Physical activity, cardiovascular disease, and mortality across obesity levels.

Aims: High physical activity (PA) is associated with decreased risk of cardiovascular disease (CVD) and mortality. However, whether PA can be sufficient to reduce the risk of CVD and mortality contributing to adiposity remains unclear. From the standpoint of predictive, preventive, and personalized medicine (PPPM/3PM), joint assessment of PA and adiposity provides novel insights for individual risk assessment, targeted prevention, and personalized intervention of CVD. Methods: This prospective cohort study included 92,931 participants in the Kailuan study in Tangshan, followed between the years 2006 and 2020. Adiposity was assessed by body mass index (BMI) and waist circumference (WC). The CVD incidence and all-cause mortality associated with 3 PA levels (low, medium, and high PA) were analyzed by applying Cox regression models to different adiposity subgroups. Results: After a median follow-up period of 14.02 years, 9997 incident CVD cases and 12,586 deaths occurred. Surprisingly, low PA and lean body mass were at a lower risk for CVD than other phenotypes. Participants with high PA still had a 35% higher CVD risk from obesity (hazard ratio (HR) Conclusion: High PA did not attenuate the risk of CVD associated with adiposity compared with lean body mass among the Chinese population, whereas the combination of high PA and healthy WC might improve healthy aging and longevity. In addition, this study revealed the importance of maintaining muscle health in obese individuals via PA or other ways. It provides a novel strategy for mitigating the risk of CVD by exercising intervention or maintaining body mass, thereby enhancing effective prevention and targeted intervention. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-025-00397-5.