Toshiaki Ohkuma1, Min Jun1, Mark Woodward1,2,3, Sophia Zoungas1,4, Mark E Cooper5, Diederick E Grobbee6, Pavel Hamet7, Giuseppe Mancia8, Bryan Williams9, Paul Welsh10, Naveed Sattar10, Jonathan E Shaw11, Kazem Rahimi2, John Chalmers12. 1. The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia. 2. The George Institute for Global Health, University of Oxford, Oxford, U.K. 3. Department of Epidemiology, Johns Hopkins University, Baltimore, MD. 4. School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. 5. Diabetic Complications Division, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. 6. Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands. 7. Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada. 8. Instituto Auxologico Italiano, University of Milan-Bicocca, Milan, Italy. 9. Institute of Cardiovascular Sciences, University College London (UCL) and National Institute of Health Research UCL Hospitals Biomedical Research Centre, London, U.K. 10. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K. 11. Department of Clinical Diabetes and Epidemiology, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia. 12. The George Institute for Global Health, University of Sydney, Sydney, New South Wales, Australia chalmers@georgeinstitute.org.au.
Abstract
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 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. The 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, 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.
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 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. The 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, 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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