Abstract 3820: Determinants of Progression of Coronary artery Calcification in Type 2 Diabetes: The Role of Plasma Osteoprotegerin levels
Background: Osteoprotegerin (OPG) is a cytokine that has been recently implicated in the regulation of vascular calcification. We sought to evaluate the relationship between plasma OPG levels, inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6) and the severity and progression of coronary artery calcification (CAC) in type 2 diabetic subjects without previous coronary artery disease.
Methods: 398 asymptomatic type 2 diabetic subjects (mean age = 52±8 years, 61% male, mean HbA1c = 8±1.5) were evaluated serially by coronary calcium imaging (mean follow-up = 2.5 ± 0.4 years). Progression/regression of CAC score was defined as a change in square root transformed volumetric CAC score ≥ 2.5 mm3, based on previously published data. Demographic data, risk factors, glycemic control, medication use, serum hs-CRP, IL-6 and plasma OPG levels were measured at baseline and during follow-up.
Results: At baseline CAC was present in 211 patients (53%). Progression of CAC was found in 119 patients (29.9%). Regression of CAC was seen in 4 patients (1%). Hs-CRP and IL-6 levels did not correlate with the extent of baseline CAC (r = 0.02 and 0.09 respectively). Plasma OPG levels were positively correlated with age, duration of diabetes and the severity of CAC at baseline (0.42, p<0.0001). Age, male gender, presence of hypertension, baseline HbA1c, CAC score, serum IL-6 and plasma OPG were univariate predictors of athersclerosis progression. Statin use was a negative predictor of CAC progression. In a multivariate logistic regression model adjusted for baseline CAC (p<0.0001), serum HbA1c (Odds ratio [OR] = 10.5 [95% CI: 2.04, 53.9], p = 0.02), plasma OPG (OR = 2.50 [1.19, 5.22], p = 0.02) and IL-6 (OR = 2.06 [1.13, 3.75], p = 0.05) were independent predictors of CAC progression. Patients in the highest tertile of plasma OPG (>9 pmol/l) had a 2.5 fold increased risk of CAC progression in comparison to those in the lowest tertile of OPG (0 - 5.2 pmol/l).
Conclusion: Suboptimal glycemic control was a strong risk factor for progression of CAC in asymptomatic type 2 diabetic subjects. Of the biomarkers studied, only plasma OPG levels predicted both the extent of atherosclerotic plaque burden and its progression.