Background: Anemia and Substance Abuse are rising public health concerns in the U.S., contributing greatly to cardiovascular complications and overdose deaths. Given their increasing prevalence and associated mortality, we analyzed demographic and regional disparities in anemia and substance abuse in the U.S. from 1999-2023.

Methods: We extracted mortality data using the CDC WONDER database. Deaths among individuals aged ≥45 years with both Anemia (ICD-10 codes: D50–D53, D55-D59, D60-D64) and Substance Abuse (F10-F19) were considered. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 population, standardized to the 2000 U.S. Census population. Joinpoint regression was used to estimate annual percent changes (APC) and average annual percent changes (AAPC), stratified by age groups, sex, and race/ethnicity. Statistical significance was set at p < 0.05.

Results: From 1999-2023, a total of 124,963 deaths were recorded. The total age-adjusted mortality rate (AAMR) increased from 0.70 per 100,000 in 1999 to 6.24 in 2023. The average annual percentage change (AAPC) was 10.28* (95% CI: 8.89 to 11.69, p<0.000001), with the most significant trend observed between 1999-2006 (APC: 26.47*; 95% CI: 20.98 to 32.21). The AAMRs showed increase in both genders, with males having a higher rate (5.32) than females (2.78). An overall greater change was observed in males (AAPC 9.67*; CI: 8.38 to 10.98, p<0.000001). Racial disparities were evident with Blacks or African American individuals having greater mortality rates (4.63) than White individuals (3.90). Both showed a significant overall increase with an AAPC of 7.60* (CI: 5.92 to 9.30, p<0.000001) for Black individuals, and an AAPC of 10.87* (CI: 9.48 to 12.29, p<0.000001) for White individuals. Regionally, the Midwest had the highest AAMR (4.90) followed by the South (3.97), Northeast (3.49) and West (2.89). Non-metropolitan areas had a higher AAMR (4.96) compared to metropolitan areas (1.71). State-level variation was significant, with the highest AAMR in North Dakota (9.13) and the lowest in California (1.00).

Conclusion: Mortality from anemia and substance abuse in U.S. adults aged ≥45 years showed a significant upward trend between 1999 and 2023. Notable disparities were observed across gender, race, region and setting of death, with African American men, and Midwest and rural areas showing the greatest mortality trends and discrepancies. This warrants the need for targeted interventions to be carried out and highlights that personalized care and system-level reforms are key to ensuring fair survival outcomes for all groups, for the profound inequities to be eradicated.

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2025
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