Abstract 10838: Impact of Diabetes on Soluble Fms-Like Tyrosine Kinase-1 and Cardiovascular Events in Patients with Suspected or Known Coronary Artery Disease: The EXCEED-J Study

Abstract

Background: Whether diabetes mellitus (DM) modifies the relationship between soluble fms-like tyrosine kinase-1 (sFlt-1), a vascular endothelial growth factor (VEGF) antagonist, and cardiovascular (CV) events in patients with suspected or known coronary artery disease (CAD) are unclear. Methods: Using data from a multicenter, prospective cohort of 3255 patients with suspected or known CAD undergoing elective coronary angiography, we assessed the impact of DM on the prognostic values of sFlt-1 and other biomarkers. Heparin-free fasting serum levels of sFlt-1, VEGF, placental growth factor, cystatin C, N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin-I (hs-cTnI), and high-sensitivity C-reactive protein (hs-CRP) were measured in 1281 DM and 1974 non-DM patients enrolled in the EXCEED-J study. The primary outcome was 3-point major adverse CV events (3P-MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. The secondary outcomes were all-cause death, CV death, and 5P-MACE defined as a composite of 3P-MACE, heart failure hospitalization, and coronary/peripheral artery revascularization. Results: After adjusting for potential clinical confounders, serum levels of sFlt-1, NT-proBNP, hs-cTnI and cystatin C, but not other biomarkers, were significantly associated with 3P-MACE in the entire cohort. These associations were still significant for sFlt-1, NT-proBNP, and hs-cTnI, but not for cystatin C, in non-DM patients. In contrast, NT-proBNP, hs-cTnI and cystatin C, but not sFlt-1, were significantly associated with 3P-MACE in DM patients. The sFlt-1 level was also significantly associated with all-cause death and CV death in the entire cohort and in non-DM patients, but not in DM patients. It was not significantly associated with 5P-MACE in the entire cohort, non-DM patients, or DM patients. Furthermore, sFlt-1 provided an incremental prognostic information for 3P-MACE and CV death to the model with potential clinical confounders in non-DM patients, but not in DM patients. Conclusions: Serum levels of sFlt-1 were independently associated with 3P-MACE and CV death in patients with suspected or known CAD. These associations were attenuated in DM patients.