Background: Ischemic heart disease (IHD) is a well-established leading cause of death in the United States, contributing significantly to cardiovascular morbidity and mortality. Anemia, frequently observed in patients with chronic diseases—including IHD—may exacerbate progression and worsen outcomes by compromising oxygen delivery and increasing myocardial stress. While IHD has been extensively studied, the combined burden of IHD and anemia has not been comprehensively characterized at the population level over time. This study aims to fill that gap by analyzing long-term national mortality trends, regional variations, and demographic disparities in deaths involving both ischemic heart disease and anemia from 1999 to 2023.

Methods: Data on age-adjusted mortality rates (AAMRs) related to ischemic heart disease (ICD-10 codes: I20–I25), with concurrent anemia (ICD-10 codes: D50–D64), were extracted from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER) platform. The analysis spanned a 25-year period (1999–2023) and included stratification by sex, race/ethnicity, age group, geographic region (census divisions), and state-level location. Trends over time were evaluated using Joinpoint regression models, which identify statistically significant changes in trends through estimation of Average Annual Percent Change (AAPC) and Annual Percent Change (APC). Statistical significance was determined using 95% confidence intervals and p-values.

Results: From 1999 to 2023, a total of 264,424 deaths in the United States were recorded in which both ischemic heart disease and anemia were contributing factors. The national AAMR declined over the study period, from 6.90 deaths per 100,000 in 1999 to 5.11 in 2023, with an overall mean AAMR of 5.62. Joinpoint analysis identified four significant segments: an initial modest decline from 1999 to 2003 [APC = -0.62; 95% CI: -2.46 to 1.24; p = 0.4822], followed by a steeper and statistically significant decline from 2003 to 2018 [APC = -2.96; 95% CI: -3.24 to -2.68; p < 0.000001]. This improving trend was interrupted by a sharp and significant rise from 2018 to 2021 [APC = 8.91; 95% CI: 2.78 to 15.41; p = 0.007], potentially linked to healthcare disruptions during the COVID-19 pandemic, followed by a recent decline from 2021 to 2023 [APC = -4.22; 95% CI: -9.42 to 1.28; p = 0.1200]. Sex-based differences were notable: males had a higher AAMR (mean: 7.04) than females (mean: 4.68), although females showed a more favorable decline over time [female AAPC = -2.06 vs. male AAPC = -0.62]. Racial and ethnic disparities persisted. Non-Hispanic (NH) Black individuals had the highest AAMR (mean: 7.08), followed by NH Whites (5.53), NH American Indians (4.83), and NH Asians (4.19). A statistically significant decline was observed only in the American Indian population [AAPC = -1.53]. Crude mortality rates varied significantly across age groups: older adults had the highest mean rate (26.9), followed by middle-aged adults (1.16), and young adults (0.078). The elderly also showed significant improvement [AAPC = -1.92]. Regionally, the Midwest recorded the highest mean AAMR (6.03), followed by the Northeast (5.82), South (5.52), and West (5.08). A significant long-term decline was seen only in the Northeast [AAPC = -1.83]. State-level analyses revealed marked disparities: between 1999 and 2020, AAMRs ranged from 2.01 in Nevada to 11.17 in Rhode Island. From 2021 to 2023, Utah recorded the lowest AAMR (2.26), while South Dakota had the highest (8.92).

Conclusion: This comprehensive national study underscores the complex and evolving mortality landscape of ischemic heart disease when co-occurring with anemia. While there has been an encouraging overall decline over the past two decades, the sharp uptick from 2018 to 2021 highlights emerging vulnerabilities—possibly linked to systemic healthcare disruptions. Furthermore, persistent disparities indicate that the burden of this dual pathology is unequally distributed. These findings reinforce the urgent need for targeted public health interventions, particularly among high-risk populations and regions. Improved chronic disease management, early anemia detection in cardiovascular patients, and equitable healthcare access remain critical to mitigating this combined disease burden.

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2025
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