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Scope of Problem of Pulmonary Arterial Hypertension

      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.

      Keywords

      Clinical Significance
      • The rate of emergency department visits for pulmonary arterial hypertension decreased from 2007 to 2011.
      • The rate of hospitalizations for pulmonary arterial hypertension decreased from 2007 to 2011.
      • Population-based death rates from pulmonary arterial hypertension decreased from 2007 to 2011.
      • Improved treatment of pulmonary arterial hypertension has had significant impact in recent years.
      The hemodynamic definition of pulmonary arterial hypertension, adopted by the American College of Cardiology, American Heart Association, and others,
      • McLaughlin V.V.
      • Archer S.L.
      • Badesch D.B.
      • et al.
      ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association.
      is mean pulmonary artery pressure >25 mm Hg with pulmonary capillary wedge pressure, left atrial pressure, or left ventricular end-diastolic pressure ≤15 mm Hg and pulmonary vascular resistance >3 Wood units (>240 dyne-sec-cm−5). 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.
      • Simonneau G.
      • Gatzoulis M.A.
      • Adatia I.
      • et al.
      Updated clinical classification of pulmonary hypertension.
      • Hatano S.
      • Strasser T.
      Primary Pulmonary Hypertension. Report on a WHO Meeting. October 15-17, 1973.
      In 1998, pulmonary hypertension was classified by the World Health Organization into 5 categories that share similar pathological findings, hemodynamic characteristics, and management.
      • Simonneau G.
      • Galiè N.
      • Rubin L.J.
      • et al.
      Clinical classification of pulmonary arterial hypertension.
      This general clinical classification was maintained through 2013.
      • Simonneau G.
      • Gatzoulis M.A.
      • Adatia I.
      • et al.
      Updated clinical classification of pulmonary hypertension.
      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).
      • Simonneau G.
      • Gatzoulis M.A.
      • Adatia I.
      • et al.
      Updated clinical classification of pulmonary hypertension.
      The classification of pulmonary arterial hypertension, Group 1, however, was updated in 2013.
      • Simonneau G.
      • Gatzoulis M.A.
      • Adatia I.
      • et al.
      Updated clinical classification of pulmonary hypertension.
      Subcategories of Group 1 pulmonary artery hypertension are: idiopathic, drug and toxin, connective tissue disease, human immunodeficiency virus infection, portal hypertension, congenital heart disease, schistosomiasis, heritable mutations of bone morphogenetic protein receptor type II, and mutations of other genes including activin-like receptor kinase-1, endoglin, mothers against decapentaplegic 9 (SMAD9), caveolin-1, and potassium channel super family K member-3.
      • Simonneau G.
      • Gatzoulis M.A.
      • Adatia I.
      • et al.
      Updated clinical classification of pulmonary hypertension.
      As with many “orphan diseases,” data are sparse on the number and rates of patients seen with group 1 pulmonary arterial hypertension in the emergency service, the number and rates hospitalized, and the number of deaths and death rates in the emergency department and after hospital admission. Administrative data from the Nationwide Emergency Department Sample allows an assessment of large 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.

      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.

      Healthcare Cost and Utilization Project (HCUP). Overview of the Nationwide Emergency Department Sample. Available at: www.hcup-us.ahrq.gov/nedsoverview.jsp. Accessed April 10, 2015.

      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.

      Healthcare Cost and Utilization Project (HCUP). Overview of the Nationwide Emergency Department Sample. Available at: www.hcup-us.ahrq.gov/nedsoverview.jsp. Accessed April 10, 2015.

      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.

      Healthcare Cost and Utilization Project (HCUP). Overview of the Nationwide Emergency Department Sample. Available at: www.hcup-us.ahrq.gov/nedsoverview.jsp. Accessed April 10, 2015.

      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.

      Healthcare Cost and Utilization Project (HCUP). Overview of the Nationwide Emergency Department Sample. Available at: www.hcup-us.ahrq.gov/nedsoverview.jsp. Accessed April 10, 2015.

      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.

      Healthcare Cost and Utilization Project (HCUP). Overview of the Nationwide Emergency Department Sample. Available at: www.hcup-us.ahrq.gov/nedsoverview.jsp. Accessed April 10, 2015.

      The large sample size of the NEDS permits study of relatively uncommon disorders.

      Healthcare Cost and Utilization Project (HCUP). Overview of the Nationwide Emergency Department Sample. Available at: www.hcup-us.ahrq.gov/nedsoverview.jsp. Accessed April 10, 2015.

      The main objective of a stratified sample is to ensure that it is representative of the target universe. By stratifying on important hospital characteristics, the NEDS is a “microcosm” of emergency departments in the US.

      Healthcare Cost and Utilization Project (HCUP). Overview of the Nationwide Emergency Department Sample. Available at: www.hcup-us.ahrq.gov/nedsoverview.jsp. Accessed April 10, 2015.

      To obtain nationwide estimates, weights were developed using the American Heart Association universe as the standard.

      Healthcare Cost and Utilization Project (HCUP). Overview of the Nationwide Emergency Department Sample. Available at: www.hcup-us.ahrq.gov/nedsoverview.jsp. Accessed April 10, 2015.

      The International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) codes used for identification of patients with pulmonary arterial hypertension are shown in Table 1. We assessed all patients with a diagnosis of primary pulmonary arterial hypertension (ICD-9-CM code 416.0). We included those in whom the only ICD-9-CM code was 416.0 for primary pulmonary arterial hypertension. We also included those with a discharge code for primary 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 classification
      • Simonneau G.
      • Gatzoulis M.A.
      • Adatia I.
      • et al.
      Updated clinical classification of pulmonary hypertension.
      ; 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.
      • Peacock A.J.
      • Murphy N.F.
      • McMurray J.J.V.
      • et al.
      An epidemiological study of pulmonary arterial hypertension.
      • Kirson N.Y.
      • Birnbaum H.G.
      • Ivanova J.I.
      • et al.
      Prevalence of pulmonary hypertension and chronic thromboembolic pulmonary hypertension in the United States.
      All-cause mortality was determined in the emergency department and during hospitalization.
      Table 1International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) Codes Used for Identification of Subcategories of Patients with Pulmonary Arterial Hypertension (Group 1)
      ICD-9-CM CodeDescription
      Pulmonary artery hypertension416.0Primary pulmonary hypertension
      Subcategories
       Congenital heart disease745.4Eisenmenger defect, ventricular septal defect
       Systemic connective tissue disease710.0Systemic lupus erythematosus
      710.1Scleroderma, systemic sclerosis
      710.2Sjögren disease
      710.3Dermatomyositis
      710.4Polymyositis
       Rheumatoid arthritis714.0Rheumatoid arthritis
       Schistosomiasis120
       Human immunodeficiency virus (HIV)042HIV disease
       Portopulmonary hypertension572.3Portal hypertension
       Hereditary hemorrhagic telangiectasia448.0
       Pulmonary venoocclusive disease516.1Idiopathic pulmonary hemosiderosis
      Table 2Exclusions
      ICD-9-CM CodeDescription
      Left heart failure428.1
      Mitral stenosis394.0
      Chronic respiratory disease491-496Chronic bronchitis
      492Emphysema
      493Asthma
      494Bronchiectasis
      495Extrinsic allergic alveolitis
      496Chronic obstructive pulmonary disease
      500, 502, 503, 505Pneumoconioses (coal workers, silicates, inorganic dust, unspecified)
      Chronic hemolytic anemia PAH282.0Hereditary spherocytosis
      282.6Sickle cell disease
      282.40Thalassemia
      Residence or prolonged visit at high altitudeE902.0
      Sleep-related hypoxia327.24
      Pulmonary embolism415.1
      ICD-9-CM = International Classification of Diseases, 9th Edition, Clinical Modification; PAH = pulmonary arterial hypertension.
      The population of the US according to year and according to age was obtained from the National Center for Health Statistics.

      National Center for Health Statistics. CDC WONDER. Compressed mortality file: underlying cause-of-death. Available at: http://wonder.cdc.gov/mortSQL.html. Accessed November 15, 2013.

      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. Two-tailed 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 (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).
      Figure thumbnail gr1
      Figure 1Flow 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.

      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.
      Table 3Emergency Department Visits for Pulmonary Arterial Hypertension According to Year
      YearPAH in EDPAH ED Visits/100,000 ED Visits
      200715,60016.4
      200814,41814.6
      200912,87512.8
      201012,24111.8
      201193178.9
      Average12,89012.8
      ED = emergency department; PAH = pulmonary arterial hypertension.
      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).
      Figure thumbnail gr2
      Figure 2Number 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 = −0.982, slope = −0.710 visits/100,000 patients/year, P = .003).
      The number of emergency department visits for pulmonary arterial hypertension increased with age, as did the age-specific emergency department visit rate (Table 4).
      Table 4Emergency Department Visits for Pulmonary Arterial Hypertension According to Age
      Age (y)PAH ED Visits/y
      Values are shown as average from 2007-2011.
      Population
      Values are shown as average from 2007-2011.
      PAH ED Visits/100,000 Population/y
      21-3032542,170,7910.8
      31-4070240,232,4861.7
      41-50124744,201,5822.8
      51-60183040,326,3184.5
      61-70223926,615,8408.4
      71-80283215,792,40417.9
      >8036639,814,58237.3
      ED = emergency department; PAH = pulmonary arterial hypertension.
      Values are shown as average from 2007-2011.

      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).
      Table 5Hospitalizations for Pulmonary Arterial Hypertension According to Year
      YearPAH HospitalizedPAH Hospitalized/PAH ED visits (%)PAH Hospitalized/100,000 Hospitalizations
      200714,1589179
      200812,4038668
      200998047653
      201095237851
      201168917438
      Average10,5568258
      ED = emergency department; PAH = pulmonary arterial hypertension.
      The population-based hospitalization rate from 2007-2011 was, on average, 4.5/100,000 population ≥ aged 18 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).
      Figure thumbnail gr3
      Figure 3Number 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 = −0.985, slope = −0.800 hospitalizations/100,000 patients/year, P = .002).
      Table 6Hospitalizations for Pulmonary Arterial Hypertension According to Age
      Age (y)PAH Hospitalized/y
      Values are shown as average from 2007-2011. Age-specific populations are shown in Table 4.
      PAH Hospitalized/100,000 Hospitalizations/yPAH Hospitalized/100,000 Population/y
      Values are shown as average from 2007-2011. Age-specific populations are shown in Table 4.
      21-30199150.5
      31-40447301.1
      41-50912392.1
      51-601430503.5
      61-701880647.1
      71-8024397515.4
      >8032148432.7
      PAH = pulmonary arterial hypertension.
      Values are shown as average from 2007-2011. Age-specific populations are shown in Table 4.

      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 = .002).
      Table 7Deaths from Pulmonary Artery Hypertension According to Year
      YearPAH Deaths/PAH ED Visits

      n/N (%)
      PAH Hospital Deaths/PAH Hospitalizations

      n/N (%)
      Total PAH Deaths/PAH ED Visits

      n/N (%)
      200726/15,600 (0.17)1009/14,158 (7.1)1035/15,600 (6.6)
      200825/14,418 (0.17)862/12,403 (6.9)887/14,418 (6.2)
      200925/12,875 (0.19)607/9804 (6.2)632/12,875 (4.9)
      201014/12,241 (0.11)548/9523 (5.8)562/12,241 (4.6)
      201113/9317 (0.14)380/6891 (5.5)393/9317 (4.2)
      Average21/12,890 (0.16)681/10,556 (6.4)702/12,890 (5.4)
      ED = emergency department; PAH = pulmonary arterial hypertension.
      Deaths from pulmonary arterial hypertension were, on average, 3.0/million population/year. Population-based 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. Age-specific death rates increased exponentially with age (Figure 5).
      Figure thumbnail gr4
      Figure 4Number 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 = −0.985, slope = −0.730 deaths/million patients/year, P = .002).
      Table 8Deaths 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 (%)
      31-4020/447 (4.5)24/702 (3.4)
      41-5035/912 (3.9)39/1247 (3.2)
      51-6075/1430 (5.2)77/1830 (4.2)
      61-70112/1880 (5.9)113/2239 (5.1)
      71-80181/2439 (7.4)186/2832 (6.5)
      >80248/3214 (7.7)253/3663 (6.9)
      Values are shown as average from 2007-2011.
      All deaths in an emergency department were <10 per year.
      Deaths in the hospital among patients 21-30 years were <10 per year. Age-specific populations are shown in Table 4.
      ED = emergency department; PAH = pulmonary arterial hypertension.
      Figure thumbnail gr5
      Figure 5Number of deaths of patients with pulmonary arterial hypertension (PAH)/million population/year according to age. The death rate increased exponentially with age r = 0.992, P = .0001).

      Discussion

      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 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).
      • Peacock A.J.
      • Murphy N.F.
      • McMurray J.J.V.
      • et al.
      An epidemiological study of pulmonary arterial hypertension.
      • Kirson N.Y.
      • Birnbaum H.G.
      • Ivanova J.I.
      • et al.
      Prevalence of pulmonary hypertension and chronic thromboembolic pulmonary hypertension in the United States.
      • Humbert M.
      • Sistbon O.
      • Chaouat A.
      • et al.
      Pulmonary arterial hypertension in France: results from a national registry.
      • Escribano-Subias P.
      • Blanco I.
      • Lopez-Messeguer M.
      • et al.
      Survival in pulmonary hypertension in Spain: insights from the Spanish registry.
      • Ling Y.
      • Johnson M.K.
      • Kiely D.G.
      • et al.
      Changing demographics, epidemiology, and the survival of incident pulmonary arterial hypertension. Results from the pulmonary hypertension registry of the United Kingdom and Ireland.
      • Jansa P.
      • Jarkovsky J.
      • Al-Hiti H.
      • et al.
      Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry.
      Prevalence rates increased with age.
      • Kirson N.Y.
      • Birnbaum H.G.
      • Ivanova J.I.
      • et al.
      Prevalence of pulmonary hypertension and chronic thromboembolic pulmonary hypertension in the United States.
      Most investigations reported results in fewer than 1000 patients. The prevalence of pulmonary arterial hypertension in Scotland, 52/million adults,
      • Peacock A.J.
      • Murphy N.F.
      • McMurray J.J.V.
      • et al.
      An epidemiological study of pulmonary arterial hypertension.
      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.
      • Peacock A.J.
      • Murphy N.F.
      • McMurray J.J.V.
      • et al.
      An epidemiological study of pulmonary arterial hypertension.
      • Humbert M.
      • Sistbon O.
      • Chaouat A.
      • et al.
      Pulmonary arterial hypertension in France: results from a national registry.
      • Escribano-Subias P.
      • Blanco I.
      • Lopez-Messeguer M.
      • et al.
      Survival in pulmonary hypertension in Spain: insights from the Spanish registry.
      • Ling Y.
      • Johnson M.K.
      • Kiely D.G.
      • et al.
      Changing demographics, epidemiology, and the survival of incident pulmonary arterial hypertension. Results from the pulmonary hypertension registry of the United Kingdom and Ireland.
      • Jansa P.
      • Jarkovsky J.
      • Al-Hiti H.
      • et al.
      Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry.
      • Appelbaum L.
      • Yigla M.
      • Bendayan D.
      • et al.
      Primary pulmonary hypertension in Israel: a national survey.
      Most patients with pulmonary arterial hypertension (64.8%-79.5%) were women.
      • Peacock A.J.
      • Murphy N.F.
      • McMurray J.J.V.
      • et al.
      An epidemiological study of pulmonary arterial hypertension.
      • Kirson N.Y.
      • Birnbaum H.G.
      • Ivanova J.I.
      • et al.
      Prevalence of pulmonary hypertension and chronic thromboembolic pulmonary hypertension in the United States.
      • Humbert M.
      • Sistbon O.
      • Chaouat A.
      • et al.
      Pulmonary arterial hypertension in France: results from a national registry.
      • Escribano-Subias P.
      • Blanco I.
      • Lopez-Messeguer M.
      • et al.
      Survival in pulmonary hypertension in Spain: insights from the Spanish registry.
      • Ling Y.
      • Johnson M.K.
      • Kiely D.G.
      • et al.
      Changing demographics, epidemiology, and the survival of incident pulmonary arterial hypertension. Results from the pulmonary hypertension registry of the United Kingdom and Ireland.
      • Jansa P.
      • Jarkovsky J.
      • Al-Hiti H.
      • et al.
      Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry.
      • Appelbaum L.
      • Yigla M.
      • Bendayan D.
      • et al.
      Primary pulmonary hypertension in Israel: a national survey.
      • Badesch D.B.
      • Raskob G.E.
      • Elliott C.G.
      • et al.
      Pulmonary arterial hypertension: baseline characteristics from the REVEAL Registry.
      We showed that 66.9% were women.
      Table 9Prevalence and Incidence of Pulmonary Arterial Hypertension
      Country, (First Author)YearsnPrevalenceIncidence
      France (Humbert)
      • Humbert M.
      • Sistbon O.
      • Chaouat A.
      • et al.
      Pulmonary arterial hypertension in France: results from a national registry.
      2002-200367415/million adults ≥ 18 y2.4/million adults/y
      Scotland (Peacock)
      • Peacock A.J.
      • Murphy N.F.
      • McMurray J.J.V.
      • et al.
      An epidemiological study of pulmonary arterial hypertension.
      1986-200137452/million adults 16-65 y7.1/million adults/y
      Spain (Escribano-Subias)
      • Escribano-Subias P.
      • Blanco I.
      • Lopez-Messeguer M.
      • et al.
      Survival in pulmonary hypertension in Spain: insights from the Spanish registry.
      1998-200686616/million adults ≥ 14 y3.7/million adults/y
      UK and Ireland (Ling)
      • Ling Y.
      • Johnson M.K.
      • Kiely D.G.
      • et al.
      Changing demographics, epidemiology, and the survival of incident pulmonary arterial hypertension. Results from the pulmonary hypertension registry of the United Kingdom and Ireland.
      20094826.6/million population1.1/million population/y
      Czech Republic (Jansa)
      • Jansa P.
      • Jarkovsky J.
      • Al-Hiti H.
      • et al.
      Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry.
      2000-200719122.4/million population ≥ 18 y10.7/million adults/y
      United States (Kirson)
      • Kirson N.Y.
      • Birnbaum H.G.
      • Ivanova J.I.
      • et al.
      Prevalence of pulmonary hypertension and chronic thromboembolic pulmonary hypertension in the United States.
      1999-20071605109/million < 65 y

      451/million ≥ 65 y
      Israel (Appelbaum)
      • Appelbaum L.
      • Yigla M.
      • Bendayan D.
      • et al.
      Primary pulmonary hypertension in Israel: a national survey.
      1988-1997441.4/million population/y
      We showed an in-hospital all-cause mortality of 6.4% in patients with pulmonary arterial hypertension. Mortality from pulmonary arterial hypertension in 1 year was reported as 12% of 674 patients
      • Humbert M.
      • Sistbon O.
      • Chaouat A.
      • et al.
      Pulmonary arterial hypertension in France: results from a national registry.
      and 13% of 866 patients.
      • Escribano-Subias P.
      • Blanco I.
      • Lopez-Messeguer M.
      • et al.
      Survival in pulmonary hypertension in Spain: insights from the Spanish registry.
      Mortality was higher in the patients >60 years than in younger patients.
      • Jansa P.
      • Jarkovsky J.
      • Al-Hiti H.
      • et al.
      Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry.
      A fundamental observation of registries reported in 2013 is that survival in the modern treatment era has improved compared with that observed previously.
      • McGoon M.D.
      • Benza R.L.
      • Escribano-Subias P.
      • et al.
      Pulmonary arterial hypertension: epidemiology and registries.
      Our observation of decreasing deaths from 2007-2011 is concordant with this observation and may be a reflection of improving treatment during the period of observation. Drugs available for the treatment of pulmonary arterial hypertension from 2007-2011 and dates of US Food and Drug Administration approval are shown in Table 10. Meta-analysis indicated that therapy with some classes of drugs compared with placebo or standard therapy was associated with reduced hospitalization rates of patients with pulmonary arterial hypertension.
      • Coeytaux R.R.
      • Schmit K.M.
      • Kraft B.D.
      • et al.
      Comparative effectiveness and safety of drug therapy for pulmonary arterial hypertension: a systematic review and meta-analysis.
      Our observation of decreasing hospitalizations of patients with pulmonary arterial hypertension from 2007-2011 is concordant with this.
      Table 10Drugs for Treatment of Pulmonary Arterial Hypertension Available 2007-2011 and FDA Approval Dates
      DrugFDA Approval Date
      BosentanNovember 20, 2001
      IloprostDecember 29, 2004
      SildenafilJune 3, 2005
      AmbrisentanJune 15, 2007
      TadalafilMay 26, 2009
      EpoprostenolNovember 1, 2010
      FDA = US Food and Drug Administration.

      Strengths of this Investigation

      We showed the scope of the problem of pulmonary arterial hypertension in terms of trends in the number of emergency department visits/100,000 population, hospitalizations/100,000 population, deaths/million population, and deaths according to age. This investigation of pulmonary artery hypertension is the largest reported and the only investigation that shows the number and rates of emergency department visits, hospitalizations, and mortality, age-specific rates, and trends over years.
      Our results are concordant with reduced mortality in the modern era of patients with pulmonary arterial hypertension shown by others in registries.
      • McGoon M.D.
      • Benza R.L.
      • Escribano-Subias P.
      • et al.
      Pulmonary arterial hypertension: epidemiology and registries.
      Our results are also concordant with reduced hospitalization rates shown by meta-analysis of therapy with modern drugs.
      • Coeytaux R.R.
      • Schmit K.M.
      • Kraft B.D.
      • et al.
      Comparative effectiveness and safety of drug therapy for pulmonary arterial hypertension: a systematic review and meta-analysis.
      Our results are also compatible with the increased mortality in older patients shown by others.
      • Jansa P.
      • Jarkovsky J.
      • Al-Hiti H.
      • et al.
      Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry.
      The clear trends with high correlation coefficients that we observed serve as an internal validation of our results. Finally, we excluded patients with known causes of pulmonary hypertension that are not classified as Group 1 according to the updated clinical classification. This filter strengthened the specificity of the discharge codes.

      Weaknesses of the Investigation

      Administrative databases suffer from errors in coding. We do not know the accuracy of the diagnostic code for primary pulmonary hypertension (ICD-9-CM code 416.0). Also, we do not know the basis for the diagnosis of pulmonary artery hypertension, which may have assisted in strengthening the validity of the diagnostic codes. Diagnostic codes are infrequently validated.
      • van Walraven C.
      • Bennett C.
      • Forster A.J.
      Administrative database research infrequently used validated diagnostic or procedural codes.
      Codes are likely to be more accurate when there is a clear definition of the disease with observable signs and symptoms,
      • O'Malley K.J.
      • Cook K.F.
      • Price M.D.
      • et al.
      Measuring diagnoses: ICD code accuracy.
      as is the case with pulmonary arterial hypertension. For 4 common chronic diseases (chronic obstructive pulmonary disease/asthma, depression, heart disease, and diabetes), sensitivities were low, ranging from 34% to 75%.
      • Singh J.A.
      Accuracy of Veterans Affairs databases for diagnoses of chronic diseases.
      Specificities, however, were high (94%-98%). Positive predictive values ranged from 73% to 91%.
      • Singh J.A.
      Accuracy of Veterans Affairs databases for diagnoses of chronic diseases.
      If these observations apply to pulmonary arterial hypertension, many patients with pulmonary arterial hypertension may not have been identified, but if the patients did not have pulmonary arterial hypertension, the code rarely was misapplied to them.
      Although we showed a considerable amount of information on the scope of the problem, the database does not allow a determination of the number of patients hospitalized or seen in the emergency department more than once or the number of patients with pulmonary artery hypertension who were not seen in the emergency department or hospitalized. Therefore, the prevalence or incidence of pulmonary artery hypertension could not be obtained. Also, some bias may have been introduced if patients visited the emergency department or were hospitalized more than once.
      Other items of information may have been of interest, but the inability to obtain this information does not detract from the data that we obtained. For example, we do not know the number of new patients diagnosed yearly, which may have been of interest, but was not essential. Additional items of potential interest that we were unable to obtain were pulmonary arterial pressure, drugs used for treatment of pulmonary artery hypertension, and functional outcome.
      In conclusion, from 2007 to 2011, rates of emergency department visits, hospitalizations, and deaths decreased in patients with pulmonary arterial hypertension. We speculate that this is a reflection of improved treatment during the period of observation.

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