Serum Osteoprotegerin Levels Are Associated With the Presence and Severity of Coronary Artery Disease

Abstract

Background-Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family.OPG-deficient mice develop severe osteoporosis and medial arterial calcification of the aorta and renal arteries. OPG immunoreactivity was demonstrated in the normal blood vessels and in early atherosclerotic lesions. A recent clinical study suggests that there is a significant correlation between elevated serum OPG levels and cardiovascular mortality. We examined whether serum OPG levels are associated with the progression of coronary artery disease (CAD). Methods and Results-Serum OPG levels were examined in 201 patients who underwent coronary angiography because of stable chest pain. The number of diseased vessels was used to represent the severity of CAD. Serum OPG levels were measured by ELISA and were significantly greater in patients with significant stenosis of the coronary arteries than in those without stenosis. As the severity of CAD increased, there was a significant increase in serum OPG levels. Serum OPG levels were 0.94Ϯ0. 1 Recently, it has been demonstrated that OPG is produced by a variety of tissues, including the cardiovascular system (heart, arteries, veins), lung, kidney, and immune tissues, as well as bone, 1,2 and that the expression and production of OPG are regulated by various cytokines and hormones. 3 It has been shown that OPGdeficient mice develop severe osteoporosis and medial arterial calcification of the aorta and renal arteries, 4 and that the development of osteoporosis and arterial calcification was completely prevented by restoration of the gene. 5 OPG is also expressed in vascular cells such as coronary smooth muscle cells and endothelial cells in vitro. 6 In endothelial cells, OPG has been demonstrated to act as an anti-apoptotic factor. 7 Moreover, OPG immunoreactivity was demonstrated not only in the nondiseased vessel wall, but also in early atherosclerotic lesions in human tissues. 8 These findings suggest that OPG may play an important role in the development of vascular disease. A recent clinical study reported that there is a significant correlation between elevated serum OPG levels and cardiovascular mortality, 9 suggesting that OPG may contribute to the progression of coronary artery disease (CAD). In this study, we assessed the severity of CAD by coronary angiography and examined whether serum OPG levels are associated with the progression of CAD. Methods PatientsThe present study involved 201 patients who underwent coronary angiography. All patients fulfilled the criteria of stable chest pain and/or signs of myocardial ischemia on exercise electrocardiography for clinical indication for cardiac catheterization. Patients with an acute coronary syndrome were excluded. At the time of a physical examination, blood pressure, body mass index (BMI), and a hematological and biochemical profile were determined. Age and history of cigarette use were assessed through an interview preceding the physical examination. Ninety-six subjects were receiving antian...

Osteoprotegerin Inactivation Accelerates Advanced Atherosclerotic Lesion Progression and Calcification in Older ApoE −/− Mice

“…However, a potential role for OPG/ RANKL in atherosclerosis has recently been outlined in several reviews. 15,16,27 This is in light of data showing a correlation between plasma OPG levels and the severity and extent of coronary heart disease 28 and heart failure 29 in humans. Furthermore, plasma OPG appears to be predictive of poor prognosis in at least one cohort of patients 30 and polymorphisms in the human OPG gene are associated with increased carotid intimal thickness.…”

Serum osteoprotegerin concentrations are decreased in women with the polycystic ovary syndrome

“…However, increased circulating OPG levels have also been found in association with the presence and severity of coronary artery disease (36)(37)(38), peripheral artery disease (39), and stroke (40), suggesting that OPG may serve as a biomarker of established atherosclerosis in humans (41,42). The apparent paradox of increased levels of a cardiovascular protective molecule in subjects with established atherosclerotic disease may result from a local compensatory response to atherosclerosis.…”

Plasma osteoprotegerin levels predict cardiovascular and all-cause mortality and deterioration of kidney function in type 1 diabetic patients with nephropathy

“…Plasma levels are increased in patients with diabetes [12,13] as well as in non-diabetic individuals with coronary artery disease [12,14,15]. Of particular interest, the plasma osteoprotegerin concentration correlates to the degree of arterial calcification [16,17], a phenomenon often observed in patients with diabetes [16,17].…”