Relation of Osteoprotegerin to Coronary Calcium and Aortic Plaque (from the Dallas Heart Study)

University of Oslo, Kristiania (historical), Oslo, Norway
The American Journal of Cardiology (Impact Factor: 3.28). 03/2007; 99(4):513-8. DOI: 10.1016/j.amjcard.2006.08.064
Source: PubMed


Circulating osteoprotegerin (OPG) has been shown to be elevated in patients with vascular disease. The role of OPG as a biomarker for atherosclerosis in a large, unselected population is not well known. Plasma OPG levels were measured in 3,386 subjects in the Dallas Heart Study, a multiethnic, population-based probability sample of adults aged 30 to 65 years. Coronary artery calcium (CAC) was measured by electron beam computed tomography. Aortic plaque was assessed by magnetic resonance imaging. Multivariable logistic regression was used to assess associations among OPG, cardiovascular risk factors, CAC, and aortic plaque. Age, female gender, black race, smoking, personal and family history of coronary artery disease (CAD), diabetes mellitus, hyperlipidemia, CAC, and aortic plaque were significantly associated with higher plasma OPG levels (p <0.01) in univariable analyses. The prevalence of CAC and aortic plaque increased across OPG quartiles (p <0.001 for each). An OPG level in the fourth quartile was independently associated with CAC (RR 1.39, 95% confidence interval 1.01 to 1.93) and aortic plaque (RR 1.42, 95% confidence interval 1.09 to 1.86) after adjustment for age, gender, smoking, diabetes, hyperlipidemia, and family history of premature CAD. In conclusion, plasma OPG is independently associated with CAC and aortic plaque in an unselected population, suggesting it may be a novel biomarker for atherosclerosis in humans.

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    • "We have recently shown that increased serum OPG levels on admission for acute myocardial infarct (AMI) are associated with decreased microcirculation after revascularization (Logstrup et al. 2013). In population-based cohort studies, increased OPG levels were found to be associated with the future risk of myocardial infarct, ischemic stroke, and CV mortality (Kiechl et al. 2004; Vik et al. 2011; Mogelvang et al. 2013; Abedin et al. 2007). In an investigation of a large number of patients with different types of CVD, we found associations between increasing OPG levels and the severity of CVD (Figure 1). "
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    ABSTRACT: Osteoprotegerin (OPG) is a glycoprotein involved in bone metabolisms and with a regulatory role in immune, skeletal and vascular systems. Recently, circulating OPG levels have emerged as independent biomarkers of cardiovascular disease (CVD) in patients with acute or chronic heart disease, as well as in the healthy population. Furthermore, OPG has been implicated in various inflammations and linked to diabetes and poor glycaemic control. This review focuses on the relations between circulating OPG levels and cardiovascular complications, with special emphasis on diabetic patients. OPG levels were observed to increase concurrently with the severity of diabetic complications, that is, with the highest circulating OPG levels observed in diabetic patients dying from CVD. Although the clinical prognostic use of OPG may seem far away, OPG does look promising as a biomarker in order to help the cardiologist to a better risk-stratification of the patients.
    Full-text · Article · Dec 2013 · SpringerPlus
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    • "OPG is expressed by endothelial cells, vascular smooth muscle cells and osteoblasts and acts as a decoy receptor for receptor activator NF-B ligand (RANKL) [10, 11] and TNF-related apoptosis-inducing ligand (TRAIL) [12]. Human studies have demonstrated that elevated OPG is related to the severity and progression of coronary and aortic calcification [13] [14]. Elevated OPG is also associated with mortality in the general population [15] [16] and in several other high risk subpopulations [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27]. "
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    ABSTRACT: Background: Patients treated with hemodialysis (HD) have an increased mortality, mainly caused by cardiovascular disease (CVD). Osteoprotegerin (OPG) is a glycoprotein involved in the regulation of the vascular calcification process. Previous studies have demonstrated that OPG is a prognostic marker of mortality. The aim of this study was to investigate if OPG was a prognostic marker of all-cause mortality in high-risk patients with end-stage renal disease and CVD. Methods: We prospectively followed 206 HD patients with CVD. OPG was measured at baseline and the patients were followed for 2 years or until reaching the primary endpoint, i.e., all-cause mortality. Results: All-cause mortality during follow-up was 44% (90/206). High OPG was associated with increased mortality, using the first tertile as reference, with an unadjusted HR of 1.70 (CI 1.00 - 2.88) for the second tertile and HR of 1.63 (CI 0.96 - 2.78) for the third tertile. In a multivariate Cox-regression analysis age, CRP and OPG in both the second and third tertile were significantly associated with increased mortality In the unadjusted survival analysis, a test for trend of OPG yielded a p-value of 0.08; in the adjusted analyses, the p-value for trend was 0.03. Conclusions: In a high-risk population of hemodialysis patients with previously documented cardiovascular disease, a high level of OPG was an independent risk marker of all-cause mortality.
    Full-text · Article · Apr 2013 · Clinical nephrology
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    • "OPG, which has been shown to be present in atherosclerotic plaques [8], might be involved in vascular calci�cation [38]. Data from the Dallas Heart Study have shown that OPG is associated with coronary artery calcium and aortic plaque in an unselected population [8]. OPG has moreover been shown to enhance the matrix content in plaques [30]. "
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    ABSTRACT: Atherosclerosis is the principal cause of cardiovascular disease (CVD) and has many risk factors, among which is diabetes. Osteoprotegerin (OPG) is a soluble glycoprotein, involved in bone metabolism. OPG is also found in other tissues, and studies have shown that it is expressed in vascular smooth muscle cells. OPG has been implicated in various inflammations and also has been linked to diabetes mellitus. Increased serum OPG levels were found in patients with diabetes and poor glycemic control. Furthermore, prepubertal children with type 1 diabetes have significantly increased OPG levels. Receptor activator of nuclear factor kappa-B ligand (RANKL) is not found in the vasculature in normal conditions, but may appear in calcifying areas. OPG and RANKL are important regulators of mineral metabolism in both bone and vascular tissues. Few data are available on the relationship between plasma OPG/RANKL levels and endothelial dysfunction as assessed using noninvasive methods like ultrasound indexes, neither in the general population nor, more specifically, in diabetic patients. The aim of our review study was to investigate, based on the existing data, these interrelationships in order to identify a means of predicting, via noninvasive methods, later development of endothelial dysfunction and vascular complications in diabetic patients.
    Full-text · Article · Jan 2013 · International Journal of Endocrinology
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