Plasma COOH-Terminal Proendothelin-1

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OBJECTIVEThe aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes.RESEARCH DESIGN AND METHODSA total of 1,225 patients with type 2 diabetes participated in this prospective observational study of two combined cohorts. Three clinical end points were studied: fatal cardiovascular events, all-cause mortality, and new-onset albuminuria. After a median follow-up of 3 or 10 years, Cox proportional hazard modeling was used to investigate the association between CT-proET-1 and the end points. Harrell C statistic, the Groennesby and Borgan test, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI) were used to evaluate whether CT-proET-1 is of additional value compared with classic cardiovascular and renal risk factors.RESULTSDuring follow-up, 364 (30%) patients died, 150 (42%) of whom died of cardiovascular disease; 182 (26.7%) of 688 patients with normoalbuminuria at baseline developed albuminuria. CT-proET-1 was associated with fatal cardiovascular events, all-cause mortality, and new-onset albuminuria with hazard ratios of 1.59 (95% CI 1.15–2.20), 1.41 (95% CI 1.14–1.74), and 1.48 (95% CI 1.10–2.01), respectively. Addition of CT-proET-1 to a model containing traditional risk factors leads only to improved prediction of fatal cardiovascular events. The IDI appeared significant for fatal cardiovascular events (0.82 [0.1–1.54]) and all-cause mortality (0.4 [0.05–0.92]), but not for new-onset albuminuria.CONCLUSIONSCT-proET-1 has additional value for the prediction of fatal cardiovascular events and new-onset albuminuria in patients with type 2 diabetes, compared with conventional risk factors, but not for all-cause mortality.