Abstract Background: Hemolytic anemia encompasses a group of disorders defined by premature destruction of red blood cells and is increasingly recognized for its cardiovascular implications. Yet, there is limited national evidence on the long-term trends and disparities in cardiac mortality among this population. This study investigates temporal changes and sociodemographic disparities in cardiac mortality among individuals with hemolytic anemia in the United States between 1999 and 2023.

Methods: Mortality data were obtained from the CDC WONDER database, identifying deaths in which hemolytic anemia was a contributing cause and cardiovascular disease was the underlying cause. Age-adjusted mortality rates (AAMRs) were calculated per million population. Temporal trends were assessed using Joinpoint regression, and annual percent change (APC) estimates were generated. Statistical significance was defined as p < 0.05.

Results: The overall AAMR for cardiac mortality among individuals with hemolytic anemia was 4.44 per million. A statistically significant decline occurred between 1999 and 2014 (APC –1.84), followed by a significant increase from 2014 to 2023 (APC 3.84), indicating a reversal in long-standing improvements.

Among females, the AAMR was 3.93 per million, with a significant decline from 1999 to 2014 (APC –2.03) and a significant rise from 2014 to 2023 (APC 4.83). Males had an AAMR of 4.44 per million. Cardiac mortality significantly declined from 1999 to 2015 (APC –1.89), followed by a statistically significant increase from 2015 to 2023 (APC 5.60).

Black or African American individuals experienced the highest burden, with an AAMR of 17.49 per million. From 1999 to 2014, the APC was –0.66 and not statistically significant, followed by a significant rise from 2014 to 2023 (APC 4.01). White individuals had an AAMR of 2.56 per million, with a statistically significant decline from 1999 to 2014 (APC –3.38) and a significant increase thereafter (APC 3.22). Hispanic or Latino individuals had the lowest AAMR at 2.01 per million, with a significant decrease from 1999 to 2010 (APC –6.85) and a significant increase from 2010 to 2023 (APC 3.19).

Regionally, the South reported the highest AAMR at 4.95 per million. A statistically significant decline occurred from 1999 to 2015 (APC –1.39), followed by a significant increase from 2015 to 2021 (APC 6.89), and a non-significant decline from 2021 to 2023 (APC –6.22). In the Northeast, the AAMR was 4.53 per million, with a significant decline from 1999 to 2012 (APC –2.27) and a significant increase from 2012 to 2023 (APC 2.58). The Midwest showed a fluctuating pattern with an AAMR of 3.98 per million and five trend segments, none statistically significant: an increase from 1999 to 2004 (APC 1.93), a sharp decline from 2004 to 2007 (APC –9.10), a modest decline from 2007 to 2018 (APC –0.53), a spike from 2018 to 2021 (APC 12.37), and a decrease from 2021 to 2023 (APC –6.67). The West had an AAMR of 3.95 per million, with a significant decline from 1999 to 2012 (APC –2.89) and a significant increase from 2012 to 2023 (APC 2.45).

Urban-rural differences were also notable. The AAMR in urban areas was higher, at 5.5 per million, compared to 3.78 per million in rural areas. In urban settings, cardiac mortality declined significantly from 1999 to 2015 (APC –1.89), then increased significantly from 2015 to 2020 (APC 5.35). In rural areas, a statistically significant decline occurred from 1999 to 2016 (APC –2.14), followed by a sharp and statistically significant increase from 2016 to 2020 (APC 15.37).

Conclusions: After a period of sustained improvement, cardiac mortality among individuals with hemolytic anemia has risen markedly since the mid-2010s. The increases are disproportionately affecting males, Black individuals, urban residents, and populations in the South and Northeast.These findings emphasize the urgent need for targeted cardiovascular interventions in these high-risk populations. This data highlights the need for equity-focused public health strategies to address the re-emergence of preventable cardiac deaths in this high-risk group.

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2025
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