Rising mortality from coexisting hypertension and aplastic anemia in the United States, 1999–2023: A 25-year analysis of national disparities and public health gaps

Abstract Background Hypertension is one of the most prevalent chronic conditions in the United States and a leading contributor to cardiovascular morbidity and mortality. Aplastic anemia, a rare but serious bone marrow failure disorder, may complicate the clinical course of hypertensive patients through increased risks of fatigue, bleeding, and infection. Despite the known burden of both conditions individually, population-level mortality trends involving their coexistence remain poorly characterized. This study examines national, demographic, and geographic mortality trends related to both conditions from 1999 to 2023. Methods Mortality data were obtained from the CDC WONDER platform for 1999–2023. Age-adjusted mortality rates (AAMRs) per 100,000 were calculated for deaths listing both hypertension (ICD-10: I10–I15) and aplastic anemia (ICD-10: D60–D61) as contributing causes. Joinpoint regression identified significant changes in Annual Percent Change (APC) and Average Annual Percent Change (AAPC). Analyses were stratified by sex, race/ethnicity, age group, U.S. Census region, and urbanization. Statistical significance was defined by 95% confidence intervals and p-values. Results From 1999 to 2023, the national AAMR for deaths involving both hypertension and aplastic anemia rose from 2.35 to 8.16 (mean: 5.90). Five temporal segments were identified : an initial sharp rise from 1999 to 2001 [APC: 32.69, (95% CI: 15.86 to 51.96)], followed by continued increase from 2001 to 2011 [APC: 3.21 (95% CI: 2.14 to 4.29)]. A plateau occurred between 2011 and 2016 [APC: –1.02, (95% CI: –2.10 to 0.08)], followed by a rapid increase from 2016 to 2021 [APC: 13.58, (95% CI: 5.57 to 22.19], and a non-significant decline from 2021 to 2023 [APC: -2.12, (95% CI: -8.35 to 4.54)]. The full-period AAPC [4.72 (95% CI: 3.20–6.27)], indicating a statistically significant long-term increase. Males and females had similar mean AAMRs (5.97 vs. 5.79), but males experienced a steeper increase [AAPC: 5.43 vs. 4.28]. Racial disparities were substantial: NH Black individuals had the highest mean AAMR (11.20), followed by NH Whites (5.39) and Asians/Pacific Islanders (5.25). All showed significant upward trends, with the steepest rise in Whites [AAPC: 5.22]. Age-stratified data showed older adults with the highest mean (26.8), followed by middle-aged adults (1.68) and young adults (0.14); the middle-aged group experienced a significant rise [AAPC: 6.18]. Regionally, the South had the highest mean AAMR (6.5) and most rapid increase [AAPC: 5.34]. Non-metropolitan areas recorded both a higher mean AAMR (6.24) and faster growth [AAPC: 5.91] than metropolitan areas (AAMR: 5.44). State-level AAMRs ranged from 1.691 (Utah) to 9.658 (Rhode Island) during 1999–2020, increasing to a range of 2.412 (Utah) to 16.137 (Minnesota) during 2018–2023. Conclusion This 25-year analysis reveals a steadily rising mortality burden involving both hypertension and aplastic anemia. Although a potential plateau emerged post-2021, the long-term trend reflects increasing clinical and public health relevance. Disparities by race, region, and urbanization highlight systemic inequities in disease prevention and care. Focused efforts are needed to improve chronic disease management, expand access in rural and Southern communities, and address rising mortality among middle-aged and racially marginalized populations. Keywords Hypertension, Aplastic Anemia, CDC WONDER, Age-Adjusted Mortality, Joinpoint Regression, Racial Disparities, Urban–Rural Health, Middle-Aged Adults, Comorbid Mortality, U.S. Mortality Trends, Public Health Equity, Multiple-Cause Deaths