Temporal trends and geographic variation in mortality from hypertensive diseases with coexisting aplastic and other anemias in the United States (1999–2023): A CDC wonder analysis

Abstract Introduction: Hypertensive disease (HD) refers to a constellation of changes in heart resulting from chronic elevation of blood pressure. Aplastic anemia is characterized by bone marrow failure and pancytopenia, while secondary anemias occurring due to chronic disease, inflammation, or nutrient deficiencies are common and adversely affect cardiovascular health. Hypertensive diseases remain among the leading causes of cardiovascular mortality in the U.S. The interplay between these diseases can exacerbate the underlying condition and result in poor treatment outcomes. This study targets to evaluate their correlation and related mortality. Methods: We analyzed adults aged ≥25 years death from the CDC WONDER Multiple Cause of Death database from 1999-2023, with co-occurring Hypertensive Diseases (ICD-10 codes: I10-15) and Aplastic and other Anemias (ICD-10 codes: D60-64). Age-adjusted mortality rates per 100,000 population were calculated and stratified by all demographics and geography. Joinpoint regression analysis was used to calculate the annual percentage change (APC) in mortality trends, along with 95% confidence intervals (CI). Results: A total of 3,38,319 deaths were attributed to Hypertensive diseases and Aplastic and other anemias related mortality in the U.S. population from 1999-2023. The overall AAMR exhibited a sharp rise from 2.35 in 1999 to 4.38 in 2001 (APC: 32.23; 95%CI: 50.12 to 16.29), and a steady increase up to 6.21 by 2010 (APC: 3.22; 95%CI: 5.01 to 1.44), then by slight decrease till 6.04 in 2018 (APC: -1.01; 95%CI: -0.82 to -6.99), followed by another spike of 8.43 in 2021 (APC: 13.67; 95%CI: 17.47 to 0.31), before declining to 8.16 by 2023 (APC: -2.35; 95%CI: 6.44 to -8.39). Both males and females exhibited variable but steadily rising age-adjusted mortality rates over the study period, the AAMR for males increased from 2.12 in 1999 to 8.91 in 2023, while that of females rose from 2.43 in 1999 to 7.30 by 2020. Racial analysis revealed that Black or African American individuals had the highest AAMR, which fluctuated but overall rose from 5.97 per 100,000 in 1999 to 13.59 in 2023. This was followed by Asian and Pacific Islanders, whose rates increased from 2.35 to 5.87, and White individuals, whose mortality climbed from 1.98 to 7.74 over the same period. Nonmetropolitan areas exhibited consistently higher AAMR than metropolitan areas, averaging 6.34 vs. 5.55 per 100,000, respectively. Regional distribution revealed that the Southern U.S. had highest AAMR 1.48 times the Northeast region. Adults aged 65–85+ experienced the highest AAMR, which rose substantially from 10.87 per 100,000 in 1999 to 36.57 in 2023. States reporting mortality rates above 90th percentile included Minnesota (16.14), South Carolina (15.81), and Nebraska (14.08). Conclusion: From 1999-2023, mortality trends associated with hypertensive diseases co-occurring with aplastic and other anemias raised markedly among older adults (65+), Black or African American individuals, and residents of non-metropolitan and Southern regions. These trends reflect persistent and widening health disparities, underscoring the need for targeted interventions aimed at high-risk populations. Key Words: Hypertensive disease, Aplastic anemia, Secondary anemia, Mortality trends, Epidemiology