Joint associations of accelerometer-measured physical activity and cardiovascular-kidney-metabolic syndrome stages with the risks of cancer and all-cause mortality

BACKGROUND: Cardiovascular-kidney-metabolic syndrome clinically increases cancer and mortality risks, but the combined effects of cardiovascular-kidney-metabolic syndrome and physical activity on these outcomes remain poorly understood. METHODS: This prospective study included 66 650 UK Biobank participants with accelerometry data. Cardiovascular-kidney-metabolic syndrome was classified into 5 stages based on metabolic, kidney, and cardiovascular health. Physical activity was categorized by intensity into light, moderate, vigorous, and moderate-to-vigorous levels and further divided into tertiles by daily duration. Multivariable Cox models were used to estimate hazard ratios. RESULTS: Over a median follow-up of 8.03 years, 4301 incident cancer cases and 2442 deaths occurred. Advancing cardiovascular-kidney-metabolic stages were associated with elevated risks of cancer incidence and all-cause mortality, while increasing physical activity levels reduced these risks. Statistical interactions were observed between cardiovascular-kidney-metabolic syndrome and moderate physical activity and moderate-to-vigorous physical activity on cancer and mortality risks (P < .05 for interaction). In participants with the lowest tertile of moderate physical activity or moderate-to-vigorous physical activity, those in stages 2 and 4 had higher cancer risk, while in the highest tertile, this risk was no longer elevated. For all-cause mortality, in participants with the lowest tertile of moderate physical activity or moderate-to-vigorous physical activity, cardiovascular-kidney-metabolic stage 3 exhibited higher risks, while those in the highest tertile did not. Cardiovascular-kidney-metabolic stage 4 remained associated with higher mortality across all physical activity intensity levels, but risks decreased with increasing moderate-to-vigorous physical activity levels. CONCLUSIONS: Higher levels of moderate physical activity and moderate-to-vigorous physical activity may mitigate the elevated risks of cancer incidence and all-cause mortality associated with cardiovascular-kidney-metabolic stages 2-4.