TY - JOUR
T1 - Cardiac stress and inflammatory markers as predictors of heart failure in patients with type 2 diabetes
T2 - The ADVANCE trial
AU - Ohkuma, Toshiaki
AU - Jun, Min
AU - Woodward, Mark
AU - Zoungas, Sophia
AU - Cooper, Mark E.
AU - Grobbee, Diederick E.
AU - Hamet, Pavel
AU - Mancia, Giuseppe
AU - Williams, Bryan
AU - Welsh, Paul
AU - Sattar, Naveed
AU - Shaw, Jonathan E.
AU - Rahimi, Kazem
AU - Chalmers, John
N1 - Funding Information:
Funding. The ADVANCE trial was funded by a grant from the National Health and Medical Research Council of Australia. T.O. holds the Japan Society for the Promotion of Science Postdoctoral Fellowships for Research Abroad. M.J. is supported by an early career fellowship from theNationalHealth and Medical Research Council of Australia. M.W. is a Principal Research Fellow (1080206), S.Z. is a Senior Research Fellow (1081328), and J.E.S. is a Senior Research Fellow (1079438) of the National Health and Medical Research Council of Australia. Duality of Interest. M.W. reports consultancy fees from Amgen. S.Z. reports past participation in advisory boards and/or receiving honoraria from Amgen Australia, AstraZeneca/Bristol-Myers Squibb Australia, Janssen-Cilag, Merck Sharp & Dohme (Australia), Novartis Australia, Sanofi, Servier Laboratories, and Takeda Australia. M.E.C. has received lecturing fees from Servier. P.H. reports being a consultant to Servier. G.M. reports personal fees from Servier, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Novartis, Menarini International, Recordati, and Takeda. B.W. reports personal fees from Servier, Novartis, Boehringer Ingelheim, and Merck Sharp & Dohme. J.E.S. reports past participation in advisory boards and/or receiving honoraria from AstraZeneca, Janssen-Cilag, Merck Sharp & Dohme (Australia), Novartis Australia, Sanofi, and Mylan. J.C. reports grants from Servier, administered through the University of Sydney as Co-Principal Investigator for ADVANCE and the ADVANCE Post-Trial Observational Study (ADVANCE-ON), and personal fees from Servier. No other potential conflicts of interest relevant to this article were reported. Author Contributions. T.O. conducted statistical analysis. T.O., M.J., M.W., and J.C. contributed to the concept and rationale for the study and interpretation of the results and drafted the manuscript.S.Z.,M.E.C.,D.E.G.,P.H.,G.M.,B.W., P.W., N.S., J.E.S., and K.R. contributed to the discussion and reviewed and edited the manuscript. J.C. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Publisher Copyright:
© 2017 by the American Diabetes Association.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - OBJECTIVE This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and 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 studywas 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. The addition of NT-proBNP to the model including conventional risk factorsmeaningfully 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, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP. CONCLUSIONS Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers.
AB - OBJECTIVE This study examined the individual and combined effect of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), interleukin-6 (IL-6), and 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 studywas 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. The addition of NT-proBNP to the model including conventional risk factorsmeaningfully 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, the addition of hs-cTnT, IL-6, or hs-CRP did not improve the prediction metrics consistently in combination or when added to NT-proBNP. CONCLUSIONS Only NT-proBNP strongly and consistently improved the prediction of heart failure in patients with type 2 diabetes beyond a wide range of clinical risk factors and biomarkers.
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U2 - 10.2337/dc17-0509
DO - 10.2337/dc17-0509
M3 - Article
C2 - 28684396
AN - SCOPUS:85028081661
SN - 1935-5548
VL - 40
SP - 1203
EP - 1209
JO - Diabetes Care
JF - Diabetes Care
IS - 9
ER -
