Trends and Disparities in Pulmonary Embolism Mortality in the United States, 1999– 2023

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We assessed trends in PE related mortality in the United States from 1999 to 2023 among adults to determine differences by gender, age, race/ethnicity, and geographic location using CDC WONDER data. Methods: We analyzed adults aged 25 to 85 + years death certificates from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) database with PE (ICD-10 codes: I26 and I26.9) from 1999–2023. Age-adjusted mortality rates (AAMR) per 1,000,000 population were stratified by gender, age, race, and geographic location. Join-point regression analysis was conducted to estimate the average annual percent changes (AAPC) with corresponding 95% confidence intervals (CI). Results: Between 1999 and 2023, mortalities due to PE caused 822482 deaths primarily in Medical Facility-Inpatient (432910) and Decedent's home (141478) deaths in adults aged 25 to 85 + years. The AAMR showed slight variations from 1999 to 2018 (APC: -0.176, 95% confidence interval (CI): -0.348 to − 0.004), increased sharply from 2018 to 2021 (APC: 15.39; 95% CI: 9.82–21.24) and finally decreased thereafter till 2023 (APC: -9.75; 95% CI: -13.79 to − 5.52). Additionally, the AAMR for males was higher than that of females. Non-Hispanic (NH) Blacks or African Americans displayed the highest AAMR, followed by NH Whites, and Hispanic or Latino. Midwest region showed highest AAMR, followed by South, Northeast, and West. District of Columbia was in the top 90th percentile. Rural areas exhibited higher AAMR than urban areas. Older adults had higher CMR than younger adults. Conclusion: PE-related mortality has risen significantly in recent years, with notable disparities across gender, race, and geographic regions. These findings highlight the urgent need for tailored public health strategies to mitigate the evolving burden of PE and promote equitable healthcare outcomes. Pulmonary embolism mortality trends disparities INTRODUCTION Pulmonary embolism (PE), a potentially life-threatening and significantly leading acute cardiovascular disorder with a severely high rate of mortality and morbidity, is caused by constriction of blood vessels of the lungs, causing ischemia and then sudden death if not addressed ( 1 ). It's one of the important clinical entities in the United States that, despite advanced diagnostic tools and prevention and treatment strategies, can cause spontaneous death as the first symptom in about one quarter (25%) of people ( 2 ). The risk factors include history of venous thromboembolism VTE, age, active malignancy or other congenital or acquired coagulation defects, as well as respiratory or CVS comorbidity enhance the likelihood of developing PE ( 3 ). There are several therapeutic measures approved, including catheter-based thrombus removal therapies; formerly, anticoagulation was considered as primary care for the high-risk patient; all leading to enhanced PE care ( 4 ). There is a remarkable change in mortality rates across various demographic and geographical populations. Understanding these disparities will not only help in framing positive public initiatives to enhance clinical outcomes, however, play a critical role in decreasing the mortality trends. Using data from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database encompasses 1999 to 2023, this analysis aims to unfold the patterns and trends in PE-related mortality, with a focus on age, sex, race/ethnicity, and geographic location. By highlighting key disparities, this study seeks to more fair and impartial healthcare interventions and reduce the burden of PE-related deaths nationwide. METHODS Study setting and population In this retrospective study, the Centers for Disease Control and Prevention, Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database was used to retrieve data on pulmonary embolism as underlying cause-of-death in adults 25 to 85 + years of age in the U.S from 1999 to 2023 ( 5 ). The underlying Cause-of-Death Public Use record death certificates were studied to select pulmonary embolism-related deaths ( 6 ). Patients were analyzed using International Statistical Classification of diseases and Health Related Problems – 10th revision (ICD-10) codes as follows: I26.0 and I26.9 for pulmonary embolism ( 7 ). Institutional review board approval was not required for this study since the CDC WONDER database, which contains deidentified data, is publicly accessible. Additionally, this study complies with the guidelines of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE). Data extraction Multiple demographic factors, including sex, region, race/ethnicity, and urban/rural classification, were included in the extensive dataset utilized for the study. There were male and female sex categories. Regions were categorized using the Census Bureau's criteria into Northeast, Midwest, South, and West. Race/ethnicities groups were characterized as Hispanic, Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Asian or Pacific Islander and Non-Hispanic American Indian/Native American. This information has also been utilized in earlier studies using the WONDER database and is based on reported death certificates ( 6 ). The National Center for Health Statistics' Urban-Rural Classification Scheme was employed to stratify the population geographically, dividing it into urban (large metropolitan area; population over a million), medium/small metropolitan area (50,000–999,999), and rural (less than 50,000) categories. Statistical Analysis To analyze the national trends in pulmonary embolism-related mortalities, we calculated crude and Age-adjusted mortality rate (AAMR) per 1,000,000 population from 1999 to 2023 by year, sex, race/ethnicity, states and urban-rural classification with 95% confidence intervals (CIs). AAMRs were calculated by standardizing deaths to the year 2000 U.S. population. To determine the national annual trends in mortality, Join-point Regression Program (Join-point Version 5.0.2, National Cancer Institute) was used to calculate the Annual Percent Change (APC) with 95% CI in AAMR ( 8 ). This program identifies significant changes in AAMR by fitting log-linear regression models to raw data trends. Annual percentage changes (APC) and Average Annual Percentage Changes (AAPCs) were calculated, with their corresponding 95% CIs for the line segments linking a Join-point. APCs were considered increasing or decreasing if the slope describing the change differed significantly from zero. The statistical significance was determined using 2-tailed t-testing with p-value < 0.05 considered statistically significant. RESULTS Annual Trends : A total of 822,482 deaths were identified among adults (≥ 25 years of age) between 1999 and 2023 attributed to pulmonary embolism (PE). The age-adjusted mortality rate (AAMR) for PE-related deaths was 141.7 per 1,000,000 in 1999 and increased to 171.4 in 2023. From 1999 to 2018, the AAMR showed a slight but statistically significant decline (APC: − 0.18; 95% CI: − 0.35 to − 0.005; p = 0.044549). This was followed by a sharp rise between 2018 and 2021 (APC: 15.39; 95% CI: 9.82–21.24; p = 0.000012), and then a statistically significant decline from 2021 to 2023 (APC: − 9.75; 95% CI: − 13.79 to − 5.52; p = 0.000195). Over the full study period, the average annual percent change (AAPC) was 0.80 (95% CI: 0.11–1.49; p = 0.023338). The trend was notably impacted by the COVID-19 pandemic years, during which mortality rates rose sharply. Gender Stratified Trends : The AAMR for men was consistently higher than that of women over the study period. In 1999, the AAMR for adult men was 149.8 (95% CI: 146.9–152.7), remaining relatively stable through 2019 at 154.9 before experiencing a sharp decline to 18.3 in 2023. The corresponding APCs were statistically insignificant from 1999 to 2019 (APC: 0.49; 95% CI: − 2.15 to 3.20; p = 0.71), followed by a statistically significant decrease from 2019 to 2023 (APC: − 46.26; 95% CI: − 57.58 to − 31.92; p = 0.000023). Among women, the AAMR declined from 135.9 (95% CI: 133.7–138.2) in 1999 to 130.6 in 2016, then dropped steeply to 13.7 in 2019, before rising to 16.1 in 2023. From 1999 to 2016, the trend was statistically insignificant (APC: 0.09; 95% CI: − 0.38 to 0.56; p = 0.70), followed by a significant drop between 2016 and 2019 (APC: − 53.52; 95% CI: − 58.94 to − 47.37; p < 0.000001), and a statistically significant increase from 2019 to 2023 (APC: 8.43; 95% CI: 4.75 to 12.24; p = 0.000123). Over the entire period from 1999 to 2023, the AAPC was − 9.47 for males (95% CI: − 13.24 to − 5.54; p = 0.000005) and − 7.84 for females (95% CI: − 9.27 to − 6.39; p < 0.000001), both indicating statistically significant long-term reductions in PE-related mortality. Race Stratification : Regarding race and ethnicity, the highest AAMRs were consistently observed among non-Hispanic (NH) Black or African American individuals, followed by NH White, and Hispanic or Latino populations. Among NH Black individuals, the AAMR declined from 94.6 in 1999 to 62.5 in 2008 (APC: − 4.6462; 95% CI: − 6.02 to − 3.25; p = 0.000001), followed by a statistically significant increase to 64.6 in 2023 (APC: 0.7817; 95% CI: 0.16 to 1.41; p = 0.016956). In NH White individuals, the AAMR decreased from 48.2 in 1999 to 44.7 in 2003 (APC: − 1.4321; 95% CI: − 4.67 to 1.91; p = 0.374613), then significantly declined to 34.9 in 2007 (APC: − 6.4210; 95% CI: − 11.67 to − 0.86; p = 0.026744), followed by a non-significant change to 33.9 in 2023 (APC: 0.3548; 95% CI: − 0.09 to 0.80; p = 0.113156). Among Hispanic or Latino individuals, the AAMR decreased from 25.5 in 1999 to 13.8 in 2009 (APC: − 5.4351; 95% CI: − 7.33 to − 3.50; p = 0.000020), rose modestly to 16.3 in 2020 (APC: 0.6145; 95% CI: − 1.08 to 2.33; p = 0.455839), and then significantly declined to 9.6 in 2023 (APC: − 14.8255; 95% CI: − 21.82 to − 7.20; p = 0.001037). Over the full study period (1999–2023), the AAPC was − 1.2891 for NH Black individuals (95% CI: − 1.91 to − 0.67; p = 0.000053), − 1.1042 for NH White individuals (95% CI: − 2.16 to − 0.04; p = 0.041796), and − 3.9725 for Hispanic or Latino individuals (95% CI: − 5.36 to − 2.56; p < 0.000001), indicating statistically significant long-term declines across all three groups. Geographical Region : State Between 1999 to 2020, District of Columbia had the highest AAMR of 248.95. Wyoming exhibited the second highest AAMR of 195.56, while Hawaii reflected the lowest AAMR at 73.00. Subsequently, a discernible increase in AAMR was documented during 2021–2023 period for several states. States that ranked in the upper 90th percentile for PE-related mortalities in 2021–2023 include District of Columbia, Colorado, Wyoming, Maryland and Mississipi. Conversely, states within the lower 10 th percentile in the same period included New Mexico, California, New Jersey, Hawaii, and Maine Regions The AAMR for pulmonary embolism (PE) showed distinct patterns across U.S. census regions over the study period. In the Northeast, the AAMR decreased from 4.34 in 1999 to 2.85 in 2019 (APC: − 2.39; 95% CI: − 4.36 to − 0.37; p = 0.022678), followed by a steep increase to 22.58 in 2023 (APC: 97.17; 95% CI: 52.74 to 154.52; p = 0.000020). The overall AAPC for the region from 1999 to 2023 was 9.75 (95% CI: 5.12 to 14.58; p = 0.000023). In the Midwest, the AAMR declined from 5.79 in 1999 to 4.18 in 2019 (APC: − 1.65; 95% CI: − 3.72 to 0.46; p = 0.117617), then rose sharply to 31.56 by 2023 (APC: 96.43; 95% CI: 51.60 to 154.50; p = 0.000025). The overall AAPC for the Midwest was 10.37 (95% CI: 5.63 to 15.31; p = 0.000010). The South region exhibited a non-significant decline from 5.93 in 1999 to 3.82 in 2019 (APC: − 1.52; 95% CI: − 3.73 to 0.74; p = 0.175023), followed by a statistically significant increase to 31.89 in 2023 (APC: 90.95; 95% CI: 45.42 to 150.75; p = 0.000077). The region’s overall AAPC was 9.97 (95% CI: 5.01 to 15.17; p = 0.000057). In the West, the AAMR dropped from 3.36 in 1999 to 2.27 in 2019 (APC: − 1.94; 95% CI: − 4.18 to 0.35; p = 0.092031), and then rose markedly to 19.06 in 2023 (APC: 97.98; 95% CI: 52.19 to 157.55; p = 0.000027). The West had an overall AAPC of 10.24 (95% CI: 5.39 to 15.31; p = 0.000021). From 1999 to 2023, all four census regions showed statistically significant increases in PE-related mortality, with the Midwest having the steepest rise (AAPC: 10.37), followed by the West (10.24), South (9.97), and Northeast (9.75). Urban-Rural From 1999 to 2020, rural areas exhibited consistently higher PE-related AAMRs compared to urban regions. The AAMR in rural areas decreased from 6.51 in 1999 to 4.56 in 2009 (APC: − 3.3699; 95% CI: − 4.4060 to − 2.3225; p = 0.000008), followed by a statistically significant increase to 5.38 in 2015 (APC: 3.1758; 95% CI: − 0.0046 to 6.4572; p = 0.050291), and a subsequent statistically non-significant decline to 5.01 in 2020 (APC: − 2.4195; 95% CI: − 5.3781 to 0.6317; p = 0.110559). In contrast, urban areas saw a steady reduction in AAMR from 4.68 in 1999 to 3.07 in 2009 (APC: − 4.3786; 95% CI: − 5.2807 to − 3.4679; p < 0.000001), followed by a slight but statistically non-significant rise to 3.44 in 2020 (APC: 0.5798; 95% CI: − 0.2349 to 1.4012; p = 0.152009). Over the full period, both areas experienced statistically significant declines in PE-related mortality, with the AAPC for urban areas at − 1.8126 (95% CI: − 2.3771 to − 1.2484; p < 0.000001), and for rural areas at − 1.3135 (95% CI: − 2.4481 to − 0.1658; p = 0.025014). Age Groups : The data were stratified by two main age categories: younger adults (25–34, 35–44, and 45–54 years) and older adults (55–64, 65–74, 75–84, and 85 + years). In the analysis stratified by age, older adults consistently exhibited markedly higher AAMRs compared to younger adults throughout the study period. Among older adults, the AAMR declined from 357.64 in 1999 to 338.93 in 2018 (APC: − 0.5071; 95% CI: − 0.6745 to − 0.3395; p = 0.000007), followed by a statistically significant surge to 503.59 in 2021 (APC: 14.8418; 95% CI: 9.4966 to 20.4480; p = 0.000011), and then a decline to 414.87 by 2023 (APC: − 7.8161; 95% CI: − 11.7441 to − 3.7134; p = 0.001048). In contrast, younger adults showed a gradual increase in AAMR from 35.11 in 1999 to 46.99 in 2018 (APC: 1.1865; 95% CI: 0.8891 to 1.4847; p < 0.000001), followed by a sharp rise to 74.05 in 2021 (APC: 17.1958; 95% CI: 7.5587 to 27.6620; p = 0.001118), and a subsequent decline to 51.22 in 2023 (APC: − 16.4995; 95% CI: − 23.3028 to − 9.0928; p = 0.000332). Over the full study period (1999–2023), the average annual percent change (AAPC) in AAMR was 0.6512 (95% CI: − 0.0107 to 1.3175; p = 0.053821) for older adults, which was statistically non-significant, and 1.4246 (95% CI: 0.2038 to 2.6603; p = 0.022047) for younger adults, which was statistically significant. Place of death From 1999 to 2023, highest number of deaths took place in Medical Facility- Inpatient, followed by Descendants’ home, Medical Facility- Outpatient or ER, Nursing home/long term care, Hospice Facility, other, Medical Facility-dead on arrival, Place of death unknown, Medical Facility-status unknown. Discussion Our analysis of pulmonary embolism (PE) mortality trends in the United States from 1999 to 2023 reveals DISTINCT patterns across time, demographic groups, and geographic regions. Although the mortality rate declined during the entire study period, a spike was observed during 2018–2021 across all groups. This significant spike can be attributed to the COVID-19 pandemic. The impact of pandemic on the mortality trends can be explained by several factors. Many studies reported that Coronavirus disease (COVID-19) that is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can increase risk of thromboembolic events. The incidence of thromboembolism increased sharply in patients with a severe COVID-19 infection who required intensive care and cardiorespiratory support ( 9 ). Similarly, one study reported that the incidence of venous thromboembolism was increased by more than 2.5 times in COVID-19 patients who required treatment in the intensive care unit ( 10 ). Not only there was increase in thromboembolism but also increase risk of thromboembolism related death. As reported by Burn et al. COVID-19 patients with complications of venous thromboembolism tend to have a higher risk of death (4.42 times higher for patients who are not hospitalized and 1.63 times higher for those who are hospitalized) ( 11 ). Another study showed that the risk of venous thromboembolism (i.e., DVT and PE) remains elevated even after COVID-19 infection is treated. The risk of developing DVT remains elevated up to 70 days after COVID-19 and 110 days for PE ( 12 ). Additionally, the healthcare systems were overburdened that resulted in delays in diagnosis and treatment of other diseases. Furthermore, behavioral changes among the population such as increase stress and less physical activity might also have contributed to more thromboembolic events during the pandemic. Pulmonary embolism (PE) is the third most common cause of cardiovascular death; however, gender disparities in PE remain understudied. Our analysis showed that men had a higher AAMR compared to women through entire period. Jarman et al. indicated that the overall age-adjusted incidence of PE is similar in women and men ( 13 ). While some older studies suggested higher incidence of PE in males ( 14 ) Nonetheless, overall AAMR due to PE has decreased in the USA likely due to improved diagnostic methods, early interventions, and therapies ( 15 ). Racial stratification indicated that Black/African American were affected more compared to other races, a finding consistent with other studies. Zghouzi et al. reported that not only was PE-related mortality 2-fold higher in Black individuals compared to non- Black individuals (in 2019 and 2020); this disparity was disproportionately exacerbated during the pandemic year, 2020 ( 16 ) Sathianathan et al also reported the racial disparities in pulmonary embolism management with Black and Hispanic group being at having higher odds of mortality major bleeding, and increased length of stay after management of PE ( 17 ). Another study by Breuer et al. reported that the racial disparities in acute pulmonary embolism treatment with NH Black patients have a higher risk of mortality from acute, nonseptic PE than White patients ( 18 ). This consistent trend in mortality among certain races requires target public health interventions directed specifically towards NH Blacks and Hispanic populations. Analysis based on regions showed significant disparities as well. Contrary to other groups, regional analysis showed increased mortality over the years, with the Midwest region showing the steepest rise. Rural areas exhibited higher mortality compared to urban areas. This may be due to poor access to better healthcare facilities in these areas. Other studies also reported rural areas have higher AAMR compared to urban areas ( 19 ). Although it is well recognized that the risk of (PE) increases with age, PE remains a major cause of mortality among younger adults in the United States ( 20 ). While older adults showed a consistent elevated AAMR compared to their young counterparts, the trends stratified by age exhibited an interesting pattern. The overall mortality rate declined in older adults and increased in younger adults. Although this decline was more prominent during 1999–2018, this trend was disturbed by COVID-19 pandemic increasing mortality rate of not only PE related deaths but also other cardiovascular related deaths ( 21 ). The overall decline in mortality rates among the older population can be attributed to early diagnosis, better management and better hospital care. PE-related mortality in adults aged 25 to 44 years has increased over the last 2 decades in the United States ( 22 ). A similar finding was observed in our analysis as well. This study also found that PE-related mortality increased by 23% among adults aged 25–64 between 2008 and 2018 ( 23 ). It is unclear why PE-related mortality is increasing among young individuals in the USA. There are certain risk factors that are associated with increased risk of PE-related mortality in younger adults Smoking, obesity, trauma, surgery, prolonged air travel, use of OCPs and hormone replacement therapy, pregnancy, post-partum status and thrombophilia ( 24 ).Further studies may be needed to know the exact cause of increased PE related mortality in young adults. Based on our analysis, most of the deaths occurred in in-patient medical facilities.Hospitalized patients are at increased risk of developing DVT (approximately 50%), increasing the risk of PE. PE is one of the most common but preventable causes of death in hospitalized patients[25].So, initiating DVT prophylaxis in hospitalized patients can save many lives. Using DVT prophylaxis in hospitalized patients decreases the risk of DVT anywhere from 10 to 80% [25]. Limitations Some limitations may be acknowledged while interpreting our findings. The study relied on data from death certificates, and certain co- existing pathologies may have influenced our results. We do not have data regarding patients' baseline characteristics, and history of any risk factors which could have influenced the results. Furthermore, the CDC WONDER does not contain information about the potential socioeconomic and other confounding factors. Conclusion An increasing trend of Pulmonary embolism-related death in adults was observed throughout the study period. The highest mortality was exhibited by older NH Black/African American males living in rural Midwest and district of Columbia. Abbreviations Abbreviation Full Form PE Pulmonary Embolism CDC Centers for Disease Control and Prevention WONDER Wide-ranging Online Data for Epidemiologic Research ICD-10 International Classification of Diseases, 10th Revision AAMR Age-Adjusted Mortality Rate CMR Crude Mortality Rate AAPC Average Annual Percent Change APC Annual Percent Change CI Confidence Interval NH Non-Hispanic VTE Venous Thromboembolism CVS Cardiovascular System DVT Deep Vein Thrombosis STROBE Strengthening the Reporting of Observational Studies in Epidemiology ER Emergency Room OCPs Oral Contraceptive Pills ORCID Open Researcher and Contributor ID Declarations Ethics approval and consent to participate Not applicable. This study is a CDC wonder of previously published studies, and no new human or animal subjects were involved. Consent for publication Not applicable. Availability of data and materials The data was taken from the publicly available CDC WONDER database https://wonder.cdc.gov/mcd.html. All data were obtained from this source and analyzed as part of this research. Competing interests The authors declare that they have no competing interests. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Clinical Trial Number : Not applicable Authors' contributions HH - discussion , MSS - supplementary file, DR - abstract and compiling , IKI - introduction, methods, extraction and analysis , JN - extraction and analysis, KAK- review manuscript, AA- literature review, MS- topic selection, NF- submission, MH- compiled manuscript Acknowledgements None to declare References Zghouzi M, Mwansa H, Shore S, Hyder SN, Kamdar N, Moles VM, et al. Sex, Racial, and Geographic Disparities in Pulmonary Embolism–related Mortality Nationwide. Ann Am Thorac Soc [Internet]. 2023 Nov 1 [cited 2025 May 30];20(11):1571–7. Available from: https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202302-091OC?download=true Data and Statistics on Venous Thromboembolism | Venous Thromboembolism (Blood Clots) | CDC [Internet]. [cited 2025 May 30]. Available from: https://www.cdc.gov/blood-clots/data-research/facts-stats/index.html Pulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism - PubMed [Internet]. [cited 2025 May 30]. Available from: https://pubmed.ncbi.nlm.nih.gov/23940438/ Sista AK, Horowitz JM, Tapson VF, Rosenberg M, Elder MD, Schiro BJ, et al. Indigo Aspiration System for Treatment of Pulmonary Embolism: Results of the EXTRACT-PE Trial. JACC Cardiovasc Interv [Internet]. 2021 Feb 8 [cited 2025 May 30];14(3):319–29. Available from: https://pubmed.ncbi.nlm.nih.gov/33454291/ CDC WONDER [Internet]. [cited 2025 May 10]. Available from: https://wonder.cdc.gov/ Deaths [Internet]. [cited 2025 May 17]. Available from: https://wonder.cdc.gov/deaths-by-underlying-cause.html ICD-10 Version:2019 [Internet]. [cited 2025 May 10]. Available from: https://icd.who.int/browse10/2019/en#!. Joinpoint Regression Program [Internet]. [cited 2025 May 10]. Available from: https://surveillance.cancer.gov/joinpoint/ Jenner WJ, Gorog DA. Incidence of thrombotic complications in COVID-19: On behalf of ICODE: The International COVID-19 Thrombosis Biomarkers Colloquium. J Thromb Thrombolysis [Internet]. 2021 Nov 1 [cited 2025 May 30];52(4):999–1006. Available from: https://pubmed.ncbi.nlm.nih.gov/34047938/ Tan BK, Mainbourg S, Friggeri A, Bertoletti L, Douplat M, Dargaud Y, et al. Arterial and venous thromboembolism in COVID-19: A study-level meta-analysis. Thorax [Internet]. 2021 Oct 1 [cited 2025 May 30];76(10):970–9. Available from: https://pubmed.ncbi.nlm.nih.gov/33622981/ Burn E, Duarte-Salles T, Fernandez-Bertolin S, Reyes C, Kostka K, Delmestri A, et al. Venous or arterial thrombosis and deaths among COVID-19 cases: a European network cohort study. Lancet Infect Dis [Internet]. 2022 Aug 1 [cited 2025 May 30];22(8):1142–52. Available from: https://pubmed.ncbi.nlm.nih.gov/35576963/ Katsoularis I, Fonseca-Rodríguez O, Farrington P, Jerndal H, Lundevaller EH, Sund M, et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ [Internet]. 2022 Apr 6 [cited 2025 May 30];377:e069590. Available from: https://pubmed.ncbi.nlm.nih.gov/35387772/ Jarman AF, Mumma BE, Singh KS, Nowadly CD, Maughan BC. Crucial considerations: Sex differences in the epidemiology, diagnosis, treatment, and outcomes of acute pulmonary embolism in non-pregnant adult patients. JACEP Open [Internet]. 2021 Feb 1 [cited 2025 May 30];2(1). Available from: https://pubmed.ncbi.nlm.nih.gov/33532761/ Horlander KT, Mannino DM, Leeper K V. Pulmonary embolism mortality in the United States, 1979-1998: An analysis using multiple-cause mortality data. Arch Intern Med [Internet]. 2003 Jul 28 [cited 2025 May 30];163(14):1711–7. Available from: https://pubmed.ncbi.nlm.nih.gov/12885687/ Vyas V, Sankari A, Goyal A. Acute Pulmonary Embolism. 2024 Dec 11 [cited 2025 May 30]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK560551/ Zghouzi M, Mwansa H, Shore S, Hyder SN, Kamdar N, Moles VM, et al. Sex, Racial, and Geographic Disparities in Pulmonary Embolism–related Mortality Nationwide. Ann Am Thorac Soc [Internet]. 2023 Nov 1 [cited 2025 May 30];20(11):1571–7. Available from: https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202302-091OC?download=true Sathianathan S, Meili Z, Romero CM, Juarez JJ, Bashir R. Racial and gender disparities in the management of acute pulmonary embolism. J Vasc Surg Venous Lymphat Disord [Internet]. 2024 May 1 [cited 2025 May 30];12(3). Available from: https://pubmed.ncbi.nlm.nih.gov/38296110/ Breuer JA, Ahmed KH, Scherr R, Sing C, Daid M, Nouizi F, et al. Racial Disparities and Other Socioeconomic Predictors of Mortality in Acute Pulmonary Embolism Treatment from the National Inpatient Sample. Journal of Vascular and Interventional Radiology [Internet]. 2024 Sep 1 [cited 2025 May 30];35(9):1377–87. Available from: https://pubmed.ncbi.nlm.nih.gov/38518999/ Zghouzi M, Mwansa H, Shore S, Hyder SN, Kamdar N, Moles VM, et al. Sex, Racial, and Geographic Disparities in Pulmonary Embolism–related Mortality Nationwide. Ann Am Thorac Soc [Internet]. 2023 Nov 1 [cited 2025 May 30];20(11):1571–7. Available from: https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202302-091OC?download=true Giordano NJ, Jansson PS, Young MN, Hagan KA, Kabrhel C. Epidemiology, Pathophysiology, Stratification, and Natural History of Pulmonary Embolism. Tech Vasc Interv Radiol [Internet]. 2017 Sep 1 [cited 2025 May 30];20(3):135–40. Available from: https://pubmed.ncbi.nlm.nih.gov/29029707/ Woodruff RC, Tong X, Khan SS, Shah NS, Jackson SL, Loustalot F, et al. Trends in Cardiovascular Disease Mortality Rates and Excess Deaths, 2010–2022. Am J Prev Med [Internet]. 2024 Apr 1 [cited 2025 May 30];66(4):582–9. Available from: https://pubmed.ncbi.nlm.nih.gov/37972797/ Zuin M, Bikdeli B, Armero A, Porio N, Rigatelli G, Bilato C, et al. Trends in Pulmonary Embolism Deaths Among Young Adults Aged 25 to 44 Years in the United States, 1999 to 2019. American Journal of Cardiology [Internet]. 2023 Sep 1 [cited 2025 May 30];202:169–75. Available from: https://pubmed.ncbi.nlm.nih.gov/37441831/ Martin KA, Molsberry R, Cuttica MJ, Desai KR, Schimmel DR, Khan SS. Time trends in pulmonary embolism mortality rates in the united states, 1999 to 2018. J Am Heart Assoc [Internet]. 2020 Sep 1 [cited 2025 May 30];9(17). Available from: https://pubmed.ncbi.nlm.nih.gov/32809909/ Gjonbrataj E, Kim JN, Gjonbrataj J, Jung HI, Kim HJ, Choi W Il. Risk factors associated with provoked pulmonary embolism. Korean J Intern Med [Internet]. 2016 Jan 1 [cited 2025 May 30];32(1):95–101. Available from: https://www.kjim.org/journal/view.php?doi=10.3904/kjim.2015.118 Badireddy M, Mudipalli VR. Deep Venous Thrombosis Prophylaxis. [Updated 2023 May 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534865/ Additional Declarations No competing interests reported. Supplementary Files supplementarytablePE.docx Appendices.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7049348","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":499976205,"identity":"a20d2848-819b-4cd5-ab86-05b0b1f6f047","order_by":0,"name":"Abdullah Afridi","email":"","orcid":"","institution":"Khyber Medical College","correspondingAuthor":false,"prefix":"","firstName":"Abdullah","middleName":"","lastName":"Afridi","suffix":""},{"id":499976207,"identity":"f509080c-23da-4507-92ab-bf34f55fe258","order_by":1,"name":"Huzefa Habib","email":"","orcid":"","institution":"King Edward Medical 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20:23:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7049348/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7049348/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108559929,"identity":"408c4d83-6fa2-4318-9aa7-d81804dfba05","added_by":"auto","created_at":"2026-05-06 02:39:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":204910,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7049348/v1/c1cf9ab4-78d5-4443-b138-4b6a7c2c42f5.pdf"},{"id":89284927,"identity":"0fc30be7-4676-4fde-95ae-82d73a0f857e","added_by":"auto","created_at":"2025-08-18 11:11:35","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":804984,"visible":true,"origin":"","legend":"","description":"","filename":"supplementarytablePE.docx","url":"https://assets-eu.researchsquare.com/files/rs-7049348/v1/95c0240596ff0660487ef8ea.docx"},{"id":89284121,"identity":"2d098a1d-5917-4c92-b5fd-0a85d2b99980","added_by":"auto","created_at":"2025-08-18 11:03:35","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":292677,"visible":true,"origin":"","legend":"","description":"","filename":"Appendices.docx","url":"https://assets-eu.researchsquare.com/files/rs-7049348/v1/ee13f1a91327de0771c0086d.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Trends and Disparities in Pulmonary Embolism Mortality in the United States, 1999– 2023","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003ePulmonary embolism (PE), a potentially life-threatening and significantly leading acute cardiovascular disorder with a severely high rate of mortality and morbidity, is caused by constriction of blood vessels of the lungs, causing ischemia and then sudden death if not addressed (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It's one of the important clinical entities in the United States that, despite advanced diagnostic tools and prevention and treatment strategies, can cause spontaneous death as the first symptom in about one quarter (25%) of people (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The risk factors include history of venous thromboembolism VTE, age, active malignancy or other congenital or acquired coagulation defects, as well as respiratory or CVS comorbidity enhance the likelihood of developing PE (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). There are several therapeutic measures approved, including catheter-based thrombus removal therapies; formerly, anticoagulation was considered as primary care for the high-risk patient; all leading to enhanced PE care (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere is a remarkable change in mortality rates across various demographic and geographical populations. Understanding these disparities will not only help in framing positive public initiatives to enhance clinical outcomes, however, play a critical role in decreasing the mortality trends. Using data from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) database encompasses 1999 to 2023, this analysis aims to unfold the patterns and trends in PE-related mortality, with a focus on age, sex, race/ethnicity, and geographic location. By highlighting key disparities, this study seeks to more fair and impartial healthcare interventions and reduce the burden of PE-related deaths nationwide.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cb\u003eStudy setting and population\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn this retrospective study, the Centers for Disease Control and Prevention, Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database was used to retrieve data on pulmonary embolism as underlying cause-of-death in adults 25 to 85 + years of age in the U.S from 1999 to 2023 (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The underlying Cause-of-Death Public Use record death certificates were studied to select pulmonary embolism-related deaths (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Patients were analyzed using International Statistical Classification of diseases and Health Related Problems – 10th revision (ICD-10) codes as follows: I26.0 and I26.9 for pulmonary embolism (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Institutional review board approval was not required for this study since the CDC WONDER database, which contains deidentified data, is publicly accessible. Additionally, this study complies with the guidelines of Strengthening the Reporting of Observational Studies in Epidemiology (STROBE).\u003c/p\u003e\u003cp\u003e\u003cb\u003eData extraction\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMultiple demographic factors, including sex, region, race/ethnicity, and urban/rural classification, were included in the extensive dataset utilized for the study. There were male and female sex categories. Regions were categorized using the Census Bureau's criteria into Northeast, Midwest, South, and West. Race/ethnicities groups were characterized as Hispanic, Non-Hispanic White, Non-Hispanic Black, Non-Hispanic Asian or Pacific Islander and Non-Hispanic American Indian/Native American. This information has also been utilized in earlier studies using the WONDER database and is based on reported death certificates (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). The National Center for Health Statistics' Urban-Rural Classification Scheme was employed to stratify the population geographically, dividing it into urban (large metropolitan area; population over a million), medium/small metropolitan area (50,000–999,999), and rural (less than 50,000) categories.\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eTo analyze the national trends in pulmonary embolism-related mortalities, we calculated crude and Age-adjusted mortality rate (AAMR) per 1,000,000 population from 1999 to 2023 by year, sex, race/ethnicity, states and urban-rural classification with 95% confidence intervals (CIs). AAMRs were calculated by standardizing deaths to the year 2000 U.S. population. To determine the national annual trends in mortality, Join-point Regression Program (Join-point Version 5.0.2, National Cancer Institute) was used to calculate the Annual Percent Change (APC) with 95% CI in AAMR (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This program identifies significant changes in AAMR by fitting log-linear regression models to raw data trends. Annual percentage changes (APC) and Average Annual Percentage Changes (AAPCs) were calculated, with their corresponding 95% CIs for the line segments linking a Join-point. APCs were considered increasing or decreasing if the slope describing the change differed significantly from zero. The statistical significance was determined using 2-tailed t-testing with p-value \u0026lt; 0.05 considered statistically significant.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003e\u003cb\u003eAnnual Trends\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eA total of 822,482 deaths were identified among adults (\u0026ge;\u0026thinsp;25 years of age) between 1999 and 2023 attributed to pulmonary embolism (PE). The age-adjusted mortality rate (AAMR) for PE-related deaths was 141.7 per 1,000,000 in 1999 and increased to 171.4 in 2023. From 1999 to 2018, the AAMR showed a slight but statistically significant decline (APC: \u0026minus;\u0026thinsp;0.18; 95% CI: \u0026minus;\u0026thinsp;0.35 to \u0026minus;\u0026thinsp;0.005; p\u0026thinsp;=\u0026thinsp;0.044549). This was followed by a sharp rise between 2018 and 2021 (APC: 15.39; 95% CI: 9.82\u0026ndash;21.24; p\u0026thinsp;=\u0026thinsp;0.000012), and then a statistically significant decline from 2021 to 2023 (APC: \u0026minus;\u0026thinsp;9.75; 95% CI: \u0026minus;\u0026thinsp;13.79 to \u0026minus;\u0026thinsp;5.52; p\u0026thinsp;=\u0026thinsp;0.000195). Over the full study period, the average annual percent change (AAPC) was 0.80 (95% CI: 0.11\u0026ndash;1.49; p\u0026thinsp;=\u0026thinsp;0.023338). The trend was notably impacted by the COVID-19 pandemic years, during which mortality rates rose sharply.\u003c/p\u003e\u003cp\u003e\u003cb\u003eGender Stratified Trends\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe AAMR for men was consistently higher than that of women over the study period. In 1999, the AAMR for adult men was 149.8 (95% CI: 146.9\u0026ndash;152.7), remaining relatively stable through 2019 at 154.9 before experiencing a sharp decline to 18.3 in 2023. The corresponding APCs were statistically insignificant from 1999 to 2019 (APC: 0.49; 95% CI: \u0026minus;\u0026thinsp;2.15 to 3.20; p\u0026thinsp;=\u0026thinsp;0.71), followed by a statistically significant decrease from 2019 to 2023 (APC: \u0026minus;\u0026thinsp;46.26; 95% CI: \u0026minus;\u0026thinsp;57.58 to \u0026minus;\u0026thinsp;31.92; p\u0026thinsp;=\u0026thinsp;0.000023).\u003c/p\u003e\u003cp\u003eAmong women, the AAMR declined from 135.9 (95% CI: 133.7\u0026ndash;138.2) in 1999 to 130.6 in 2016, then dropped steeply to 13.7 in 2019, before rising to 16.1 in 2023. From 1999 to 2016, the trend was statistically insignificant (APC: 0.09; 95% CI: \u0026minus;\u0026thinsp;0.38 to 0.56; p\u0026thinsp;=\u0026thinsp;0.70), followed by a significant drop between 2016 and 2019 (APC: \u0026minus;\u0026thinsp;53.52; 95% CI: \u0026minus;\u0026thinsp;58.94 to \u0026minus;\u0026thinsp;47.37; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), and a statistically significant increase from 2019 to 2023 (APC: 8.43; 95% CI: 4.75 to 12.24; p\u0026thinsp;=\u0026thinsp;0.000123). Over the entire period from 1999 to 2023, the AAPC was \u0026minus;\u0026thinsp;9.47 for males (95% CI: \u0026minus;\u0026thinsp;13.24 to \u0026minus;\u0026thinsp;5.54; p\u0026thinsp;=\u0026thinsp;0.000005) and \u0026minus;\u0026thinsp;7.84 for females (95% CI: \u0026minus;\u0026thinsp;9.27 to \u0026minus;\u0026thinsp;6.39; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), both indicating statistically significant long-term reductions in PE-related mortality.\u003c/p\u003e\u003cp\u003e\u003cb\u003eRace Stratification\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eRegarding race and ethnicity, the highest AAMRs were consistently observed among non-Hispanic (NH) Black or African American individuals, followed by NH White, and Hispanic or Latino populations. Among NH Black individuals, the AAMR declined from 94.6 in 1999 to 62.5 in 2008 (APC: \u0026minus;\u0026thinsp;4.6462; 95% CI: \u0026minus;\u0026thinsp;6.02 to \u0026minus;\u0026thinsp;3.25; p\u0026thinsp;=\u0026thinsp;0.000001), followed by a statistically significant increase to 64.6 in 2023 (APC: 0.7817; 95% CI: 0.16 to 1.41; p\u0026thinsp;=\u0026thinsp;0.016956). In NH White individuals, the AAMR decreased from 48.2 in 1999 to 44.7 in 2003 (APC: \u0026minus;\u0026thinsp;1.4321; 95% CI: \u0026minus;\u0026thinsp;4.67 to 1.91; p\u0026thinsp;=\u0026thinsp;0.374613), then significantly declined to 34.9 in 2007 (APC: \u0026minus;\u0026thinsp;6.4210; 95% CI: \u0026minus;\u0026thinsp;11.67 to \u0026minus;\u0026thinsp;0.86; p\u0026thinsp;=\u0026thinsp;0.026744), followed by a non-significant change to 33.9 in 2023 (APC: 0.3548; 95% CI: \u0026minus;\u0026thinsp;0.09 to 0.80; p\u0026thinsp;=\u0026thinsp;0.113156). Among Hispanic or Latino individuals, the AAMR decreased from 25.5 in 1999 to 13.8 in 2009 (APC: \u0026minus;\u0026thinsp;5.4351; 95% CI: \u0026minus;\u0026thinsp;7.33 to \u0026minus;\u0026thinsp;3.50; p\u0026thinsp;=\u0026thinsp;0.000020), rose modestly to 16.3 in 2020 (APC: 0.6145; 95% CI: \u0026minus;\u0026thinsp;1.08 to 2.33; p\u0026thinsp;=\u0026thinsp;0.455839), and then significantly declined to 9.6 in 2023 (APC: \u0026minus;\u0026thinsp;14.8255; 95% CI: \u0026minus;\u0026thinsp;21.82 to \u0026minus;\u0026thinsp;7.20; p\u0026thinsp;=\u0026thinsp;0.001037).\u003c/p\u003e\u003cp\u003eOver the full study period (1999\u0026ndash;2023), the AAPC was \u0026minus;\u0026thinsp;1.2891 for NH Black individuals (95% CI: \u0026minus;\u0026thinsp;1.91 to \u0026minus;\u0026thinsp;0.67; p\u0026thinsp;=\u0026thinsp;0.000053), \u0026minus;\u0026thinsp;1.1042 for NH White individuals (95% CI: \u0026minus;\u0026thinsp;2.16 to \u0026minus;\u0026thinsp;0.04; p\u0026thinsp;=\u0026thinsp;0.041796), and \u0026minus;\u0026thinsp;3.9725 for Hispanic or Latino individuals (95% CI: \u0026minus;\u0026thinsp;5.36 to \u0026minus;\u0026thinsp;2.56; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), indicating statistically significant long-term declines across all three groups.\u003c/p\u003e\u003cp\u003e\u003cb\u003eGeographical Region\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eState\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBetween 1999 to 2020, District of Columbia had the highest AAMR of 248.95. Wyoming exhibited the second highest AAMR of 195.56, while Hawaii reflected the lowest AAMR at 73.00.\u003c/p\u003e\u003cp\u003eSubsequently, a discernible increase in AAMR was documented during 2021\u0026ndash;2023 period for several states. States that ranked in the upper 90th percentile for PE-related mortalities in 2021\u0026ndash;2023 include District of Columbia, Colorado, Wyoming, Maryland and Mississipi. Conversely, states within the lower 10 th percentile in the same period included New Mexico, California, New Jersey, Hawaii, and Maine\u003c/p\u003e\u003cp\u003e\u003cb\u003eRegions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe AAMR for pulmonary embolism (PE) showed distinct patterns across U.S. census regions over the study period.\u003c/p\u003e\u003cp\u003eIn the Northeast, the AAMR decreased from 4.34 in 1999 to 2.85 in 2019 (APC: \u0026minus;\u0026thinsp;2.39; 95% CI: \u0026minus;\u0026thinsp;4.36 to \u0026minus;\u0026thinsp;0.37; p\u0026thinsp;=\u0026thinsp;0.022678), followed by a steep increase to 22.58 in 2023 (APC: 97.17; 95% CI: 52.74 to 154.52; p\u0026thinsp;=\u0026thinsp;0.000020). The overall AAPC for the region from 1999 to 2023 was 9.75 (95% CI: 5.12 to 14.58; p\u0026thinsp;=\u0026thinsp;0.000023).\u003c/p\u003e\u003cp\u003eIn the Midwest, the AAMR declined from 5.79 in 1999 to 4.18 in 2019 (APC: \u0026minus;\u0026thinsp;1.65; 95% CI: \u0026minus;\u0026thinsp;3.72 to 0.46; p\u0026thinsp;=\u0026thinsp;0.117617), then rose sharply to 31.56 by 2023 (APC: 96.43; 95% CI: 51.60 to 154.50; p\u0026thinsp;=\u0026thinsp;0.000025). The overall AAPC for the Midwest was 10.37 (95% CI: 5.63 to 15.31; p\u0026thinsp;=\u0026thinsp;0.000010).\u003c/p\u003e\u003cp\u003eThe South region exhibited a non-significant decline from 5.93 in 1999 to 3.82 in 2019 (APC: \u0026minus;\u0026thinsp;1.52; 95% CI: \u0026minus;\u0026thinsp;3.73 to 0.74; p\u0026thinsp;=\u0026thinsp;0.175023), followed by a statistically significant increase to 31.89 in 2023 (APC: 90.95; 95% CI: 45.42 to 150.75; p\u0026thinsp;=\u0026thinsp;0.000077). The region\u0026rsquo;s overall AAPC was 9.97 (95% CI: 5.01 to 15.17; p\u0026thinsp;=\u0026thinsp;0.000057).\u003c/p\u003e\u003cp\u003eIn the West, the AAMR dropped from 3.36 in 1999 to 2.27 in 2019 (APC: \u0026minus;\u0026thinsp;1.94; 95% CI: \u0026minus;\u0026thinsp;4.18 to 0.35; p\u0026thinsp;=\u0026thinsp;0.092031), and then rose markedly to 19.06 in 2023 (APC: 97.98; 95% CI: 52.19 to 157.55; p\u0026thinsp;=\u0026thinsp;0.000027). The West had an overall AAPC of 10.24 (95% CI: 5.39 to 15.31; p\u0026thinsp;=\u0026thinsp;0.000021).\u003c/p\u003e\u003cp\u003eFrom 1999 to 2023, all four census regions showed statistically significant increases in PE-related mortality, with the Midwest having the steepest rise (AAPC: 10.37), followed by the West (10.24), South (9.97), and Northeast (9.75).\u003c/p\u003e\u003cp\u003e\u003cb\u003eUrban-Rural\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFrom 1999 to 2020, rural areas exhibited consistently higher PE-related AAMRs compared to urban regions. The AAMR in rural areas decreased from 6.51 in 1999 to 4.56 in 2009 (APC: \u0026minus;\u0026thinsp;3.3699; 95% CI: \u0026minus;\u0026thinsp;4.4060 to \u0026minus;\u0026thinsp;2.3225; p\u0026thinsp;=\u0026thinsp;0.000008), followed by a statistically significant increase to 5.38 in 2015 (APC: 3.1758; 95% CI: \u0026minus;\u0026thinsp;0.0046 to 6.4572; p\u0026thinsp;=\u0026thinsp;0.050291), and a subsequent statistically non-significant decline to 5.01 in 2020 (APC: \u0026minus;\u0026thinsp;2.4195; 95% CI: \u0026minus;\u0026thinsp;5.3781 to 0.6317; p\u0026thinsp;=\u0026thinsp;0.110559).\u003c/p\u003e\u003cp\u003eIn contrast, urban areas saw a steady reduction in AAMR from 4.68 in 1999 to 3.07 in 2009 (APC: \u0026minus;\u0026thinsp;4.3786; 95% CI: \u0026minus;\u0026thinsp;5.2807 to \u0026minus;\u0026thinsp;3.4679; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), followed by a slight but statistically non-significant rise to 3.44 in 2020 (APC: 0.5798; 95% CI: \u0026minus;\u0026thinsp;0.2349 to 1.4012; p\u0026thinsp;=\u0026thinsp;0.152009).\u003c/p\u003e\u003cp\u003eOver the full period, both areas experienced statistically significant declines in PE-related mortality, with the AAPC for urban areas at \u0026minus;\u0026thinsp;1.8126 (95% CI: \u0026minus;\u0026thinsp;2.3771 to \u0026minus;\u0026thinsp;1.2484; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), and for rural areas at \u0026minus;\u0026thinsp;1.3135 (95% CI: \u0026minus;\u0026thinsp;2.4481 to \u0026minus;\u0026thinsp;0.1658; p\u0026thinsp;=\u0026thinsp;0.025014).\u003c/p\u003e\u003cp\u003e\u003cb\u003eAge Groups\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe data were stratified by two main age categories: younger adults (25\u0026ndash;34, 35\u0026ndash;44, and 45\u0026ndash;54 years) and older adults (55\u0026ndash;64, 65\u0026ndash;74, 75\u0026ndash;84, and 85\u0026thinsp;+\u0026thinsp;years).\u003c/p\u003e\u003cp\u003eIn the analysis stratified by age, older adults consistently exhibited markedly higher AAMRs compared to younger adults throughout the study period. Among older adults, the AAMR declined from 357.64 in 1999 to 338.93 in 2018 (APC: \u0026minus;\u0026thinsp;0.5071; 95% CI: \u0026minus;\u0026thinsp;0.6745 to \u0026minus;\u0026thinsp;0.3395; p\u0026thinsp;=\u0026thinsp;0.000007), followed by a statistically significant surge to 503.59 in 2021 (APC: 14.8418; 95% CI: 9.4966 to 20.4480; p\u0026thinsp;=\u0026thinsp;0.000011), and then a decline to 414.87 by 2023 (APC: \u0026minus;\u0026thinsp;7.8161; 95% CI: \u0026minus;\u0026thinsp;11.7441 to \u0026minus;\u0026thinsp;3.7134; p\u0026thinsp;=\u0026thinsp;0.001048).\u003c/p\u003e\u003cp\u003eIn contrast, younger adults showed a gradual increase in AAMR from 35.11 in 1999 to 46.99 in 2018 (APC: 1.1865; 95% CI: 0.8891 to 1.4847; p\u0026thinsp;\u0026lt;\u0026thinsp;0.000001), followed by a sharp rise to 74.05 in 2021 (APC: 17.1958; 95% CI: 7.5587 to 27.6620; p\u0026thinsp;=\u0026thinsp;0.001118), and a subsequent decline to 51.22 in 2023 (APC: \u0026minus;\u0026thinsp;16.4995; 95% CI: \u0026minus;\u0026thinsp;23.3028 to \u0026minus;\u0026thinsp;9.0928; p\u0026thinsp;=\u0026thinsp;0.000332).\u003c/p\u003e\u003cp\u003eOver the full study period (1999\u0026ndash;2023), the average annual percent change (AAPC) in AAMR was 0.6512 (95% CI: \u0026minus;\u0026thinsp;0.0107 to 1.3175; p\u0026thinsp;=\u0026thinsp;0.053821) for older adults, which was statistically non-significant, and 1.4246 (95% CI: 0.2038 to 2.6603; p\u0026thinsp;=\u0026thinsp;0.022047) for younger adults, which was statistically significant.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePlace of death\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFrom 1999 to 2023, highest number of deaths took place in Medical Facility- Inpatient, followed by Descendants\u0026rsquo; home, Medical Facility- Outpatient or ER, Nursing home/long term care, Hospice Facility, other, Medical Facility-dead on arrival, Place of death unknown, Medical Facility-status unknown.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur analysis of pulmonary embolism (PE) mortality trends in the United States from 1999 to 2023 reveals DISTINCT patterns across time, demographic groups, and geographic regions. Although the mortality rate declined during the entire study period, a spike was observed during 2018\u0026ndash;2021 across all groups. This significant spike can be attributed to the COVID-19 pandemic.\u003c/p\u003e\u003cp\u003eThe impact of pandemic on the mortality trends can be explained by several factors. Many studies reported that Coronavirus disease (COVID-19) that is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can increase risk of thromboembolic events. The incidence of thromboembolism increased sharply in patients with a severe COVID-19 infection who required intensive care and cardiorespiratory support (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Similarly, one study reported that the incidence of venous thromboembolism was increased by more than 2.5 times in COVID-19 patients who required treatment in the intensive care unit (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Not only there was increase in thromboembolism but also increase risk of thromboembolism related death. As reported by Burn et al. COVID-19 patients with complications of venous thromboembolism tend to have a higher risk of death (4.42 times higher for patients who are not hospitalized and 1.63 times higher for those who are hospitalized) (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAnother study showed that the risk of venous thromboembolism (i.e., DVT and PE) remains elevated even after COVID-19 infection is treated. The risk of developing DVT remains elevated up to 70 days after COVID-19 and 110 days for PE (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). Additionally, the healthcare systems were overburdened that resulted in delays in diagnosis and treatment of other diseases. Furthermore, behavioral changes among the population such as increase stress and less physical activity might also have contributed to more thromboembolic events during the pandemic.\u003c/p\u003e\u003cp\u003ePulmonary embolism (PE) is the third most common cause of cardiovascular death; however, gender disparities in PE remain understudied. Our analysis showed that men had a higher AAMR compared to women through entire period. Jarman et al. indicated that the overall age-adjusted incidence of PE is similar in women and men (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). While some older studies suggested higher incidence of PE in males (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e) Nonetheless, overall AAMR due to PE has decreased in the USA likely due to improved diagnostic methods, early interventions, and therapies (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eRacial stratification indicated that Black/African American were affected more compared to other races, a finding consistent with other studies. Zghouzi et al. reported that not only was PE-related mortality 2-fold higher in Black individuals compared to non- Black individuals (in 2019 and 2020); this disparity was disproportionately exacerbated during the pandemic year, 2020 (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) Sathianathan et al also reported the racial disparities in pulmonary embolism management with Black and Hispanic group being at having higher odds of mortality major bleeding, and increased length of stay after management of PE (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Another study by Breuer et al. reported that the racial disparities in acute pulmonary embolism treatment with NH Black patients have a higher risk of mortality from acute, nonseptic PE than White patients (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThis consistent trend in mortality among certain races requires target public health interventions directed specifically towards NH Blacks and Hispanic populations.\u003c/p\u003e\u003cp\u003eAnalysis based on regions showed significant disparities as well. Contrary to other groups, regional analysis showed increased mortality over the years, with the Midwest region showing the steepest rise. Rural areas exhibited higher mortality compared to urban areas. This may be due to poor access to better healthcare facilities in these areas. Other studies also reported rural areas have higher AAMR compared to urban areas (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eAlthough it is well recognized that the risk of (PE) increases with age, PE remains a major cause of mortality among younger adults in the United States (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). While older adults showed a consistent elevated AAMR compared to their young counterparts, the trends stratified by age exhibited an interesting pattern. The overall mortality rate declined in older adults and increased in younger adults. Although this decline was more prominent during 1999\u0026ndash;2018, this trend was disturbed by COVID-19 pandemic increasing mortality rate of not only PE related deaths but also other cardiovascular related deaths (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). The overall decline in mortality rates among the older population can be attributed to early diagnosis, better management and better hospital care.\u003c/p\u003e\u003cp\u003ePE-related mortality in adults aged 25 to 44 years has increased over the last 2 decades in the United States (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). A similar finding was observed in our analysis as well. This study also found that PE-related mortality increased by 23% among adults aged 25\u0026ndash;64 between 2008 and 2018 (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e). It is unclear why PE-related mortality is increasing among young individuals in the USA. There are certain risk factors that are associated with increased risk of PE-related mortality in younger adults Smoking, obesity, trauma, surgery, prolonged air travel, use of OCPs and hormone replacement therapy, pregnancy, post-partum status and thrombophilia (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e).Further studies may be needed to know the exact cause of increased PE related mortality in young adults.\u003c/p\u003e\u003cp\u003eBased on our analysis, most of the deaths occurred in in-patient medical facilities.Hospitalized patients are at increased risk of developing DVT (approximately 50%), increasing the risk of PE. PE is one of the most common but preventable causes of death in hospitalized patients[25].So, initiating DVT prophylaxis in hospitalized patients can save many lives. Using DVT prophylaxis in hospitalized patients decreases the risk of DVT anywhere from 10 to 80% [25].\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations\u003c/b\u003e\u003c/p\u003e\u003cp\u003eSome limitations may be acknowledged while interpreting our findings. The study relied on data from death certificates, and certain co- existing pathologies may have influenced our results. We do not have data regarding patients' baseline characteristics, and history of any risk factors which could have influenced the results. Furthermore, the CDC WONDER does not contain information about the potential socioeconomic and other confounding factors.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eAn increasing trend of Pulmonary embolism-related death in adults was observed throughout the study period. The highest mortality was exhibited by older NH Black/African American males living in rural Midwest and district of Columbia.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"3\" cellpadding=\"0\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAbbreviation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp; \u0026nbsp; Full Form\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003ePE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ePulmonary Embolism\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCDC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCenters for Disease Control and Prevention\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eWONDER\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eWide-ranging Online Data for Epidemiologic Research\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eICD-10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eInternational Classification of Diseases, 10th Revision\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAAMR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAge-Adjusted Mortality Rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCMR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCrude Mortality Rate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAAPC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAverage Annual Percent Change\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eAPC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eAnnual Percent Change\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eConfidence Interval\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eNH\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eNon-Hispanic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eVTE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eVenous Thromboembolism\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eCVS\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eCardiovascular System\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eDVT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eDeep Vein Thrombosis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eSTROBE\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eStrengthening the Reporting of Observational Studies in Epidemiology\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eER\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eEmergency Room\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eOCPs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eOral Contraceptive Pills\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cstrong\u003eORCID\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003eOpen Researcher and Contributor ID\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This study is a CDC wonder of previously published studies, and no new human or animal subjects were involved.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data was taken from the publicly available CDC WONDER database https://wonder.cdc.gov/mcd.html. \u0026nbsp; All data were obtained from this source and analyzed as part of this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Number\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHH - discussion , MSS - supplementary file, DR - abstract and compiling , IKI - introduction, methods, extraction and analysis , JN - extraction\u0026nbsp;and\u0026nbsp;analysis, KAK- review manuscript, AA- literature review, MS- topic selection, NF- submission, MH- compiled manuscript\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone to declare\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZghouzi M, Mwansa H, Shore S, Hyder SN, Kamdar N, Moles VM, et al. Sex, Racial, and Geographic Disparities in Pulmonary Embolism\u0026ndash;related Mortality Nationwide. Ann Am Thorac Soc [Internet]. 2023 Nov 1 [cited 2025 May 30];20(11):1571\u0026ndash;7. Available from: https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202302-091OC?download=true\u003c/li\u003e\n\u003cli\u003eData and Statistics on Venous Thromboembolism | Venous Thromboembolism (Blood Clots) | CDC [Internet]. [cited 2025 May 30]. Available from: https://www.cdc.gov/blood-clots/data-research/facts-stats/index.html\u003c/li\u003e\n\u003cli\u003ePulmonary embolism, part I: Epidemiology, risk factors and risk stratification, pathophysiology, clinical presentation, diagnosis and nonthrombotic pulmonary embolism - PubMed [Internet]. [cited 2025 May 30]. Available from: https://pubmed.ncbi.nlm.nih.gov/23940438/\u003c/li\u003e\n\u003cli\u003eSista AK, Horowitz JM, Tapson VF, Rosenberg M, Elder MD, Schiro BJ, et al. Indigo Aspiration System for Treatment of Pulmonary Embolism: Results of the EXTRACT-PE Trial. JACC Cardiovasc Interv [Internet]. 2021 Feb 8 [cited 2025 May 30];14(3):319\u0026ndash;29. Available from: https://pubmed.ncbi.nlm.nih.gov/33454291/\u003c/li\u003e\n\u003cli\u003eCDC WONDER [Internet]. [cited 2025 May 10]. Available from: https://wonder.cdc.gov/\u003c/li\u003e\n\u003cli\u003eDeaths [Internet]. [cited 2025 May 17]. Available from: https://wonder.cdc.gov/deaths-by-underlying-cause.html\u003c/li\u003e\n\u003cli\u003eICD-10 Version:2019 [Internet]. [cited 2025 May 10]. Available from: https://icd.who.int/browse10/2019/en#!.\u003c/li\u003e\n\u003cli\u003eJoinpoint Regression Program [Internet]. [cited 2025 May 10]. Available from: https://surveillance.cancer.gov/joinpoint/\u003c/li\u003e\n\u003cli\u003eJenner WJ, Gorog DA. Incidence of thrombotic complications in COVID-19: On behalf of ICODE: The International COVID-19 Thrombosis Biomarkers Colloquium. J Thromb Thrombolysis [Internet]. 2021 Nov 1 [cited 2025 May 30];52(4):999\u0026ndash;1006. Available from: https://pubmed.ncbi.nlm.nih.gov/34047938/\u003c/li\u003e\n\u003cli\u003eTan BK, Mainbourg S, Friggeri A, Bertoletti L, Douplat M, Dargaud Y, et al. Arterial and venous thromboembolism in COVID-19: A study-level meta-analysis. Thorax [Internet]. 2021 Oct 1 [cited 2025 May 30];76(10):970\u0026ndash;9. Available from: https://pubmed.ncbi.nlm.nih.gov/33622981/\u003c/li\u003e\n\u003cli\u003eBurn E, Duarte-Salles T, Fernandez-Bertolin S, Reyes C, Kostka K, Delmestri A, et al. Venous or arterial thrombosis and deaths among COVID-19 cases: a European network cohort study. Lancet Infect Dis [Internet]. 2022 Aug 1 [cited 2025 May 30];22(8):1142\u0026ndash;52. Available from: https://pubmed.ncbi.nlm.nih.gov/35576963/\u003c/li\u003e\n\u003cli\u003eKatsoularis I, Fonseca-Rodr\u0026iacute;guez O, Farrington P, Jerndal H, Lundevaller EH, Sund M, et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ [Internet]. 2022 Apr 6 [cited 2025 May 30];377:e069590. Available from: https://pubmed.ncbi.nlm.nih.gov/35387772/\u003c/li\u003e\n\u003cli\u003eJarman AF, Mumma BE, Singh KS, Nowadly CD, Maughan BC. Crucial considerations: Sex differences in the epidemiology, diagnosis, treatment, and outcomes of acute pulmonary embolism in non-pregnant adult patients. JACEP Open [Internet]. 2021 Feb 1 [cited 2025 May 30];2(1). Available from: https://pubmed.ncbi.nlm.nih.gov/33532761/\u003c/li\u003e\n\u003cli\u003eHorlander KT, Mannino DM, Leeper K V. Pulmonary embolism mortality in the United States, 1979-1998: An analysis using multiple-cause mortality data. Arch Intern Med [Internet]. 2003 Jul 28 [cited 2025 May 30];163(14):1711\u0026ndash;7. Available from: https://pubmed.ncbi.nlm.nih.gov/12885687/\u003c/li\u003e\n\u003cli\u003eVyas V, Sankari A, Goyal A. Acute Pulmonary Embolism. 2024 Dec 11 [cited 2025 May 30]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK560551/\u003c/li\u003e\n\u003cli\u003eZghouzi M, Mwansa H, Shore S, Hyder SN, Kamdar N, Moles VM, et al. Sex, Racial, and Geographic Disparities in Pulmonary Embolism\u0026ndash;related Mortality Nationwide. Ann Am Thorac Soc [Internet]. 2023 Nov 1 [cited 2025 May 30];20(11):1571\u0026ndash;7. Available from: https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202302-091OC?download=true\u003c/li\u003e\n\u003cli\u003eSathianathan S, Meili Z, Romero CM, Juarez JJ, Bashir R. Racial and gender disparities in the management of acute pulmonary embolism. J Vasc Surg Venous Lymphat Disord [Internet]. 2024 May 1 [cited 2025 May 30];12(3). Available from: https://pubmed.ncbi.nlm.nih.gov/38296110/\u003c/li\u003e\n\u003cli\u003eBreuer JA, Ahmed KH, Scherr R, Sing C, Daid M, Nouizi F, et al. Racial Disparities and Other Socioeconomic Predictors of Mortality in Acute Pulmonary Embolism Treatment from the National Inpatient Sample. Journal of Vascular and Interventional Radiology [Internet]. 2024 Sep 1 [cited 2025 May 30];35(9):1377\u0026ndash;87. Available from: https://pubmed.ncbi.nlm.nih.gov/38518999/\u003c/li\u003e\n\u003cli\u003eZghouzi M, Mwansa H, Shore S, Hyder SN, Kamdar N, Moles VM, et al. Sex, Racial, and Geographic Disparities in Pulmonary Embolism\u0026ndash;related Mortality Nationwide. Ann Am Thorac Soc [Internet]. 2023 Nov 1 [cited 2025 May 30];20(11):1571\u0026ndash;7. Available from: https://www.atsjournals.org/doi/pdf/10.1513/AnnalsATS.202302-091OC?download=true\u003c/li\u003e\n\u003cli\u003eGiordano NJ, Jansson PS, Young MN, Hagan KA, Kabrhel C. Epidemiology, Pathophysiology, Stratification, and Natural History of Pulmonary Embolism. Tech Vasc Interv Radiol [Internet]. 2017 Sep 1 [cited 2025 May 30];20(3):135\u0026ndash;40. Available from: https://pubmed.ncbi.nlm.nih.gov/29029707/\u003c/li\u003e\n\u003cli\u003eWoodruff RC, Tong X, Khan SS, Shah NS, Jackson SL, Loustalot F, et al. Trends in Cardiovascular Disease Mortality Rates and Excess Deaths, 2010\u0026ndash;2022. Am J Prev Med [Internet]. 2024 Apr 1 [cited 2025 May 30];66(4):582\u0026ndash;9. Available from: https://pubmed.ncbi.nlm.nih.gov/37972797/\u003c/li\u003e\n\u003cli\u003eZuin M, Bikdeli B, Armero A, Porio N, Rigatelli G, Bilato C, et al. Trends in Pulmonary Embolism Deaths Among Young Adults Aged 25 to 44 Years in the United States, 1999 to 2019. American Journal of Cardiology [Internet]. 2023 Sep 1 [cited 2025 May 30];202:169\u0026ndash;75. Available from: https://pubmed.ncbi.nlm.nih.gov/37441831/\u003c/li\u003e\n\u003cli\u003eMartin KA, Molsberry R, Cuttica MJ, Desai KR, Schimmel DR, Khan SS. Time trends in pulmonary embolism mortality rates in the united states, 1999 to 2018. J Am Heart Assoc [Internet]. 2020 Sep 1 [cited 2025 May 30];9(17). Available from: https://pubmed.ncbi.nlm.nih.gov/32809909/\u003c/li\u003e\n\u003cli\u003eGjonbrataj E, Kim JN, Gjonbrataj J, Jung HI, Kim HJ, Choi W Il. Risk factors associated with provoked pulmonary embolism. Korean J Intern Med [Internet]. 2016 Jan 1 [cited 2025 May 30];32(1):95\u0026ndash;101. Available from: https://www.kjim.org/journal/view.php?doi=10.3904/kjim.2015.118\u003c/li\u003e\n\u003cli\u003eBadireddy M, Mudipalli VR. Deep Venous Thrombosis Prophylaxis. [Updated 2023 May 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534865/\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Pulmonary embolism, mortality, trends, disparities","lastPublishedDoi":"10.21203/rs.3.rs-7049348/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7049348/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground:\u003c/h2\u003e\u003cp\u003ePulmonary embolism (PE) is a potentially life-threatening condition associated with significant morbidity, and mortality in adults aged 25 to 85\u0026thinsp;+\u0026thinsp;years. We assessed trends in PE related mortality in the United States from 1999 to 2023 among adults to determine differences by gender, age, race/ethnicity, and geographic location using CDC WONDER data.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eWe analyzed adults aged 25 to 85\u0026thinsp;+\u0026thinsp;years death certificates from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC-WONDER) database with PE (ICD-10 codes: I26 and I26.9) from 1999\u0026ndash;2023. Age-adjusted mortality rates (AAMR) per 1,000,000 population were stratified by gender, age, race, and geographic location. Join-point regression analysis was conducted to estimate the average annual percent changes (AAPC) with corresponding 95% confidence intervals (CI).\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eBetween 1999 and 2023, mortalities due to PE caused 822482 deaths primarily in Medical Facility-Inpatient (432910) and Decedent's home (141478) deaths in adults aged 25 to 85\u0026thinsp;+\u0026thinsp;years. The AAMR showed slight variations from 1999 to 2018 (APC: -0.176, 95% confidence interval (CI): -0.348 to \u0026minus;\u0026thinsp;0.004), increased sharply from 2018 to 2021 (APC: 15.39; 95% CI: 9.82\u0026ndash;21.24) and finally decreased thereafter till 2023 (APC: -9.75; 95% CI: -13.79 to \u0026minus;\u0026thinsp;5.52). Additionally, the AAMR for males was higher than that of females. Non-Hispanic (NH) Blacks or African Americans displayed the highest AAMR, followed by NH Whites, and Hispanic or Latino. Midwest region showed highest AAMR, followed by South, Northeast, and West. District of Columbia was in the top 90th percentile. Rural areas exhibited higher AAMR than urban areas. Older adults had higher CMR than younger adults.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003ePE-related mortality has risen significantly in recent years, with notable disparities across gender, race, and geographic regions. These findings highlight the urgent need for tailored public health strategies to mitigate the evolving burden of PE and promote equitable healthcare outcomes.\u003c/p\u003e","manuscriptTitle":"Trends and Disparities in Pulmonary Embolism Mortality in the United States, 1999– 2023","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-18 11:03:30","doi":"10.21203/rs.3.rs-7049348/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"31daf749-6ac1-4097-93a8-387f3e585ed1","owner":[],"postedDate":"August 18th, 2025","published":true,"recentEditorialEvents":[{"type":"decision","content":"Rejected","date":"2026-05-06T02:24:29+00:00","index":"","fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-05-06T02:39:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-18 11:03:30","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7049348","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7049348","identity":"rs-7049348","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}