Determinants of cardio-cerebrovascular mortality in middle-aged lung cancer patients: a population-based study
Y Lee, W Woo, A KimAbstract
Background
Improvements in precision oncology and earlier detection have increased survival rates for patients with lung cancer, thereby resulting in -increasing relevance of non-cancer causes of death, particularly cardiovascular and cerebrovascular diseases. Despite this shift, data on cardio-cerebrovascular mortality among middle-aged adults remain limited.
Purpose
Cardio-cerebrovascular mortality is a significant concern among patients with lung cancer because of shared risk factors, cancer associated thrombosis, and treatment related toxicity. This study evaluates the incidence, patterns, and determinants of cardio-cerebrovascular mortality among adults aged 30 to 59 years with lung cancer.
Methods
Patients aged 30 to 59 years with pathologically confirmed lung cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) 17 registries (2000 to 2021). Demographic, socioeconomic, tumor, and treatment variables were analyzed. Cardio-cerebrovascular mortality was defined as death due to cardiovascular or cerebrovascular causes. Kaplan-Meier curves compared outcomes across demographic and clinical strata. Univariate and Multivariable Cox proportional hazards models were used to identify independent predictors of cardio-cerebrovascular mortality.
Results
Among 185,296 patients, cardio-cerebrovascular mortality occurred in 2.2% of patients. Incidence increased with after age 50 (2.59% at 55-59 years). Ischemic heart disease accounted for most Cardio-cerebrovascular mortality events (51 %), followed by cerebrovascular events (15.1 %). Multivariable models showed that advanced cancer stage was strongly associated with cardio-cerebrovascular mortality. Stage III (HR 1.58, p=0.001) and stage IV (HR 1.64, p<0.001) were both associated with higher risk. Squamous cell carcinoma conferred a higher cardio-cerebrovascular mortality risk than adenocarcinoma (HR 1.56, p<0.001). Non-Hispanic Black patients had more than twice the hazard of cardio-cerebrovascular mortality compared with other racial groups (HR 2.54, p<0.001). Socioeconomic indicators, including household income and urban-rural classification, were not independently associated with cardio-cerebrovascular mortality.
Conclusion
In middle aged adults with lung cancer, cardio-cerebrovascular mortality increases markedly after age 50, and affects individuals with advanced stage, squamous cell carcinoma, and those identifying as Non-Hispanic Black. These findings highlight key biological, therapeutic, and disparity-related contributors to cardio-cerebrovascular mortality in a population with increasing post-cancer survival. Implementation of structured cardio oncology surveillance, early cardiovascular risk assessment, and targeted preventive strategies, particularly for high-risk histologic and demographic groups, may reduce competing mortality and improve long-term survivorship.