Association between onset age and mortality gradients in advanced cardiovascular-kidney-metabolic syndrome

Advanced cardiovascular-kidney-metabolic (A-CKM) syndrome portends severe prognosis, but how onset age affects mortality risk remains unquantified.

This study analyzed 179,328 participants from the Kailuan cohort in Tangshan, China (2006-2022). Using weighted Cox models and stratified analyses, we assessed the association of age at onset with all-cause mortality risk.

Among 17,283 incident A-CKM cases matched to age-stratified controls, early-onset patients (<45 y) had the highest relative mortality risk (HR = 3.35), which was amplified by smoking (HR = 5.27) and inflammation (hsCRP≥3mg/L: HR = 10.15); midlife onset (45- 54 y) represented the optimal prevention window (NNT = 15), yet with extreme female vulnerability (Stage 4 HR=14.25 vs. male HR=2.54); late-adulthood onset (55-64y) incurred peak absolute burden (ΔRate +8.61/1000PY), while elderly cases (≥65 y) had an attenuated attributable impact despite higher mortality (33.95 vs. 2.48/1000 PY).

These findings support an age-stratified management framework: core age phased priorities (risk containment <45 y, preventive interception 45 - 54 y, complication management 55 - 64 y, and renoprotective optimization ≥65 y) augmented by sex-specific refinements-aggressive inflammation control in young men and intensified midlife monitoring for women-resolving the efficiency-burden paradox through calibrated implementation.

https://www.chictr.org.cn/showproj.html?proj=8050, identifier ChiCTR-TNRC-11001489.