CLINICAL RESEARCH STUDY
Scope of Problem of Pulmonary Arterial Hypertension Paul D. Stein, MD,a Fadi Matta, MD,a Patrick G. Hughes, DOb a Department of Osteopathic Medical Specialties, Michigan State University College of Osteopathic Medicine, East Lansing; bDepartment of Emergency Medicine, Summa Akron City Hospital, Akron, Ohio.
ABSTRACT BACKGROUND: As with many uncommon diseases, data in patients with pulmonary arterial hypertension are sparse in regard to emergency service visits, hospitalizations, and mortality. The purpose of this investigation is to assess the scope of the problem of Group 1 pulmonary arterial hypertension in adults in the US and trends from 2001 to 2007. METHODS: The Nationwide Emergency Department Sample, 2007-2011, was used to determine the number of emergency department visits, hospitalizations, and all-cause mortality of patients aged 18 years with Group 1 pulmonary arterial hypertension. We assessed patients with a discharge code for “primary pulmonary hypertension,” and excluded patients with known causes of pulmonary hypertension that are not classified as Group 1. RESULTS: There were 64,451 emergency department visits and 52,779 hospitalizations for pulmonary arterial hypertension from 2007-2011 in patients aged 18 years. The proportion of all emergency department visits that were for pulmonary arterial hypertension decreased from 16.4/100,000 visits in 2007 to 8.9/100,000 visits in 2011 (P < .0001). The proportion of all hospitalizations that were for pulmonary arterial hypertension decreased from 79/100,000 hospitalizations in 2007 to 38/100,000 hospitalizations in 2011 (P < .0001). Population-based death rates in patients with pulmonary arterial hypertension decreased from 4.6/million population in 2007 to 1.7/million population in 2011 (P < .0001). CONCLUSIONS: Decreasing rates of emergency department visits, hospitalizations, and deaths in patients with Group 1 pulmonary arterial hypertension were shown from 2007-2011. We speculate that this resulted from improved treatment during the period of observation. Ó 2015 Elsevier Inc. All rights reserved. The American Journal of Medicine (2015) -, --KEYWORDS: Emergency department; Hospitalizations; Mortality; Pulmonary hypertension
The hemodynamic definition of pulmonary arterial hypertension, adopted by the American College of Cardiology, American Heart Association, and others,1 is mean pulmonary artery pressure >25 mm Hg with pulmonary capillary wedge pressure, left atrial pressure, or left ventricular enddiastolic pressure 15 mm Hg and pulmonary vascular Funding: This investigation was supported by a grant from Bayer Healthcare, (Grant number: PH-2013-007). Conflict of Interest: None of the authors have a conflict of interest with any of the information in this manuscript. Authorship: All of the authors had access to the data and participated in writing the manuscript. Requests for reprints should be addressed to Paul D. Stein, MD, Michigan State University, College of Osteopathic Medicine, Detroit Medical Center, 4707 St Antoine - Box 402, Detroit, MI 48201. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2015.03.007
resistance >3 Wood units (>240 dyne-sec-cm5). Pulmonary arterial hypertension was classified into 2 categories in 1975: 1) primary pulmonary hypertension, or 2) secondary pulmonary hypertension according to the presence of identified causes or risk factors.2,3 In 1998, pulmonary hypertension was classified by the World Health Organization into 5 categories that share similar pathological findings, hemodynamic characteristics, and management.4 This general clinical classification was maintained through 2013.2 The categories are pulmonary arterial hypertension (Group 1), pulmonary hypertension due to left heart disease (Group 2), pulmonary hypertension due to chronic lung disease or hypoxia (Group 3), chronic thromboembolic pulmonary hypertension (Group 4), and pulmonary hypertension due to unclear multifactorial factors (Group 5).2 The classification of pulmonary arterial hypertension, Group 1, however, was
2
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2015
updated in 2013.2 Subcategories of Group 1 pulmonary The large sample size of the NEDS permits study of artery hypertension are: idiopathic, drug and toxin, conrelatively uncommon disorders.5 The main objective of a nective tissue disease, human immunodeficiency virus stratified sample is to ensure that it is representative of the infection, portal hypertension, congenital heart disease, target universe. By stratifying on important hospital charschistosomiasis, heritable mutations of bone morphogenetic acteristics, the NEDS is a “microcosm” of emergency deprotein receptor type II, and mutations of other genes includpartments in the US.5 To obtain nationwide estimates, ing activin-like receptor kinase-1, weights were developed using the endoglin, mothers against decapAmerican Heart Association uniCLINICAL SIGNIFICANCE entaplegic 9 (SMAD9), caveolin-1, verse as the standard.5 and potassium channel super famThe International Classification The rate of emergency department visits ily K member-3.2 of Diseases, 9th Edition, Clinical for pulmonary arterial hypertension Modification (ICD-9-CM) codes As with many “orphan disdecreased from 2007 to 2011. used for identification of patients eases,” data are sparse on the The rate of hospitalizations for pulmowith pulmonary arterial hypertennumber and rates of patients seen sion are shown in Table 1. We with group 1 pulmonary arterial nary arterial hypertension decreased assessed all patients with a hypertension in the emergency from 2007 to 2011. diagnosis of primary pulmonary service, the number and rates Population-based death rates from pularterial hypertension (ICD-9-CM hospitalized, and the number of monary arterial hypertension decreased code 416.0). We included those deaths and death rates in the from 2007 to 2011. in whom the only ICD-9-CM emergency department and after code was 416.0 for primary pulhospital admission. Administra Improved treatment of pulmonary artemonary arterial hypertension. tive data from the Nationwide rial hypertension has had significant We also included those with a Emergency Department Sample impact in recent years. discharge code for primary pulallows an assessment of large monary arterial hypertension numbers of patients and an evaluation of trends. The purpose of this investigation is to assess the scope of the problem of pulmonary arterial hypertension in adults in the United States, and trends from 2007-2011. Table 1 International Classification of Diseases, 9th Edition,
METHODS This is an investigation of administrative data obtained from the Nationwide Emergency Department Sample (NEDS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality.5 The NEDS tracks information about emergency department visits across the country. Information includes geographic characteristics, hospital characteristics, patient characteristics, and diagnoses. The NEDS in 2007 contains information from about 27 million emergency department visits at about 970 hospitals that approximate a 20% stratified sample of US hospital-based emergency departments.5 The NEDS in 2011 contains 29 million emergency department records from 951 hospitals that approximate a 20% stratified sample of US hospital-based emergency departments.5 Weights are provided to calculate national estimates pertaining to over 120 million emergency department visits in 2007 and 131 million emergency department visits in 2011.5 The NEDS is drawn from states that provide the Healthcare Cost and Utilization Project with data from emergency department visits that may or may not have resulted in hospital admission. Twenty-seven Healthcare Cost and Utilization Project states participated in the 2007 NEDS, and 28 Healthcare Cost and Utilization Project states participated in the 2011 NEDS.5
Clinical Modification (ICD-9-CM) Codes Used for Identification of Subcategories of Patients with Pulmonary Arterial Hypertension (Group 1) ICD-9-CM Code Description Pulmonary artery hypertension
416.0
Primary pulmonary hypertension
Subcategories Congenital heart disease
745.4
Eisenmenger defect, ventricular septal defect Systemic lupus erythematosus Scleroderma, systemic sclerosis Sjögren disease Dermatomyositis Polymyositis Rheumatoid arthritis
Systemic connective tissue disease
710.0 710.1
Rheumatoid arthritis Schistosomiasis Human immunodeficiency virus (HIV) Portopulmonary hypertension Hereditary hemorrhagic telangiectasia Pulmonary venoocclusive disease
710.2 710.3 710.4 714.0 120 042 572.3
HIV disease Portal hypertension
448.0 516.1
Idiopathic pulmonary hemosiderosis
Stein et al
Pulmonary Arterial Hypertension
(ICD-9-CM code 416.0) and a code for a diagnosis included in a subcategory of diseases included in Group 1 pulmonary arterial hypertension (Table 1). We excluded patients with causes of pulmonary hypertension that are not classified as Group 1 according to the updated clinical classification2; these are shown in Table 2. This filter strengthens the specificity of the discharge codes for pulmonary arterial hypertension Group 1. A similar selection of ICD-9-CM codes was used by others to identify patients with pulmonary arterial hypertension.6,7 All-cause mortality was determined in the emergency department and during hospitalization. The population of the US according to year and according to age was obtained from the National Center for Health Statistics.8 Age-specific populations were for decades of age 21-30 through 71-80 and for those > aged 80 years and based on averages from 2007-2011.
Statistical Methods Data were analyzed using SPSS Version 22 for Windows (SPSS Inc., Chicago, IL). Differences of 2 proportions were assessed by chi-squared test using 2-tailed P values. Twotailed P values < .05 were considered statistically significant. GraphPad Software (San Diego, CA) was used. Linear and nonlinear regression analyses were done with SPSS. There were no missing data on diagnoses or mortality. The only missing data were on sex of patients in 12 of 64,451
Table 2
Exclusions
Left heart failure Mitral stenosis Chronic respiratory disease
ICD-9-CM Code
Description
428.1 394.0 491-496
Chronic bronchitis
492 493 494 495 496 500, 502, 503, 505
Chronic hemolytic anemia PAH
Residence or prolonged visit at high altitude Sleep-related hypoxia Pulmonary embolism
282.0 282.6 282.40 E902.0
3 (0.019%) emergency department visits. We reported the distribution of sex in those for whom we had the information.
RESULTS There were 64,451 emergency department visits for pulmonary arterial hypertension from 2007-2011 in patients aged 18 years (Figure 1). Most patients with pulmonary arterial hypertension (66.9%) were women (P < .0001).
Emergency Department Visits On average, there were 12,890 emergency department visits/ year for pulmonary arterial hypertension from 2007-2011 (Table 3). This represented 5.5 emergency department visits/100,000 population/year aged 18 years. The population of the US aged 18 years increased from 227,221,802 in 2007 to 237,680,342 in 2011. Average population aged 18 years from 2007-2011 was 232,545,122. The proportion of emergency visits for pulmonary arterial hypertension was, on average, 12.8/ 100,000 adult visits. From 2007-2011, the number of patients seen in the emergency department for pulmonary arterial hypertension decreased, and the proportion of all emergency department visits that were for pulmonary arterial hypertension decreased (Table 3). On average, there were 5.5 emergency department visits/100,000 population aged 18 years from 2007-2011. The number of emergency department visits for pulmonary arterial hypertension/100,000 population decreased from 2007-2011 (Figure 2).
Emphysema Asthma Bronchiectasis Extrinsic allergic alveolitis Chronic obstructive pulmonary disease Pneumoconioses (coal workers, silicates, inorganic dust, unspecified) Hereditary spherocytosis Sickle cell disease Thalassemia
327.24 415.1
ICD-9-CM ¼ International Classification of Diseases, 9th Edition, Clinical Modification; PAH ¼ pulmonary arterial hypertension.
Figure 1 Flow diagram showing number of visits of patients with pulmonary arterial hypertension (PAH) Group 1 in the emergency department (ED), number hospitalized, and number of all-cause deaths in the ED and in hospital, 2007-2011.
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Table 3 Emergency Department Visits for Pulmonary Arterial Hypertension According to Year
-
2015
Table 4 Emergency Department Visits for Pulmonary Arterial Hypertension According to Age
Year
PAH in ED
PAH ED Visits/100,000 ED Visits
PAH ED Visits/100,000 Age (y) PAH ED Visits/y* Population* Population/y
2007 2008 2009 2010 2011 Average
15,600 14,418 12,875 12,241 9317 12,890
16.4 14.6 12.8 11.8 8.9 12.8
21-30 31-40 41-50 51-60 61-70 71-80 >80
ED ¼ emergency hypertension.
department;
PAH
¼
pulmonary
arterial
The number of emergency department visits for pulmonary arterial hypertension increased with age, as did the agespecific emergency department visit rate (Table 4).
Hospitalizations Over the 5-year period of investigation, 52,779 patients were hospitalized with pulmonary arterial hypertension. On average, there were 10,556 hospitalizations/year for pulmonary arterial hypertension from 2007-2011. The number of hospitalizations/year decreased from 2007-2011 (Table 5). The proportion of patients seen in the emergency department with pulmonary arterial hypertension who were hospitalized from 2007-2011 was, on average, 82%. The proportion of patients with pulmonary arterial hypertension in the emergency department who were hospitalized decreased from 2007 to 2011 (Table 5). The population-based hospitalization rate from 20072011 was, on average, 4.5/100,000 population aged 18
325 702 1247 1830 2239 2832 3663
42,170,791 40,232,486 44,201,582 40,326,318 26,615,840 15,792,404 9,814,582
0.8 1.7 2.8 4.5 8.4 17.9 37.3
ED ¼ emergency department; PAH ¼ pulmonary hypertension. *Values are shown as average from 2007-2011.
arterial
years. The population-based hospitalization rate from 2007-2011 decreased (Figure 3). The proportion of hospitalizations for pulmonary arterial hypertension increased with age, as did the age-specific hospitalization rate (Table 6).
Mortality All-cause deaths in patients with pulmonary arterial hypertension from 2007-2011 were 3509. Among these, 103 died in the emergency department and 3406 died in the hospital. On average, deaths from 2007-2011 among patients seen in the emergency department with pulmonary arterial hypertension were 21 of 12,890/year (0.16%/year) (Table 7). In addition, on average, 681 died/year during hospitalization, which was 6.4%/year of hospitalizations for pulmonary arterial hypertension. Therefore, on average from 2007-2011, 702 deaths occurred among 12,890 emergency department visits/year for pulmonary arterial hypertension (5.4%/year). The proportion of deaths in-hospital among men (5.8%/year) was somewhat higher than among women (5.3%/year) (P ¼ .002). Deaths from pulmonary arterial hypertension were, on average, 3.0/million population/year. Population-based
Table 5 Hospitalizations for Pulmonary Arterial Hypertension According to Year
Figure 2 Number of visits in the emergency department (ED)/100,000 population of patients 18 years with pulmonary arterial hypertension (PAH) according to year. The number of visits decreased from 2007-2011 (r ¼ 0.982, slope ¼ 0.710 visits/100,000 patients/year, P ¼ .003).
Year
PAH Hospitalized
PAH Hospitalized/ PAH ED visits (%)
PAH Hospitalized/ 100,000 Hospitalizations
2007 2008 2009 2010 2011 Average
14,158 12,403 9804 9523 6891 10,556
91 86 76 78 74 82
79 68 53 51 38 58
ED ¼ emergency hypertension.
department;
PAH
¼
pulmonary
arterial
Stein et al
Pulmonary Arterial Hypertension
5 Table 7 Deaths from Pulmonary Artery Hypertension According to Year
Year
PAH Deaths/ PAH ED Visits n/N (%)
2007 2008 2009 2010 2011 Average
26/15,600 25/14,418 25/12,875 14/12,241 13/9317 21/12,890
death rates for pulmonary arterial hypertension decreased from 2007-2011 (Figure 4). Deaths from pulmonary arterial hypertension according to age are shown in Table 8. Agespecific death rates increased exponentially with age (Figure 5).
DISCUSSION
Total PAH Deaths/PAH ED Visits n/N (%)
(0.17) 1009/14,158 (7.1) 1035/15,600 (6.6) (0.17) 862/12,403 (6.9) 887/14,418 (6.2) (0.19) 607/9804 (6.2) 632/12,875 (4.9) (0.11) 548/9523 (5.8) 562/12,241 (4.6) (0.14) 380/6891 (5.5) 393/9317 (4.2) (0.16) 681/10,556 (6.4) 702/12,890 (5.4)
ED ¼ emergency hypertension.
Figure 3 Number of hospitalizations of patients with pulmonary arterial hypertension (PAH)/100,000 population of patients 18 years according to year. The number of hospitalizations decreased from 2007-2011 (r ¼ 0.985, slope ¼ 0.800 hospitalizations/100,000 patients/year, P ¼ .002).
PAH Hospital Deaths/PAH Hospitalizations n/N (%)
department;
PAH
¼
pulmonary
arterial
deaths decreased in patients with Group 1 pulmonary arterial hypertension. Age-specific rates of emergency department visits, hospitalizations, and deaths increased with age. The reported prevalence of pulmonary artery hypertension ranged widely, from 6.6/million population to 451/ million population aged 65 years (Table 9).6,7,9-12 Prevalence rates increased with age.7 Most investigations reported results in fewer than 1000 patients. The prevalence of pulmonary arterial hypertension in Scotland, 52/million adults,6 was similar to the number of emergency department visits that we observed for pulmonary arterial hypertension, 55/million adults/year. The reported incidence of pulmonary arterial hypertension ranged from 1.1-10.7/ million population/year.6,9-13 Most patients with pulmonary
Data from the Nationwide Emergency Department Sample showed 64,451 emergency department visits, 52,779 hospitalizations, and 3511 deaths of patients with Group 1 pulmonary arterial hypertension from 2007-2011 in the US. During this 5-year period of investigation, rates of emergency department visits, hospitalizations, and
Table 6 Hospitalizations for Pulmonary Arterial Hypertension According to Age PAH Hospitalized/ PAH Hospitalized/ PAH 100,000 100,000 Age (y) Hospitalized/y* Hospitalizations/y Population/y* 21-30 31-40 41-50 51-60 61-70 71-80 >80
199 447 912 1430 1880 2439 3214
15 30 39 50 64 75 84
0.5 1.1 2.1 3.5 7.1 15.4 32.7
PAH ¼ pulmonary arterial hypertension. *Values are shown as average from 2007-2011. Age-specific populations are shown in Table 4.
Figure 4 Number of deaths of patients with pulmonary arterial hypertension (PAH)/million population of patients 18 years according to year. The number of deaths decreased from 2007-2011 (r ¼ 0.985, slope ¼ 0.730 deaths/million patients/year, P ¼ .002).
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Table 8 Deaths from Pulmonary Artery Hypertension According to Age
Age (y)
PAH Deaths/PAH Hospitalizations/y n/N (%)
PAH Deaths in ED or Hospital/ PAH ED Visits/y n/N (%)
31-40 41-50 51-60 61-70 71-80 >80
20/447 35/912 75/1430 112/1880 181/2439 248/3214
24/702 39/1247 77/1830 113/2239 186/2832 253/3663
(4.5) (3.9) (5.2) (5.9) (7.4) (7.7)
(3.4) (3.2) (4.2) (5.1) (6.5) (6.9)
Values are shown as average from 2007-2011. All deaths in an emergency department were
Scope of Problem of Pulmonary Arterial Hypertension Paul D. Stein, MD,a Fadi Matta, MD,a Patrick G. Hughes, DOb a Department of Osteopathic Medical Specialties, Michigan State University College of Osteopathic Medicine, East Lansing; bDepartment of Emergency Medicine, Summa Akron City Hospital, Akron, Ohio.
ABSTRACT BACKGROUND: As with many uncommon diseases, data in patients with pulmonary arterial hypertension are sparse in regard to emergency service visits, hospitalizations, and mortality. The purpose of this investigation is to assess the scope of the problem of Group 1 pulmonary arterial hypertension in adults in the US and trends from 2001 to 2007. METHODS: The Nationwide Emergency Department Sample, 2007-2011, was used to determine the number of emergency department visits, hospitalizations, and all-cause mortality of patients aged 18 years with Group 1 pulmonary arterial hypertension. We assessed patients with a discharge code for “primary pulmonary hypertension,” and excluded patients with known causes of pulmonary hypertension that are not classified as Group 1. RESULTS: There were 64,451 emergency department visits and 52,779 hospitalizations for pulmonary arterial hypertension from 2007-2011 in patients aged 18 years. The proportion of all emergency department visits that were for pulmonary arterial hypertension decreased from 16.4/100,000 visits in 2007 to 8.9/100,000 visits in 2011 (P < .0001). The proportion of all hospitalizations that were for pulmonary arterial hypertension decreased from 79/100,000 hospitalizations in 2007 to 38/100,000 hospitalizations in 2011 (P < .0001). Population-based death rates in patients with pulmonary arterial hypertension decreased from 4.6/million population in 2007 to 1.7/million population in 2011 (P < .0001). CONCLUSIONS: Decreasing rates of emergency department visits, hospitalizations, and deaths in patients with Group 1 pulmonary arterial hypertension were shown from 2007-2011. We speculate that this resulted from improved treatment during the period of observation. Ó 2015 Elsevier Inc. All rights reserved. The American Journal of Medicine (2015) -, --KEYWORDS: Emergency department; Hospitalizations; Mortality; Pulmonary hypertension
The hemodynamic definition of pulmonary arterial hypertension, adopted by the American College of Cardiology, American Heart Association, and others,1 is mean pulmonary artery pressure >25 mm Hg with pulmonary capillary wedge pressure, left atrial pressure, or left ventricular enddiastolic pressure 15 mm Hg and pulmonary vascular Funding: This investigation was supported by a grant from Bayer Healthcare, (Grant number: PH-2013-007). Conflict of Interest: None of the authors have a conflict of interest with any of the information in this manuscript. Authorship: All of the authors had access to the data and participated in writing the manuscript. Requests for reprints should be addressed to Paul D. Stein, MD, Michigan State University, College of Osteopathic Medicine, Detroit Medical Center, 4707 St Antoine - Box 402, Detroit, MI 48201. E-mail address: [email protected] 0002-9343/$ -see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjmed.2015.03.007
resistance >3 Wood units (>240 dyne-sec-cm5). Pulmonary arterial hypertension was classified into 2 categories in 1975: 1) primary pulmonary hypertension, or 2) secondary pulmonary hypertension according to the presence of identified causes or risk factors.2,3 In 1998, pulmonary hypertension was classified by the World Health Organization into 5 categories that share similar pathological findings, hemodynamic characteristics, and management.4 This general clinical classification was maintained through 2013.2 The categories are pulmonary arterial hypertension (Group 1), pulmonary hypertension due to left heart disease (Group 2), pulmonary hypertension due to chronic lung disease or hypoxia (Group 3), chronic thromboembolic pulmonary hypertension (Group 4), and pulmonary hypertension due to unclear multifactorial factors (Group 5).2 The classification of pulmonary arterial hypertension, Group 1, however, was
2
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-
2015
updated in 2013.2 Subcategories of Group 1 pulmonary The large sample size of the NEDS permits study of artery hypertension are: idiopathic, drug and toxin, conrelatively uncommon disorders.5 The main objective of a nective tissue disease, human immunodeficiency virus stratified sample is to ensure that it is representative of the infection, portal hypertension, congenital heart disease, target universe. By stratifying on important hospital charschistosomiasis, heritable mutations of bone morphogenetic acteristics, the NEDS is a “microcosm” of emergency deprotein receptor type II, and mutations of other genes includpartments in the US.5 To obtain nationwide estimates, ing activin-like receptor kinase-1, weights were developed using the endoglin, mothers against decapAmerican Heart Association uniCLINICAL SIGNIFICANCE entaplegic 9 (SMAD9), caveolin-1, verse as the standard.5 and potassium channel super famThe International Classification The rate of emergency department visits ily K member-3.2 of Diseases, 9th Edition, Clinical for pulmonary arterial hypertension Modification (ICD-9-CM) codes As with many “orphan disdecreased from 2007 to 2011. used for identification of patients eases,” data are sparse on the The rate of hospitalizations for pulmowith pulmonary arterial hypertennumber and rates of patients seen sion are shown in Table 1. We with group 1 pulmonary arterial nary arterial hypertension decreased assessed all patients with a hypertension in the emergency from 2007 to 2011. diagnosis of primary pulmonary service, the number and rates Population-based death rates from pularterial hypertension (ICD-9-CM hospitalized, and the number of monary arterial hypertension decreased code 416.0). We included those deaths and death rates in the from 2007 to 2011. in whom the only ICD-9-CM emergency department and after code was 416.0 for primary pulhospital admission. Administra Improved treatment of pulmonary artemonary arterial hypertension. tive data from the Nationwide rial hypertension has had significant We also included those with a Emergency Department Sample impact in recent years. discharge code for primary pulallows an assessment of large monary arterial hypertension numbers of patients and an evaluation of trends. The purpose of this investigation is to assess the scope of the problem of pulmonary arterial hypertension in adults in the United States, and trends from 2007-2011. Table 1 International Classification of Diseases, 9th Edition,
METHODS This is an investigation of administrative data obtained from the Nationwide Emergency Department Sample (NEDS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality.5 The NEDS tracks information about emergency department visits across the country. Information includes geographic characteristics, hospital characteristics, patient characteristics, and diagnoses. The NEDS in 2007 contains information from about 27 million emergency department visits at about 970 hospitals that approximate a 20% stratified sample of US hospital-based emergency departments.5 The NEDS in 2011 contains 29 million emergency department records from 951 hospitals that approximate a 20% stratified sample of US hospital-based emergency departments.5 Weights are provided to calculate national estimates pertaining to over 120 million emergency department visits in 2007 and 131 million emergency department visits in 2011.5 The NEDS is drawn from states that provide the Healthcare Cost and Utilization Project with data from emergency department visits that may or may not have resulted in hospital admission. Twenty-seven Healthcare Cost and Utilization Project states participated in the 2007 NEDS, and 28 Healthcare Cost and Utilization Project states participated in the 2011 NEDS.5
Clinical Modification (ICD-9-CM) Codes Used for Identification of Subcategories of Patients with Pulmonary Arterial Hypertension (Group 1) ICD-9-CM Code Description Pulmonary artery hypertension
416.0
Primary pulmonary hypertension
Subcategories Congenital heart disease
745.4
Eisenmenger defect, ventricular septal defect Systemic lupus erythematosus Scleroderma, systemic sclerosis Sjögren disease Dermatomyositis Polymyositis Rheumatoid arthritis
Systemic connective tissue disease
710.0 710.1
Rheumatoid arthritis Schistosomiasis Human immunodeficiency virus (HIV) Portopulmonary hypertension Hereditary hemorrhagic telangiectasia Pulmonary venoocclusive disease
710.2 710.3 710.4 714.0 120 042 572.3
HIV disease Portal hypertension
448.0 516.1
Idiopathic pulmonary hemosiderosis
Stein et al
Pulmonary Arterial Hypertension
(ICD-9-CM code 416.0) and a code for a diagnosis included in a subcategory of diseases included in Group 1 pulmonary arterial hypertension (Table 1). We excluded patients with causes of pulmonary hypertension that are not classified as Group 1 according to the updated clinical classification2; these are shown in Table 2. This filter strengthens the specificity of the discharge codes for pulmonary arterial hypertension Group 1. A similar selection of ICD-9-CM codes was used by others to identify patients with pulmonary arterial hypertension.6,7 All-cause mortality was determined in the emergency department and during hospitalization. The population of the US according to year and according to age was obtained from the National Center for Health Statistics.8 Age-specific populations were for decades of age 21-30 through 71-80 and for those > aged 80 years and based on averages from 2007-2011.
Statistical Methods Data were analyzed using SPSS Version 22 for Windows (SPSS Inc., Chicago, IL). Differences of 2 proportions were assessed by chi-squared test using 2-tailed P values. Twotailed P values < .05 were considered statistically significant. GraphPad Software (San Diego, CA) was used. Linear and nonlinear regression analyses were done with SPSS. There were no missing data on diagnoses or mortality. The only missing data were on sex of patients in 12 of 64,451
Table 2
Exclusions
Left heart failure Mitral stenosis Chronic respiratory disease
ICD-9-CM Code
Description
428.1 394.0 491-496
Chronic bronchitis
492 493 494 495 496 500, 502, 503, 505
Chronic hemolytic anemia PAH
Residence or prolonged visit at high altitude Sleep-related hypoxia Pulmonary embolism
282.0 282.6 282.40 E902.0
3 (0.019%) emergency department visits. We reported the distribution of sex in those for whom we had the information.
RESULTS There were 64,451 emergency department visits for pulmonary arterial hypertension from 2007-2011 in patients aged 18 years (Figure 1). Most patients with pulmonary arterial hypertension (66.9%) were women (P < .0001).
Emergency Department Visits On average, there were 12,890 emergency department visits/ year for pulmonary arterial hypertension from 2007-2011 (Table 3). This represented 5.5 emergency department visits/100,000 population/year aged 18 years. The population of the US aged 18 years increased from 227,221,802 in 2007 to 237,680,342 in 2011. Average population aged 18 years from 2007-2011 was 232,545,122. The proportion of emergency visits for pulmonary arterial hypertension was, on average, 12.8/ 100,000 adult visits. From 2007-2011, the number of patients seen in the emergency department for pulmonary arterial hypertension decreased, and the proportion of all emergency department visits that were for pulmonary arterial hypertension decreased (Table 3). On average, there were 5.5 emergency department visits/100,000 population aged 18 years from 2007-2011. The number of emergency department visits for pulmonary arterial hypertension/100,000 population decreased from 2007-2011 (Figure 2).
Emphysema Asthma Bronchiectasis Extrinsic allergic alveolitis Chronic obstructive pulmonary disease Pneumoconioses (coal workers, silicates, inorganic dust, unspecified) Hereditary spherocytosis Sickle cell disease Thalassemia
327.24 415.1
ICD-9-CM ¼ International Classification of Diseases, 9th Edition, Clinical Modification; PAH ¼ pulmonary arterial hypertension.
Figure 1 Flow diagram showing number of visits of patients with pulmonary arterial hypertension (PAH) Group 1 in the emergency department (ED), number hospitalized, and number of all-cause deaths in the ED and in hospital, 2007-2011.
4
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Table 3 Emergency Department Visits for Pulmonary Arterial Hypertension According to Year
-
2015
Table 4 Emergency Department Visits for Pulmonary Arterial Hypertension According to Age
Year
PAH in ED
PAH ED Visits/100,000 ED Visits
PAH ED Visits/100,000 Age (y) PAH ED Visits/y* Population* Population/y
2007 2008 2009 2010 2011 Average
15,600 14,418 12,875 12,241 9317 12,890
16.4 14.6 12.8 11.8 8.9 12.8
21-30 31-40 41-50 51-60 61-70 71-80 >80
ED ¼ emergency hypertension.
department;
PAH
¼
pulmonary
arterial
The number of emergency department visits for pulmonary arterial hypertension increased with age, as did the agespecific emergency department visit rate (Table 4).
Hospitalizations Over the 5-year period of investigation, 52,779 patients were hospitalized with pulmonary arterial hypertension. On average, there were 10,556 hospitalizations/year for pulmonary arterial hypertension from 2007-2011. The number of hospitalizations/year decreased from 2007-2011 (Table 5). The proportion of patients seen in the emergency department with pulmonary arterial hypertension who were hospitalized from 2007-2011 was, on average, 82%. The proportion of patients with pulmonary arterial hypertension in the emergency department who were hospitalized decreased from 2007 to 2011 (Table 5). The population-based hospitalization rate from 20072011 was, on average, 4.5/100,000 population aged 18
325 702 1247 1830 2239 2832 3663
42,170,791 40,232,486 44,201,582 40,326,318 26,615,840 15,792,404 9,814,582
0.8 1.7 2.8 4.5 8.4 17.9 37.3
ED ¼ emergency department; PAH ¼ pulmonary hypertension. *Values are shown as average from 2007-2011.
arterial
years. The population-based hospitalization rate from 2007-2011 decreased (Figure 3). The proportion of hospitalizations for pulmonary arterial hypertension increased with age, as did the age-specific hospitalization rate (Table 6).
Mortality All-cause deaths in patients with pulmonary arterial hypertension from 2007-2011 were 3509. Among these, 103 died in the emergency department and 3406 died in the hospital. On average, deaths from 2007-2011 among patients seen in the emergency department with pulmonary arterial hypertension were 21 of 12,890/year (0.16%/year) (Table 7). In addition, on average, 681 died/year during hospitalization, which was 6.4%/year of hospitalizations for pulmonary arterial hypertension. Therefore, on average from 2007-2011, 702 deaths occurred among 12,890 emergency department visits/year for pulmonary arterial hypertension (5.4%/year). The proportion of deaths in-hospital among men (5.8%/year) was somewhat higher than among women (5.3%/year) (P ¼ .002). Deaths from pulmonary arterial hypertension were, on average, 3.0/million population/year. Population-based
Table 5 Hospitalizations for Pulmonary Arterial Hypertension According to Year
Figure 2 Number of visits in the emergency department (ED)/100,000 population of patients 18 years with pulmonary arterial hypertension (PAH) according to year. The number of visits decreased from 2007-2011 (r ¼ 0.982, slope ¼ 0.710 visits/100,000 patients/year, P ¼ .003).
Year
PAH Hospitalized
PAH Hospitalized/ PAH ED visits (%)
PAH Hospitalized/ 100,000 Hospitalizations
2007 2008 2009 2010 2011 Average
14,158 12,403 9804 9523 6891 10,556
91 86 76 78 74 82
79 68 53 51 38 58
ED ¼ emergency hypertension.
department;
PAH
¼
pulmonary
arterial
Stein et al
Pulmonary Arterial Hypertension
5 Table 7 Deaths from Pulmonary Artery Hypertension According to Year
Year
PAH Deaths/ PAH ED Visits n/N (%)
2007 2008 2009 2010 2011 Average
26/15,600 25/14,418 25/12,875 14/12,241 13/9317 21/12,890
death rates for pulmonary arterial hypertension decreased from 2007-2011 (Figure 4). Deaths from pulmonary arterial hypertension according to age are shown in Table 8. Agespecific death rates increased exponentially with age (Figure 5).
DISCUSSION
Total PAH Deaths/PAH ED Visits n/N (%)
(0.17) 1009/14,158 (7.1) 1035/15,600 (6.6) (0.17) 862/12,403 (6.9) 887/14,418 (6.2) (0.19) 607/9804 (6.2) 632/12,875 (4.9) (0.11) 548/9523 (5.8) 562/12,241 (4.6) (0.14) 380/6891 (5.5) 393/9317 (4.2) (0.16) 681/10,556 (6.4) 702/12,890 (5.4)
ED ¼ emergency hypertension.
Figure 3 Number of hospitalizations of patients with pulmonary arterial hypertension (PAH)/100,000 population of patients 18 years according to year. The number of hospitalizations decreased from 2007-2011 (r ¼ 0.985, slope ¼ 0.800 hospitalizations/100,000 patients/year, P ¼ .002).
PAH Hospital Deaths/PAH Hospitalizations n/N (%)
department;
PAH
¼
pulmonary
arterial
deaths decreased in patients with Group 1 pulmonary arterial hypertension. Age-specific rates of emergency department visits, hospitalizations, and deaths increased with age. The reported prevalence of pulmonary artery hypertension ranged widely, from 6.6/million population to 451/ million population aged 65 years (Table 9).6,7,9-12 Prevalence rates increased with age.7 Most investigations reported results in fewer than 1000 patients. The prevalence of pulmonary arterial hypertension in Scotland, 52/million adults,6 was similar to the number of emergency department visits that we observed for pulmonary arterial hypertension, 55/million adults/year. The reported incidence of pulmonary arterial hypertension ranged from 1.1-10.7/ million population/year.6,9-13 Most patients with pulmonary
Data from the Nationwide Emergency Department Sample showed 64,451 emergency department visits, 52,779 hospitalizations, and 3511 deaths of patients with Group 1 pulmonary arterial hypertension from 2007-2011 in the US. During this 5-year period of investigation, rates of emergency department visits, hospitalizations, and
Table 6 Hospitalizations for Pulmonary Arterial Hypertension According to Age PAH Hospitalized/ PAH Hospitalized/ PAH 100,000 100,000 Age (y) Hospitalized/y* Hospitalizations/y Population/y* 21-30 31-40 41-50 51-60 61-70 71-80 >80
199 447 912 1430 1880 2439 3214
15 30 39 50 64 75 84
0.5 1.1 2.1 3.5 7.1 15.4 32.7
PAH ¼ pulmonary arterial hypertension. *Values are shown as average from 2007-2011. Age-specific populations are shown in Table 4.
Figure 4 Number of deaths of patients with pulmonary arterial hypertension (PAH)/million population of patients 18 years according to year. The number of deaths decreased from 2007-2011 (r ¼ 0.985, slope ¼ 0.730 deaths/million patients/year, P ¼ .002).
6
The American Journal of Medicine, Vol -, No -,
Table 8 Deaths from Pulmonary Artery Hypertension According to Age
Age (y)
PAH Deaths/PAH Hospitalizations/y n/N (%)
PAH Deaths in ED or Hospital/ PAH ED Visits/y n/N (%)
31-40 41-50 51-60 61-70 71-80 >80
20/447 35/912 75/1430 112/1880 181/2439 248/3214
24/702 39/1247 77/1830 113/2239 186/2832 253/3663
(4.5) (3.9) (5.2) (5.9) (7.4) (7.7)
(3.4) (3.2) (4.2) (5.1) (6.5) (6.9)
Values are shown as average from 2007-2011. All deaths in an emergency department were
