Key result
Lower retinal vascular complexity is linked to higher cardiovascular risk via 8 inflammatory mediators.
Why the study?
Do genetic determinants of retinal vascular complexity and circulating proteins mediate the relationship between inflammation, cardiovascular disease risk, and lifespan?
Observational (n=74,434)
Yes
Do genetic determinants of retinal vascular complexity and circulating proteins mediate the relationship between inflammation, cardiovascular disease risk, and lifespan?
Mendelian randomization identifies specific inflammatory proteins, such as MMP12, that causally link vascular aging (measured by retinal fractal dimension) to increased cardiovascular risk and reduced lifespan.
With the increasing proportion of elderly individuals, understanding biological mechanisms of aging is critical. Retinal vascular complexity, measured as fractal dimension ( D f ) from fundus photographs, has emerged as a vascular aging indicator. We conducted a genome-wide association study of D f on 74,434 participants from the Canadian Longitudinal Study on Aging, Genetics of Diabetes Audit and Research in Tayside Scotland, and UK Biobank cohorts. We identified a novel locus near DAAM1 . We found negative genetic correlations between D f and cardiovascular disease, stroke, and inflammation but a positive correlation with life span. By combining the genetic determinants of 1159 circulating proteins from the Prospective Urban and Rural Epidemiological cohort with those of D f using Mendelian randomization, we identified eight causal mediators, including MMP12 and IgG–Fc receptor IIb, which link higher inflammation to lower D f , increased cardiovascular disease risk, and shorter life span. These results extend our understanding of the biological pathways underlying aging processes and inform targets to prevention and treatment.
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Villaplana-Velasco et al. (2025) conducted an observational in Aging and cardiovascular disease (n=74,434). Inflammaging biomarkers was evaluated on Cardiovascular disease, stroke, inflammation, and life span. A GWAS of 74,434 participants identified 8 causal mediators linking higher inflammation to lower retinal vascular complexity, increased cardiovascular disease risk, and shorter life span.
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