Abstract
BACKGROUND: Lung cancer (LC) is a leading cause of morbidity and mortality worldwide. Cardiovascular disease is the primary cause of non-cancer-related death among cancer survivors. Frailty, characterized by a decline in physiological reserves, has been identified as a predictor of poor outcomes in cancer. However, the relationship between frailty, pre-frailty, and long-term cardiovascular outcomes in LC patients remains insufficiently explored. METHODS: This retrospective analysis of a cohort study utilized prospectively collected data from the UK Biobank, with baseline assessment between 2006 and 2010 and follow-up until October 31, 2022. Frailty was defined using the frailty phenotype according to five components (weight loss, exhaustion, low physical activity, slow gait speed, and low grip strength). Participants were categorized as non-frail, pre-frail or frail. The outcome was defined as major adverse cardiac and cerebrovascular events (MACCE). Cox proportional hazards models adjusted for confounders including age, sex, obesity, smoking status, socioeconomic status, diabetes, hypertension, COPD, and tumor type were employed to estimate hazard ratios (HR) for MACCE. RESULTS: Of the 500,530 participants in this cohort, 6095 were diagnosed with LC after recruitment. Among LC patients, 43.79% were non-frail, 48.20% pre-frail, and 8.01% frail. Frail individuals had a significantly higher risk of MACCE (HR = 1.21, 95% CI: 1.07-1.38, p = 0.002) compared to non-frail patients, while pre-frail individuals also exhibited an elevated risk (HR = 1.10, 95% CI: 1.02-1.18, p = 0.010). Specific frailty components, particularly low physical activity and slow gait speed, were strongly associated with increased risks of both MACCE and all-cause mortality. In contrast, low grip strength did not show a significant association with adverse outcomes. CONCLUSIONS: LC participants had a higher prevalence of pre-frailty and frailty. The presence of frailty and pre-frailty significantly increased the risk of MACCE in long-term LC survivors. Notably, slow gait speed and low physical activity were strongly associated with MACCE compared to other frailty components.