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CLINICAL RESEARCH: CARDIAC IMAGING

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

Dhakshinamurthy Vijay Anand, MBBS, MRCP^_*,,,_*, Avijit Lahiri, MBBS, MSc, MRCP, FACC, FESC^_*, Eric Lim, MBChB, MA, MRCP^_*, David Hopkins, BSc, MBChB, FRCP and Roger Corder, PhD, MRPharmS

^_* Cardiac Imaging and Research Centre, Wellington Hospital
William Harvey Research Institute, Barts and The London, Queen Mary's School of Medicine and Dentistry
Department of Cardiology, Royal Free Hospital
Department of Endocrinology, Kings College Hospital, London, United Kingdom

Manuscript received July 10, 2005; revised manuscript received November 24, 2005, accepted December 5, 2005.

^_* Reprint requests and correspondence: Dr. Dhakshinamurthy Vijay Anand, Cardiac Imaging and Research Centre, Wellington Hospital (South), Wellington Road, St. John's Wood, London, NW8 9LE, United Kingdom (Email: vdanand{at}hotmail.com).

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.

Abbreviations and Acronyms   AU = Agatston units   CAC = coronary artery calcification   CAD = coronary artery disease   EBCT = electron beam computed tomography   hs-CRP = high-sensitivity C-reactive protein   IL = interleukin   IQR = interquartile range   OPG = osteoprotegerin   OR = odds ratio   UKPDS = United Kingdom Prospective Diabetes Study

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