Yuhree Kim1, Kunihiro Matsushita2, Yingying Sang3, Morgan E Grams4, Hicham Skali5, Amil M Shah5, Ron C Hoogeveen6, Scott D Solomon5, Christie M Ballantyne6, Josef Coresh1. 1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. Electronic address: kmatsush@jhsph.edu. 3. Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD. 4. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Division of Nephrology, The Johns Hopkins University School of Medicine, Baltimore, MD. 5. Cardiovascular Division, Brigham and Women's Hospital, Boston, MA. 6. Department of Medicine, Baylor College of Medicine, Houston, TX; Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX.
Abstract
BACKGROUND: Epidemiologic data for cardiac abnormality predating decreased kidney function are sparse. We investigated the associations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with end-stage renal disease (ESRD) risk in a community-based cohort. STUDY DESIGN: A prospective cohort study. SETTING & PARTICIPANTS: 10,749 white and black participants at the fourth visit (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study with follow-up through 2010. PREDICTOR: hs-cTnT (3, 6, 9, and 14ng/L) and NT-proBNP (41.6, 81.0, 142.5, and 272.5pg/mL) levels were divided into 5 categories at the same percentiles (32th, 57th, 77th, and 91th; corresponding to ordinary thresholds of hs-cTnT), with the lowest category as a reference. OUTCOMES: Incident ESRD defined as initiation of dialysis therapy, transplantation, or death due to kidney disease. MEASUREMENTS: Relative risk and risk prediction of ESRD according to hs-cTnT and NT-proBNP levels based on Cox proportional hazards models. RESULTS: During a median follow-up of 13.1 years, 235 participants developed ESRD (1.8 cases/1,000 person-years). hs-cTnT and NT-proBNP levels were associated with ESRD risk independently of each other and of potential confounders, including kidney function and albuminuria (adjusted HRs for highest category, 4.43 [95% CI, 2.43-8.09] and 2.28 [95% CI, 1.44-3.60], respectively). For hs-cTnT level, the association was significant even at the third category (HR for 6-8ng/L of hs-cTnT, 2.74 [95% CI, 1.54-4.88]). Their associations were largely consistent even among persons without decreased kidney function or history of cardiovascular disease. hs-cTnT and NT-proBNP levels both significantly improved ESRD prediction (C statistic differences of 0.0084 [95% CI, 0.0005-0.0164] and 0.0045 [95% CI, 0.0004-0.0087], respectively, from 0.884 with conventional risk factors). LIMITATIONS: Relatively small number of ESRD cases and single measurement of hs-cTnT and NT-proBNP. CONCLUSIONS: hs-cTnT and NT-proBNP levels independently predicted ESRD risk in the general population, with more evident results for hs-cTnT. These results suggest the involvement of cardiac abnormality, particularly cardiac injury, in the progression of reduced kidney function and/or may reflect the useful property of hs-cTnT as an end-organ damage marker.
BACKGROUND: Epidemiologic data for cardiac abnormality predating decreased kidney function are sparse. We investigated the associations of high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with end-stage renal disease (ESRD) risk in a community-based cohort. STUDY DESIGN: A prospective cohort study. SETTING & PARTICIPANTS: 10,749 white and black participants at the fourth visit (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) Study with follow-up through 2010. PREDICTOR: hs-cTnT (3, 6, 9, and 14ng/L) and NT-proBNP (41.6, 81.0, 142.5, and 272.5pg/mL) levels were divided into 5 categories at the same percentiles (32th, 57th, 77th, and 91th; corresponding to ordinary thresholds of hs-cTnT), with the lowest category as a reference. OUTCOMES: Incident ESRD defined as initiation of dialysis therapy, transplantation, or death due to kidney disease. MEASUREMENTS: Relative risk and risk prediction of ESRD according to hs-cTnT and NT-proBNP levels based on Cox proportional hazards models. RESULTS: During a median follow-up of 13.1 years, 235 participants developed ESRD (1.8 cases/1,000 person-years). hs-cTnT and NT-proBNP levels were associated with ESRD risk independently of each other and of potential confounders, including kidney function and albuminuria (adjusted HRs for highest category, 4.43 [95% CI, 2.43-8.09] and 2.28 [95% CI, 1.44-3.60], respectively). For hs-cTnT level, the association was significant even at the third category (HR for 6-8ng/L of hs-cTnT, 2.74 [95% CI, 1.54-4.88]). Their associations were largely consistent even among persons without decreased kidney function or history of cardiovascular disease. hs-cTnT and NT-proBNP levels both significantly improved ESRD prediction (C statistic differences of 0.0084 [95% CI, 0.0005-0.0164] and 0.0045 [95% CI, 0.0004-0.0087], respectively, from 0.884 with conventional risk factors). LIMITATIONS: Relatively small number of ESRD cases and single measurement of hs-cTnT and NT-proBNP. CONCLUSIONS:hs-cTnT and NT-proBNP levels independently predicted ESRD risk in the general population, with more evident results for hs-cTnT. These results suggest the involvement of cardiac abnormality, particularly cardiac injury, in the progression of reduced kidney function and/or may reflect the useful property of hs-cTnT as an end-organ damage marker.
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