Plasma COOH-terminal proendothelin-1: a marker of fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in type 2 diabetes? (ZODIAC-29).

Abstract

OBJECTIVE:

The 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 METHODS:

A 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.

RESULTS:

During 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.

CONCLUSIONS:

CT-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.

• Authors: Iefke Drion, Nanne Kleefstra, Gijs W D Landman, Alaa Alkhalaf, Joachim Struck, Klaas H Groenier, Stephan J L Bakker, Henk J G Bilo
• Journal: Diabetes care (Diabetes Care) Vol. 35 Issue 11 Pg. 2354-8 (Nov 2012) ISSN: 1935-5548 [Electronic] United States
• PMID: 22837372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• C-terminal proendothelin-1
• Endothelin-1
• Peptide Fragments

Topics

• Adult
• Albuminuria (blood)
• Biomarkers (blood)
• Cardiovascular Diseases (blood, mortality)
• Diabetes Mellitus, Type 2 (blood, mortality)
• Endothelin-1 (blood)
• Female
• Humans
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Peptide Fragments (blood)
• Prospective Studies
• Young Adult