Front Endocrinol (Lausanne). 2026 Jul 31;17:1844167. doi: 10.3389/fendo.2026.1844167. eCollection 2026.
ABSTRACT
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome spans stages 0-4, with stage 4 denoting clinical cardiovascular disease (CVD). While individuals in stages 0-3 face elevated incident CVD risk, how different durations of physical activity (PA) associate with this risk remains unclear.
METHODS: This prospective UK Biobank cohort included 88,281 participants aged 37-73 in CKM syndrome stages 0-3, excluding those with baseline CVD. Overall and stage-specific analyzes were performed to evaluate the associations between PA and incident CVD risk. PA was categorized into light PA (LPA) and moderate-to-vigorous PA (MVPA), then divided into quartiles by weekly duration. Multivariable Cox models were used to estimate hazard ratios. An isochronous substitution model using component analysis was used to assess the associated risk differences of replacing LPA with MVPA.
RESULTS: During a median follow-up of 7.29 years, 7,514 new CVD cases occurred among 88,281 individuals with CKM syndrome stages 0-3. LPA was associated with a lower CVD risk most markedly in stage 2 individuals, with the highest quartile showing a 18% lower risk versus the lowest (HR = 0.82; 95% CI 0.75-0.90). MVPA was associated with a lower CVD risk in stages 1 and 2, with the highest quartile associated with a 42% (HR = 0.58; 95% CI 0.50-0.66) and 33% (HR = 0.67; 95% CI 0.61-0.73) lower risk, respectively. Overall, LPA and MVPA exhibited nonlinear L-shaped relationships across stages 0-3, with overall inflection points at 2,357 (95% CI: 2335-2379) min/week for LPA and 213 (95% CI: 207-219) min/week for MVPA. Specifically, MVPA in stage 3 population exhibited a U-shaped CVD risk curve, increasing beyond 460 (95%CI: 449-472) min/week. In the general population at stages 0-3, when LPA exceeded 2,551 min/week, third-quartile MVPA was associated with a similarly lower risk as the fourth quartile. Substituting MVPA for LPA was associated with further lower risk in stages 1 and 2, while these inverse associations plateaued or declined after reaching 350 min/week in stage 0 and 300 min/week in stage 3, respectively.
CONCLUSION: Associations between physical activity and incident CVD differ across CKM stages 0-3. These stage-specific differences for LPA and MVPA warrant further validation to inform future guidelines.
PMID:42601879 | PMC:PMC13472813 | DOI:10.3389/fendo.2026.1844167