Associations of the TyG index with circulating endothelial progenitor cells and skin microvascular reactivity in hypertensive patients

Background Insulin resistance contributes to early vascular injury, and the triglyceride–glucose (TyG) index has emerged as a practical surrogate associated with subclinical atherosclerosis and endothelial dysfunction. Circulating endothelial progenitor cells (cEPCs), microvascular reactivity assessed by post-occlusive reactive hyperemia (PORH), and cholesterol efflux capacity (CEC) represent complementary markers of vascular repair, microvascular function, and HDL-related atheroprotection, yet their interrelationships in metabolic stress remain unclear. Purpose This study aimed to investigate the associations among the TyG index, cEPC levels, microvascular function, and CEC to better characterize early vascular impairment linked to insulin resistance. Methods This retrospective cohort study included 259 hypertensive patients with fasting glucose 70–125 mg/dL from a coronary angiography registry, in whom the triglyceride–glucose (TyG) index, circulating endothelial progenitor cells (cEPCs), skin microvascular reactivity by post-occlusive reactive hyperemia (PORH), and cholesterol efflux capacity (CEC) were systematically assessed. Baseline clinical data and laboratory measurements were collected, and cEPC levels were quantified by flow cytometry, while PORH and CEC were evaluated using standardized protocols. Associations between the TyG index and vascular biomarkers were analyzed using inverse probability weighting and multivariable regression models, with subgroup and mediation analyses performed to explore potential mechanisms. Results After inverse probability weighting, baseline characteristics were well balanced between groups stratified by the median triglyceride–glucose (TyG) index. A higher TyG index was associated with significantly lower levels of CD34⁺KDR⁺ and CD34⁺KDR⁺CD133⁺ circulating endothelial progenitor cells, reduced post-occlusive reactive hyperemia responses, and no significant differences in cholesterol efflux capacity. Multivariable weighted regression analyses demonstrated that each 1-SD increase in TyG was independently associated with lower EPC levels and impaired microvascular reactivity, with mediation analysis indicating that EPC depletion partially mediated the relationship between TyG and PORH. Conclusions In this retrospective analysis of hypertensive patients with fasting blood glucose ≤ 125 mg/dL, higher triglyceride–glucose (TyG) index values were associated with both lower cEPC counts and reduced PORH responses, indicating impaired endothelial repair capacity and microvascular function under metabolic stress. Mediation analysis further suggested that cEPCs depletion partially contributes to the adverse relationship between the TyG index and PORH. These findings, consistent across diabetes and CAD subgroups, support an early TyG–cEPC–microvascular mechanistic pathway relevant to cardiometabolic disease progression.