Abstract Body (Do not enter title and authors here): Introduction: Aging is strongly associated with increased vascular inflammation, particularly in individuals over 65. Given that the development of coronary artery disease (CAD) is positively correlated with age-related inflammation, the precise distribution of myeloid subsets across different ages and CAD severity remains unclear. Objective: To investigate the influence of aging on myeloid heterogeneity using peripheral blood samples from the Coronary Assessment in Virginia (CAVA) cohort. Methods: PBMC samples from CAVA subjects (older ≥65, younger ≤64) were analyzed using AbSeq-based high-dimensional analysis. The Gensini score assessed CAD severity (high_CAD >32, low_CAD ≤ 6). Our analysis included 61 subjects in total, 33 older (18 high_CAD) and 28 younger (14 high_CAD). We examined age-wise associations across myeloid subsets. Results: We identified six major myeloid clusters: classical monocytes (cMo), intermediate monocytes (iMo), non-classical monocytes (nMo), plasmacytoid dendritic cells (pDC), conventional dendritic cells (cDC), and DC3. In all major clusters identified, the proportion of cMos (>75%) was consistently higher across all age groups. Although no significant differences were noted in frequencies of major myeloid populations with age, further analysis revealed significant age-related changes in subclusters. A notable decrease was observed in the cMo_CD33^hiCD9^hi (p=0.043) subsets in older individuals. Ingenuity Pathway Analysis of genes associated with this cluster indicated activation of IL-4, and IL-13 signaling pathways. In older subjects with high_CAD, significant decreases were identified in two specific CXCR3⁺ subsets, cMo_CD14^loCD33^loCXCR3⁺ (p=0.0001) and cMo_CCR6⁺CXCR3⁺ (p=0.006) compared to those with low_CAD. Gensini correlation analysis in the older population also revealed a significant negative association with two cMo_CXCR3⁺ subsets. Within myeloid-specific genes in the older population, positive correlations with Gensini scores were observed for Ctsa, Flt3, Ncf1, Cd38, and C1Qb. Conversely, Nr4a1, Cxcl1, Cxcl2, Cxcl8, Cd83, and Dusp2 showed negative correlations. We observed an increase in cMo_TLR4^lo (p=0.02) and a decrease in cMo_CD33^hiCD9^hi (p=0.006) in younger populations with high_CAD compared to low_CAD. Conclusion: Our finding highlights age-related changes in myeloid populations and their association with increased cardiovascular risk, suggesting potential targets for therapeutic intervention.