Associations of Cardiovascular-Kidney-Metabolic Syndrome With Age-Related Macular Degeneration Risk

No study has explored the longitudinal association between cardiovascular-kidney-metabolic (CKM) syndrome and age-related macular degeneration (AMD). We aimed to investigate the associations between CKM syndrome, genetic predisposition, and AMD risk.

Retrospective cohort study.

A total of 319,638 participants from the UK Biobank who did not have AMD at baseline.

CKM syndrome was diagnosed based on the presence of chronic kidney disease, cardiovascular disease, and metabolic risk factors. We categorized participants into stages 0 to 4 according to their CKM syndrome status. A genetic risk score was used to estimate genetic predisposition to AMD. Cox proportional hazards regression models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident AMD.

AMD incidence.

During a median follow-up of 12.5 years, 4982 AMD cases were identified. After multivariable adjustment, the HRs (95% CIs) for AMD were 1.15 (1.02-1.30), 1.25 (1.13-1.38), 1.22 (1.08-1.38), and 1.48 (1.30-1.68) for participants in CKM stage 1, 2, 3, and 4, respectively, compared to those in CKM stage 0. No significant interaction between genetic predisposition and CKM syndrome was observed (P for interaction = .06). Joint analyses showed that compared to those with CKM stage 0 and low genetic predisposition, individuals with CKM stage 4 and high genetic predisposition exhibited the highest risk of AMD (HR = 2.67, 95% CI: 2.22-3.33).

Poor CKM health was positively associated with AMD risk, independent of genetic predisposition.