Baseline Physical Activity Guideline Attainment and Mortality Across Cardiovascular-Kidney-Metabolic Syndrome Stages
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Background
The 2023 American Heart Association cardiovascular-kidney-metabolic (CKM) staging framework supports risk stratification, but evidence on guideline-level physical activity across stages remains limited.
Methods
We emulated a target-trial protocol using NHANES 2007-2018 and National Death Index linkage through December 31, 2019. Adults aged 20 to 79 years with CKM stages 1 to 4, estimated glomerular filtration rate of at least 15 mL/min/1.73 m 2 , complete activity data, no cancer history, and eligible follow-up were included. Baseline activity was classified as meeting or not meeting the guideline. Within-stage propensity-score weights were used in weighted Cox models. All-cause and cardiovascular mortality were the primary and secondary outcomes; 5-year risks used weighted survival curves, with competing-risk cumulative incidence also estimated for cardiovascular mortality.
Results
Among 19,654 participants, 1,190 all-cause deaths occurred during 134,037 person-years. Baseline attainment was associated with lower all-cause mortality overall (HR, 0.774; 95% CI, 0.675-0.888). Stage-specific HRs were 1.030, 0.803, 0.642, and 0.727 for stages 1 to 4, respectively; estimates were nonmonotonic. Five-year risk differences were +0.040, -0.830, -1.790, and -3.840 percentage points; only the stage 4 interval excluded the null. Cardiovascular mortality showed a similar overall cause-specific association (HR, 0.707; 95% CI, 0.547-0.914).
Conclusions
Observed baseline guideline attainment was associated with mortality in this observational target-trial emulation. The findings are consistent with current physical activity recommendations but do not estimate the effect of an activity-promotion intervention; prospective trials are needed to establish clinical benefit.
Research Perspective
What Is New?
In a nationally representative US sample, observed baseline attainment of the physical activity guideline was associated with lower all-cause mortality overall, while stage-specific relative associations were nonmonotonic and five-year absolute differences were imprecise except at CKM stage 4.
What Question Should Be Addressed Next?
Future research should determine whether these stage-specific observational patterns are reproducible across populations and should use prospective intervention designs to investigate the mechanisms and potential clinical relevance of activity associations across CKM stages.
