Association between serum osteoprotegerin levels and disease severity and cardiovascular risk factors in patients with coronary artery diseases

Rhee, Eun Jung; Lee, Won Young; Yoo, Tae Woo; Lee, Ho Cheol; Kim, Byung Jin; Sung, Ki Chul; Kim, Bum Su; Kang, Jin Ho; Oh, Ki Won; Oh, Eun Sook; Im, Jee Aee; Baek, Ki Hyun; Kang, Moo Il; Kim, Sun Woo; Lee, Man Ho; Park, Jung Roe

Abstract

BACKGROUND: Osteoprotegerin (OPG) is a glycoprotein that acts as a decoy receptor to receptor-activated RANKL (receptor-activated NF-kappa B ligand) and inhibits the differentiation of osteoclasts. OPG knock-out mice showed severe osteoporosis and aortic calcification and high serum OPG levels have been shown to predict future cardiovascular mortality in old Caucasian females. We measured serum OPG levels in coronary artery disease patients, compared serum OPG levels among different groups according to the number of stenotic vessels and observed the correlation with aortic calcification and cardiovascular risk factors.
METHODS
One hundred subjects were enrolled in which coronary angiograms were performed due to chest pain in Kangbuk Samsung Hospital from April to August, 2003 (59 males, 41 females, mean age 56.9 +/- 11.9 yrs). Blood pressure, body mass index, fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol levels were measured in every subject. Cardiac echocardiograms were checked in 82 subjects and left ventricular mass indices (LV mass index) were calculated. Serum OPG levels were measured with enzyme-linked immunosorbent assay (ELISA) method. The presence of calcifications in aortic knob was checked in simple chest X-ray.
RESULTS
Subjects were divided in 4 groups according to the number of stenotic vessels (significant stenosis>or=50%); 45 subjects in normal group, 30 in 1-vessel disease group, 15 in 2-vessel disease group and 10 in 3-vessel disease group. Mean value for age was significantly different among groups (p<0.01). Mean serum HDL-cholesterol level of normal group was higher than that of 1-vessel disease or 2-vessel disease group (p<0.05). Serum OPG levels increased significantly as the number of stenotic vessels increased and in post-hoc analysis, mean serum OPG levels were higher in 3-vessel disease group than normal or 1-vessel disease groups (p<0.05). Age, LV mass index and number of stenotic vessels showed significantly positive correlation with serum OPG levels, although only number of stenotic vessels showed persistently significant correlation after adjustment for age. There were no differences of serum OPG levels according to the presence of fasting hyperglycemia or aortic calcifications.
CONCLUSION
Serum OPG levels increased as the number of stenotic coronary arteries increased and showed positive relationships with age, LV mass index. OPG seems to be elevated as a compensatory mechanism to the progression of atherosclerosis in humans.