The relationship between plasma osteoprotegerin levels and coronary artery calcification in uncomplicated type 2 diabetic subjects

J Am Coll Cardiol. 2006 May 2;47(9):1850-7. doi: 10.1016/j.jacc.2005.12.054. Epub 2006 Apr 19.


Objectives: This study sought to prospectively evaluate the relationship between plasma osteoprotegerin (OPG), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], coronary artery calcification (CAC), and cardiovascular events in patients with type 2 diabetes.

Background: Arterial calcification is a prominent feature of atherosclerosis and is associated with an increased risk of cardiovascular events. Osteoprotegerin is a cytokine that has recently been implicated in the regulation of vascular calcification.

Methods: A total of 510 type 2 diabetic patients (53 +/- 8 years; 61% male) free of symptoms of cardiovascular disease were evaluated by CAC imaging. Risk factors, hs-CRP, IL-6, and OPG levels were measured. Patients were followed up for cardiovascular events (cardiac death, myocardial infarction, acute coronary syndrome, late revascularization, and nonhemorrhagic stroke).

Results: Significant CAC (>10 Agatston units) was seen in 236 patients (46.3%); OPG was significantly elevated in patients with increased CAC. In multivariable analyses, OPG retained a strong association with elevated CAC scores after adjustment for age, gender, and other risk factors (odds ratio = 2.84, 95% confidence interval 2.2 to 3.67; p < 0.01). Sixteen cardiovascular events occurred during a mean follow-up of 18 +/- 5 months. The waist-to-hip ratio, United Kingdom Prospective Diabetes Study (UKPDS) risk score, OPG level, and CAC score were significant predictors of time to cardiovascular events in a univariate Cox proportional hazards model. In the multivariate model, the CAC score was the only independent predictor of adverse events. Levels of hs-CRP and IL-6 were related to neither the extent of CAC nor short-term events.

Conclusions: A high proportion of asymptomatic diabetic patients have significant subclinical atherosclerosis. Of the biomarkers studied, only OPG predicted both subclinical disease and near-term cardiovascular events. Therefore, measurement of OPG merits further investigation as a simple test for identifying high-risk type 2 diabetic patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Calcinosis / blood
  • Calcinosis / diagnosis*
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / mortality
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnosis*
  • Diabetes Mellitus, Type 2 / complications*
  • Female
  • Glycoproteins / blood*
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Osteoprotegerin
  • Prognosis
  • Proportional Hazards Models
  • Receptors, Cytoplasmic and Nuclear / blood*
  • Receptors, Tumor Necrosis Factor / blood*
  • Risk Factors
  • Sensitivity and Specificity
  • Survival Rate


  • Biomarkers
  • Glycoproteins
  • Interleukin-6
  • Osteoprotegerin
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • TNFRSF11B protein, human
  • C-Reactive Protein