Temporal trends and forecast of cardiovascular mortality in non-Hodgkin lymphoma patients in the United States: A 1999–2030 population-based analysis

Abstract

Abstract Background Non-Hodgkin lymphoma (NHL) represents a heterogeneous group of hematologic malignancies that predominantly affects older adults and is characterized by clonal proliferation of B-cells, T-cells, or natural killer cells. Cardiovascular complications have emerged as significant contributors to morbidity and mortality in NHL patients, attributed to both disease-related factors and treatment-related cardiotoxicity from chemotherapeutic agents and radiation therapy. Despite the recognized cardiovascular risk in this population, comprehensive national-level data on long-term cardiovascular mortality trends in NHL patients remain limited. Understanding temporal and demographic patterns of cardiovascular-related deaths in NHL patients is essential for risk stratification, treatment optimization, and developing targeted preventive strategies.Methods We conducted a retrospective population-based analysis using the CDC WONDER Multiple Cause of Death database to examine cardiovascular-related mortality among individuals with NHL between 1999 and 2023. Age-adjusted mortality rates (AAMRs) were calculated per million using U.S. Census data as the denominator. Temporal trends were assessed using Jointpoint regression to determine average annual percent changes (AAPCs). ARIMA models with Box-Cox transformation were fitted after ADF/KPSS tests, with validation by residual checks to forecast future trends from 2024–2030. Subgroup analyses were stratified by race, ethnicity, and urbanization zones.Results Between 1999 and 2023, there were 22,292 cardiovascular-related deaths among individuals with NHL in the United States. Over this period, the overall AAMR declined from 2.17 per million in 1999 to 1.85 per million in 2023, representing a 14.6% decrease. However, notable temporal fluctuations were observed, with peak mortality rates occurring in the early 2000s and periodic increases in 2021-2022. Significant racial disparities persisted throughout the study period. White individuals accounted for the majority of deaths (16,365 deaths), with AAMR declining from 2.2 to 1.9 per million (13.6% decrease). Whereas, Black or African American individuals experienced a slight increase from 1.4 to 1.5 per million (7.1% increase) over the study period, totaling 1,100 deaths. Asian or Pacific Islander individuals showed the most dramatic improvement, with AAMR declining from 2.2 to 0.8 per million (63.6% decrease), representing 257 total deaths. Ethnicity-based analysis revealed contrasting trends between Hispanic and non-Hispanic populations. Hispanic or Latino individuals experienced an increase in AAMR from 1.4 to 1.6 per million (14.3% increase), while non-Hispanic individuals saw a decline from 2.2 to 1.8 per million (18.2% decrease). Both groups exhibited peak mortality rates in the 2019-2022 period before declining in 2023. Urbanization analysis demonstrated varying patterns across geographic classifications. Large Central Metro areas consistently showed lower burden compared to smaller metropolitan and rural areas throughout the study period. Small metro and micropolitan areas maintained higher AAMRs, suggesting potential disparities in healthcare access and specialized cardiovascular care for NHL patients in less urbanized regions. Based on ARIMA modeling incorporating recent trend patterns, the AAMR for cardiovascular-related mortality in NHL is projected to stabilize with modest fluctuations. Forecasted rates include 1.82 in 2024, 1.79 in 2026, 1.81 in 2028, and 1.83 per million by 2030 (95% CI: 1.65–2.05), suggesting a plateau pattern with potential slight increases in the latter part of the decade.Conclusion Cardiovascular-related mortality among NHL patients in the U.S. has shown an overall declining trend over the past two decades, likely reflecting improvements in cardiovascular risk management and treatment protocols. However, persistent disparities by race and ethnicity highlight the need for targeted interventions. The projected stabilization through 2030 suggests that while significant progress has been made, continued vigilance and specialized cardiovascular care protocols remain essential. These findings signify the importance of integrated cardio-oncology approaches in NHL management, particularly for high-risk demographic subgroups and patients in less urbanized areas with potential healthcare access limitations.