Trends in cardiovascular mortality in Hodgkin and non-Hodgkin lymphoma: A nationwide analysis from 1999 to 2020

Abstract Background: Cardiovascular disease (CVD) is a leading cause of non-cancer-related death among cancer survivors, particularly those treated for lymphomas, due to the cardiotoxic effects of chemotherapy, like anthracyclines, and radiation. While long-term survival after lymphoma has improved, concerns have emerged regarding late cardiovascular complications such as coronary artery disease, heart failure, and arrhythmias. It remains unclear whether improvements in cancer care have translated into parallel reductions in CVD mortality in this population. Objectives: To evaluate national trends in cardiovascular disease mortality among individuals with lymphoma in the United States from 1999 to 2020, stratified by sex, demographics, and Hodgkin and Non-Hodgkin lymphoma, using Age-Adjusted Mortality Rates (AAMR) and Average Annual Percent Change (AAPC). Methods: This retrospective trend analysis utilized national death certificate data from 1999 to 2020, sourced from the CDC Wonder Database. Deaths attributed to CVD in individuals diagnosed with Hodgkin and Non-Hodgkin lymphoma were identified. Joinpoint regression analysis was performed to estimate temporal trends, including AAMRs per 100,000 (age-adjusted to the 2000 U.S. standard population) and APCs across identified time segments. Subgroup analyses were conducted by sex, race/ethnicity, U.S. census region, and Cardiovascular causes. Results: There was a total of 200,135 deaths recorded associated with lymphoma and cardiovascular causes from 1999 to 2020. The AAMR for Non-Hodgkin lymphoma-associated CVD deaths decreased from approximately 4.5 to 3.3 per 100,000 between 1999 and 2017 (APC: –1.82%, p0.05) but rose to 3.6 by 2020 (APC: +3.85%, p0.05). Hodgkin lymphoma-related CVD mortality remained low and declined steadily (AAPC: –1.12%, p0.05). Demographically, Asian or Pacific Islander individuals experienced the greatest decline in CVD mortality (AAPC: –2.33%, p0.05), while White individuals saw a significant post-2017 increase (APC: +4.21%). Males and females experienced declines through 2017 (APCs: –1.69%, p0.05 and –2.14%, p0.05, respectively), followed by sharp increases (APCs: +4.83%, p0.05 and +5.85%). Regionally, the Midwest exhibited the most pronounced reversal in trends, shifting from an APC of –1.96% to +7.36%, p0.05 after 2017. The major CVS causes were arrhythmia 30%, Ischemic heart disease 18.9%, Hypertension 16% and Heart failure 13.4%. Conclusion: Despite early progress in reducing cardiovascular mortality among lymphoma patients, a reversal in trends has emerged since 2017, which is worrisome. The reversal can be attributed to the increased detection of arrhythmia. Now, with increases observed across multiple demographic and geographic groups, particularly in the Midwest and among White individuals. These findings highlight the need for integrated cardio-oncology surveillance and proactive intervention strategies to address rising CVD risk in lymphoma survivors to preserve the long-term survival gains achieved.