Introduction: Anemia and sepsis are interrelated and significant contributors to morbidity and mortality in the United States, especially among the elderly population. Anemia decreases the oxygen-carrying capacity of blood, leading to tissue hypoxia. Sepsis increases the oxygen demand of tissue, and when concomitant with anemia, exacerbates tissue hypoxia further, as well as accelerating organ dysfunction and thus mortality. Anemia is a common complication of sepsis, as the profound inflammatory response from sepsis leads to the suppression of erythropoiesis, resulting in new-onset anemia or the worsening of pre-existing anemia. While the epidemiology of anemia and sepsis has been well documented separately, limited research has examined national mortality trends associated with their coexistence. This study investigates long-term patterns and demographic disparities in mortality among the elderly U.S population with anemia and sepsis, utilizing data from the CDC WONDER database extending from 1999 to 2023.

Methods: An observational retrospective analysis was conducted using mortality data from the CDC WONDER platform spanning 1999 to 2023 in adults aged ≥ 65 years. ICD-10 codes were used to identify Anemia (D55-D59, D60-64) and Sepsis (A02.1, A22.7, A26.7, A32.7, A40, A41, A42.7 and B37.7) as contributing conditions on death certificates. Age-adjusted mortality rates (AAMRs), annual percent changes (APCs), and average annual percent changes (AAPCs) were calculated using Joinpoint regression modeling. Mortality rates were reported per 100,000 population, and crude mortality rates (CMRs) were calculated with 95% confidence intervals (95% CI). Results were stratified by place of death, age, sex, race, U.S. census region, and state. A P value of <0.05 was considered to be statistically significant.

Results: Between 1999 and 2023, a total of 105,361 deaths related to Anemia and Sepsis occurred in the U.S. adult population aged ≥ 65 years. The majority of these deaths occurred in medical facilities (81.42%), followed by nursing home/long-term care facilities (9.50%), the decedent's home (4.48%), hospices (3.25%), and other/place of death unknown (1.36%). Overall AAMRs initially increased from 8.93 in 1999 to 9.70 in 2018 (APC: 0.36; 95%CI: 0.10 to 0.58) and to 12.73 in 2021 (APC: 10.07; 95%CI: 7.43 to 11.57), followed by stable rates until 12.12 in 2023. From 1999 to 2023, this culminates in an overall increase in mortality rates (AAPC: 1.37; 95%CI: 1.14 to 1.56). Men had a higher average AAMR (10.90) compared to women (8.67), as well as a higher rate of increase (AAPC men: 1.49; 95%CI: 1.20 to 1.72; AAPC women: 1.21; 95%CI: 0.98 to 1.41). In terms of age groups, average CMRs increased with age. Adults aged ≥85 years (22.93) had the highest average CMR, followed by adults aged 75-84 years (11.20) and adults aged 65-74 years (5.33). The rate of increase in CMRs showed an opposite trend as adults aged 65-74 years had the highest rate of increase, followed by adults aged 75-84 years, and adults aged ≥85 years (AAPC adults aged 65-74 years: 2.26; 95%CI: 1.93 to 2.58; AAPC adults aged 75-84 years: 1.48; 95%CI: 1.09 to 1.99; AAPC adults aged ≥85 years: 0.42; 95%CI: 0.12 to 0.70). Racially, non-Hispanic (NH) Black/African Americans had the highest average AAMR (19.21), followed by Hispanics/Latinos (10.85), NH Asian/Pacific Islanders (9.93), and NH Whites (8.48). NH Whites and Hispanic/Latinos had increasing mortality rates (AAPC NH White: 1.76; 95%CI: 1.48 to 2.00; AAPC Hispanic/Latinos: 1.28; 95%CI: 0.78 to 1.91), while NH Asian/Pacific Islanders and NH Black/African Americans had stable rates. Regionally, the highest average AAMR was observed in the South (10.70), followed by the Northeast (9.33), the West (8.73), and the Midwest (8.65). States in the top 90th percentile of deaths included California, Texas, Florida, New Jersey, and Pennsylvania. States in the bottom 10th percentile of deaths were Alaska, Wyoming, Vermont, North Dakota, and Idaho.

Conclusion: From 1999 to 2023, anemia and sepsis-related mortality rates for adults aged ≥ 65 years increased. Critical disparities among demographic and geographic locations were observed, highlighting the need for more comprehensive and tailored approaches to improve mortality outcomes in at-risk communities moving forward.

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2025
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