TY - JOUR
T1 - Cardiovascular outcomes according to urinary albumin and kidney disease in patients with type 2 diabetes at high cardiovascular risk
T2 - Observations from the SAVOR-TIMI 53 Trial
AU - Scirica, Benjamin M.
AU - Mosenzon, Ofri
AU - Bhatt, Deepak L.
AU - Udell, Jacob A.
AU - Steg, Ph Gabriel
AU - McGuire, Darren K
AU - Im, Kyungah
AU - Kanevsky, Estella
AU - Stahre, Christina
AU - Sjöstrand, Mikaela
AU - Raz, Itamar
AU - Braunwald, Eugene
N1 - Publisher Copyright:
© 2017 American Medical Association. All rights reserved.
PY - 2018/2
Y1 - 2018/2
N2 - IMPORTANCE An elevated level of urinary albumin to creatinine ratio (UACR) is a marker of renal dysfunction and predictor of kidney failure/death in patients with type 2 diabetes. The prognostic use of UACR in established cardiac biomarkers is not well described. OBJECTIVE To evaluate whether UACR offers incremental prognostic benefit beyond risk factors and established plasma cardiovascular biomarkers. DESIGN, SETTING, AND PARTICIPANTS The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 study was performed from May 2010 toMay 2013 and evaluated the safety of saxagliptin vs placebo in patients with type 2 diabetes with overt cardiovascular disease or multiple risk factors. Median follow-up was 2.1 years (interquartile range, 1.8-2.3 years). INTERVENTIONS Patients were randomized to saxagliptin vs placebo plus standard care. MAIN OUTCOMES AND MEASURES Baseline UACRwas measured in 15 760 patients (95.6%of the trial population) and categorized into thresholds. RESULTS Of 15 760 patients, 5205 were female (33.0%). The distribution of UARC categories were: 5805 patients (36.8%) less than 10mg/g, 3891 patients (24.7%) at 10 to 30mg/g, 4426 patients (28.1%) at 30 to 300mg/g, and 1638 patients (10.4%) at more than 300mg/g. When evaluated without cardiac biomarkers, there was a stepwise increase with each higher UACR category in the incidence of the primary composite end point (cardiovascular death, myocardial infarction, or ischemic stroke) (3.9%, 6.9%, 9.2%, and 14.3%); cardiovascular death (1.4%, 2.6%, 4.1%, and 6.9%); and hospitalization for heart failure (1.5%, 2.5%, 4.0%, and 8.3%) (adjusted P < .001 for trend). The net reclassification improvement at the event rate for each end point was 0.081 (95%CI, 0.025 to 0.161), 0.129 (95%CI, 0.029 to 0.202), and 0.056 (95%CI, -0.005 to 0.141), respectively. The stepwise increased cardiovascular risk associated with a UACR of more than 10mg/g was also present within each chronic kidney disease category. The UACR was associated with outcomes after including cardiac biomarkers. However, the improvement in discrimination and reclassification was attenuated; net reclassification improvement at the event rate was 0.022 (95%CI, -0.022 to 0.067), -0.008 (-0.034 to 0.053), and 0.043 (-0.030 to 0.052) for the primary end point, cardiovascular death, and hospitalization for heart failure, respectively. CONCLUSIONS AND RELEVANCE In patients with type 2 diabetes, UACR was independently associated with increased risk for a spectrum of adverse cardiovascular outcomes. However, the incremental cardiovascular prognostic value of UACR was minimal when evaluated together with contemporary cardiac biomarkers. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01107886.
AB - IMPORTANCE An elevated level of urinary albumin to creatinine ratio (UACR) is a marker of renal dysfunction and predictor of kidney failure/death in patients with type 2 diabetes. The prognostic use of UACR in established cardiac biomarkers is not well described. OBJECTIVE To evaluate whether UACR offers incremental prognostic benefit beyond risk factors and established plasma cardiovascular biomarkers. DESIGN, SETTING, AND PARTICIPANTS The Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus-Thrombolysis in Myocardial Infarction (SAVOR-TIMI) 53 study was performed from May 2010 toMay 2013 and evaluated the safety of saxagliptin vs placebo in patients with type 2 diabetes with overt cardiovascular disease or multiple risk factors. Median follow-up was 2.1 years (interquartile range, 1.8-2.3 years). INTERVENTIONS Patients were randomized to saxagliptin vs placebo plus standard care. MAIN OUTCOMES AND MEASURES Baseline UACRwas measured in 15 760 patients (95.6%of the trial population) and categorized into thresholds. RESULTS Of 15 760 patients, 5205 were female (33.0%). The distribution of UARC categories were: 5805 patients (36.8%) less than 10mg/g, 3891 patients (24.7%) at 10 to 30mg/g, 4426 patients (28.1%) at 30 to 300mg/g, and 1638 patients (10.4%) at more than 300mg/g. When evaluated without cardiac biomarkers, there was a stepwise increase with each higher UACR category in the incidence of the primary composite end point (cardiovascular death, myocardial infarction, or ischemic stroke) (3.9%, 6.9%, 9.2%, and 14.3%); cardiovascular death (1.4%, 2.6%, 4.1%, and 6.9%); and hospitalization for heart failure (1.5%, 2.5%, 4.0%, and 8.3%) (adjusted P < .001 for trend). The net reclassification improvement at the event rate for each end point was 0.081 (95%CI, 0.025 to 0.161), 0.129 (95%CI, 0.029 to 0.202), and 0.056 (95%CI, -0.005 to 0.141), respectively. The stepwise increased cardiovascular risk associated with a UACR of more than 10mg/g was also present within each chronic kidney disease category. The UACR was associated with outcomes after including cardiac biomarkers. However, the improvement in discrimination and reclassification was attenuated; net reclassification improvement at the event rate was 0.022 (95%CI, -0.022 to 0.067), -0.008 (-0.034 to 0.053), and 0.043 (-0.030 to 0.052) for the primary end point, cardiovascular death, and hospitalization for heart failure, respectively. CONCLUSIONS AND RELEVANCE In patients with type 2 diabetes, UACR was independently associated with increased risk for a spectrum of adverse cardiovascular outcomes. However, the incremental cardiovascular prognostic value of UACR was minimal when evaluated together with contemporary cardiac biomarkers. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01107886.
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U2 - 10.1001/jamacardio.2017.4228
DO - 10.1001/jamacardio.2017.4228
M3 - Article
C2 - 29214305
AN - SCOPUS:85043519644
SN - 2380-6583
VL - 3
SP - 155
EP - 163
JO - JAMA Cardiology
JF - JAMA Cardiology
IS - 2
ER -