Paul Welsh1, Mark Woodward2, Graham S Hillis2, Qiang Li2, Michel Marre3, Bryan Williams4, Neil Poulter5, Louise Ryan6, Stephen Harrap7, Ansuhka Patel2, John Chalmers2, Naveed Sattar8. 1. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K. 2. George Institute for Global Health, University of Sydney, Sydney, Australia. 3. Service d'Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat-Claude Bernard, Paris, France. 4. Institute of Cardiovascular Sciences, University College London, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre, London, U.K. 5. Department of Clinical Pharmacology, Imperial College London, London, U.K. 6. School of Mathematical Sciences, University of Technology, Sydney, Sydney, Australia. 7. University of Melbourne and Royal Melbourne Hospital, Melbourne, Australia. 8. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, U.K. naveed.sattar@glasgow.ac.uk.
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. 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 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.
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 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.
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