Predicting Mortality in African Americans With Type 2 Diabetes Mellitus: Soluble Urokinase Plasminogen Activator Receptor, Coronary Artery Calcium, and High‐Sensitivity C‐Reactive Protein

Abstract

Background Type 2 diabetes mellitus is a major risk factor for cardiovascular disease; however, outcomes in individual patients vary. Soluble urokinase plasminogen activator receptor (su PAR ) is a bone marrow–derived signaling molecule associated with adverse cardiovascular and renal outcomes in many populations. We characterized the determinants of su PAR in African Americans with type 2 diabetes mellitus and assessed whether levels were useful for predicting mortality beyond clinical characteristics, coronary artery calcium ( CAC ), and high‐sensitivity C‐reactive protein (hs‐ CRP ). Methods and Results We measured plasma su PAR levels in 500 African Americans with type 2 diabetes mellitus enrolled in the African American‐Diabetes Heart Study. We used Kaplan‐Meier curves and Cox proportional hazards models adjusting for clinical characteristics, CAC , and hs‐ CRP to examine the association between su PAR and all‐cause mortality. Last, we report the change in C‐statistics comparing the additive values of su PAR , hs‐ CRP , and CAC to clinical models for prediction of mortality. The su PAR levels were independently associated with female sex, smoking, insulin use, decreased kidney function, albuminuria, and CAC . After a median 6.8‐year follow‐up, a total of 68 deaths (13.6%) were recorded. In a model incorporating su PAR , CAC , and hs‐ CRP , only su PAR was significantly associated with mortality (hazard ratio 2.66, 95% confidence interval 1.63‐4.34). Addition of su PAR to a baseline clinical model significantly improved the C‐statistic for all‐cause death (Δ0.05, 95% confidence interval 0.01‐0.10), whereas addition of CAC or hs‐ CRP did not. Conclusions In African Americans with type 2 diabetes mellitus, su PAR was strongly associated with mortality and improved risk discrimination metrics beyond traditional risk factors, CAC and hs‐ CRP . Studies addressing the clinical usefulness of measuring su PAR concentrations are warranted.