Associations of Physical Activity and Diet Quality With Mortality and Cardiovascular Disease in Cardiovascular-Kidney-Metabolic Syndrome

BACKGROUND: Physical activity (PA) and diet are cornerstones for cardiovascular disease (CVD) prevention, yet their associations with CVD within the cardiovascular-kidney-metabolic (CKM) framework remain unexplored. OBJECTIVES: This study aims to evaluate the independent and joint associations of PA and/or diet quality with mortality and incident CVD across CKM stages. METHODS: Our study included 339,074 UK Biobank participants (51.3% women, mean age 56.4 years) with CKM syndrome stage 0 to 4. PA was categorized as high (≥150 min/wk of walking or moderate-to-vigorous activity) or low using self-reported and accelerometer-measured data. Diet quality was classified as low/median/high. Cox proportional hazards models assessed associations with incident CVD, cause-specific CVD mortality, and all-cause mortality across CKM stages. RESULTS: High PA was associated with lower risks of all-cause mortality (HR: 0.76 [95% CI: 0.74-0.79]), composite CVD mortality (0.74 [0.70-0.77]), and incident composite CVD (0.90 [0.88-0.92]); for high diet quality, corresponding HRs (95% CIs) were 0.81 (0.77-0.85), 0.81 (0.75-0.88), and 0.87 (0.84-0.90). PA showed nonlinear associations with these outcomes, plateauing at approximately 2,500 metabolic equivalent min/wk. High PA combined with high diet quality showed stronger inverse associations with all-cause mortality (0.64 [0.60-0.68]), composite CVD mortality (0.61 [0.54-0.68]), and incident composite CVD (0.83 [0.79-0.88]). Significant multiplicative interactions between PA and diet quality were observed for stroke mortality, composite CVD, and heart failure. The joint associations with these outcomes were stronger at more advanced CKM syndrome stages. CONCLUSIONS: Beyond individual benefits, joint PA-diet modification was associated with lower risk of mortality and CVD across CKM stages, highlighting the value of integrated behavioral strategies.