Analysis of 148 participants in the Barilla Offspring Study revealed that specific gene expression patterns in peripheral blood mononuclear cells (PBMCs) correlate with carotid artery wall thickening over 18 years. Cross-sectional analyses at both time points showed enrichment of immune pathways including leukocyte activation and antigen presentation, while longitudinal signatures highlighted metabolic regulation and redox processes. Despite limited overlap at individual gene levels, functional pathways converged on shared immunometabolic mechanisms associated with vascular remodeling. This research advances our understanding of how systemic immune states contribute to cardiovascular aging. The ability to predict long-term arterial changes from blood-based molecular signatures could enable earlier identification of individuals at risk for cardiovascular disease, potentially decades before clinical symptoms appear. However, the study's single-center design and relatively modest sample size limit generalizability. The rank-based regression method that performed best represents a methodological advance for transcriptomic analysis. As a preprint awaiting peer review, these findings require validation in larger, more diverse populations before clinical translation. This work represents an incremental but meaningful step toward precision medicine approaches for cardiovascular risk prediction.