This research investigates the relationship between biological age acceleration and the progression of cardiovascular-kidney-metabolic (CKM) syndrome. The study analyzed data from two significant cohorts: the UK Biobank, which included longitudinal data from 326,218 participants, and NHANES, which provided cross-sectional data from 5,228 adults.
The authors utilized two biological age measures, PhenoAge and KDMAge, which were calculated by regressing each measure on chronological age. This method allowed for the assessment of biological age acceleration as a residual value. The study modeled transitions in the UK Biobank using cause-specific Cox and competing-risk models and compared stages in NHANES using survey-weighted logistic regression.
Over a median follow-up of 13.48 years, the findings indicated that 2,567 participants progressed from stage 0/1 to stage 2/3, and 42,835 participants progressed from stage 1 or 2/3 to stage 4. The results showed that for each 1-SD increment in PhenoAge acceleration, there were significant associations with both transitions, with hazard ratios (HRs) of 1.234 (95% CI 1.189-1.281) and 1.208 (95% CI 1.197-1.218), respectively. Similarly, KDMAge acceleration was associated with HRs of 1.229 (95% CI 1.180-1.280) and 1.220 (95% CI 1.207-1.232), all with P-values less than 0.001.
In the NHANES cohort, PhenoAge acceleration was significantly associated with stages 1, 2/3, and 4 compared to stage 0, with corresponding odds ratios (ORs) of 1.154 (95% CI 1.107-1.202), 1.221 (95% CI 1.176-1.268), and 1.333 (95% CI 1.249-1.423), all with P-values less than 0.001. KDMAge acceleration also showed significant associations with ORs of 1.025 (95% CI 1.006-1.044; P = 0.012), 1.038 (95% CI 1.019-1.057; P < 0.001), and 1.041 (95% CI 1.011-1.073; P = 0.010).
Despite these findings, the authors noted that the comparability of KDMAge remains uncertain, and the incremental predictive and clinical utility of biological age acceleration has not been tested. The study concludes that biological age acceleration is associated with CKM progression and baseline burden, suggesting its potential as a complementary marker for assessing CKM risk.
What this study does not show
This study does not establish a causal relationship between biological age acceleration and CKM syndrome progression, nor does it confirm the clinical utility of these measures in practice.
Evidence scorecard
- Analytic validity: Established
- Clinical validity: Partial
- Clinical utility: Not established