20-LB: Impact of Optimal Medical Therapy, Insulin Sensitization, and Revascularization Strategies on Soluble Urokinase Plasminogen Activator Receptor and Its Association with Cardiovascular Outcomes—A BARI-2D Ancillary Study

Chronic inflammation is a hallmark of type 2 diabetes (T2D) and a driver of its complications. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived signaling glycoprotein involved in the pathogenesis of diabetes-related outcomes, notably atherosclerosis and nephropathy. We aimed to determine if optimal medical therapy, insulin sensitization, and revascularization strategy impact suPAR levels and modulate its association with outcomes. We leveraged the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI-2D) trial, a study of patients with T2D and coronary artery disease (CAD) who underwent either revascularization or optimized medical therapy, and were randomized to either insulin-sensitization or insulin-provision therapy. We measured plasma suPAR levels in 2316 patients at baseline and 1-year follow-up and examined the association between suPAR and major adverse cardiovascular events (MACE). The median suPAR level at baseline was 3.02 ng/ml (IQR 2.32-3.95) and 3.15 ng/ml (2.4-4.2) at 1-year. SuPAR levels were notably higher in patients who underwent CABG (2.94 vs 2.70, p<0.001), but were unchanged post-PCI, insulin sensitization or insulin provisioning at 1 year. In multivariable analyses, baseline and 1-years suPAR levels were predictive of MACE, without difference in the strengths of the association between the two time points (HR of 2.18 (95%CI[1.57-3.03]) at baseline and 2.13 (95%CI[1.45-3.13]) at follow-up for the 3rd tertile compared to the first. Our findings suggest that inflammation as measured by suPAR is not reduced by revascularization or T2D treatment strategy, and likely accounts for the residual CV risk in patients with T2D. The advent of anti-suPAR therapies may offer new promise for patients with T2D and co-morbid CAD.