Letters to the Editor
593
Coronary vasculitis in granulomatosis with polyangiitis E. Imbalzano a,⁎, A. Lo Gullo a, R. Costantino a, C. Tomasello a, V. Giugno b, A. Saitta a a b
Department of Internal Medicine, University of Messina, Italy U.O. of Internal Medicine, Hospital of Locri, Italy
a r t i c l e
i n f o
Article history: Received 28 January 2014 Accepted 14 March 2014 Available online 21 March 2014 Keywords: Coronary artery disease Vasculitis Granulomatosis with polyangiitis Wegener's granulomatosis Arterial hypertension
Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a granulomatous disorder usually associated with vasculitis involving the small and medium-sized blood vessels. It most commonly affects the upper and lower respiratory tracts and the kidneys, but almost any organ can be involved [1,2]. Cardiac involvement in GPA is rare and different manifestations are described such as pericarditis, valvular lesions, coronary arteritis, myocarditis and cardiac rhythm disorders [3,4]. We described a young woman, with a previous diagnosis of GPA, who has been subjected to coronography after a positive cardiac stress test. A 35-year old woman was admitted to our outpatient clinic for a recent history of dyspnea on moderate exertion, fever and cough. She denied a familiar history of cardiac disease. She was no smoker. The patient was diagnosed a year earlier with GPA with upper and lower respiratory tract involvement, renal failure at second stage, positive for antineutrophil cytoplasmic antibodies, anti-proteinase 3 (cANCA). No renal biopsy was performed. Moreover a previous brain MRI showed a brain involvement with microvascular inflammatory lesions in various stages of development. She also had arterial hypertension for 2 years before admission, for which she was taking 20 mg of olmesartan with normal blood pressure values and she had a hypothyroidism secondary to thyroidectomy for multinodular goiter. She was on therapy with prednisone at 25 mg/day, esome-
prazole and in the weeks prior our hospitalization she had a bronchiolitis with resolution after antibiotic therapy. On admission, she complained of constrictive chest pain during moderate effort; blood pressure was 130/70 mm Hg, heart rate was 72/min, clinical examination was unremarkable, with no respiratory or cardiac pathological findings on auscultation. The chest radiograph was normal. The ECG looks almost normal (Fig. 1A). Laboratory showed an elevated sedimentation rate (73 mm/h) and C-reactive protein levels (5.93 mg/dl). Troponin I and myoglobin were normal; c-ANCA was 63 (normal value 0.0–2.0 UI/ml). Creatinine was 1.5 mg/dl, hemoglobin was 12.9 mg/dl, white blood cell was 9700 mm3. Echocardiogram showed: mild concentric hypertrophy of the left ventricle, hypokinesia of the distal segment of the anterolateral wall with preserved global pump function, sclerosis and calcification of mitral and aortic valves; small pericardial effusion rear right atrium and systolic pericardial dissection of the free wall of the right ventricle (Fig. 1B and C); I degree diastolic dysfunction. For further diagnostic evaluation the patient undergone to dobutamine stress echocardiography [5,6], early stopped (20 γ/kg/ min) for the onset of constrictive retrosternal pain associated with electrocardiographic changes suggestive of ischemia in the absence of new mechanical alterations (Fig. 2). The following coronary angiography showed a diffuse coronary artery disease without hemodynamically significant stenosis with the exception of a 90% stenosis of the proximal portion of the left anterior descending artery, engaging the emergence of the first diagonal branch (Fig. 3A and B), treated with percutaneous transluminal coronary angioplasty (PTCA) with position of stent (Fig. 3C). Cardiac involvement in GPA has been reported to range between 6% and 44% [3,4] with coronary artery disease reported in the 50% of all cases of heart involvement in GPA [7]. Accelerated atherogenesis, one of the most important mechanisms triggering coronary disease, is well documented in GPA and patients affected by Wegener's granulomatosis are at a significantly increased risk of cardiovascular morbidity and mortality [8,9]. Moreover the GPA patients were found to have a 3.6-fold increased risk of acute MI occurring 5.0 years after the date of the GPA diagnosis [10,11].
Fig. 1. Panel A: normale ECG. Panels B and C: echocardiographic images of subxiphoid section showing the presence of small pericardial effusion at the back of the right atrium and at the level of the right ventricle free wall.
⁎ Corresponding author at: Unità Operativa Complessa di Medicina Interna, Azienda Ospedaliera Universitaria “Policlinico G. Martino” Via Consolare Valeria n.1, 98125 Messina, Italy. Tel.: + 39 3392894665. E-mail address: [email protected] (E. Imbalzano).
594
Letters to the Editor
Fig. 2. ECG during dobutamine stress echocardiography showing left bundle branch block which was not present in baseline ECG and in the presence of chest constricting pain.
Clinical manifestation of angina or myocardial infarction could be rare in patients with GPA, but fatal myocardial infarction may occur [7]. In our patient, symptoms and a history of hypertension, vasculitis and cerebral vascular disease could raise the suspicion of cardiac involvement. In fact the subsequent cardiac ultrasound revealed an impaired kinetics and dobutamin stress test induced a constrictive pain, due to severe stenosis of anterior descending coronary artery. This case suggests that provocative test might be useful to early detect cardiac involvement and might prevent the onset of serious consequences. The authors of this manuscript have certified that they adhere to the statement of ethical publishing as appears in the International Journal of Cardiology.
References [1] Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener's granulomatosis: an analysis of 158 patients. Ann Intern Med 1992;116:488–98. [2] Lo Gullo A, Bajocchi G, Cassone G, Cavazza A, Zanichelli M, Salvarani C. Granulomatosis with polyangiitis presenting as a renal mass successfully treated with rituximab. Clin Exp Rheumatol 2013 [Epub ahead of print]. [3] Knockaert DC. Cardiac involvement in systemic inflammatory diseases. Eur Heart J 2007;28:1797–804. [4] Korantzopoulos P, Papaioannides D, Siogas K. The heart in Wegener's granulomatosis. Cardiology 2004;102:7–10. [5] Imbalzano E, Trapani G, Creazzo M, Lizio G, Saitta A. Coronary artery disease in radiotherapy. Int J Cardiol Oct 9, 2013;168(4):e125–126. [6] Forstot JZ, Overlie PA, Neufeld GK, Harmon CE, Forstot SL. Cardiac complications of Wegener granulomatosis: a case report of complete heart block and review of the literature. Semin Arthritis Rheum 1980;10:148–54.
Fig. 3. Coronary angiography. Panels A and B: 90% stenosis at the level of proximal segment of the LAD involving the emergence of D1. Panel C: results after PTCA + stent.
Letters to the Editor [7] De Leeuw K, Sanders JS, Stegeman C, et al. Accelerated atherosclerosis in patients with Wegener's granulomatosis. Ann Rheum Dis 2005;64:753–9. Ann Intern Med 2005;141:764–70. [8] Imbalzano E, Dattilo G, Scarpelli M, Lo Gullo A, Saitta A. Left coronary artery fistula to right ventricle complicated heart failure in a patient on hemodialysis. Intern Emerg Med Dec 2013;8(8):765–6. [9] Suppiah R, Judge A, Batra R, et al. A model to predict cardiovascular events in patients with newly diagnosed Wegener's granulomatosis and microscopic polyangiitis. Arthritis Care Res Apr 2011;63(4):588–96.
595
[10] Faurschou M, Mellemkjaer L, Sorensen IJ, et al. Increased morbidity from ischemic heart disease in patients with Wegener's granulomatosis. Arthritis Rheum Apr 2009;60(4):1187–92. [11] Sajeev CG, Fassaludeen M, Venugopal K. Wegener's granulomatosis presenting as cardiac failure. Int J Cardiol Feb 15, 2005;98(2):337–8.
http://dx.doi.org/10.1016/j.ijcard.2014.03.099 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
The incidence of acute kidney injury after cardiac catheterization or PCI: A comparison of radial vs. femoral approach☆ Abdulla Damluji a, Mauricio G. Cohen a, Ramez Smairat a, Robert Steckbeck b,c, Mauro Moscucci a, Ian C. Gilchrist b,c,⁎ a b c
Cardiovascular Division, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, United States Penn State Heart and Vascular Institute, Hershey, PA, United States Penn State College of Medicine, Hershey, PA, United States
a r t i c l e
i n f o
Article history: Received 26 January 2014 Accepted 14 March 2014 Available online 20 March 2014 Keywords: Nephropathy Outcome Percutaneous coronary intervention Cardiac catheterization/adverse events Radial artery/surgery
The incidence of acute kidney injury (AKI) is a vexing complication of cardiac catheterization procedures. The incidence of AKI varies widely due to different definition criteria [1]. Regardless of the criteria used, the risk of AKI rises significantly in patients with diabetes mellitus (DM), chronic kidney disease (CKD), and congestive heart failure (CHF) [2,3]. Due to the increased risk of in-hospital mortality and poor long-term outcomes associated with AKI [1], there has been continued interest in understanding the epidemiology and prevention of AKI. We sought to evaluate the difference in incidence of AKI according to transradial or transfemoral arterial access for cardiac catheterization or percutaneous coronary interventions (PCI). All patients aged 18 years or older who underwent cardiac catheterization or PCI at a tertiary academic medical center between April 1, 2009 and September 30, 2012 were included in the study. AKI was defined as a rise in serum creatinine N0.5 (mg/dl) or 50% from the baseline value within 72 h post cardiac catheterization or PCI. The individual baseline AKI risk was calculated for each patient using a simple risk score [4]. Propensity matching scores were used to adjust for selection bias and imbalances between the two access sites in the cohort. The matching process included year of procedure, procedure duration, length of stay, pre-procedure hemoglobin, and pre-procedure GFR. Propensity matched multivariable logistic regression adjusting for AKI risk score and traditional risk factors ☆ This is an original manuscript and has not has been previously published or submitted to another journal. ⁎ Corresponding author at: Division of Cardiology, Penn State Heart and Vascular Institute, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, United States. E-mail address: [email protected] (I.C. Gilchrist).
was used to assess the independent relationship between access site and AKI. All analyses were performed using Stata 11.0 software (Stata Corporation, College Station, TX). The Institutional Review Board at the Pennsylvania State University approved the study. Of the 1637 consecutive patients who undergone cardiac catheterizations, 996 (61%) had transradial access and 641 (39%) had transfemoral arterial access. Baseline characteristics are depicted in (Table 1).
Table 1 Demographic and baseline characteristics of patients who underwent cardiac catheterization or PCI by different arterial access sites (transradial vs. transfemoral).
Demographic data Age, years, median [IQR] Male, n (%) White race, n (%) BMI, kg/m2, median [IQR] GFR N 60 ml/min/1.73 m2, median [IQR] Family history of CAD, n (%) Previous hypertension, n (%) Previous dyslipidemia, n (%) Previous diabetes mellitus, n (%) Previous PVD, n (%) Previous CABG, n (%) Previous MI, n (%) Previous CHF, n (%) Procedure data Admission heparin, n (%) Antiplatelet, n (%) Thrombin inhibitors, n (%) Left main disease N 50% stenosis, n (%) Proximal LAD N 50% stenosis, n (%) Circumflex N 50 stenosis, n (%) RCA N 50% stenosis, n (%) Cardiogenic shock, n (%) Contrast volume, ml, median [IQR] Procedure duration, minutes, median [IQR] Hospital length of stay, days, median [IQR] Simple risk prediction score, median [IQR]
Transradial n = 996
Transfemoral n = 641
p-Value
62 [53, 71] 775 (79) 942 (96) 29.9 [26.6, 34] 811 (84)
60 [51, 69] 464 (72) 602 (95) 29.7 [26, 33.8] 462 (72)
0.011 0.013 0.333 0.354 b0.001
396 (40) 772 (78) 780 (79) 323 (32) 73 (7) 100 (10) 167 (17) 122 (12)
256 (40) 524 (82) 527 (82) 260 (41) 56 (9) 168 (26) 136 (21) 94 (15)
0.974 0.039 0.067 0.001 0.309 b0.001 0.025 0.164
822 (83) 909 (92) 430 (43) 48 (5)
477 (75) 558 (87) 198 (31) 58 (9)
b0.001 0.006 b0.001 0.001
323 (32) 509 (51) 614 (62) 42 (4) 180 [140, 225] 75 [60, 95]
229 (36) 352 (55) 432 (67) 36 (6) 165 [130, 200] 75 [60, 100]
0.169 0.132 0.018 0.198 b0.001 0.208
2 [1, 3]
2 [1, 3]
0.519
5 [2, 8]
5 [3, 9]
b0.001
593
Coronary vasculitis in granulomatosis with polyangiitis E. Imbalzano a,⁎, A. Lo Gullo a, R. Costantino a, C. Tomasello a, V. Giugno b, A. Saitta a a b
Department of Internal Medicine, University of Messina, Italy U.O. of Internal Medicine, Hospital of Locri, Italy
a r t i c l e
i n f o
Article history: Received 28 January 2014 Accepted 14 March 2014 Available online 21 March 2014 Keywords: Coronary artery disease Vasculitis Granulomatosis with polyangiitis Wegener's granulomatosis Arterial hypertension
Granulomatosis with polyangiitis (GPA), formerly known as Wegener's granulomatosis, is a granulomatous disorder usually associated with vasculitis involving the small and medium-sized blood vessels. It most commonly affects the upper and lower respiratory tracts and the kidneys, but almost any organ can be involved [1,2]. Cardiac involvement in GPA is rare and different manifestations are described such as pericarditis, valvular lesions, coronary arteritis, myocarditis and cardiac rhythm disorders [3,4]. We described a young woman, with a previous diagnosis of GPA, who has been subjected to coronography after a positive cardiac stress test. A 35-year old woman was admitted to our outpatient clinic for a recent history of dyspnea on moderate exertion, fever and cough. She denied a familiar history of cardiac disease. She was no smoker. The patient was diagnosed a year earlier with GPA with upper and lower respiratory tract involvement, renal failure at second stage, positive for antineutrophil cytoplasmic antibodies, anti-proteinase 3 (cANCA). No renal biopsy was performed. Moreover a previous brain MRI showed a brain involvement with microvascular inflammatory lesions in various stages of development. She also had arterial hypertension for 2 years before admission, for which she was taking 20 mg of olmesartan with normal blood pressure values and she had a hypothyroidism secondary to thyroidectomy for multinodular goiter. She was on therapy with prednisone at 25 mg/day, esome-
prazole and in the weeks prior our hospitalization she had a bronchiolitis with resolution after antibiotic therapy. On admission, she complained of constrictive chest pain during moderate effort; blood pressure was 130/70 mm Hg, heart rate was 72/min, clinical examination was unremarkable, with no respiratory or cardiac pathological findings on auscultation. The chest radiograph was normal. The ECG looks almost normal (Fig. 1A). Laboratory showed an elevated sedimentation rate (73 mm/h) and C-reactive protein levels (5.93 mg/dl). Troponin I and myoglobin were normal; c-ANCA was 63 (normal value 0.0–2.0 UI/ml). Creatinine was 1.5 mg/dl, hemoglobin was 12.9 mg/dl, white blood cell was 9700 mm3. Echocardiogram showed: mild concentric hypertrophy of the left ventricle, hypokinesia of the distal segment of the anterolateral wall with preserved global pump function, sclerosis and calcification of mitral and aortic valves; small pericardial effusion rear right atrium and systolic pericardial dissection of the free wall of the right ventricle (Fig. 1B and C); I degree diastolic dysfunction. For further diagnostic evaluation the patient undergone to dobutamine stress echocardiography [5,6], early stopped (20 γ/kg/ min) for the onset of constrictive retrosternal pain associated with electrocardiographic changes suggestive of ischemia in the absence of new mechanical alterations (Fig. 2). The following coronary angiography showed a diffuse coronary artery disease without hemodynamically significant stenosis with the exception of a 90% stenosis of the proximal portion of the left anterior descending artery, engaging the emergence of the first diagonal branch (Fig. 3A and B), treated with percutaneous transluminal coronary angioplasty (PTCA) with position of stent (Fig. 3C). Cardiac involvement in GPA has been reported to range between 6% and 44% [3,4] with coronary artery disease reported in the 50% of all cases of heart involvement in GPA [7]. Accelerated atherogenesis, one of the most important mechanisms triggering coronary disease, is well documented in GPA and patients affected by Wegener's granulomatosis are at a significantly increased risk of cardiovascular morbidity and mortality [8,9]. Moreover the GPA patients were found to have a 3.6-fold increased risk of acute MI occurring 5.0 years after the date of the GPA diagnosis [10,11].
Fig. 1. Panel A: normale ECG. Panels B and C: echocardiographic images of subxiphoid section showing the presence of small pericardial effusion at the back of the right atrium and at the level of the right ventricle free wall.
⁎ Corresponding author at: Unità Operativa Complessa di Medicina Interna, Azienda Ospedaliera Universitaria “Policlinico G. Martino” Via Consolare Valeria n.1, 98125 Messina, Italy. Tel.: + 39 3392894665. E-mail address: [email protected] (E. Imbalzano).
594
Letters to the Editor
Fig. 2. ECG during dobutamine stress echocardiography showing left bundle branch block which was not present in baseline ECG and in the presence of chest constricting pain.
Clinical manifestation of angina or myocardial infarction could be rare in patients with GPA, but fatal myocardial infarction may occur [7]. In our patient, symptoms and a history of hypertension, vasculitis and cerebral vascular disease could raise the suspicion of cardiac involvement. In fact the subsequent cardiac ultrasound revealed an impaired kinetics and dobutamin stress test induced a constrictive pain, due to severe stenosis of anterior descending coronary artery. This case suggests that provocative test might be useful to early detect cardiac involvement and might prevent the onset of serious consequences. The authors of this manuscript have certified that they adhere to the statement of ethical publishing as appears in the International Journal of Cardiology.
References [1] Hoffman GS, Kerr GS, Leavitt RY, et al. Wegener's granulomatosis: an analysis of 158 patients. Ann Intern Med 1992;116:488–98. [2] Lo Gullo A, Bajocchi G, Cassone G, Cavazza A, Zanichelli M, Salvarani C. Granulomatosis with polyangiitis presenting as a renal mass successfully treated with rituximab. Clin Exp Rheumatol 2013 [Epub ahead of print]. [3] Knockaert DC. Cardiac involvement in systemic inflammatory diseases. Eur Heart J 2007;28:1797–804. [4] Korantzopoulos P, Papaioannides D, Siogas K. The heart in Wegener's granulomatosis. Cardiology 2004;102:7–10. [5] Imbalzano E, Trapani G, Creazzo M, Lizio G, Saitta A. Coronary artery disease in radiotherapy. Int J Cardiol Oct 9, 2013;168(4):e125–126. [6] Forstot JZ, Overlie PA, Neufeld GK, Harmon CE, Forstot SL. Cardiac complications of Wegener granulomatosis: a case report of complete heart block and review of the literature. Semin Arthritis Rheum 1980;10:148–54.
Fig. 3. Coronary angiography. Panels A and B: 90% stenosis at the level of proximal segment of the LAD involving the emergence of D1. Panel C: results after PTCA + stent.
Letters to the Editor [7] De Leeuw K, Sanders JS, Stegeman C, et al. Accelerated atherosclerosis in patients with Wegener's granulomatosis. Ann Rheum Dis 2005;64:753–9. Ann Intern Med 2005;141:764–70. [8] Imbalzano E, Dattilo G, Scarpelli M, Lo Gullo A, Saitta A. Left coronary artery fistula to right ventricle complicated heart failure in a patient on hemodialysis. Intern Emerg Med Dec 2013;8(8):765–6. [9] Suppiah R, Judge A, Batra R, et al. A model to predict cardiovascular events in patients with newly diagnosed Wegener's granulomatosis and microscopic polyangiitis. Arthritis Care Res Apr 2011;63(4):588–96.
595
[10] Faurschou M, Mellemkjaer L, Sorensen IJ, et al. Increased morbidity from ischemic heart disease in patients with Wegener's granulomatosis. Arthritis Rheum Apr 2009;60(4):1187–92. [11] Sajeev CG, Fassaludeen M, Venugopal K. Wegener's granulomatosis presenting as cardiac failure. Int J Cardiol Feb 15, 2005;98(2):337–8.
http://dx.doi.org/10.1016/j.ijcard.2014.03.099 0167-5273/© 2014 Elsevier Ireland Ltd. All rights reserved.
The incidence of acute kidney injury after cardiac catheterization or PCI: A comparison of radial vs. femoral approach☆ Abdulla Damluji a, Mauricio G. Cohen a, Ramez Smairat a, Robert Steckbeck b,c, Mauro Moscucci a, Ian C. Gilchrist b,c,⁎ a b c
Cardiovascular Division, Department of Medicine, University of Miami, Miller School of Medicine, Miami, FL, United States Penn State Heart and Vascular Institute, Hershey, PA, United States Penn State College of Medicine, Hershey, PA, United States
a r t i c l e
i n f o
Article history: Received 26 January 2014 Accepted 14 March 2014 Available online 20 March 2014 Keywords: Nephropathy Outcome Percutaneous coronary intervention Cardiac catheterization/adverse events Radial artery/surgery
The incidence of acute kidney injury (AKI) is a vexing complication of cardiac catheterization procedures. The incidence of AKI varies widely due to different definition criteria [1]. Regardless of the criteria used, the risk of AKI rises significantly in patients with diabetes mellitus (DM), chronic kidney disease (CKD), and congestive heart failure (CHF) [2,3]. Due to the increased risk of in-hospital mortality and poor long-term outcomes associated with AKI [1], there has been continued interest in understanding the epidemiology and prevention of AKI. We sought to evaluate the difference in incidence of AKI according to transradial or transfemoral arterial access for cardiac catheterization or percutaneous coronary interventions (PCI). All patients aged 18 years or older who underwent cardiac catheterization or PCI at a tertiary academic medical center between April 1, 2009 and September 30, 2012 were included in the study. AKI was defined as a rise in serum creatinine N0.5 (mg/dl) or 50% from the baseline value within 72 h post cardiac catheterization or PCI. The individual baseline AKI risk was calculated for each patient using a simple risk score [4]. Propensity matching scores were used to adjust for selection bias and imbalances between the two access sites in the cohort. The matching process included year of procedure, procedure duration, length of stay, pre-procedure hemoglobin, and pre-procedure GFR. Propensity matched multivariable logistic regression adjusting for AKI risk score and traditional risk factors ☆ This is an original manuscript and has not has been previously published or submitted to another journal. ⁎ Corresponding author at: Division of Cardiology, Penn State Heart and Vascular Institute, Pennsylvania State University, 500 University Drive, Hershey, PA 17033, United States. E-mail address: [email protected] (I.C. Gilchrist).
was used to assess the independent relationship between access site and AKI. All analyses were performed using Stata 11.0 software (Stata Corporation, College Station, TX). The Institutional Review Board at the Pennsylvania State University approved the study. Of the 1637 consecutive patients who undergone cardiac catheterizations, 996 (61%) had transradial access and 641 (39%) had transfemoral arterial access. Baseline characteristics are depicted in (Table 1).
Table 1 Demographic and baseline characteristics of patients who underwent cardiac catheterization or PCI by different arterial access sites (transradial vs. transfemoral).
Demographic data Age, years, median [IQR] Male, n (%) White race, n (%) BMI, kg/m2, median [IQR] GFR N 60 ml/min/1.73 m2, median [IQR] Family history of CAD, n (%) Previous hypertension, n (%) Previous dyslipidemia, n (%) Previous diabetes mellitus, n (%) Previous PVD, n (%) Previous CABG, n (%) Previous MI, n (%) Previous CHF, n (%) Procedure data Admission heparin, n (%) Antiplatelet, n (%) Thrombin inhibitors, n (%) Left main disease N 50% stenosis, n (%) Proximal LAD N 50% stenosis, n (%) Circumflex N 50 stenosis, n (%) RCA N 50% stenosis, n (%) Cardiogenic shock, n (%) Contrast volume, ml, median [IQR] Procedure duration, minutes, median [IQR] Hospital length of stay, days, median [IQR] Simple risk prediction score, median [IQR]
Transradial n = 996
Transfemoral n = 641
p-Value
62 [53, 71] 775 (79) 942 (96) 29.9 [26.6, 34] 811 (84)
60 [51, 69] 464 (72) 602 (95) 29.7 [26, 33.8] 462 (72)
0.011 0.013 0.333 0.354 b0.001
396 (40) 772 (78) 780 (79) 323 (32) 73 (7) 100 (10) 167 (17) 122 (12)
256 (40) 524 (82) 527 (82) 260 (41) 56 (9) 168 (26) 136 (21) 94 (15)
0.974 0.039 0.067 0.001 0.309 b0.001 0.025 0.164
822 (83) 909 (92) 430 (43) 48 (5)
477 (75) 558 (87) 198 (31) 58 (9)
b0.001 0.006 b0.001 0.001
323 (32) 509 (51) 614 (62) 42 (4) 180 [140, 225] 75 [60, 95]
229 (36) 352 (55) 432 (67) 36 (6) 165 [130, 200] 75 [60, 100]
0.169 0.132 0.018 0.198 b0.001 0.208
2 [1, 3]
2 [1, 3]
0.519
5 [2, 8]
5 [3, 9]
b0.001
