Trends and disparities in cerebrovascular disease–related mortality in patients with chronic lymphocytic leukemia: A retrospective analysis across two decades.

Abstract

e18633 Background: Cerebrovascular disease (CVD) is an important cause of morbidity and mortality in patients with chronic lymphocytic leukemia (CLL), driven by aging, cancer-related inflammation, hypercoagulability, and treatment-associated vascular toxicity. National trends in CVD-related mortality among patients with CLL remain poorly characterized. Methods: This population-based cohort study analyzed CVD-related mortality trends among U.S. adults aged ≥55 years with CLL from 1999–2023 using CDC WONDER Multiple Cause of Death data. Deaths were identified using ICD-10 codes for CLL (C91.1) and cerebrovascular disease (I60–I69). Analyses were stratified by age, sex, race/ethnicity, census region, and urbanization. Age-adjusted mortality rates (AAMRs) were calculated using the 2000 U.S. standard population. Joinpoint regression was used to estimate annual percent change (APC) with 95% confidence intervals (CIs). Statistical significance was defined as P<0.05. Results: Between 1999 and 2023, 9,260 CVD-related deaths occurred among patients with CLL aged ≥55 years (54.3% male). Overall AAMRs declined from 1999–2016 (APC −3.4%; 95% CI −4.1 to −2.7; P<0.001) but increased from 2016–2023 (APC 7.9%; 95% CI 5.1 to 10.8; P<0.001), with similar trends in both sexes. Among adults aged 55–74 years, mortality declined from 1999–2017 (APC −4.7%; 95% CI −6.2 to −3.2) followed by a sharp increase from 2017–2023 (APC 13.6%; 95% CI 3.6 to 24.6; P=0.009). A similar pattern was observed in those aged ≥75 years, with declines until 2015 (APC −3.4%) and subsequent increases from 2016–2023 (APC 6.5%; 95% CI 4.3 to 8.8; P<0.001). The South exhibited the highest mortality burden, with rising AAMRs after 2016 (APC 9.1%; 95% CI 5.4 to 12.9; P<0.001) following earlier declines. Urban areas demonstrated the most pronounced recent increase, including a marked rise from 1999–2020 (APC 20.7%; 95% CI 0.02 to 45.8; P=0.05) after prolonged declines. Conclusions: CVD-related mortality among U.S. patients with CLL has increased substantially since 2016, particularly among older adults and residents of urban and Southern regions. These findings highlight a growing cardio-oncologic burden and underscore the need for improved vascular risk assessment, treatment monitoring, and preventive strategies in patients with CLL.