title: Natriuretic Peptide and High-Sensitivity Troponin for Cardiovascular Risk Prediction in Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study.
abstract: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in diabetes; yet, heterogeneity in CVD risk has been suggested in diabetes, providing a compelling rationale for improving diabetes risk stratification. We hypothesized that N-terminal prohormone brain natriuretic peptide (NTproBNP) and high-sensitivity troponin T may enhance CVD risk stratification beyond commonly used markers of risk and that CVD risk is heterogeneous in diabetes.
  
  
  
  Among 8,402 participants without prevalent CVD at visit 4 (1996-1998) of the Atherosclerosis Risk in Communities (ARIC) study there were 1,510 subjects with diabetes (mean age 63 years, 52% women, 31% African American, and 60% hypertensive).
  
  
  
  Over a median follow-up of 13.1 years, there were 540 incident fatal/nonfatal CVD events (coronary heart disease, heart failure, and stroke). Both troponin T ≥14 ng/L (hazard ratio [HR] 1.96 [95% CI 1.57-2.46]) and NTproBNP >125 pg/mL (1.61 [1.29-1.99]) were independent predictors of incident CVD events at multivariable Cox proportional hazard models. Addition of circulating cardiac biomarkers to traditional risk factors, abnormal electrocardiogram (ECG), and conventional markers of diabetes complications including retinopathy, nephropathy, and peripheral arterial disease significantly improved CVD risk prediction (net reclassification index 0.16 [95% CI 0.07-0.22]). Compared with individuals without diabetes, subjects with diabetes had 1.6-fold higher adjusted risk of incident CVD. However, participants with diabetes with normal cardiac biomarkers and no conventional complications/abnormal ECG (n = 725 [48%]) were at low risk (HR 1.12 [95% CI 0.95-1.31]), while those with abnormal cardiac biomarkers, alone (n = 186 [12%]) or in combination with conventional complications/abnormal ECG (n = 243 [16%]), were at greater risk (1.99 [1.59-2.50] and 2.80 [2.34-3.35], respectively).
  
  
  
  Abnormal levels of NTproBNP and troponin T may help to distinguish individuals with high diabetes risk from those with low diabetes risk, providing incremental risk prediction beyond commonly used markers of risk.
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA Cardiovascular Department, Azienda Ospedaliera Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Gori
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA Vanderbilt Heart and Vascular Institute, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Deepak K
authors.initials: DK
authors.lastname: Gupta
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Brian
authors.initials: B
authors.lastname: Claggett
authors.affiliation: Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore MD, and Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.affiliation: Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Folsom
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore, MD.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA NewYork-Presbyterian/Columbia University Medical Center, New York, NY.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Bello
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Amil
authors.initials: A
authors.lastname: Shah
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA.
authors.forename: Hicham
authors.initials: H
authors.lastname: Skali
authors.affiliation: Department of Pharmacy, University of Wisconsin School of Pharmacy, Madison, WI.
authors.forename: Orly
authors.initials: O
authors.lastname: Vardeny
authors.affiliation: National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD.
authors.forename: Hanyu
authors.initials: H
authors.lastname: Ni
authors.affiliation: Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX.
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.affiliation: Departments of Medicine and Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Brad C
authors.initials: BC
authors.lastname: Astor
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Klein
authors.affiliation: Section of Cardiology, Department of Medicine, Baylor College of Medicine, Houston, TX.
authors.forename: David
authors.initials: D
authors.lastname: Aguilar
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA ssolomon@rics.bwh.harvard.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Solomon
mesh_terms: D050197:Atherosclerosis / Q000097:blood* / Q000150:complications / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D048909:Diabetes Complications / Q000097:blood / Q000150:complications / Q000401:mortality*; D003920:Diabetes Mellitus / Q000097:blood / Q000401:mortality*; D004562:Electrocardiography; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000097:blood; D015994:Incidence; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D015995:Prevalence; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D020107:Troponin T / Q000097:blood*
chemical_list: D015415:Biomarkers; D020107:Troponin T; D020097:Natriuretic Peptide, Brain