lower leg fracture or surgery, and cancer. In the multivariable Cox model, only heart failure attained significance. Further data analysis was performed to evaluate the interaction between AF and heart failure. Because oestrogen is presumably mostly for females, an interaction between atrial fibrillation and oestrogen in female patients should be considered. We further performed an analysis to evaluate the AF-estrogen interaction in female patients. Considering the potential effects of competing events of the other endpoint or other censoring events will lead to a biased estimate of the cumulative incidence, we compared the Kaplan-Meier analyses to competing risk cumulative incidence curves using the Aalen-Johansen estimator (14). We plotted a 12-year cumulative incidence of DVT and PE, using the cumulative risk method, which considers death events as the competing risk.
Men
25489(55.9)
6389(55.8)
≤ 65
12168(26.7)
3042(26.6)
66–75
12372(27.1)
3093(27.0)
21097(46.2)
5323(46.5)
70.5(13.2)
71.6(13.2)
