Estimated pulse wave velocity and CKM stage4 among middle-aged and older population: insights from 3 prospective cohorts

Cardiovascular-kidney-metabolic (CKM) stage 4 is an advanced systemic disorder with disproportionately high risks for adverse clinical outcomes, underscoring the need for accessible screening tools like estimated pulse wave velocity (ePWV) to predict its onset. To investigate the longitudinal association between baseline ePWV and incident CKM stage 4, this study analyzed harmonized data from 22,530 participants across three large-scale prospective aging cohorts-the US Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), and the China Health and Retirement Longitudinal Study (CHARLS)-using Kaplan-Meier survival curves, Cox proportional hazards regression models, and restricted cubic splines. The survival analysis revealed that higher baseline ePWV quartiles were significantly associated with a progressively lower probability of remaining CKM4-free across all three cohorts (p < 0.001). Furthermore, fully adjusted multivariable models confirmed that continuous ePWV is an independent, significant predictor of incident CKM4 (HRS: HR 1.373; ELSA: HR 1.397; CHARLS: HR 1.288; all p < 0.001), demonstrating a continuous, positive dose-response relationship, although this predictive association lost statistical significance among participants with pre-existing diabetes mellitus. Ultimately, elevated baseline ePWV independently and consistently predicts the risk of progressing to CKM stage 4 across diverse global populations, supporting its utility as a cost-effective, non-invasive screening tool to identify high-risk individuals for early clinical intervention.