title: Do cardiac biomarkers NT-proBNP and hsTnT predict microvascular events in patients with type 2 diabetes? Results from the ADVANCE trial.
abstract: OBJECTIVE
  We investigated microvascular event risk in people with type 2 diabetes and assessed whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT) improved prediction.
  
  
  METHODS
  We performed a case-cohort study, including 439 incident cases of microvascular events (new or worsening nephropathy or retinopathy) and 2,946 noncase subjects identified from participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. NT-proBNP and hsTnT were measured in stored plasma samples using automated commercial assays.
  
  
  RESULTS
  After adjustment for age, sex, and randomized treatment, the hazard ratios for microvascular events per 1-SD increase in the log-transformed hsTnT and NT-proBNP were 1.67 (95% CI 1.51-1.85) and 1.63 (1.44-1.84), respectively. After further adjustment for classical and diabetes-related cardiovascular disease risk factors, the hazard ratios attenuated to 1.40 (1.24-1.58) and 1.41 (1.24-1.60), respectively. While the C statistic did not improve on addition of hsTnT or NT-proBNP for the total microvascular end point, a combination of both markers improved the prediction of nephropathy (P = 0.033) but not retinopathy (P = 0.72). The corresponding net reclassification indices in a three-risk category model (<10%, 10-15%, and >15% 5-year risk) for all microvascular events were 7.31% (95% CI 2.24-12.79) for hsTNT addition, 6.23% (1.74-11.5) for NT-proBNP addition, and 7.1% (1.5-12.9) for both markers together.
  
  
  CONCLUSIONS
  These data suggest that cardiac biomarkers moderately improve microvascular event risk prediction, in particular the risk of nephropathy. Further studies examining the value of this approach for trial design and clinical use are warranted.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K.
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.affiliation: George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Graham S
authors.initials: GS
authors.lastname: Hillis
authors.affiliation: George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Service d'Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat-Claude Bernard, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.affiliation: Institute of Cardiovascular Sciences, University College London, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, U.K.
authors.forename: Bryan
authors.initials: B
authors.lastname: Williams
authors.affiliation: Department of Clinical Pharmacology, Imperial College London, London, U.K.
authors.forename: Neil
authors.initials: N
authors.lastname: Poulter
authors.affiliation: School of Mathematical Sciences, University of Technology, Sydney, Sydney, Australia.
authors.forename: Louise
authors.initials: L
authors.lastname: Ryan
authors.affiliation: University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harrap
authors.affiliation: George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: Ansuhka
authors.initials: A
authors.lastname: Patel
authors.affiliation: George Institute for Global Health, University of Sydney, Sydney, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K. naveed.sattar@glasgow.ac.uk.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D015994:Incidence; D007674:Kidney Diseases / Q000097:blood* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors; D014336:Troponin / Q000097:blood*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D014336:Troponin; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain