Determinants of progression of coronary artery calcification in type 2 diabetes

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 [HbA(1)c] 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, HbA(1)c > 7, waist-hip ratio, IL-6, OPG, use of beta-blockers, calcium channel antagonists, anglotensin-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), HbAc > 7 (OR 1.95, Cl 1.08 to 3.52, p 0.03), and statin use (OR 2.27, Cl 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.