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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

Determinants of Progression of Coronary Artery Calcification in Type 2 Diabetes

Role of Glycemic Control and Inflammatory/Vascular Calcification Markers

Dhakshinamurthy Vijay Anand, MBBS, MRCP^_*,,_*, Eric Lim, MBChB, MA, MRCP^_*, Daniel Darko, MD, MRCP, Paul Bassett, MSc, David Hopkins, BSc, MBChB, FRCP^||, David Lipkin, BSc, MD, FRCP^_*,¶, Roger Corder, PhD, MRPharmS and Avijit Lahiri, MBBS, MSc, MRCP, FACC, FESC^_*

^_* Cardiac Imaging and Research Centre, Wellington Hospital, London, United Kingdom
William Harvey Research Institute at Barts and the London, Queen Mary’s School of Medicine and Dentistry, London, United Kingdom
Department of Endocrinology, Central Middlesex Hospital, London, United Kingdom
Stats Consultancy, London, United Kingdom
^|| Department of Endocrinology, Kings College Hospital, London, United Kingdom
^¶ Department of Cardiology, Royal Free Hospital, London, United Kingdom.

Manuscript received February 19, 2007; revised manuscript received August 23, 2007, accepted August 27, 2007.

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

Objectives: This study prospectively evaluated the relationship between cardiovascular risk factors, selected biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, and osteoprotegerin [OPG]), and the progression of coronary artery calcification (CAC) in type 2 diabetic subjects.

Background: Coronary artery calcification is pathognomonic of coronary atherosclerosis. Osteoprotegerin is a signaling molecule involved in bone remodeling that has been implicated in the regulation of vascular calcification and atherogenesis.

Methods: Three hundred ninety-eight type 2 diabetic subjects without prior coronary disease or symptoms (age 52 ± 8 years, 61% male, glycated hemoglobin [HbA₁c] 8 ± 1.5) were evaluated serially by CAC imaging (mean follow-up 2.5 ± 0.4 years). Progression/regression of CAC was defined as a change 2.5 between the square root transformed values of baseline and follow-up volumetric CAC scores. Demographic data, risk factors, glycemic control, medication use, serum hs-CRP, IL-6, and plasma OPG levels were measured at baseline and follow-up.

Results: Two hundred eleven patients (53%) had CAC at baseline. One hundred eighteen patients (29.6%) had CAC progression, whereas 3 patients (0.8%) had regression. Age, male gender, hypertension, baseline CAC, HbA₁c >7, waist-hip ratio, IL-6, OPG, use of beta-blockers, calcium channel antagonists, angiotensin-converting enzyme (ACE) inhibitors, statins, and Framingham/UKPDS (United Kingdom Prospective Diabetes Study) risk scores were univariable predictors of CAC progression. In the multivariate model, baseline CAC (odds ratio [OR] for CAC >400 = 6.38, 95% confidence interval [CI] 2.63 to 15.5, p < 0.001), HbA₁c >7 (OR 1.95, CI 1.08 to 3.52, p = 0.03), and statin use (OR 2.27, CI 1.38 to 3.73, p = 0.001) were independent predictors of CAC progression.

Conclusions: Baseline CAC severity and suboptimal glycemic control are strong risk factors for CAC progression in type 2 diabetic subjects.

Abbreviations and Acronyms   CAC = coronary artery calcification   CHD = coronary heart disease   CI = confidence interval   EBCT = electron beam computed tomography   HbA1c = glycated hemoglobin   hs-CRP = high-sensitivity C-reactive protein   IL = interleukin   IQR = interquartile range   LAD = left anterior descending coronary artery   LDL = low-density lipoprotein   OPG = osteoprotegerin   OR = odds ratio

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