First, we agree that the use of biomarkers is beneficial for early detection of heart failure and prevention of subsequent other cardiovascular diseases.
Second, we agree with the need for careful monitoring of the incidence of cardiovascular diseases other than heart failure, as heart failure is the second most common initial presentation of cardiovascular disease in patients with type 2 diabetes after peripheral arterial disease (3).
Third, we agree with the possible influence of glycemic control on the incidence of heart failure. As cited by Dr. Kawada, intensive glucose-lowering therapy significantly decreased the risk of a composite of major cardiovascular events including heart failure in the Veterans Affairs Diabetes Trial (VADT) (4). Although a later meta-analysis of randomized controlled trials including the VADT found that the intensive glucose-lowering treatment did not decrease the risk of heart failure (5), we included randomized blood pressure–lowering intervention as well as HbA1c as covariates, given the possible confounding of these factors.
Finally, we agree that electrocardiogram findings were important for the risk prediction of heart failure and thus included them in the model as covariates. However, as the primary objective of our paper was to examine the predictive ability of biomarkers for heart failure, we did not test the prognostic ability of the combination of electrocardiogram findings and biomarkers. We also agree that there is a possible adverse effect for heart failure of medication such as dipeptidyl peptidase 4 inhibitors used to treat type 2 diabetes. However, dipeptidyl peptidase 4 inhibitors were not on the market when the ADVANCE trial started.
Article Information
Funding. The ADVANCE trial was funded by a grant from the National Health and Medical Research Council of Australia and from Servier. T.O. holds the Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad. M.W. is a National Health and Medical Research Council of Australia Principal Research Fellow (1080206).
Duality of Interest. M.W. reports consultancy fees from Amgen. J.C. reports grants from Servier, administered through the University of Sydney as Co-Principal Investigator for ADVANCE and ADVANCE-ON, and personal fees from Servier. No other potential conflicts of interest relevant to this article were reported.
