Do cardiac biomarkers NT-proBNP and hsTnT predict microvascular events in patients with type 2 diabetes? Results from the ADVANCE trial

Paul Welsh, Mark Woodward, Graham S. Hillis, Qiang Li, Michel Marre, Bryan Williams, Neil Poulter, Louise Ryan, Stephen Harrap, Ansuhka Patel, John Chalmers, Naveed Sattar

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


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. RESEARCH DESIGN AND 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 NTproBNP 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.

Original languageEnglish (US)
Pages (from-to)2202-2210
Number of pages9
JournalDiabetes care
Issue number8
StatePublished - Aug 2014
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing


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