Abstract 1632: Coronary Calcification Relates to Bone Metabolism and CD4+ T-Cell Activation
Background: Osteopontin (OPN) facilitates bone resorption by enhancing the binding of osteoclast to hydroxyapatite. OPN is expressed in both the intima and the medial layers when arterial calcification is present. OPN is the most abundant molecule secreted by activated T-cells. We previously demonstrated that CD4+ T-cells play an important role in acute coronary syndrome and coronary artery disease (CAD). Osteoprotegerin (OPG) is associated with the progression of vascular calcification in diabetic patients or in patients on long term hemodialysis. Either an intravenous injection of recombinant OPG protein or the transgenic overexpression of OPG has been shown to reverse osteoporosis and prevent vascular calcification. Collagen Type I constitutes the most substantive proportion of the matrix protein of bone. Analysis of a Collagen Type I breakdown product, a Cross-linked N-terminal Telopeptide of Type I Collagen (NTX), has been used to estimate rates of bone degradation. We therefore investigated whether these markers (OPN, OPG, NTX) reflected coronary calcification as detected by multislice computed tomography (MSCT) in patients with CAD and assessed the association these markers with CD4+ T-cell activation.
Methods and Results: We measured serum OPN, OPG, and NTX levels of 76 consecutive patients who received MSCT. The frequency of OPN producing CD4+ T-cells was determined with flow cytometry. Coronary calcification was present in 41 of the 76 patients. Serum OPN, OPG, and NTX levels were all significantly higher in patients with coronary calcification than in those without. Multiple logistic regression analysis revealed that age >70 years, hypertension and serum OPN level >630 ng/ml were determinants of coronary calcification independent of other coronary risk factors. The frequency of osteopontin producing CD4+ T-cells was higher in patients with coronary calcification and it was negatively correlated with serum OPG levels.
Conclusions: The presence of coronary calcification is reflected better by an osteoporosis facilitating factor (OPN) than by an osteoporosis inhibiting factor (OPG) or by a marker of the bone degradation rate (NTX). Assessment of bone metabolism could be useful for clinical determinations of coronary heart disease.