Abstract
BACKGROUND: Cancer-associated signaling pathways, particularly the ALK/LTK receptor tyrosine kinases and their ligand ALKAL2, have recently been implicated in chronic inflammation and myocardial remodeling. However, the relationship between ALKAL2 and coronary artery disease (CAD) pathogenesis in type 2 diabetes mellitus (T2DM) remains undefined. METHODS: From January 2019 to December 2020, patients with type 2 diabetes mellitus (T2DM) undergoing coronary angiography were consecutively enrolled at Ruijin Hospital. Plasma ALKAL2 levels were measured using an ELISA assay. The association between ALKAL2 and CAD severity was assessed by Spearman correlation analysis. Logistic regression models were used to measure the association between ALKAL2 and CAD risk. RESULTS: 275 T2DM patients with CAD and 275 age- and sex-matched T2DM patients without CAD were included in the final analysis. Plasma ALKAL2 levels were increased in T2DM patients with CAD (0.25 [0.21, 0.37] ng/mL, median [IQR] vs. 0.18 [0.14, 0.24]ng/mL) (p < 0.001) and were positively associated with CAD severity (Spearman rho = 0.53, p < 0.001). Multivariate analysis revealed that plasma ALKAL2 levels were independently associated with the incidence of CAD after adjusting for LDL-C, hsCRP, and other traditional risk factors (OR, 2.24 [95% CI, 1.79-2.85]; p < 0.001). CONCLUSIONS: Elevated plasma ALKAL2 levels are an independent risk factor for T2DM CAD and are associated with the severity of CAD.