Abstract
Age-related macular degeneration (AMD) and cardiovascular disease (CVD) share numerous risk factors; however, protein biomarkers for AMD are lacking. We investigated whether circulating cardiovascular peptide biomarkers are associated with AMD in the population-based Białystok PLUS cohort. This cross-sectional analysis included 699 participants aged ≥ 50 years (AMD + = 93; AMD⁻ = 606) examined between 2018 and 2023. AMD was graded from fundus photos with the use of the Wisconsin and modified International Classification systems. Ninety-two cardiovascular proteins were quantified in serum with the Olink Target Cardiovascular III panel. Age-adjusted linear or logistic regressions assessed biomarker-AMD associations, and receiver-operating-characteristic (ROC) curves evaluated discriminative performance. After adjustment, AMD+ participants exhibited lower galectin-4 (β = - 0.15, p = 0.043) and TNF-receptor-superfamily-member-10 C (TNFRSF10C) (β = - 0.17, p = 0.037) concentrations and higher von Willebrand factor (vWF) levels (β = 0.22, p = 0.036) versus AMD⁻ individuals. Galectin-4, TNFRSF10C, and vWF predicted AMD with areas under the ROC curve of 0.613 (95% confidence interval [CI] 0.516-0.709), 0.606 (0.520-0.692), and 0.594 (0.500-0.687), respectively. Optimal cut-offs were 4.05 NPX for galectin-4, 5.09 NPX for TNFRSF10C, and 8.03 NPX for vWF, yielding sensitivities/specificities of 57%/63%, 58%/62% and 55%/63%, respectively. Elevated vWF and reduced galectin-4 and TNFRSF10C are independently associated with AMD, suggesting overlapping vascular, inflammatory and apoptotic pathways with CVD. Incorporation of these peptides into risk-stratification algorithms could enhance early AMD detection and motivate mechanistic studies targeting the TRAIL-TNFRSF10C axis and galectin-mediated signaling.