Advanced Cardiovascular-Kidney-Metabolic Syndrome Linked to Higher AMD Risk: Study
China: A large population-based study published in the American Journal of Ophthalmology has found that worsening cardiovascular-kidney-metabolic (CKM) syndrome is associated with a higher risk of developing age-related macular degeneration (AMD), independent of genetic susceptibility. The research was led by Fengyue Wu from the Department of Ophthalmology at Shengjing Hospital of China Medical University, Shenyang, China, and colleagues.
Although CKM syndrome—an integrated framework encompassing metabolic risk factors, chronic kidney disease, cardiovascular risk, and established cardiovascular disease—has been linked to systemic vascular damage, its long-term relationship with AMD has not previously been clarified. To address this gap, investigators conducted a retrospective cohort study using data from 319,638 UK Biobank participants who were free of AMD at enrollment between 2006 and 2010.
Participants, with a mean age of 56.3 years and 51.7% women, were categorized into CKM stages 0 through 4 based on adapted American Heart Association criteria. Stage 0 represented optimal cardiometabolic health, defined by normal body mass index and waist circumference without additional risk factors. Higher stages reflected increasing metabolic abnormalities, kidney dysfunction, cardiovascular risk, or established cardiovascular disease. Genetic susceptibility to AMD was estimated using a polygenic risk score, allowing researchers to classify individuals into low- or high-genetic-risk groups.
The following findings were reported:
- Over a median follow-up of 12.5 years, 4,982 participants (1.56%) developed age-related macular degeneration (AMD).
- The risk of AMD increased progressively with advancing CKM stage after adjustment for confounders.
- Compared with CKM stage 0, adjusted hazard ratios for AMD were 1.15 for stage 1, 1.25 for stage 2, 1.22 for stage 3, and 1.48 for stage 4.
- Each one-stage increase in CKM status was associated with an approximately 9% higher risk of AMD.
- CKM stage 4 was linked to a 48% increased risk of AMD compared with stage 0.
- A higher genetic risk score was independently associated with about a 70% increased risk of AMD.
- No significant interaction was observed between CKM stage and genetic predisposition.
- Participants with CKM stage 4 and high genetic predisposition had the highest risk of AMD, with a hazard ratio of 2.67 compared to those with CKM stage 0 and low genetic risk.
The findings highlight the broader systemic impact of cardiometabolic dysfunction on ocular health. While genetic background remains an important determinant of AMD, maintaining optimal cardiovascular, kidney, and metabolic health may play a meaningful role in reducing retinal disease risk.
The authors emphasize that routine identification and management of CKM syndrome could contribute not only to cardiovascular protection but also to preserving visual health, reinforcing the importance of integrated, preventive care strategies.
Reference:
Wu F, Xu K, Zhao Y, Wang W, Yang H, Li Y, Zheng G, Li Z, Xia Y, Liu Y, Wu H, Bai S. Associations of cardiovascular-kidney-metabolic syndrome with age-related macular degeneration risk. Am J Ophthalmol. 2026 Jan 23:S0002-9394(26)00030-9. doi: 10.1016/j.ajo.2026.01.023. Epub ahead of print. PMID: 41581636.
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