Introduction: Anemia and cardiac arrest are both common diseases in the United States, and when concomitant, they accelerate morbidity and mortality. Growing clinical evidence suggests that anemia is an independent predictor of escalated mortality post-cardiac arrest. Anemia decreases the blood's oxygen-carrying capacity, resulting in cardiac tissue hypoxia that disrupts post-resuscitation perfusion and contributes to myocardial injury. Lack of adequate tissue perfusion also increases the risk of hypoxic brain damage, contributing to inferior survival and neurological outcomes compared to non-anemic patients. Mortality trend analyses stratified by demographic and geographic factors related to anemia and cardiac arrest amongst adults in the United States are limited. This study examines national mortality trends in adults aged ≥ 25 years with anemia and cardiac arrest from 1999 to 2023.

Methods: The CDC WONDER Multiple Cause-of-Death dataset (1999-2023) was used to analyze mortality trends in adults aged ≥ 25 years using ICD-10 codes for anemia (D55-D59, D60-D64) and cardiac arrest (I46). Results were stratified by place of death, year, sex, age group, race, census region, state, and urbanization. Age-adjusted mortality rates (AAMRs) were quantified per 100,000 persons by standardizing crude mortality rates (CMRs) with 95% confidence intervals (95%CI). Annual percent change (APC) and average annual percent change (AAPC) were calculated using Joinpoint regression software. Statistical significance was defined as a P value < 0.05.

Results:A total of 205,203 anemia and cardiac arrest-related deaths occurred in adults ≥ 25 years in the United States from 1999 to 2023. Most of the deaths occurred in medical facilities (54.55%), followed by nursing home/long-term care facilities (23.02%), the decedent's home (18.38%), other/place of death unknown (2.90%), and hospices (1.14%). Overall, AAMR decreased from 3.86 in 1999 to 3.43 in 2018 (APC: -0.78; 95%CI: -1.20 to -0.40), followed by statistically stable rates until 3.74 in 2023. This culminated in overall stable rates from 1999 to 2023. Men had a higher average AAMR (4.18) compared to women (3.35), and both sexes had stable rates spanning the study duration. Average CMRs increased with age, as adults ≥ 65 years had the highest average CMR (15.31), followed by 45-64 year olds (1.64), and 25-44 year olds (0.31). Adults aged 45-64 years and 25-44 years had increasing AAMRs while those ≥ 65 years had declining rates (AAPC 45-64 years: 2.32; 95%CI: 1.83 to 2.88; AAPC 25-44 years: 1.28; 95%CI: 0.49 to 2.36; AAPC ≥ 65 years: -0.75; 95%CI: -0.99 to -0.40). Racially, non-Hispanic (NH) Black/African Americans had the highest average AAMR (7.00), followed by NH Asian/Pacific Islanders (5.312), Hispanic/Latinos (5.07), NH American Indian/Alaska Native (4.16), and NH Whites (3.09). NH American Indian/Alaska Natives had increasing rates (AAPC:1.30; 95%CI: 0.39 to 2.52), NH Asian/Pacific Islanders and NH Black/African Americans had decreasing rates (AAPC NH Asian/Pacific Islander: -2.01; 95%CI: -2.33 to -1.54; AAPC NH Black/African American: -0.70; 95%CI: -1.10 to -0.41) while NH Whites and Hispanic or Latinos had stable rates spanning the duration of the study. Amongst census regions, the West had the highest average AAMR (5.72), followed by the Northeast (4.45), the South (3.06), and the Midwest (2.11). The South had declining rates (AAPC: -0.39; 95%CI: -0.79 to -0.11) while other regions had stable rates. State-wise, California had the greatest number of deaths at 54,021

accounting for 26.33% of deaths. From 1999 to 2020, urban areas had a higher average AAMR (3.76) compared to rural areas (3.18). Urban areas had declining rates (AAPC: -0.35; 95%CI: -0.88 to -0.05) while rural areas had stable rates.

Conclusion: Although anemia and cardiac arrest-related mortality rates amongst adults in the United States have remained stable from 1999 to 2023, key disparities among demographic and geographical stratifications were noted. The mechanistic interplay between anemia and cardiac arrest on mortality outcomes is an important area of research to address these discrepancies in the future. Focused public health strategies to address such vulnerable populations are crucial to provide equitable health care.

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2025
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