Endothelial markers may link kidney function to cardiovascular events in type 2 diabetes.
OBJECTIVE
The increased cardiovascular risk in diabetes has been linked to endothelial and renal dysfunction. The aim of this study was to investigate the role of stable fragments of the precursors of adrenomedullin, endothelin-1, vasopressin, and atrial natriuretic peptide in progression of cardiovascular disease in patients with diabetes.


METHODS
This was a prospective, observational study design with a composite end point (death or unexpected admission to hospital due to a cardiovascular event) on 781 patients with type 2 diabetes (54 events, median duration of observation 15 months). The four stable precursor peptides midregional adrenomedullin (MR-proADM), midregional proatrial natriuretic peptide (MR-proANP), COOH-terminal proendothelin-1 (CT-proET-1), and COOH-terminal provasopressin or copeptin (CT-proAVP) were determined at baseline, and their association to renal function and cardiovascular events was studied using stepwise linear and Cox logistic regression analysis and receiver operating characteristic analysis, respectively.


RESULTS
MR-proADM, CT-proET-1, CT-proAVP, and MR-proANP were all elevated in patients with future cardiovascular events and independently correlated to serum creatinine. MR-proADM and MR-proANP were significant predictors of a future cardiovascular event, with MR-proANP being the stronger (area under the curve 0.802 +/- 0.034, sensitivity 0.833, specificity 0.576, positive predictive value 0.132, and negative predictive value 0.978 with a cutoff value of 75 pmol/l).


CONCLUSIONS
The four serum markers of vasoactive and natriuretic peptides are related to both kidney function and cardiovascular events, thus linking two major complications of diabetes, diabetic nephropathy and cardiovascular disease.
Maier
Christina
C
Department of Endocrinology, Medical University Hospital Vienna, Vienna, Austria.
Clodi
Martin
M
Neuhold
Stephanie
S
Resl
Michael
M
Elhenicky
Marie
M
Prager
Rudolf
R
Moertl
Deddo
D
Strunk
Guido
G
Luger
Anton
A
Struck
Joachim
J
Pacher
Richard
R
Hülsmann
Martin
M
D053607:Adrenomedullin / Q000378:metabolism*; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000209:etiology / Q000378:metabolism*; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000378:metabolism; D019332:Endothelin-1 / Q000378:metabolism*; D005260:Female; D006020:Glycopeptides / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011498:Protein Precursors / Q000378:metabolism*
D019332:Endothelin-1; D006020:Glycopeptides; D011498:Protein Precursors; C048197:copeptins; C093240:proendothelin 1; D053607:Adrenomedullin; D009320:Atrial Natriuretic Factor; D003404:Creatinine