Cardiovascular-kidney-metabolic (CKM) syndrome, integrating cardiovascular disease (CVD), chronic kidney disease (CKD), type 2diabetes, and metabolic dysfunction, is a growing public health challenge that increases premature mortality and health care burden. While pharmacological therapies have advanced, prevention through modifiable lifestyle factors remains essential. Physical activity (PA) is protective for cardiovascular, kidney, and metabolic health, yet most research emphasizes total volume or intensity; the impact of PA timing on CKM development and progression remains unknown. This study aims to
Primary objective
Evaluate the association between the timing of moderate-to-vigorous physical activity (MVPA) (morning, afternoon, evening, or mixed) and the risk of developing cardiovascular-kidney-metabolic (CKM) syndrome and their progression to death.
Secondary objectives
1. Investigate subgroup variations in the association between MVPA timing and CKM risk, stratified by age, sex, obesity (defined by body mass index or/and waist circumference or body roundness index), and other relevant clinical factors.
2. Examine the association between MVPA timing and individual components of CKM including cardiovascular disease, chronic kidney disease, and type 2 diabetes.
3. Investigate the association between MVPA timing and the composite outcomes of all-cause mortality, major cardiovascular events (MACE) and major kidney events (MAKE) in people with CKM stage 0-3.
4. Examine the joint effects of MVPA timing with other behavioral patterns (e.g., sleep patterns and dietary timing) on CKM risk and progression.
5. Explore potential mediators of the MVPA timing-CKM relationship, including blood pressure, glycemic control, and systemic inflammation.
6. Explore whether the genetic risk (e.g., polygenic risk scores for cardiovascular disease) of CKM modifies or mediates the association between MVPA timing and CKM risk.
