Introduction: Atrial fibrillation and anemia are both common in the United States and are interrelated. There is emerging evidence to suggest that anemia may worsen outcomes in patients with atrial fibrillation, such as an increased rate of hospitalization and mortality. Anemia and atrial fibrillation are related through various mechanisms. Anemia leads to decreased oxygen-carrying capacity, leading to tissue ischemia, and cardiac myocytes compensate for this by increasing stroke volume and heart rate, and in susceptible patients with underlying heart disease, may trigger or worsen atrial fibrillation. Furthermore, many atrial fibrillation patients are also on anticoagulants, which may worsen the degree of blood loss in those prone to anemia or have anemia from baseline. Demographic and geographically stratified mortality trend analyses concerning atrial fibrillation and anemia amongst the elderly in the United States are limited. This study examines national mortality trends in adults aged ≥ 25 years with atrial fibrillation and anemia 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 atrial fibrillation (I48) and anemia (D55-D59, D60-D64). 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.

Results: A total of 142,888 atrial fibrillation and anemia-related deaths occurred in adults ≥ 25 years in the United States from 1999 to 2023. Most of the deaths occurred in medical facilities (42.35%), followed by nursing home/long term care facilities (28.21%), the decedent's home (21.26%), hospices (4.56%), and other/place of death unknown (3.63%). Overall AAMRs increased from 1.26 in 1999 to 2.35 in 2011 (APC: -4.75; 95%CI:4.24 to 5.88), further increasing to 2.93 in 2018 (APC: 2.58; 95%CI: 0.23 to 3.40), and to 4.235 in 2021 (APC: 14.04; 95%CI: 11.59 to 15.98) followed by a period of statistical stability until 4.21 (APC: 0.65; 95%CI: -2.05 to 3.41). This culminates in rising AAMRs represented by an AAPC of 4.88 (95%CI: 4.65 to 5.18) from 1999-2023. Men had a higher average AAMR (2.90) compared to women (2.15), and a higher rate of increase throughout the study period (AAPC men: 5.09; 95%CI: 4.85 to 5.45; AAPC women: 4.47; 95%CI: 4.23 to 4.77). In terms of age group, adults ≥ 65 years had the highest average CMR (11.72), while adults aged 45-64 years had the highest rate of increase (AAPC: 9.29; 95%CI: 8.76 to 9.93). Racially, non-Hispanic (NH) Whites had the highest average AAMR (2.65), while Hispanic/Latinos had the highest rate of increase (AAPC: 5.77; 95%CI: 5.06 to 6.93). Amongst census regions, the West had the highest average AAMR (2.63), while the South had the highest rate of increase (AAPC: 5.59; 95%CI: 5.25 to 6.18). Statewise, California had the highest number of deaths at 15,463, accounting for 10.82% of statewide deaths. States in the top 90th percentile of deaths include California, Florida, Ohio, Pennsylvania, and Texas, while states in the bottom 10th percentile of deaths include Alaska, Delaware, Utah, Wyoming, and the District of Columbia. From 1999-2020, rural areas had a higher average AAMR (2.66) compared to urban areas (2.12). Both rural and urban areas had increasing rates of AAMR, though rural areas had a higher rate of increase (AAPC rural: 5.42; 95%CI: 5.06 to 5.91; AAPC urban: 4.52; 95%CI: 4.27 to 4.91).

Conclusion: Atrial fibrillation and anemia-related mortality rates have increased significantly from 1999 to 2023. Crucial disparities among demographic and geographical stratifications were observed. Further research into the interplay between mortality from atrial fibrillation and anemia is paramount to address such disparities and the implementation of public health strategies to address at-risk communities is vital to improve mortality from atrial fibrillation and anemia.

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2025
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