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02-08-2011 | Diabetes | Article

Osteoprotegerin predicts CAD in asymptomatic Type 2 diabetes


Free abstract

MedWire News: Elevated levels of the plasma biomarker osteoprotegerin (P-OPG) may help predict the presence of coronary artery disease (CAD) in asymptomatic Type 2 diabetic patients with microalbuminuria, say researchers.

The findings partly explain a previous study by the group showing the elevated P-OPG predicted all-cause and cardiovascular (CVD) mortality in a similar group of patients.

"The diagnosis of subclinical CAD is likely to encourage the efforts of both the patient and his/her physician to reduce conventional risk factors more effectively, which can diminish CVD morbidity as well as mortality in these patients," say Henrik Reinhard (Steno Diabetes Center, Gentofte, Denmark) and colleagues.

OPG is a member of the tumor necrosis factor (TNF) receptor superfamily and acts to prevent osteoclast activation and bone resorption as well as participating in immune regulation and cell survival. OPG mRNA has been detected in a variety of human tissues, including the lung, heart, and kidney. Indeed, OPG is present in the arterial wall and increases in the protein have been linked with atherosclerosis.

In the current study Reinhard and colleagues evaluated whether P-OPG could serve as a biomarker for subclinical CAD in 200 asymptomatic Type 2 diabetic patients with microalbuminuria.

Firstly patients were stratified by risk for CAD, where those individuals with a plasma N-terminal pro-B-type natriuretic peptide level >45.2 ng/l and/or a coronary calcium score ≥400 were stratified as high risk (n=133), and all other patients as low risk (n=67).

High-risk patients were then examined by a combination of myocardial perfusion imaging (MPI), CT-angiography, and coronary angiography (CAG).

Significant CAD was defined by the presence of significant myocardial perfusion defects at MPI (n=70) or >70% coronary artery stenosis at CAG (n=23).

Reinhard et al report that among high-risk patients, increased P-OPG was an independent predictor of significant CAD, with adjusted odds ratios (OR) of 3.11 and 3.03 for second- and third-tertile versus first-tertile P-OPG levels, respectively.

High P-OPG was also associated with presence of >70% coronary artery stenosis, with an adjusted OR of 14.20 for the third versus first tertile of P-OPG.

Reinhard et al say that "P-OPG may represent a simple test for excluding patients at high risk of subclinical CAD," adding that studies should be conducted to assess the effect of various treatments on P-OPG, and the possible relationship of the protein with clinical outcome.

The research is published in the journal Cardiovascular Diabetology.

MedWire ( is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Andrew Czyzewski