PMID- 30477800 OWN - NLM STAT- MEDLINE DCOM- 20191105 LR - 20191105 IS - 1879-1913 (Electronic) IS - 0002-9149 (Linking) VI - 123 IP - 3 DP - 2019 Feb 1 TI - Relation of Serum and Urine Renal Biomarkers to Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus and Recent Acute Coronary Syndromes (From the EXAMINE Trial). PG - 382-391 LID - S0002-9149(18)32050-2 [pii] LID - 10.1016/j.amjcard.2018.10.035 [doi] AB - A deeper understanding of the interplay between the renal axis and cardiovascular (CV) disease is needed in type 2 diabetes mellitus (T2DM). We aimed to explore the prognostic value of a comprehensive panel of renal biomarkers in patients with T2DM at high CV risk. We evaluated the prognostic performance of both serum (Cystatin C) and urine renal biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1 protein, and indices of urinary protein excretion) in 5,380 patients with T2DM and recent acute coronary syndromes in the EXAMINE trial. Patients requiring dialysis within 14 days were excluded. Single- and multimarker covariate-adjusted Cox proportional hazards models were developed to predict times to events. Primary endpoint was composite nonfatal myocardial infarction, nonfatal stroke, or CV death. Median age was 61 years, 68% were men, and mean baseline estimated glomerular filtration rate (eGFR) was 74 mL/min/1.73 m(2). During median follow-up of 18 months, 621 (11.5%) experienced the primary endpoint and 326 (6.1%) patients had died. All renal biomarkers were robustly associated with adverse CV events in step-wise fashion, independent of baseline eGFR. However, in the multimarker prediction model, only Cystatin C (per 1 SD) was associated with the primary endpoint (hazard ratio [HR] 1.28 [1.14 to 1.45]; p 0.05). In conclusion, serum and urine renal biomarkers, when tested alone, independently predict long-term adverse CV events in high-risk patients with T2DM. In an integrative panel of renal biomarkers, only serum Cystatin C remained independently associated with subsequent CV risk. Renal biomarkers informing various aspects of kidney function may further our understanding of the complex interplay between diabetic kidney disease and CV disease. CI - Copyright (c) 2018. Published by Elsevier Inc. FAU - Vaduganathan, Muthiah AU - Vaduganathan M AD - Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: muthu@md.northwestern.edu. FAU - White, William B AU - White WB AD - Calhoun Cardiology Center, University of Connecticut School of Medicine, Farmington, Connecticut. FAU - Charytan, David M AU - Charytan DM AD - Brigham and Women's Hospital, Boston, Massachusetts; Baim Institute for Clinical Research, Boston, Massachusetts. FAU - Morrow, David A AU - Morrow DA AD - Brigham and Women's Hospital, Boston, Massachusetts. FAU - Liu, Yuyin AU - Liu Y AD - Baim Institute for Clinical Research, Boston, Massachusetts. FAU - Zannad, Faiez AU - Zannad F AD - INSERM Unite 9501, Universite de Lorraine and Centre Hospitalier Universitaire, Nancy, France. FAU - Cannon, Christopher P AU - Cannon CP AD - Brigham and Women's Hospital, Boston, Massachusetts; Baim Institute for Clinical Research, Boston, Massachusetts. FAU - Bakris, George L AU - Bakris GL AD - Department of Medicine and ASH Comprehensive Hypertension Center University of Chicago, The University of Chicago School of Medicine, Chicago, Illinois. CN - EXAMINE Investigators LA - eng PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20181106 PL - United States TA - Am J Cardiol JT - The American journal of cardiology JID - 0207277 RN - 0 (Biomarkers) RN - 0 (Cystatin C) RN - 0 (HAVCR1 protein, human) RN - 0 (Hepatitis A Virus Cellular Receptor 1) RN - 0 (Lipocalin-2) SB - IM MH - Acute Coronary Syndrome/*epidemiology MH - Biomarkers/analysis MH - Cystatin C/analysis MH - Diabetes Mellitus, Type 2/*epidemiology MH - Female MH - Glomerular Filtration Rate MH - Heart Failure/*epidemiology MH - Hepatitis A Virus Cellular Receptor 1/analysis MH - Hospitalization/*statistics & numerical data MH - Humans MH - Lipocalin-2/analysis MH - Male MH - Middle Aged MH - Myocardial Infarction/*epidemiology MH - Prognosis MH - Proportional Hazards Models MH - Risk Assessment MH - Stroke/*epidemiology EDAT- 2018/11/28 06:00 MHDA- 2019/11/07 06:00 CRDT- 2018/11/28 06:00 PHST- 2018/08/13 00:00 [received] PHST- 2018/10/21 00:00 [revised] PHST- 2018/10/25 00:00 [accepted] PHST- 2018/11/28 06:00 [pubmed] PHST- 2019/11/07 06:00 [medline] PHST- 2018/11/28 06:00 [entrez] AID - S0002-9149(18)32050-2 [pii] AID - 10.1016/j.amjcard.2018.10.035 [doi] PST - ppublish SO - Am J Cardiol. 2019 Feb 1;123(3):382-391. doi: 10.1016/j.amjcard.2018.10.035. Epub 2018 Nov 6.