Abstract P307: The Incremental Value of Fourteen Novel Biomarkers for the Prediction of Cardiovascular Risk in Patients with Type 2 Diabetes
Background: Type 2 diabetes patients are at a two to four fold increased risk of cardiovascular disease (CVD). Treatments guidelines recommend risk scores to estimate CVD risk of type 2 diabetes patients. However, such risk scores only have moderate discriminative ability to predict CVD.
Aim: This study aimed to evaluate whether fourteen novel biomarkers representing several pathophysiological pathways could improve CVD prediction in patients with type 2 diabetes beyond traditional risk factors.
Methods: We prospectively followed 1002 patients with type 2 diabetes from the Second Manifestations of ARTerial disease (SMART) study. The associations of fourteen biomarkers (adiponectin, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), matrix metalloproteinases (MMP) 1, 3 and 9, basic fibroblast growth factor, placental growth factor, soluble fms-like tyrosine kinase, vascular endothelial growth factor, osteocalcin, osteonectin, osteopontin, heart-type and epidermal-type fatty acid binding protein) with CVD risk were evaluated using Cox proportional hazards analyses adjusting for predictors from the UKPDS risk score, history of CVD and albuminuria. Incremental predictive performance was assessed by the c-statistic, the continuous net reclassification index (cNRI) and the categorical NRI.
Results: During a median follow-up of 9.2 years, 248 major cardiovascular events occurred.
NT-proBNP, osteopontin and MMP-3 were independently associated with an increased CVD risk and improved predictive performance. The base model showed a c-statistic of 0.70 (0.67-0.74). Addition of NT-proBNP resulted in a c-statistic increase of 0.02 [95%CI 0.00-0.04] and a cNRI of 0.27 [95% CI 0.10-0.45]. Addition of osteopontin resulted in a c-statistic increase of 0. 01[95%CI 0.00-0.03] and a cNRI of 0.33 [95%CI 0.17-0.48]. Addition of MMP-3 resulted in a c-statistic increase of 0.01 [95%CI 0.01-0.03] and a cNRI of 0.25 [95%CI 0.08-0.42]. Addition of the other biomarkers did not result in significant changes of the c-statistic or cNRI. The categorical NRI was 0. 08[95%CI-0.01-0.17] for NT-proBNP, 0.05 [95%CI-0.02-013] for osteopontin and 0. 05[95%CI -0.03-0.13] for MMP-3. Replication of these findings in two independent cohorts is ongoing.
Conclusions: Of fourteen evaluated biomarkers, NT-proBNP, osteopontin and MMP-3 improved the accuracy of CVD risk prediction in patients with type 2 diabetes on top of traditional risk factors. Future research should evaluate the economic costs and clinical benefits of routine measurement of these biomarkers.
Author Disclosures: J. van der Leeuw: None. J.W. Beulens: None. L.M. Peelen: None. S. van Dieren: None. S.J. Bakker: None. I.J. Riphagen: None. C.G. Schalkwijk: None. Y. van der Graaf: None. F.L.J. Visseren: None. Y.T. van der Schouw: None.
- © 2015 by American Heart Association, Inc.