Association of a Comprehensive Healthy Lifestyle Score with Risk of All-Cause, Cancer, and Cardiovascular Mortality: Evidence from an 18-Year Cohort Study

Background/Objectives: Comprehensive management of lifestyle factors is important for long-term survival. This study aims to examine whether a comprehensive healthy lifestyle score (HLS) incorporating overall diet assessment predicts all-cause, cancer, and cardiovascular mortality in Korean population. Methods: This prospective cohort study was conducted among men and women (n = 111, 633, 64. 6% women) aged 40 to 85 years who participated in the Korean Genome and Epidemiology StudyHealth Examinees (Mean age = 55. 2, SD = 8. 8). Participants completed a baseline questionnaire between 2004 and 2013 and were followed until December 2023. The HLS consisted of five components classified as healthy behaviors: never or former smoking; engaging in ≥30 min/day of moderate-to-vigorous physical activity on ≥5 days/week; alcohol intake ≤40 g/day for men and ≤20 g/day for women; a BMI of 18. 5–24. 9 kg/m2; and an unhealthful plant-based diet index (uPDI) in the bottom 40th percentile, which reflects overall diet quality and aligns with the traditional plant-rich dietary pattern of Koreans. Diet was assessed using data from baseline and the first follow-up, while the remaining components were measured at baseline only. Cox proportional hazards models were applied to evaluate multivariable-adjusted associations between the HLS and all-cause, cancer, and cardiovascular mortality. Results: During 1, 538, 490 person-years of follow-up, 5246 all-cause deaths, 2362 cancer deaths, and 815 cardiovascular deaths were documented. Compared with the lowest HLS category, men with the highest HLS had lower risks of all-cause (HR: 0. 65, 95% CI: 0. 53–0. 80), cancer (HR: 0. 62, 95% CI: 0. 46–0. 85), and cardiovascular mortality (HR: 0. 34, 95% CI: 0. 17–0. 66). Among women, the corresponding HRs were 0. 38 (95% CI: 0. 26–0. 55), 0. 52 (95% CI: 0. 29–0. 90), and 0. 30 (95% CI: 0. 11–0. 84), respectively. The inverse association was stronger in older adults (≥55 years) than in younger adults. All five individual lifestyle components, including diet (quintile 5 vs. quintile 1 of uPDI: HR 0. 74, 95% CI: 0. 66–0. 83 in men; HR 0. 67, 95% CI: 0. 58–0. 76 in women), were significantly associated with a lower risk of all-cause mortality. However, when smoking was excluded from the HLS, the inverse association was attenuated, particularly among men. Conclusions: Greater adherence to a healthy lifestyle score was strongly associated with reduced risks of all-cause, cancer, and cardiovascular mortality. These findings underscore the importance of promoting integrated, multi-behavior lifestyle interventions, especially smoking cessation, to reduce premature mortality.