Abstract 12845: Renal Biomarkers Predict Long-Term Adverse Events in Patients With Type 2 Diabetes Mellitus and Recent Acute Coronary Syndrome: Insights From the EXAMINE Trial

Abstract

Introduction: Prediction of cardiovascular (CV) risk in patients with type 2 diabetes mellitus (T2DM) remains incomplete. Measurement of renal biomarkers may facilitate early risk stratification in high-risk patients with T2DM. Methods: We evaluated the prognostic performance of 4 urinary and 1 serum renal biomarkers for major cardiovascular events in 5,380 patients with T2DM and recent acute coronary syndrome (ACS, within 15-90d) enrolled in the EXAMINE trial. Patients requiring dialysis within 14d of screening were excluded. Cystatin C, markers of kidney injury, including neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule (KIM)-1 protein, and indices of urinary protein excretion were measured at randomization (a median of 45 days after ACS). CV events at 24-mo were estimated by the Kaplan-Meier method. Single- and multi-biomarker covariate-adjusted Cox proportional hazards models were created to predict times to events. Results: In EXAMINE, median age was 61y, 68% were male, and median baseline estimated glomerular filtration rate (eGFR) was 71.2 ml/min/1.73 m 2 . During follow-up, 326 (6.1%) patients had died. All renal biomarkers were robustly associated with long-term adverse CV events in graded fashion (P≤0.006 for all trends; Table ). Risk prediction for all 5 renal biomarkers was independent of major covariates including baseline eGFR for all major clinical endpoints ( Table ). However, when simultaneously accounting for all biomarkers, only Cystatin C (standardized) was predictive of all-cause mortality (HR 1.51 [1.30, 1.74]; p≤0.001), heart failure hospitalization (HR 1.20 [0.96, 1.49]; p=0.107), and major CV events (HR 1.28 [1.14, 1.45]; p≤0.001). Conclusions: These data from the EXAMINE trial represent one of the largest experiences to support the prognostic value of multiple novel and traditional renal biomarkers in predicting long-term adverse CV events in high-risk patients with T2DM, beyond baseline eGFR.