Cardiac stress and inflammatory markers as predictors of heart failure in patients with type 2 diabetes: the ADVANCE trial

Objective: This study examined the individual and combined impact of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hs-CRP) on the prediction of heart failure incidence or progression in patients with type 2 diabetes. Research Design and Methods: A nested case-cohort study was conducted in 3,098 participants with type 2 diabetes in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Results: A higher value of each biomarker was significantly associated with a higher risk of heart failure incidence or progression, after adjustment for major risk factors. The hazard ratios per 1-SD increase were 3.06 (95% CI 2.37-3.96) for NT-proBNP, 1.50 (1.27-1.77) for hs-cTnT, 1.48 (1.27-1.72) for IL-6, and 1.32 (1.12-1.55) for hs-CRP. Addition of NT-proBNP to the model including conventional risk factors meaningfully improved 5-year risk predictive performance (c-statistic 0.8162 to 0.8800; continuous net reclassification improvement [NRI] 73.1%; categorical NRI [<5%, 5-10%, >10% 5-year risk] 24.2%). In contrast, addition of hs-cTnT, IL-6 or hs-CRP did not improve the prediction metrics consistently either in combination or when added to NT-proBNP. Conclusions: Only NT-proBNP, strongly and consistently improved prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers