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
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 m2. 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.
Author Disclosures: M. Vaduganathan: None. W.B. White: Other; Modest; Takeda Development Center Americas, Inc. D.M. Charytan: Employment; Significant; Brigham & Women’s Hospital. Research Grant; Significant; Janssen, Medtronic. Expert Witness; Modest; Fresenius. Consultant/Advisory Board; Modest; Lilly/Boehringer Ingelheim, Medtronic. D.A. Morrow: Research Grant; Significant; Abbott Laboratories, Amgen, Inc.; AstraZeneca Pharmaceuticals LP; Daichii Sankyo, Inc.; Eisai Co., Ltd, GlaxoSmithKline; Johnson & Johnson Pharmaceutical Research & Development, L.L.C, Lilly; MedImmune, Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Roche Diagnostics. Consultant/Advisory Board; Modest; Abbott Laboratories, AstraZeneca, diaDexus, Gilead Sciences, Inc.; GlaxoSmithKline, Merck & Co., Inc, Novartis, Roche Diagnostics. Y. Liu: None. C. Wilson: Employment; Significant; Takeda Development Center Americas, Inc. S. Kupfer: Employment; Significant; Takeda Development Center Americas, Inc. F. Zannad: Research Grant; Modest; Roche Diagnostics. Other; Modest; Air Liquide, Bayer HealthCare, Biomérieux, Biotronik, Boston Scientific, CVRx, Janssen Pharmaceuticals, Inc., Novartis AG, Pfizer Inc., ResMed, Sanofi U.S., Servier, St. Jude Medical, , Takeda Development Center Americas, Inc., Mitsubishi, CardioRenal Diagnostics. C.P. Cannon: Research Grant; Significant; Arisaph, Astra Zeneca, Bristol-Myers Squibb (BMS), Boehringer-Ingelheim (BI), GlaxoSmithKline, Janssen, Merck, Takeda. Other; Modest; Alnylam, Amgen, Arisaph, BI, BI/Lilly, BMS, GlaxoSmithKline, Kowa, Merck, Takeda, Pfizer. Other; Significant; Lipimedix, Regeneron, Sanofi. G.L. Bakris: Research Grant; Modest; Bayer HealthCare, Medtronic, Inc., Relypsa, Inc., Takeda Development Center Americas, Inc., AbbVie Inc. Other; Modest; Boehringer Ingelheim GmbH, Janssen Pharmaceuticals, Inc., NxStage.
- © 2016 by American Heart Association, Inc.