Pulmonary hypertension (PH) is a disorder of the pulmonary vasculature that results in increased pulmonary arterial pressure and is defined as a mean pulmonary arterial pressure (mPAP) ≥25 mm Hg at rest, the pressure being measured invasively with a pulmonary artery catheter [
To examine trends in PH mortality, we analyzed data from the Centers for Disease Control (CDC) National Vital Statistics System (NVSS). The NVSS classified diseases and conditions reported on death certificates during 1999–2010 according to the
To examine trends in PH hospitalization, we analyzed data from the Centers for Disease Control (CDC) National Hospital Discharge Survey (NHDS) for 1999–2009 [
We used the U.S. civilian population for the period 1999–2009 from the U.S. Census Bureau to calculate age- and sex-specific diagnosis rates per 100,000 population. To examine trends in diagnoses during 1999–2009, we aggregated data into one 3-year and two 4-year periods (1999–2001, 2002–2005) and (2006–2009) as for mortality (see above).
Supplementary Material provides detailed tables not included in this report. (See Supplementary Tables in the Supplementary Material available online at
During 1999–2008, the total number of deaths with PH listed as any contributing cause of death increased from 15,046 in 1999 to 19,373 in 2008. For the reporting periods 1999–2002 and 2003–2008, 57.7% and 61%, respectively, of decedents with PH-related mortality were female. In 1999–2002, 11.2% of males and 9.7% of females were <45 years; in 2003–2008, 8.4% of males and 6.9% of females were aged <45 years. The proportion of decedents aged ≥85 years increased from 17.6% to 22.4%. At all ages in 1999–2008, the most common underlying cause of death was pulmonary hypertension (29.4–30.8%), followed by chronic lower respiratory disease (20.2–27.0%). Among decedents aged <45 years, the most common underlying causes of death were PH; congenital malformations; complications of pregnancy, childbirth, and the puerperium; or conditions originating in the perinatal period. Supplementary Material provides further detailed mortality data in supplementary Tables 1–9.
In 1999–2008, age-standardized death rates for the total U.S. population remained relatively stable from 1999 through 2008 (Table
Age-standardized and age-specific death rates
Characteristic | 1999–2001 | 2002–2005 | 2006–2008 |
---|---|---|---|
Age-standardized†† death rate | |||
All | 5.5 | 5.5 | 5.8 |
Men | 5.6 | 5.3 | 5.3 |
Women | 5.4 | 5.7 | 6.1 |
Race | |||
Black | 7.4 | 7.6 | 8.1 |
White | 5.3 | 5.3 | 5.6 |
Asian/Pacific Islander | 2.6 | 2.5 | 2.8 |
American Indian | 4.0 | 3.9 | 3.9 |
Hispanic origin | |||
Hispanic | 3.2 | 3.1 | 3.1 |
Non-Hispanic | 5.6 | 5.7 | 5.9 |
Age-specific death rate | |||
0–44 yrs | 0.9 | 0.8 | 0.7 |
45–54 yrs | 2.8 | 2.7 | 2.8 |
55–64 yrs | 7.2 | 7.0 | 7.0 |
65–74 yrs | 19.4 | 19.0 | 18.3 |
75–84 yrs | 37.1 | 39.0 | 43.0 |
|
60.8 | 67.4 | 80.0 |
Age-standardized death rate per 100,000 population for decedents with pulmonary hypertension listed as any contributing cause of death by sex and year—United States 1999–2008. Age is standardized using the 2000 U.S. standard population.
From 1999 to 2009, the estimated number of all-listed diagnoses of PH increased by 1.5 times from 257 thousand to 386 thousand. Women accounted for 59.3–60.3% and patients aged ≥65 years accounted for 62.6–66.7% of all-listed diagnoses of PH. All-listed diagnosis rates in 2006–2009 were 1.2–1.4 times higher in men and 1.5 times higher in women than earlier (Table
Estimated rate
Characteristic | 1999–2001 |
2002–2005 |
2006–2009 |
---|---|---|---|
Total | 96.3 | 90.8 | 115.1 |
Male | 79.7 | 74.1 | 93.4 |
Female | 112.2 | 106.9 | 135.4 |
15–44 years | 14.1 | 18.3 | 20.2 |
45–64 years | 103.4 | 104.5 | 100.0 |
65 and over | 527.2 | 453.0 | 598.7 |
Northeast | 120.8 | 103.4 | 132.6 |
Midwest | 99.0 | 92.0 | 112.6 |
South | 90.6 | 91.3 | 122.1 |
West | 79.3 | 78.1 | 92.6 |
Estimated annual rate per 100,000 population of all-listed diagnoses of pulmonary hypertension by year and sex: National Hospital Discharge Survey, United States, 1999–2009.
During 1999–2008, rates for PH as any contributing cause of death and as all-listed hospital diagnoses increased. The number of PH-related deaths and number of hospitalizations increased, particularly among women, blacks, and older adults. In addition, PH was the most common reported underlying cause of death among all decedents with PH as any contributing cause of death during 2000–2008. PH might have been diagnosed more often as diagnostic and therapeutic options improve. Increased survival of patients with PH receiving more effective therapy over the last two decades could also play a role.
The observed increases in reporting of PH as any-listed diagnosis on hospital records might indicate an actual increase in the number of patients or, more likely, a greater awareness among physicians. Increased awareness of PH as a fatal condition could lead to increased reporting of PH as a contributing cause of death [
Although the question cannot be directly addressed with these data, one may wish to consider the possible effect on PH mortality and hospitalizations of the introduction of new drugs for PH, namely, epoprostenol sodium, followed by bosentan and sildenafil to the US market. Epoprostenol (for injection) was approved for PH by the United States Food and Drug Administration (FDA) in 1995. Bosentan (oral) was approved for PH by the United States Food and Drug Administration (FDA) in 2001. Sildenafil (for injection and oral) is marketed for PH and was approved for PH by the United States Food and Drug Administration (FDA) in 2005 (Source Pulmonary Hypertension Association,
Our findings are similar to those of Davis et al., who suggested that annual age-adjusted mortality for idiopathic pulmonary arterial hypertension increased between 1979–1996 and 1994–1998, the greatest increase was among black women and that the disease may not be uncommon in the elderly [
Estimates for prevalence of idiopathic pulmonary arterial hypertension cannot be ascertained from our report. However, registry data suggest that the average age and percent female have increased in the last two decades [
The highest hospital diagnosis rate was observed in the Northeast United States and highest death rates for PH were observed in Vermont and in the Rocky Mountain Western United States (Colorado, Idaho, Montana, New Mexico, and Wyoming). Possible explanations for this geographic pattern include the following: first, these cases might be more likely to be detected by physicians affiliated with PH centers that are located in Denver (CO) and Philadelphia (PA). Second, altitude might also play an important role in the development of PH in states such as Colorado, Montana, and Wyoming [
Our study has several limitations. First, mortality data are subject to diagnosis and reporting errors by physicians, medical examiners, and coroners. Second, the current ICD classifications do not allow data users to differentiate specific diseases that are associated with PH. For example, the current ICD codes do not allow differentiation of the five major categories of PH [
The authors declare that there is no conflict of interests regarding the publication of this paper.
The authors acknowledge the helpful comments by Rosanna Setse, M.D., Ph.D., Thomas O. Obisesan, M.D., M.P.H., Alicia N. Thomas, M.D., Alvin Thomas Jr., M.D., Octavius Polk, M.D., Wayne P. Davis, M.D., and Patricia O’Neal, M.D.