The Relationship Between Plasma Osteoprotegerin Levels and Coronary Artery Calcification in Uncomplicated Type 2 Diabetic Subjects

• Published in: Journal of the American College of Cardiology Vol. 47; no. 9; pp. 1850 - 1857
• Main Authors: Anand, Dhakshinamurthy Vijay, Lahiri, Avijit, Lim, Eric, Hopkins, David, Corder, Roger
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 02.05.2006; Elsevier Science; Elsevier Limited
• Subjects: Biological and medical sciences; Biomarkers - blood; Body mass index; C-Reactive Protein - analysis; Calcinosis - blood; Calcinosis - diagnosis; Cardiology; Cardiology. Vascular system; Cardiovascular; Cardiovascular disease; Cardiovascular Diseases - complications; Cardiovascular Diseases - mortality; Cholesterol; Coronary Artery Disease - blood; Coronary Artery Disease - complications; Coronary Artery Disease - diagnosis; Diabetes Mellitus, Type 2 - complications; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Glycoproteins - blood; Health risk assessment; Heart attacks; Humans; Interleukin-6 - blood; Male; Medical sciences; Middle Aged; Osteoprotegerin; Plasma; Prognosis; Proportional Hazards Models; Receptors, Cytoplasmic and Nuclear - blood; Receptors, Tumor Necrosis Factor - blood; Risk Factors; Sensitivity and Specificity; Studies; Survival Rate; United States > US; California; IL; OR; AU; CAC; CAD; OPG; UKPDS; IQR; hs-CRP; EBCT; coronary artery disease; electron beam tomography; high-sensitivity C-reactive protein; coronary artery calcification; odds ratio; Agatston units; EBT; interleukin; osteoprotegerin; United Kingdom Prospective Diabetes Study; Endocrinopathy; Type 2 diabetes; Human; Coronary artery; Calcification; Metabolic diseases; Level; Circulatory system; Cardiology; Phlebology; Blood plasma; Osteoprotegerin
• DOI: 10.1016/j.jacc.2005.12.054
• ISSN: 0735-1097; 1558-3597

The Relationship Between Plasma Osteoprotegerin Levels and Coronary Artery Calcification in Uncomplicated Type 2 Diabetic Subjects Dhakshinamurthy Vijay Anand, Avijit Lahiri, Eric Lim, David Hopkins, Roger Corder Osteoprotegerin (OPG) is a cytokine that has been implicated in the regulation of vascular calcification. Risk factors, biomarkers (high-sensitivity C-reactive protein, interleukin-6), OPG levels, and coronary artery calcium (CAC) scores were prospectively measured in 510 type 2 diabetic patients without prior cardiovascular disease. Significant CAC (>10 Agatston units) was seen in 46%. Sixteen cardiovascular events occurred during a mean follow-up of 18 ± 5 months. The OPG predicted both subclinical disease (CAC) and near-term cardiovascular events. In a multivariate Cox proportional hazards model, CAC score was the only independent predictor of adverse events. Measurement of OPG merits further investigation as a simple test for identifying high-risk diabetic patients. 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. 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. 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). 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. 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.