Matrix Gla Protein is Associated with Risk Factors for Atherosclerosis but not with Coronary Artery Calcification

Authors: O'DONNELL, CHRISTOPHER - FRAMINGHAM HEART STUDY; PRICE, PAUL - UNIV OF CA, SAN DIEGO; SHEA, KYLA - HNRCA AT TUFTS; GAGNON, DAVID - BOSTON UNIVERSITY; WILSON, PETER - FRAMINGHAM HEART STUDY; LARSON, MARTIN - FRAMINGHAM HEART STUDY; KIEL, DOUGLAS - HEBREW SENIOR LIFE; HOFFMAN, UDO - MASS GENERAL HOSPITAL; FERENCIK, MAROS - MASS GENERAL HOSPITAL; CLOUSE, MELVIN - BETH ISRAEL DEACONNESS; WILLIAMSON, MATTHEW - UNIV OF CA, SAN DIEGO; CUPPLES, ADRIENNE - BOSTON UNIVERSITY; Dawson-Hughes, Bess; Booth, Sarah

Submitted to: Arteriosclerosis Thrombosis and Vascular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/30/2006
Publication Date: 12/1/2006
Citation: O'Donnell, C., Price, P.A., Shea, K.M., Gagnon, D.R., Wilson, P.W., Larson, M.G., Kiel, D.P., Hoffman, U., Ferencik, M., Clouse, M.E., Williamson, M.K., Cupples, A.L., Dawson-Hughes, B., Booth, S.L. 2006. Matrix Gla Protein is Associated with Risk Factors for Atherosclerosis but not with Coronary Artery Calcification. Arteriosclerosis Thrombosis and Vascular Biology. 26(12):2769-2774.

Interpretive Summary: Matrix Gla Protein (MGP) is a protein that stops the calcification process in arteries when studied in animal models. This is important because calcification of the arteries in the heart increases risk for coronary heart disease (CHD). However, little is known about the association between MGP and risk for CHD humans. In two separate population studies, blood levels of MGP, CHD risk factors, and coronary artery calcification (CAC) were measured in 768 men and women with an average age of 68 years and who were free of clinically apparent CHD. In both studies, blood levels of MGP increased with individual CHD risk factors and with the overall Framingham CHD risk score. Individuals with the highest circulating levels of MGP were at higher overall risk for CHD, but circulating MGP was not associated with coronary calcification (CAC). The relation between MGP and CAC deserves further study.

Technical Abstract: Objectives: Atherosclerotic coronary artery calcification (CAC) is associated with increased coronary heart disease (CHD) risk. Matrix Gla Protein (MGP) is an inhibitor of calcification in vivo. However, little is known regarding the distribution of circulating MGP, and its associations with CHD risk factors or with CAC in humans. Methods and Results: Serum MGP concentrations were determined in two independent populations of men and women free of clinically apparent cardiovascular disease: Study A: n=316, mean age 58 years, and Study B: n=452; mean age 68 years. CAC was determined by computed tomography. Mean MGP concentrations were 98.4 and 198 ng/mL in men, and 97.4 and 201 ng/mL in women, in Study A and B, respectively. In both cohorts, MGP levels were higher with increasing age. In age-adjusted analyses, there was an association of circulating MGP with increasing Framingham CHD risk score (in Study A, p=0.003 in men and p=0.016 in women, respectively; in Study B, a non-significant increase in men and p=0.05 in women, respectively). Significant associations of circulating MGP with HDL and other individual CHD risk factors were also noted in both cohorts. There were no consistent associations between MGP and CAC after adjustment for CHD risk score in the two cohorts. Conclusions: MGP is associated with individual CHD risk factors and the Framingham CHD risk score in men and women free of clinically apparent CHD. The relation of MGP with CAC deserves further study in larger populations.