Retinal Arteriosclerosis in a Large Health Screening Cohort: Associations with Systemic Vascular Comorbidities and...

Background: Routine fundus photography is widely accessible; however, its utility in stratifying systemic vascular risk in asymptomatic, general populations remains understudied. We utilized a large-scale health screening cohort in South Korea to evaluate the clinical validity of the retinal arteriosclerosis index (RAI) in a generally healthy population. Methods: We conducted a cross-sectional study of 74,608 adults who underwent routine health screening (2003-2010) at a tertiary center. Retinal arteriosclerosis was graded (0-4) by masked readers with a modified Scheie classification; a higher eye grade was defined as a person-level grade. High-grade RAI was prespecified as ≥2. Associations with systemic conditions (hypertension, type 2 diabetes, hyperlipidemia, metabolic syndrome, cardiovascular disease, and stroke) were examined by using multivariable logistic regression adjusted for demographic, lifestyle, and laboratory covariates; moreover, analyses were stratified by age and sex. Results: High-grade RAI was present in 4.5% of the participants and increased with age. After adjustment, high-grade RAI was associated with hypertension (OR, 2.97; 95% CI, 2.73-3.23), diabetes mellitus (OR, 1.35; 95% CI, 1.22-1.50), cardiovascular disease (OR, 1.46; 95% CI, 1.25-1.71), metabolic syndrome (OR, 1.63; 95% CI, 1.49-1.78), and stroke (OR, 1.98; 95% CI, 1.41-2.79) but not with hyperlipidemia. Sex-stratified analyses revealed broadly similar patterns, although high-grade RAI was associated with stroke in women and cardiovascular disease in men. Age-stratified analyses demonstrated consistent associations with hypertension, metabolic syndrome, and stroke across all age groups, with stronger effect sizes being observed in younger individuals. With respect to lifestyle factors, frequent alcohol consumption was associated with higher odds of high-grade RAI. Laboratory correlates included higher uric acid levels and lower red blood cell, albumin, and bilirubin levels (all p < 0.001). Conclusions: Fundus-defined arteriosclerotic changes were independently associated with multiple systemic vascular and metabolic conditions. An association with stroke in adults younger than 40 years of age was also observed, although this finding should be interpreted with caution given the cross-sectional design and limited number of events. These findings support the potential role of retinal vascular changes as cross-sectional correlates of systemic vascular health. Longitudinal studies are needed to clarify temporal relationships and causality.