Disparities and reversal of declines: A 22-year analysis of mortality trends in patients with concurrent anemia and heart failure in the United States (1999–2020)

Abstract Introduction Anemia is a common comorbidity among patients with heart failure (HF), associated with worse functional status, reduced quality of life, and increased mortality. Despite this clinical relevance, national mortality trends in patients with both HF and anemia have not been extensively studied. Given shifting population demographics and changes in heart failure care delivery, this study aims to characterize longitudinal mortality trends and disparities associated with the dual burden of HF and anemia in the United States.Methods We used the CDC WONDER Multiple Cause of Death database to identify deaths from 1999–2020 in which both HF (ICD-10: I50) and anemia (ICD-10: D50–D64) were listed as causes in individuals aged ≥25 years. Crude mortality rates per 100,000 population were calculated annually. Joinpoint regression was used to assess temporal trends and calculate annual percent changes (APCs) and average annual percent change (AAPC) with 95% confidence intervals. Analyses were stratified by sex, race/ethnicity, age, U.S. census region, and 2013 urbanization classification.Results From 1999 to 2020, a total of 47,390 deaths were attributed to concurrent heart failure and anemia among individuals aged ≥25 years. The overall crude mortality rate increased from 1.25 to 1.84 per 100,000, with a statistically significant upward trend (AAPC: +1.6%, p < 0.001). Males consistently exhibited higher mortality than females (2.18 vs. 1.58 per 100,000 in 2020), with rates rising significantly in both sexes (AAPC: +1.2% for males, +1.9% for females; p < 0.001 for both). Racial analysis revealed that Black individuals experienced the steepest increase in mortality (AAPC: +2.13%, p < 0.001), followed by White (AAPC: +1.45%, p < 0.001) and Hispanic populations (AAPC: +1.38%, p = 0.001). Among U.S. census regions, the South bore the highest mortality burden in 2020 (2.08 per 100,000), with the Northeast showing the sharpest rise over time (AAPC: +2.11%, p < 0.001). Mortality also rose significantly in the South (AAPC: +1.46%, p < 0.001), Midwest (+1.12%, p = 0.004), and West (+1.38%, p = 0.001). Urbanization trends indicated that non-core rural areas had the highest crude mortality rates (2.37 per 100,000), while medium metro areas exhibited the most rapid rise (AAPC: +2.09%, p < 0.001), suggesting disproportionate increases in semi-urban and rural populations. Age-stratified analysis revealed stable or declining mortality during the early 2000s across most age groups, followed by significant uptrends in the past decade. Specifically, individuals aged 25–34 showed a steep rise from 2012–2020 (APC: +10.18%, p < 0.001), while the 35–44 and 45–54 groups demonstrated sharp increases post-2017 (APC: +16.49% and +9.25%, respectively). In older cohorts (65–74, 75–84, and 85+), significant reversals were observed around 2015–2017, transitioning from prior declines to rising mortality trends (APC range: +4.11% to +10.69%, all p < 0.05). These inflection points reflect a concerning national shift in the burden of HF with anemia, now extending across nearly all adult age groups and demographic subgroups.Conclusion Although national mortality rates from concurrent heart failure and anemia have increased only modestly, the pace of this rise has accelerated in recent years, especially after 2015. The most pronounced increases were seen in younger adults, Black individuals, and residents of medium metro and Northeastern regions. These patterns highlight concerning disparities and suggest that the dual burden of heart failure and anemia is becoming more widespread across age and demographic groups. Focused efforts on early diagnosis, improved management, and equitable access to care are essential to address these emerging trends and improve outcomes for high-risk patients.