Circulating SCGB3A2 Is Associated With Impaired Coronary Collateralization in Patients With Chronic Total Occlusion...

Type 2 diabetes mellitus (T2DM) is associated with impaired coronary collateralization in patients with chronic total occlusion (CTO), but circulating biomarkers reflecting defective collateral remodeling remain poorly defined.

Olink proteomic profiling was performed in a discovery cohort of 88 CTO patients with T2DM stratified by collateral status. Candidate proteins were prioritized using nominal differential expression and partial least squares-discriminant analyses. Secretoglobin family 3A member 2 (SCGB3A2) was selected for validation by ELISA in an independent cohort of 832 CTO patients (425 with T2DM and 407 without diabetes). Associations with collateralization and incremental predictive value beyond clinical risk factors were evaluated.

Among 265 proteins, eight showed nominal differential expression, with SCGB3A2 exhibiting the strongest signal and highest variable importance. In the T2DM cohort, serum SCGB3A2 levels were significantly higher in patients with poor collateralization and inversely correlated with Rentrop grades (both p < 0.001). SCGB3A2 remained independently associated with poor collateralization after multivariable adjustment (OR per 10 ng/mL increase, 1.63; 95% CI, 1.39-1.94; p < 0.001). Addition of SCGB3A2 to a clinical model improved discrimination with an increase in C-statistic from 0.73 to 0.78 and reclassification (NRI 0.62; IDI 0.08). Similar associations were observed in patients without diabetes.

Circulating SCGB3A2 is independently associated with impaired coronary collateralization in CTO patients. It may reflect biological processes underlying collateral failure and improve risk stratification, particularly in patients with T2DM.