Introduction: Anemia and cardiovascular disease (CVD) are common and interrelated diseases that significantly contribute to morbidity and mortality, especially in older adults. Anemia mechanistically plays a key role in attenuating cardiac performance in a vicious circle, as anemia-mediated tissue hypoxia exacerbates the elevated strain on cardiac tissue in CVD. Growing evidence suggests that anemia is not only associated with an increased risk of all-cause mortality in older adults but also with an increased risk and prevalence of major adverse cardiovascular events (MACE). Long-term mortality trend analyses that are demographically and geographically stratified concerning CVD-related mortality in elderly anemic patients in the United States are limited. This descriptive study intends to evaluate and analyze the trends and disparities in CVD-related mortality in anemic adults aged ≥ 65 years from 1999 to 2023 in the United States.

Methods: Data from death certificates among adults aged ≥ 65 years were obtained from the CDC WONDER database from 1999 to 2023. Temporal trend analysis using death certificates related to CVD (ICD-10: I00-I99) was defined as the underlying cause, and anemia (ICD-10: D55-D59, D60-64) as a contributing cause of death was conducted. Results were grouped by place of death, year, sex, age group, race, U.S. census region, and state, utilizing the 2000 U.S. standard population. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 persons by standardizing crude mortality rates (CMRs), each with corresponding 95% confidence intervals (95%CI). Joinpoint regression software was used to estimate the average annual percent change (AAPC) from 1999 to 2023. Statistical significance was set at a p-value < 0.05.

Results: CVD-related mortality in adults aged ≥ 65 years with anemia accounted for 283,386 deaths between 1999 and 2023. Overall AAMRs declined from 34.6 in 1999 to 26.3 in 2023 (AAPC: -1.48; 95%CI: -1.76 to -1.13). Men consistently exhibited a higher average AAMR compared to females, although women experienced a more pronounced rate of decline over the study period (AAPC women: -1.86; 95%CI: -2.07 to -1.63; AAPC men: -1.11; 95%CI: -1.44 to -0.78). Interms of age groups, adults aged 75-84 years had the highest average CMR, while adultsaged ≥ 85 years had the highest rate of decline (AAPC adults aged ≥ 85 years: -1.81; 95%CI: -2.09 to -1.54). Racially, non-Hispanic (NH) Black/African Americans experienced the highest average AAMR, while NH Asian/Pacific Islanders demonstrated the greatest reduction in mortality rates (AAPC NH Asian/Pacific Islander: -3.02; 95%CI: -3.32 to-2.54). Regionally, the Midwest had the highest average AAMR, along with the greatest rate of decline (AAPC Midwest: -1.91; 95%CI: -2.33 to -1.42). State-wise, California had the greatest number of deaths at 37,505, accounting for 13.23% of state deaths from 1999 to 2023. From 1999 to 2020, states in the top 90th percentile of AAMRs included Maryland, Ohio, Rhode Island, Vermont, and West Virginia, while states in the bottom 10th percentile were Utah, Nevada, Louisiana, Colorado, and Arizona. From 2021 to 2023, states in the top 90th percentile of AAMRs included Maryland, Minnesota, Nebraska, South Dakota, and Vermont, while states in the bottom 10th percentile were Utah, New Mexico, Georgia, Connecticut, and Alabama.

Conclusion: Although CVD-related mortality rates in patients with anemia aged 65 years and older have declined from 1999 to 2023, significant disparities among demographic and

geographical groups were found. Further research is needed so anemia can be appropriately treated early and thus lessen its influence on CVD-related mortality, especially in at-risk

communities.

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2025
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