Background:

Respiratory failure and anemia are major contributors to mortality in the United States, particularly among older adults and socioeconomically disadvantaged populations. When these conditions co-occur, they can synergistically impair oxygen delivery and significantly worsen clinical outcomes. Despite their clinical overlap, long-term national trends in combined mortality have not been thoroughly studied. This study examined U.S. mortality patterns involving both conditions from 1999 to 2023, with a particular focus on demographic disparities and geographic variation.

Methods:

Mortality data were obtained from the CDC WONDER database, using ICD-10 codes J96.x for respiratory failure and D50–D64 for anemia. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated based on the 2000 U.S. standard population. Trends were analyzed using Joinpoint regression to estimate the Annual Percent Change (APC) and Average Annual Percent Change (AAPC), with statistical significance defined by 95% confidence intervals and p-values < 0.05. Analyses were stratified by sex, race/ethnicity, age group, region, and state.

Results:

Between 1999 and 2023, a total of 188,978 deaths in the U.S. were attributed to the co-occurrence of respiratory failure and anemia. The national AAMR rose from 1.23 in 1999 to 3.56 in 2023 (mean: 2.09). Mortality increased steadily from 1999 to 2018 (APC: 3.89; 95% CI: 3.65–4.12; p < 0.000001), followed by a sharp spike from 2018 to 2021 (APC: 16.97; 95% CI: 11.2–23.1; p = 0.000006), and then a decline through 2023 (APC: -5.31; 95% CI: -9.57 to -0.85; p = 0.0228). Males exhibited higher mean AAMRs than females (2.37 vs. 1.90), with significant increases observed in both groups (Men: AAPC: 4.40; Women: AAPC: 4.74). Racial disparities were evident: Non-Hispanic (NH) Black individuals had the highest mean AAMR (3.20), followed by NH White (2.06), and NH Asian or Pacific Islander (1.92). A significant increase was particularly noted in NH White individuals (AAPC: 5.17). Crude mortality rates increased significantly with age. Older adults had the highest mean rate (12.63), followed by middle-aged (1.73) and younger adults (0.29). Middle-aged adults experienced the steepest increase (AAPC: 7.05). Regionally, the West had the highest mean AAMR (3.45), followed by the South (3.35), Northeast (2.99), and Midwest (2.92). The South showed a significant increase over time (AAPC: 4.98). At the state level, AAMRs ranged from 1.439 (Utah) to 4.711 (Texas) during 1999–2020. In the 2018–2023 period, the range widened significantly, from 1.686 (Maine) to 10.378 (Montana).

Conclusion:

The co-occurrence of respiratory failure and anemia represents an increasing mortality burden in the U.S., with rates more than doubling over the past two decades and peaking during the COVID-19 pandemic. Although rates have declined slightly since 2021, they remain elevated. Persistent disparities based on sex, race, age, and geography underscore ongoing gaps in prevention and chronic disease management. Targeted public health strategies—such as early anemia screening in patients with respiratory disease and improved healthcare access in high-burden regions—are urgently needed to reduce preventable deaths.

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2025
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