TY - JOUR
T1 - Do cardiac biomarkers NT-proBNP and hsTnT predict microvascular events in patients with type 2 diabetes?
T2 - Results from the ADVANCE trial
AU - Welsh, Paul
AU - Woodward, Mark
AU - Hillis, Graham S.
AU - Li, Qiang
AU - Marre, Michel
AU - Williams, Bryan
AU - Poulter, Neil
AU - Ryan, Louise
AU - Harrap, Stephen
AU - Patel, Ansuhka
AU - Chalmers, John
AU - Sattar, Naveed
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - microvascular event risk
KW - type 2 diabetes
KW - cardiac biomarkers
UR - http://www.scopus.com/inward/record.url?scp=84904966103&partnerID=8YFLogxK
UR - http://purl.org/au-research/grants/NHMRC/211086
UR - http://purl.org/au-research/grants/NHMRC/358395
UR - http://purl.org/au-research/grants/NHMRC/571281
UR - http://purl.org/au-research/grants/NHMRC/632507
U2 - 10.2337/dc13-2625
DO - 10.2337/dc13-2625
M3 - Article
C2 - 24879844
AN - SCOPUS:84904966103
VL - 37
SP - 2202
EP - 2210
JO - Diabetes Care
JF - Diabetes Care
SN - 0149-5992
IS - 8
ER -