osteoprotegerin and Coronary-Artery-Disease

Coronary artery calcification (CAC) is one of the critical cardiovascular complications that lead to elevated morbidity and mortality among patients with type 2 diabetes (T2M). The association between osteoprotegerin (OPG) and CAC could potentially provide a reasonable chance for preventive therapy in type 2 diabetic patients and benefit the rate of mortality. Since measurement of CAC score is relatively expensive and requires radiation exposure, the current systematic review aims to provide clinical evidence for evaluating the prognostic role of OPG in determining CAC risk among subjects with T2M. Web of Science, PubMed, Embase, and Scopus, were investigated until July 2022. We assessed human studies investigating the association of OPG with CAC in type 2 diabetic patients. Quality assessment was performed by Newcastle-Ottawa quality assessment scales (NOS). Out of 459 records, 7 studies remained eligible to be included. Observational studies that provided odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between OPG and the risk of CAC were analyzed by random-effects model. In order to provide a visual summary of our findings, the estimation of pooled OR from cross-sectional studies was reported as 2.86 [95% CI 1.49-5.49], which is consistent with the findings of the cohort study. Results revealed that the association between OPG and CAC was significant among diabetic patients. OPG is hypothesized to be a potential marker in predicting the presence of high coronary calcium score among subjects with T2M that could be recognized as a novel target for further pharmacological investigations.

Topics: Biomarkers; Cohort Studies; Coronary Artery Disease; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Humans; Osteoprotegerin; Risk Factors; Vascular Calcification

This meta-analysis included published data on the relationship between levels of osteoprotegerin, an important molecule in the bone production process, and the risk of accumulation of calcium deposits in the vessels supplying blood to the heart. Since these calcium deposits are an early sign of heart disease and subsequently heart attacks, understanding the mechanisms and finding ways to treat patients earlier can be of great importance. This study found that the higher the osteoprotegerin level a patient has, the higher the patient's chance of having calcium deposits in his or her heart vessels.

Topics: Biomarkers; Calcinosis; Coronary Artery Disease; Coronary Vessels; Humans; Osteoprotegerin; Prognosis; Prospective Studies; Risk Factors

Osteoprotegerin (OPG) is involved in the development of atherosclerosis and cardio-cerebrovascular disease. The goal of this meta-analysis was to evaluate the association of OPG single nucleotide polymorphisms (SNPs) with coronary artery disease (CAD) and ischemic stroke. A total of 15 eligible studies were extracted from electronic databases. Odds ratios (ORs) were presented, with 95% confidence intervals (CIs), to assess the associations. Meta-analysis was conducted using MetaGenyo, STATA, and Comprehensive Meta-Analysis. Meta-analysis of our data showed that the OPG SNP T950C was significantly associated with increased CAD risk among Asians via recessive (OR 1.55, 95% CI 1.18-2.04, P=0.002), CC vs TT (OR 1.57, 95% CI 1.16-2.11, P=0.003) and allelic (OR 1.21, 95% CI 1.05-1.38, P=0.007) models. No strong associations were observed for the OPG SNP G1181C, T245G and G209A with CAD risk. When evaluating the OPG SNP T245G and T950C associations with ischemic stroke, we found the OPG SNP T245G to be significantly associated with increased risk of ischemic stroke among Chinese via recessive (OR 1.53, 95% CI 1.02-2.29, P=0.039) and CC vs AA (OR 1.61, 95% CI 1.07-2.42, P=0.021) models. Our results suggested that the OPG SNP T950C was associated with increased risk of CAD among Asians, and the OPG SNP T245G was associated with enhanced ischemic stroke risk among Chinese.

Topics: Asian People; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Ischemic Stroke; Osteoprotegerin; Polymorphism, Single Nucleotide; Risk Factors

Molecules that govern bone metabolism, such as osteoprotegerin (OPG) and osteopontin (OPN), have been isolated from other tissues, including blood vessels. Atherosclerosis and coronary artery disease (CAD) are leading causes of mortality worldwide. Despite novel biochemical and imaging techniques, early detection of CAD is still unsatisfactory. Experimental data indicate that bone turnover markers (BTMs) contribute to the development of atherosclerosis. This finding has sparked interest in their clinical use. This narrative review analyzed information from >50 human studies, which strongly suggest that OPG, OPN, and alkaline phosphatase (ALP) serum concentrations are altered in patients with CAD. Osteoprotegerin seems to be more useful for the detection of early disease, while OPN and ALP are recruited in vessels after the establishment of disease. Osteocalcin may be used as a flow cytometry marker for endothelial progenitor cells and can constitute a marker to monitor response to interventional treatments and risk of restenosis. However, most data derive from observational studies. Incorporation of BTMs in multifactorial computational algorithms could further determine their role in CAD diagnosis and prognosis together with other imaging techniques and biochemical markers.

Topics: Biomarkers; Bone and Bones; Coronary Artery Disease; Humans; Osteopontin; Osteoprotegerin; Risk Assessment

Osteoprotegerin (OPG), sclerostin and DKK1 constitute opposite bone turnover inhibitors, OPG inhibiting osteoclastogenesis while sclerostin and DKK1 exerting their inhibitory effects on osteoblastogenesis. Both proteins have been recognized as strong risk factors of vascular calcifications in non-dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between these inhibitors and coronary artery calcifications (CAC) in this population.. A total of 241 ND-CKD patients [143 males; 69.0 (25.0-95.0) years; median estimated glomerular filtration rate using CKD-EPI 35.1 (6.7-120.1) mL/min/1.73 m(2)] were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. OPG, sclerostin, DKK1 and mineral metabolism markers including PTH and bone alkaline phosphatase were measured. Logistic regression analyses were used to study the relationships between CAC and these markers.. Decline in renal function was associated with a significant increase in OPG and sclerostin while a slight but significant decrease in DKK1 was observed. The main crude associations with presence of CAC were a high level of OPG [OR = 2.55 95% confidence interval (95% CI) (1.35-4.82) for a level ranging from 6.26 to 9.15 pmol/L and OR = 5.74 95% CI (2.87-11.5) for a level ≥9.15 pmol/L; P < 0.0001] and a high level of sclerostin [OR = 2.64 95% CI (1.39-5.00) for a level ranging from 0.748 to 1.139 ng/mL and OR = 3.78 95% CI (1.96-7.31) for a level ≥1.139 ng/mL; P = 0.0002]. A logistic regression model clearly showed that the risk to present CAC was significantly increased when both OPG (≥6.26 pmol/L) and sclerostin (≥0.748 ng/mL) levels were high [crude model: OR = 11.47 95% CI (4.54-29.0); P < 0.0001; model adjusted for age, gender, diabetes, body mass index and smoking habits: OR = 5.69 95% CI (1.76-18.4); P = 0.02]. No association between DKK1 and presence of CAC was observed.. Our results strongly suggest that bone turnover inhibitors, OPG and sclerostin, are independently associated with CAC with potential additive effects in ND-CKD patients.

Topics: Adaptor Proteins, Signal Transducing; Adult; Aged; Aged, 80 and over; Biomarkers; Bone Morphogenetic Proteins; Bone Remodeling; Coronary Artery Disease; Cross-Sectional Studies; Female; Genetic Markers; Glomerular Filtration Rate; Humans; Male; Middle Aged; Osteoprotegerin; Renal Dialysis; Renal Insufficiency, Chronic; Risk Factors; Vascular Calcification

Osteoprotegerin (OPG) may be involved in development of atherosclerosis. To evaluate plasma concentrations of OPG in individuals with stable coronary artery disease (CAD), acute coronary syndrome (ACS), peripheral artery disease (PAD), and cerebrovascular disease (CBVD) a systematic literature review was performed.. Studies investigating OPG concentrations in stable CAD, ACS, PAD, and CBVD were extracted from PubMed and the Cochrane Library, retrieving 280 articles. Nonrelevant articles were excluded and after thorough evaluation, and only 14 studies with clearly defined cohorts qualified for this review.. In 11 studies, OPG concentrations were elevated. Severity of atherosclerosis was significantly associated with higher OPG concentrations compared to healthy controls. No association between PAD and OPG concentrations was observed.. OPG concentrations are associated with the presence and severity of stable CAD, ACS, and CBVD. Larger studies are needed to reach conclusions concerning OPG concentrations in PAD. Studies addressing a putative role for OPG in suspected CAD and CBVD are warranted.

Topics: Acute Coronary Syndrome; Biomarkers; Cerebrovascular Disorders; Coronary Artery Disease; Disease Progression; Humans; Osteoprotegerin; Peripheral Arterial Disease; Prognosis; Risk Assessment

Topics: Coronary Artery Disease; Humans; Osteoprotegerin

Osteoprotegerin (OPG) is a glycoprotein that acts as a decoy receptor for receptor activator of nuclear factor kappaB ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand. The OPG/RANKL/receptor activator of nuclear factor kappaB axis plays an important regulatory role in the skeletal, immune, and vascular systems. The protective role of OPG, in animal models, against vascular calcification has not been replicated in human trials; moreover, increased OPG levels have been consistently associated with the incidence and prevalence of coronary artery disease. There seems to be some dichotomy in the role of OPG, RANKL, and tumor necrosis factor-related apoptosis-inducing ligand in atherosclerosis and plaque stability. In this review, we integrate the findings from some of the important studies and try to draw conclusions with a view to gaining some insight into the complex interactions of the OPG/RANKL/receptor activator of nuclear factor kappaB axis and tumor necrosis factor-related apoptosis-inducing ligand in the pathophysiology of atherosclerosis.

Topics: Animals; Coronary Artery Disease; Humans; Osteoprotegerin; Predictive Value of Tests; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; TNF-Related Apoptosis-Inducing Ligand

Coronary artery disease (CAD) represents the most relevant cause of death and morbidity in the adult population of developed and developing countries. During the last decades, a strong research effort has been performed to identify more selective markers and better assess the cardiovascular risk in both primary and secondary prevention.. This review updates current knowledge regarding the pathophysiological relevance as possible markers of coronary calcification of the receptor activator of nuclear factor-kappa ligand (RANKL)/osteoprotegerin (OPG) system. Furthermore, the potential clinical use of both RANKL/OPG and coronary calcium score (CAC) to assess cardiovascular vulnerability has been discussed.. Emerging evidence indicates that atherosclerotic plaque calcification is positively correlated with vulnerability. Several inflammatory mediators have been shown to modulate arterial calcification, thus increasing the risk of plaque rupture. Among these factors, RANKL/OPG axis might be of particular interest as a promising biomarker of plaque vulnerability in subjects with diffuse coronary calcification.. Together with clinical parameters of coronary calcification (such as CAC), circulating RANKL/OPG levels could contribute to better assess and predict cardiac events.

Topics: Biomarkers; Calcinosis; Cardiovascular Diseases; Coronary Artery Disease; Humans; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Risk Factors

Recently, the multidetector computed tomography (CT) is available to measure quantitative analysis of coronary vascular calcification (coronary calcification score [CACscore]). Vascular calcification is recognized not only in the end stage of atherosclerosis but also in the early stage of atherosclerosis. Recent data suggested that bone- related factors are closely related to coronary artery disease and vascular calcification. In this review, we discuss for regulatory mechanisms of vascular calcification.

Topics: Alkaline Phosphatase; alpha-2-HS-Glycoprotein; Biomarkers; Blood Proteins; Calcinosis; Calcium-Binding Proteins; Coronary Artery Disease; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Osteopontin; Osteoprotegerin; Parathyroid Hormone; Phosphates; Tomography, Spiral Computed

Severity of coronary artery calcification is closely related to atherosclerotic plaque burden and cardiac event rate. Recent data have suggested that vascular calcification is an actively regulated process similar to the bone formation, and that bone-related factors may be involved in the development of vascular calcification. Non-invasive prediction of calcified coronary artery disease is important using serum bone-related markers. Among them, we focus on matrix Gla protein, osteoprotegerin and fetuin-A as such candidates in this review.

Topics: alpha-2-HS-Glycoprotein; Animals; Biomarkers; Blood Proteins; Calcinosis; Calcium-Binding Proteins; Coronary Artery Disease; Coronary Disease; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Myocardial Infarction; Osteoprotegerin; Predictive Value of Tests; Severity of Illness Index

Arterial stiffness and vascular calcification significantly contribute to coronary atherosclerosis progression. The prognostic value of increased arterial stiffness and vascular calcification in subjects with stable coronary artery disease (CAD) after percutaneous coronary intervention(PCI) is currently under question.. We randomly enrolled 262 patients with stable CAD 1 month after successful PCI. Carotid-femoral pulse wave velocity (PWV) was measured as a well-established index of central aortic stiffness. Osteoprotegerin (OPG) plasma levels were measured as a biomarker of vascular calcification. Patients were followed up prospectively up to 52 months. The primary endpoint was the composite of death from cardiovascular causes, myocardial infarction, stroke or hospitalization for cardiovascular causes.. During the follow-up period, 48 patients presented the primary composite endpoint. Subjects who presented the primary endpoint, compared to subjects free of cardiovascular events, had significantly increased PWV (9.45 ± 2.19 m/s vs 8.73 ± 2.07 m/s, P = .04) and OPG levels (4.21 ± 2.19 pmol/L vs 3.18 ± 1.74 pmol/L, P = .003). Survival analysis indicated that PWV predicted adverse cardiac events MACE (Hazard ratio = 1.29 95%CI: 1.07-1.57, P = .008) independently from confounders such as age, sex, smoking habits, ejection fraction, extent of coronary artery disease, hypertension and diabetes mellitus. Interestingly, for every increase in pulse wave velocity by 1 m/s, there is an anticipated increase in the risk of major adverse cardiovascular event (MACE) by 29%.. These findings extend the current knowledge concerning the role of arterial stiffness as powerful biomarkers in cardiovascular disease. Measurement of PWV might have a role in ascertaining prognosis and managing treatment in patients with stable CAD after PCI.

Topics: Biomarkers; Cardiovascular Diseases; Coronary Artery Disease; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Osteoprotegerin; Prognosis; Risk Factors; Vascular Stiffness

Increased circulating osteoprotegerin (OPG) levels have been associated with the prevalence and severity of coronary artery disease and the risk of cardiovascular death. OPG is a cytokine of the tumor necrosis factor receptor superfamily and is expressed in various cell types in the body, including osteoblasts, inflammatory cells, vascular smooth muscle cells/endothelial cells and cardiomyocytes. The main sources determining OPG levels in the circulation however, are not well understood, and whether reversible myocardial ischemia influences OPG levels are not known. Accordingly, OPG levels were measured in 198 patients referred for exercise stress testing and myocardial perfusion imaging (MPI). In addition OPG levels were measured in 8 healthy control subjects performing a maximal bicycle stress test. Plasma samples were collected before, immediately after, 1.5h and 4.5h after exercise stress testing with MPI. OPG levels at baseline were not different in patient with reversible myocardial ischemia (n=19) and patients without reversible ischemia (n=179) (4.7 [3.6-5.5]pmol/L vs. 4.3 [3.4-5.2]pmol/L, p=0.21), and there was an increase in OPG levels immediately after exercise regardless of whether or not the patient had reversible ischemia on MPI (absolute increase: 0.2 [0-0.55]pmol/L vs. 0.3 [0-0.5]pmol/L, p=0.72). OPG levels also increased immediately after stress in the 8 control subjects (3.5 (3.2-3.8)pmol/L at baseline to 3.8 (3.5-4.7), p=0.008). In conclusion, OPG levels increase acutely during exercise stress testing, but this increase is likely caused by mechanisms other than myocardial ischemia.

Topics: Adult; Coronary Artery Disease; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Osteoprotegerin

The biomarker Osteoprotegerin (OPG) is associated with coronary artery disease (CAD). The main purpose of this study was to evaluate the diagnostic value of OPG in healthy subjects and in patients with suspected angina pectoris (AP).. A total of 1805 persons were enrolled: 1152 healthy subjects and 493 patients with suspected AP. For comparison 160 patients with acute myocardial infarction (MI) were included. To uncover subclinical coronary atherosclerosis, a non-contrast cardiac-CT scan was performed in healthy subjects; while in patients with suspected AP a contrast coronary angiography was used to detect significant stenosis. OPG concentrations were analyzed and compared between groups. ROC-analyses were performed to estimate OPG cut-off values.. OPG concentrations increased according to disease severity with the highest levels found in patients with acute MI. No significant difference (p = 0.97) in OPG concentrations was observed between subgroups of healthy subjects according to severity of coronary calcifications. A significant difference (p < 0.0001) in OPG concentrations was found between subgroups of patients with suspected stable AP according to severity of CAD. ROC-analysis showed an AUC of 0.62 (95% CI: 0.57-0.67). The optimal cut-off value of OPG (<2.29 ng/mL) had a sensitivity of 56.2% (95% CI: 49.2-63.0%) and a specificity of 62.9% (95% CI: 57.3-68.2%).. OPG cannot be used to differentiate between healthy subjects with low versus high levels of coronary calcifications. In patients with suspected AP a single OPG measurement is of limited use in the diagnosis of CAD.

Topics: Angina Pectoris; Area Under Curve; Biomarkers; Calcinosis; Calcium; Comorbidity; Coronary Angiography; Coronary Artery Disease; Coronary Disease; Diabetes Mellitus; Female; Humans; Hyperlipidemias; Hypertension; Male; Middle Aged; Myocardial Infarction; Osteoprotegerin; ROC Curve; Sampling Studies; Severity of Illness Index; Smoking; Tomography, X-Ray Computed

Topics: Bone Density; Coronary Artery Disease; Double-Blind Method; Fenofibrate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypolipidemic Agents; Middle Aged; Osteoprotegerin; RANK Ligand; Simvastatin; Solubility

Plasma osteoprotegerin (OPG) and vascular smooth muscle cell (VSMC) derived extracellular vesicles (EVs) are important regulators in the process of vascular calcification (VC). In population studies, high levels of OPG are associated with events. In animal studies, however, high OPG levels result in reduction of VC. VSMC-derived EVs are assumed to be responsible for OPG transport and VC but this role has not been studied. For this, we investigated the association between OPG in plasma and circulating EVs with coronary artery calcium (CAC) as surrogate for VC in symptomatic patients. We retrospectively assessed 742 patients undergoing myocardial perfusion imaging (MPI). CAC scores were determined on the MPI-CT images using a previously developed automated algorithm. Levels of OPG were quantified in plasma and two EV-subpopulations (LDL and TEX), using an electrochemiluminescence immunoassay. Circulating levels of OPG were independently associated with CAC scores in plasma; OR 1.39 (95% CI 1.17-1.65), and both EV populations; EV-LDL; OR 1.51 (95% CI 1.27-1.80) and EV-TEX; OR 1.21 (95% CI 1.02-1.42). High levels of OPG in plasma were independently associated with CAC scores in this symptomatic patient cohort. High levels of EV-derived OPG showed the same positive association with CAC scores, suggesting that EV-derived OPG mirrors the same pathophysiological process as plasma OPG.

Topics: Aged; Biomarkers; Chronic Disease; Coronary Artery Disease; Coronary Vessels; Extracellular Vesicles; Female; Humans; Male; Middle Aged; Myocardial Perfusion Imaging; Osteoprotegerin; Prospective Studies; Retrospective Studies; Risk Assessment; Risk Factors; Syndrome; Vascular Calcification

Osteoprotegerin and osteopontin have recently emerged as key factors in both vascular remodelling and atherosclerosis progression. Interleukin-6 (IL-6) is an inflammatory cytokine with a key role in atherosclerosis. The relationship of osteoprotegerin, osteopontin, and IL-6 serum levels with endothelial function and arterial stiffness was evaluated in patients with coronary artery disease (CAD).. We enrolled 219 patients with stable CAD and 112 control subjects. Osteoprotegerin, osteopontin and IL-6 serum levels were measured using an ELISA assay. Endothelial function was evaluated by flow-mediated dilation (FMD) in the brachial artery and carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness.. There was no significant difference between control subjects and CAD patients according to age and sex. Compared with control subjects, CAD patients had significantly impaired FMD (p<0.001) and increased PWV (p=0.009). CAD patients also had significantly higher levels of osteoprotegerin (p<0.001), osteopontin (p<0.001) and IL-6 (p=0.03), compared with control subjects. Moreover, IL-6 levels were correlated with osteoprotegerin (r=0.17, p=0.01) and osteopontin (r=0.30, p<0.001) levels. FMD was correlated with osteoprotegerin levels independent of possible confounders [b coefficient= - 0.79, 95% CI (-1.54, -0.05), p=0.04].. CAD patients have increased osteoprotegerin, osteopontin and IL-6 levels. Moreover, there is a consistent association between osteoprotegerin and osteopontin serum levels, vascular function and inflammation in CAD patients. These findings suggest another possible mechanism linking osteoprotegerin and osteopontin serum levels with CAD progression through arterial wall stiffening and inflammation.

Topics: Aged; Biomarkers; Case-Control Studies; Coronary Artery Disease; Female; Humans; Inflammation; Interleukin-6; Male; Middle Aged; Osteopontin; Osteoprotegerin; Vascular Stiffness; Vasodilation

Elevated circulating levels of osteoprotegerin (OPG) are known to add to the prediction of cardiovascular mortality. Our objective was to clarify the long-term risk associated with serum OPG and the possible influence of diabetes and statins on OPG levels in patients with stable coronary artery disease (CAD).. We assessed the placebo-treated group (n = 1998) from the CLARICOR trial (NCT00121550), a cohort with stable CAD. At entry, 15% of the participants had diabetes and 41% received statins. Serum OPG levels were measured in blood drawn at randomization. Participants were followed through public registers for 10 years.. OPG levels correlated positively with diabetes status, age, CRP and female sex, but negatively with the use of statins. CAD participants with diabetes had significantly elevated serum OPG levels compared to participants without diabetes, p < 0.0001. The participants without diabetes treated with statins presented with significantly lower serum OPG levels than the corresponding non-statin-users (p < 0.0001). However, statin use showed no association with OPG levels in the participants with diabetes. High OPG levels at entry showed long-term associations with all-cause mortality and cardiovascular events (hazard ratio associated with factor 10 OPG increase 15.9 (95% CI 11.0-22.9) and 6.38 (4.60-8.90), p = 0.0001, even after adjustment for standard predictors (3.16 (1.90-5.25) and 2.29 (1.53-3.44), p < 0.0001).. Circulating OPG holds long-term independent predictive ability for all-cause mortality and cardiovascular events in CAD participants. OPG levels were associated with diabetes, age, and female sex and statin treatment was associated with lower OPG levels in the absence of diabetes.

Topics: Biomarkers; Coronary Artery Disease; Diabetes Mellitus; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Osteoprotegerin; Risk Factors

Basic and clinical research have demonstrated that osteoprotegerin (OPG) plays an important role in the development and progression of cardiovascular diseases. The aim of this study was to evaluate the association of four polymorphic sites (rs2073618, rs3134069, rs3134070, and rs3102735) of

Topics: Aged; Cardiovascular Diseases; Coronary Artery Disease; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Haplotypes; Humans; Male; Mexico; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; Risk Factors

There is little data as to whether osteoprotegerin (OPG) is associated with target organ damage (TOD), so we evaluated the association in patients at high risk of coronary artery disease (CAD).Methods and Results:A total of 349 patients who underwent invasive coronary angiography (ICA) for suspected CAD were prospectively recruited. During the index admission, 6 TOD parameters were collected: extent of CAD, glomerular filtration rate (GFR), left ventricular mass index (LVMI), E/e', brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI). Serum OPG levels were measured using enzyme-linked immunosorbent assay. The OPG level was significantly higher in patients with ≥1 TOD parameter than in those without (314±186 vs. 202±74 pg/mL, P<0.001). For each TOD parameter, the serum OPG level was significantly higher in patients with TOD than in those without (P<0.05 for each) except for ABI. In correlation analysis, OPG was significantly associated with GFR, LVMI, E/e', baPWV and ABI (P<0.05 for each). The OPG concentration increased proportionally with increasing TOD (P<0.001). Higher OPG concentrations (≥198 pg/mL) was significantly associated with the presence of TOD (odds ratio 3.22; 95% confidence interval 1.51-6.85; P=0.002) even after controlling for potential confounders.. Serum OPG level was significantly associated with a variety of TOD in patients undergoing ICA. OPG may be a useful marker for TOD and in the risk stratification of patients at high risk of CAD.

Topics: Ankle Brachial Index; Coronary Angiography; Coronary Artery Disease; Glomerular Filtration Rate; Humans; Osteoprotegerin; Pulse Wave Analysis; Risk Factors

Topics: Angiotensin-Converting Enzyme 2; Biomarkers; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Echocardiography, Doppler; Heart Failure; Humans; Microcirculation; Microvessels; Osteoprotegerin; Peptidyl-Dipeptidase A; Protein Interaction Maps; Regression Analysis; Ventricular Function, Left

Osteoprotegerin (OPG) is a tumor necrosis factor receptor super-family member. It specifically acts on bone by increasing bone mineral density and bone volume. Recent studies have evidenced its close relation to the development of atherosclerosis and plaque destabilization. Elevated OPG level has also been associated with the degree of coronary calcification in the general population and it has been considered to be a marker of coronary atherosclerosis.. The aim of this study was to determine the relation between OPG levels and Coronary Artery Calcification score (CACs) in Type 2 diabetic patients in comparison to healthy controls.. Our study included 45 type 2 diabetic patients (mean age 51.7 years; 51.1% male) without evidence of previous CVD and 45 healthy age and sex matched subjects as control. All participants were subjected to full history, full examination and lab investigations. Serum OPG concentration was measured by an enzyme-linked immunosorbent assay (ELISA) and CAC imaging was performed using non contrast Multi detector CT of the heart.. Significant CAC (<10 Agatston units) was seen in 23 patients (51.11 %). OPG was significantly high in diabetic patients in comparison to controls with mean 12.9±5.7 pmol/l in cases, and 8.6±0.5 pmol/l in controls (P value < 0.001). The Coronary Artery Calcification Score (CACS) was positively correlated with age and duration of diabetes. The OPG was positively correlated with age, fasting blood sugar and duration of diabetes. The CACS showed a significantly positive correlation with OPG.. Findings suggested that increasing in serum OPG was consistent with CAC and could be used for the early diagnosis of subclinical atherosclerosis.

Topics: Adult; Asymptomatic Diseases; Atherosclerosis; Biomarkers; Calcinosis; Case-Control Studies; Coronary Artery Disease; Coronary Vessels; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Early Diagnosis; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Multidetector Computed Tomography; Osteoprotegerin; Predictive Value of Tests; Severity of Illness Index

Heterozygous familial hypercholesterolemia (FH) is a genetic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C). The magnitude of atherosclerotic cardiovascular disease (ASCVD) risk in FH patients is highly variable, and this can result from genetic factors. The aim of our study was to characterize whether polymorphisms in VEGFR2 and OPG genes could influence the expression of ASCVD in FH patients.. We studied 318 FH patients from the SAFEHEART registry, without clinical diagnosis of ASCVD. A coronary tomographic angiography (CTA) was performed to determine and evaluate the presence of coronary stenosis and coronary artery calcium, as measured by coronary calcium score (CCS). Genotyping of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms was performed using TaqMan 5'-exonuclease allelic discrimination assays.. Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of developing coronary artery stenosis. In the analysis of OPG rs2073618 and VEGFR2 rs2071559 polymorphisms, according to the presence of coronary artery calcium, we found significant differences in both polymorphisms. Homozygous GG genotype and G allele of VEGFR2 rs2071559 polymorphism were associated with decreased risk of accumulation of coronary artery calcium measured by CCS in CTA. Moreover, being a carrier of the GG genotype and G allele of the OPG rs2073618 polymorphism increased the risk of the presence of coronary artery calcium measured by CCS in CTA.. Polymorphisms in VEGFR2 and OPG genes modify the risk of ASCVD in FH patients.

Topics: Adult; Coronary Artery Disease; Female; Genotype; Homozygote; Humans; Hyperlipoproteinemia Type II; Male; Middle Aged; Osteoprotegerin; Polymorphism, Genetic; Prospective Studies; Risk Assessment; Vascular Endothelial Growth Factor Receptor-2

High plasma osteoprotegerin (OPG) and asymmetric dimethylarginine (ADMA) and low homoarginine (hArg) predict adverse renal and cardiovascular (CV) outcomes. In patients with chronic kidney disease and stable coronary artery disease, plasma OPG correlated with hArg (r = - 0.37, P = 0.03) and the hArg/ADMA molar ratio (r = - 0.46, P = 0.009), which was maintained upon adjustment for renal function. Elevated OPG levels and decreased hArg/ADMA ratios independently predicted 4-year composite CV and renal endpoints (CV death or progression to dialysis). Thus, high OPG and low hArg/ADMA ratio, albeit interrelated, appear to independently contribute to adverse clinical outcome.

Topics: Aged; Arginine; Biomarkers; Coronary Artery Disease; Homoarginine; Humans; Male; Middle Aged; Osteoprotegerin; Renal Insufficiency, Chronic

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Coronary Artery Disease; Female; Genetic Markers; Genetic Predisposition to Disease; Genotype; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Osteopontin; Osteoprotegerin; Peripheral Arterial Disease; Polymorphism, Single Nucleotide; Risk Factors; Taiwan

In response to various stimuli, vascular smooth muscle cells (SMCs) can de-differentiate, proliferate and migrate in a process known as phenotypic modulation. However, the phenotype of modulated SMCs in vivo during atherosclerosis and the influence of this process on coronary artery disease (CAD) risk have not been clearly established. Using single-cell RNA sequencing, we comprehensively characterized the transcriptomic phenotype of modulated SMCs in vivo in atherosclerotic lesions of both mouse and human arteries and found that these cells transform into unique fibroblast-like cells, termed 'fibromyocytes', rather than into a classical macrophage phenotype. SMC-specific knockout of TCF21-a causal CAD gene-markedly inhibited SMC phenotypic modulation in mice, leading to the presence of fewer fibromyocytes within lesions as well as within the protective fibrous cap of the lesions. Moreover, TCF21 expression was strongly associated with SMC phenotypic modulation in diseased human coronary arteries, and higher levels of TCF21 expression were associated with decreased CAD risk in human CAD-relevant tissues. These results establish a protective role for both TCF21 and SMC phenotypic modulation in this disease.

Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Cells, Cultured; Coronary Artery Disease; Humans; Mice; Mice, Inbred C57BL; Myocytes, Smooth Muscle; Osteoprotegerin; Phenotype; Polymorphism, Single Nucleotide; Sequence Analysis, RNA; Single-Cell Analysis

Coronary artery calcification (CAC) and atherosclerotic inflammation associate with increased risk of myocardial infarction (MI). Vascular calcification is regulated by osteogenic proteins (OPs). It is unknown whether an association exists between CAC and plasma OPs and if they are affected by atherothrombotic inflammation. We tested the association of osteogenic and inflammatory proteins with CAC and assessed these biomarkers after MI.. Circulating OPs (osteoprotegerin, RANKL, fetuin-A, Matrix Gla protein [MGP]) and inflammatory proteins (C-reactive protein, oxidized-LDL, tumoral necrosis factor-α, transforming growth factor [TGF]-β1) were compared between stable patients with CAC (CAC ≥ 100 AU, n = 100) and controls (CAC = 0 AU, n = 30). The association between biomarkers and CAC was tested by multivariate analysis. In patients with MI (n = 40), biomarkers were compared between acute phase and 1-2 months post-MI, using controls as a baseline.. MGP and fetuin-A levels were higher within individuals with CAC. Higher levels of MGP and RANKL were associated with CAC (OR 3.12 [95% CI 1.20-8.11], p = 0.02; and OR 1.75 [95% CI 1.04-2.94] respectively, p = 0.035). After MI, C-reactive protein, OPG and oxidized-LDL levels increased in the acute phase, whereas MGP and TGF-β1 increased 1-2 months post-MI.. Higher MGP and RANKL levels associate with CAC. These findings highlight the potential role of these proteins as modulators and markers of CAC. In addition, the post-MI increase in OPG and MGP, as well as of inflammatory proteins suggest that the regulation of these OPs is affected by atherothrombotic inflammation.

Topics: Adult; Aged; alpha-2-HS-Glycoprotein; Biomarkers; C-Reactive Protein; Calcium-Binding Proteins; Coronary Artery Disease; Extracellular Matrix Proteins; Female; Humans; Lipoproteins, LDL; Male; Matrix Gla Protein; Middle Aged; Myocardial Infarction; Osteoprotegerin; RANK Ligand; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Cardiovascular calcification is one of the most severe outcomes associated with cardiovascular disease and often results in significant morbidity and mortality. Previous reports indicated that epigenomic regulation of microRNAs (miRNAs) might play important roles in vascular smooth muscle cell (VSMC) calcification. Here, we identified potential key miRNAs involved in vascular calcification in vivo and investigated the role of miR-32-5p (miR-32). According to microarray analysis, we observed increased expression of miR-125b, miR-30a, and miR-32 and decreased expression of miR-29a, miR-210, and miR-320 during the progression of vascularcalcification. Additionally, gain- and loss-of-function studies of miR-32 confirmed promotion of VSMC calcification in mice through the enhanced expression of bonemorphogenetic protein-2, runt-related transcription factor-2(RUNX2), osteopontin, and the bone-specific phosphoprotein matrix GLA protein in vitro. Moreover, miR-32 modulated vascularcalcification progression by activating phosphoinositide 3-kinase (PI3K)signaling and increasing RUNX2 expression and phosphorylation by targeting the 3'-untranslated region of phosphatase and tensin homolog Mrna (PTEN) in mouse VSMCs. Furthermore, we detected higher miR-32 levels in plasmafrom patients with coronary artery disease with coronary artery calcification (CAC) as compared with levels observed in non-CAC patients (P = 0.016), further confirming miR-32 as a critical modulator and potential diagnostic marker for CAC.

Topics: Animals; Biomarkers; Cell Line; Core Binding Factor Alpha 1 Subunit; Coronary Artery Disease; Coronary Vessels; Disease Models, Animal; Humans; Male; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; MicroRNAs; Osteogenesis; Osteoprotegerin; Phosphatidylinositol 3-Kinases; Phosphorylation; PTEN Phosphohydrolase; Vascular Calcification

Tartrate-resistant acid phosphatase (TRACP)-5b and osteoprotegerin (OPG) are specific and sensitive markers of bone resorption in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD). The TRACP-5b level is associated with the severity of RA and CKD, while the OPG level is associated with the severity of coronary atherosclerosis and calcification, and can predict a poor outcome in patients with coronary artery disease (CAD). However, the impact of TRACP-5b on coronary atherosclerosis in CAD patients remains unclear.. A total of 71 CAD patients (57 men, 14 women; mean age: 69.0±9.7 years) and 28 age- and gender- matched healthy subjects were investigated. The number of diseased vessels (a marker of the severity of coronary atherosclerosis) and the Gensini score (a marker of the extent of coronary atherosclerosis), as well as the OPG and TRACP-5b levels were measured in CAD patients. The TRACP-5b levels were classified into quartiles.. The TRACP-5b levels were significantly higher in CAD patients than in healthy subjects. Patients with higher TRACP-5b levels had higher OPG levels and Gensini scores than those with lower TRACP-5b levels. Higher TRACP-5b levels were associated with an increased number of diseased vessels. A multivariate linear regression analysis showed that the OPG level and the number of diseased vessels or the Gensini score were significantly and independently associated with the TRACP-5b level.. These data indicate that the TRACP-5b level is significantly associated with the OPG level and with the severity and extent of coronary atherosclerosis in CAD patients.

Topics: Aged; Arthritis, Rheumatoid; Biomarkers; Calcinosis; Case-Control Studies; Coronary Artery Disease; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Smoking; Tartrate-Resistant Acid Phosphatase; Treatment Outcome

Osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) are regulators of bone remodeling, but are also considered to play important roles in coronary artery disease (CAD). This study evaluated potential associations of soluble (s) RANKL and OPG with atherosclerosis-relevant cytokines. Blood was collected from 414 individuals who presented to our hospital with intermediate likelihood for CAD for further examination. Plasma concentrations of total sRANKL, OPG, and 20 cytokines were measured using sandwich-type enzyme-linked immunoassays (ELISAs; OPG and sRANKL) and Luminex laser-based fluorescence analysis and correlated with each other. The plasma levels of interferon-γ (IFN-γ) and the T-helper cell 2 cytokines interleukin-4 (IL-4) and IL-13 showed a positive correlation with sRANKL. The association with sRANKL levels was negative for IFN-γ-induced protein-10 (IP-10) and monocyte chemotactic protein-1 (MCP-1). The strongest independent association with sRANKL in multivariable analyses was found for IFN-γ (positive) and IP-10 (negative), while IL-13 showed a positive and independent association with OPG plasma levels. OPG and sRANKL plasma levels correlate strongly and independently with specific circulating atherosclerosis-related cytokines in patients with intermediate cardiovascular risk.

Topics: Adult; Aged; Aged, 80 and over; Atherosclerosis; Biomarkers; Coronary Artery Disease; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Germany; Humans; Male; Middle Aged; Morbidity; Osteoprotegerin; RANK Ligand; Risk Assessment; Risk Factors; Young Adult

The interdependence of the predictive accuracy of serum osteoprotegerin (OPG) and von Willebrand factor (vWF) levels for long-term cardiovascular outcomes has not been investigated so far. This was a prospective observational cohort study in 361 patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). Baseline levels of OPG, vWF, active vWF (act vWF) and ristocetin cofactor activity (vWF:RICO) were measured. Cardiovascular mortality was recorded over a median of five years. OPG concentrations >3.7 µg/ml emerged as the strongest predictor of cardiovascular (CV) death: 30 % of patients died during the five-year follow-up in this group, as compared to 10 % in patients with OPG ≤3.7 µg/ml (p<0.001). Act vWF had a significant prognostic impact on CV mortality when OPG levels were low (≤3.7 µg/ml): patients with act vWF concentration >1 µg/ml died in 14 %, whereas those with act vWF values ≤1 µg/ml had a mortality rate of 1 % (p=0.015). We stratified patients into three groups: high OPG, low OPG/high act vWF and low OPG/low act vWF. Patients with high OPG values had a 13-fold higher risk for CV death than those with low OPG/low act vWF concentrations (adj. HR: 12.6; 95 %CI: 1.7-94.7; p=0.014), and a two-fold higher risk as compared to those patients with low OPG/high act vWF concentrations (adj. HR: 2.0; 95 %CI: 1.1-3.7; p=0.03) in the adjusted Cox regression analysis. In conclusion, elevated OPG at the time of PCI was a strong independent predictor of five-years cardiovascular mortality, whereas act vWF had a significant prognostic impact on CV mortality when OPG levels were low.

Topics: Aged; Area Under Curve; Biomarkers; Chi-Square Distribution; Coronary Artery Disease; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Percutaneous Coronary Intervention; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Factors; ROC Curve; Time Factors; Treatment Outcome; von Willebrand Factor

Previous studies suggest a relationship of the epicardial adipose tissue (EAT) with progression and calcification of the atherosclerotic plaque; however, it is unknown if this tissue expresses genes that may participate on these processes and if the expression of these genes is regulated by high-density lipoprotein (HDL) subclasses.. To explore this possibility, we determined the mRNA expression by qPCR of a pro-calcifying gene (osteopontin (OPN)), and two anti-calcifying genes (osteoprotegerin (OPG) and osteonectin (ON)), in biopsies of EAT obtained from 15 patients with coronary artery disease (CAD) determined by angiography, and 15 patients with diagnostic of aortic valve stenosis but without CAD as control group. We determined the distribution and composition of HDL subclasses by electrophoresis and their statistical relationship with the gene expression in EAT.. EAT from CAD patients showed a higher expression level of OPN and OPG than control group, whereas ON expression was similar between groups. Large HDL subclasses were cholesterol-poor in CAD patients as estimated by the cholesterol-to-phospholipid ratio. A linear regression model showed an independent association of OPN expression with HDL3a-cholesterol, and OPG expression with the relative proportion of HDL3b protein. Logistic analysis determined that OPN expression was positively associated with the presence of atherosclerotic plaque CONCLUSION: OPN, ON, and OPG genes are transcribed in EAT; to the exception of ON, the level of expression was different in CAD patients and control group, and correlated with some HDL subclasses, suggesting a new role of these lipoproteins.

Topics: Adipose Tissue; Aged; Aortic Valve Stenosis; Case-Control Studies; Cholesterol, HDL; Coronary Artery Disease; Female; Gene Expression Regulation; Humans; Lipoproteins, HDL3; Male; Middle Aged; Osteonectin; Osteopontin; Osteoprotegerin; Pericardium; Plaque, Atherosclerotic; RNA, Messenger; Severity of Illness Index

The aim of the present study is to assess the level of specific markers of calcium and phosphate metabolism in the development of coronary atherosclerosis in patients with stable coronary artery disease, depending on the severity of osteopenic syndrome. METHODSː In the study 112 male patients aged from 49 to 73 years with verified coronary artery disease were included in the study. Calcium Score was measured using the Agatston Score. Besides, all of them were tested on the serum level of parathyroid hormone, calcitonin, osteocalcin, bone-specific alkaline phosphatase, osteoprotegerin, osteopontin, cathepsin K, estradiol and testosterone. RESULTSː The distribution of patients according to the severity of coronary atherosclerosis using the Syntax Score suggested that the levels of the studied markers did not differ significantly among the patients, despite significant differences in the severity of coronary artery disease. The levels of osteoprotegerin in patients with mild, moderate and severe calcification were significantly lower compared to patients with a zero calcium score. There were no clinical manifestations of osteopenic syndrome in all patients. However, they underwent osteodensitometry with measurement of bone mineral density at the lumbar spine and femoral neck to determine pre-clinical symptoms of bone destruction. Significant increase (P=0.03) in serum levels of osteocalcin was found in patients with radiological evidence of osteoporosis while the other markers did no differ significantly. CONCLUSIONSː We suppose that there is a reciprocal interaction of regulatory vectors with increased calcium deposition in the arterial wall and resorption of bone tissue.

Topics: Aged; Biomarkers; Bone Density; Bone Diseases, Metabolic; Calcium; Coronary Artery Disease; Humans; Male; Middle Aged; Osteocalcin; Osteopontin; Osteoprotegerin; Parathyroid Hormone; Phosphates; Vascular Calcification

To assess serum levels of the plaque calcification regulators osteoprotegerin (OPG) and Matrix Gla-proteins (MGP) in individuals with stable angina and acute myocardial infarction submitted to coronary angiography and their relation to coronary artery disease burden.. The study included 40 individuals affected by ST-elevation myocardial infarction (STEMI) and 40 individuals with stable angina who all underwent coronary angiography, with evaluation of the extent of coronary artery disease by Syntax Score calculation and measurement of serum OPG and MGP levels. Osteoporosis was excluded by femoral and vertebral computerized bone mineralometry.. Serum OPG and MGP levels were respectively 3.87 ± 1.07 pmol/l and 6.80 ± 2.43 nmol/l in the stable angina group, 7.57 ± 1.5 pmol/l and 7.18 ± 1.93 nmol/l in the STEMI group (P < 0.01 and P = 0.33, respectively). Pearson correlation coefficient for OPG and Syntax Score, MGP and Syntax score was respectively 0.79 (P < 0.01) and 0.18 (P = 0.22) in the stable angina group, -0.03 (P = 0.43) and 0.10 (P = 0.5) in the STEMI group.Serum OPG and MGP levels were respectively 5.52 ± 1.02 pmol/l and 7.56 ± 1.42 nmol/l in diabetics, 4.3 ± 0.8 pmol/l and 6.52 ± 1.14 nmol/l in nondiabetics (P < 0.05; P < 0.05).. OPG, in a relatively small group of patients with stable angina, correlates proportionally with the extent of coronary artery disease (CAD), as evaluated by the Syntax Score. Higher serum OPG levels can be observed in individuals with STEMI regardless of CAD burden. As for MGP, a potential role as marker of plaque calcification remains unproven.

Topics: Aged; Angina, Stable; Biomarkers; Bone Density; Calcinosis; Calcium-Binding Proteins; Coronary Angiography; Coronary Artery Disease; Diabetic Angiopathies; Extracellular Matrix Proteins; Humans; Male; Matrix Gla Protein; Middle Aged; Myocardial Infarction; Osteoprotegerin

Coronary artery calcification (CAC) is a prominent feature of atherosclerosis and is associated with cardiovascular events. In vitro studies have suggested that osteoprotegerin (OPG) and osteocalcin (OC) exert anticalcification potential in the vessel wall. The objective of this study was to investigate the association of CAC and serum bone biomarkers in persons with type 2 diabetes.. We examined 50 individuals with type 2 diabetes. CAC imaging was performed by multidetector computed tomography. CAC scores ≥10, expressed in Agatston units, were considered abnormal. OC, undercarboxylated OC (ucOC), and OPG levels were determined by enzyme-linked immunosorbent assay.. Abnormal CAC scores were found for 64% of the study cohort. OPG levels were significantly elevated (5.5 ± 2.0 pmol/L vs. 4.2 ± 1.7 pmol/L; P = .026) for those with abnormal CAC scores. No univariate differences were found for OC or ucOC. Logistic regression analyses revealed that an increase in serum OPG level was significantly associated with an increase in CAC score (odds ratio, 3.324; 95% confidence interval, 1.321 to 8.359; P = .011). Longer duration of diabetes was a significant covariate (P = .026), whereas nonsignificant covariates in the final model were age, gender, systolic blood pressure, body mass index, insulin resistance determined by the homeostasis model assessment for insulin resistance, leptin, adiponectin, and glycemic control. The Nagelkerke R2 for the model was 0.66. Neither OC nor ucOC were significantly associated with elevated CAC scores.. Our results suggest that OPG is a more useful serum biomarker than OC or ucOC for identifying those at increased risk of arterial calcification in type 2 diabetes.

Topics: Aged; Biomarkers; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Humans; Insulin Resistance; Logistic Models; Male; Middle Aged; Osteocalcin; Osteoprotegerin; Vascular Calcification

Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis, but there is limited information about the genetic contribution to atherosclerosis in this population. Therefore, we examined the association between selected genetic polymorphisms and coronary atherosclerosis in patients with RA.. Genotypes for single-nucleotide polymorphisms (SNPs) in 152 candidate genes linked with autoimmune or cardiovascular risk were measured in 140 patients with RA. The association between the presence of coronary artery calcium (CAC) and SNP allele frequency was assessed by logistic regression with adjustment for age, sex, and race. To adjust for multiple comparisons, a false discovery rate (FDR) threshold was set at 20%.. Patients with RA were 54±11 years old and predominantly Caucasian (89%) and female (69%). CAC was present in 70 patients (50%). A variant in rs2073618 that encodes an Asn3Lys missense substitution in the osteoprotegerin gene (OPG, TNFRSF11B) was significantly associated with the presence of CAC (OR=4.09, p<0.00026) and withstands FDR correction.. Our results suggest that a polymorphism of the TNFRSF11B gene, which encodes osteoprotegerin, is associated with the presence of coronary atherosclerosis in patients with RA. Replication of this finding in independent validation cohorts will be of interest.

Topics: Adult; Aged; Arthritis, Rheumatoid; Atherosclerosis; Coronary Artery Disease; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; White People

The objective of the study was to determine the relationship between common carotid artery intima-media thickness (CCA-IMT) and histologically assessed calcification of radial artery in relation to clinical features and laboratory markers of bone and mineral metabolism, inflammation, and oxidative stress in patients with stage 5 chronic kidney disease (CKD).. The study comprised 59 patients (36 hemodialyzed, 23 predialysis). CCA-IMT was measured by ultrasonography; the biochemical parameters examined were assessed using routine laboratory methods, ELISA micro-plate immunoassays and spectrophotometry. Fragments of radial artery obtained during creation of hemodialysis access were cryosectioned and stained for calcifications using von Kossa method and alizarin red.. Glucose, osteoprotegerin, pentraxin 3 and Framingham risk score significantly correlated with CCA-IMT. In multiple regression analysis, OPG positively predicted CCA-IMT. Radial artery calcifications were found in 34 patients who showed higher CCA-IMT (0.98 ± 0.13 vs 0.86 ± 0.14 mm; P = 0.006). Higher CCA-IMT values were also associated with more advanced calcifications. CCA-IMT and the presence of plaques in common carotid artery were positive predictors of radial artery calcifications, independent of dialysis status, Framingham risk score, CRP and Ca x Pi [OR for calcifications 2.19 (1.08-4.45) per 0.1 mm increase in CCA-IMT]. The presence of radial artery calcifications was a significant predictor of mortality, independent of dialysis status and Framingham risk score [HR 3.16 (1.03-9.64)].. In CKD patients, CCA-IMT examination can be used as a surrogate measure to assess the incidence and severity of arterial medial calcification which is associated with poor clinical outcome in these patients.

Topics: Adult; Aged; Aged, 80 and over; alpha-2-HS-Glycoprotein; Blood Glucose; C-Reactive Protein; Cardiovascular Diseases; Carotid Artery, Common; Carotid Intima-Media Thickness; Cohort Studies; Coronary Artery Disease; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Incidence; Inflammation; Insulin Resistance; Interleukin-6; Kidney Failure, Chronic; Logistic Models; Middle Aged; Multivariate Analysis; Osteocalcin; Osteopontin; Osteoprotegerin; Oxidative Stress; Radial Artery; Renal Dialysis; Renal Insufficiency, Chronic; Risk Assessment; Serum Amyloid P-Component; Severity of Illness Index; Tunica Media; Vascular Calcification

Abnormalities in the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis have been observed in HIV-infected persons and have been implicated in cardiovascular disease (CVD) pathogenesis in the general population.. To determine associations of serum OPG and RANKL concentrations with HIV infection and subclinical atherosclerosis.. Cross-sectional study nested within the Multicenter AIDS Cohort Study.. Four US academic medical centers.. There were 578 HIV-infected and 344 HIV-uninfected men.. Coronary artery calcium (CAC) was measured by noncontrast cardiac computed tomography, and coronary stenosis and plaque characteristics (composition, presence, and extent) were measured by coronary computed tomography angiography. All statistical models were adjusted for traditional CVD risk factors.. OPG concentrations were higher, and RANKL concentrations were lower among HIV-infected men compared with HIV-uninfected men (P < 0.0001 each). Among HIV-infected men, higher OPG concentrations were associated with the presence of CAC, mixed plaque, and coronary stenosis >50%, but not with plaque extent. In contrast, among HIV-uninfected men, higher OPG concentrations were associated with the extent of both CAC and calcified plaque, but not with their presence. RANKL concentrations were not associated with plaque presence or the extent among HIV-infected men, but among HIV-uninfected men, lower RANKL concentrations were associated with greater extent of CAC and total plaque.. OPG and RANKL are dysregulated in HIV-infected men, and their relationship to the presence and extent of subclinical atherosclerosis varies by HIV status. The role of these biomarkers in CVD pathogenesis and risk prediction may be different in HIV-infected men.

Topics: Academic Medical Centers; Adult; Aged; Biomarkers; Calcium; Cohort Studies; Coronary Artery Disease; Coronary Vessels; Cross-Sectional Studies; Heart; HIV Infections; Humans; Male; Middle Aged; Osteoprotegerin; RANK Ligand; Tomography, X-Ray Computed; United States

Osteoprotegerin (OPG) is a soluble glycoprotein belonging to the tumor necrosis factor receptor superfamily and is linked to vascular atherosclerosis and calcification. The carotid intima-media thickness (CIMT) correlates with carotid atherosclerosis and is a significant predictor of cardiovascular events. The OPG levels are associated with the CIMT in coronary artery disease (CAD) patients. However, the pathophysiological mechanisms underlying this pathway remain unclear. We investigated 114 CAD patients (89 men, 25 women; mean age: 68.7 ± 10.3 years) and measured the Gensini score (a marker of the extent of coronary atherosclerosis), the mean CIMT and the plasma levels of OPG and asymmetric dimethylarginine (ADMA; a marker of endothelial function). Early carotid atherosclerosis was defined as a mean CIMT > 1.0 mm. Only 33 of the 114 patients (28.9%) had early carotid atherosclerosis. Patients with early carotid atherosclerosis had higher OPG levels than those without. The OPG levels were found to be significantly associated with ADMA (r = 0.191, P = 0.046) and the mean CIMT (r = 0.319, P = 0.001), but not with the Gensini score. A receiver operating curve analysis revealed the optimal cut-off value of the OPG levels for predicting early carotid atherosclerosis to be 100 pmol/L. A multivariate logistic regression analysis showed OPG ≥ 100 pmol/L to be significantly and independently associated with early carotid atherosclerosis (odds ratio: 2.98, 95% confidence interval: 1.22-7.20, P = 0.017). These data indicate that OPG is significantly associated with endothelial function and predicts early carotid atherosclerosis in patients with CAD.

Topics: Aged; Arginine; Biomarkers; Carotid Artery Diseases; Carotid Intima-Media Thickness; Coronary Angiography; Coronary Artery Disease; Early Diagnosis; Endothelium, Vascular; Female; Humans; Japan; Male; Middle Aged; Osteoprotegerin; Predictive Value of Tests; Risk Assessment; Risk Factors; Severity of Illness Index

Statins (HMGCoA-reductase inhibitors) produce numerous non-lipid related, 'pleiotropic' effects. Our aim was to investigate whether simvastatin treatment affects serum levels of vascular calcification inhibitors, such as fetuin-A, osteoprotegerin (OPG) and osteopontin (OPN), in patients with coronary artery disease (CAD).. A total of 98 statin-free patients with angiographically proven, newly diagnosed CAD were treated with simvastatin (20-40 mg daily) for 6 months to target a low-density lipoprotein (LDL) level <100 mg/dL (the statin group [SG]). Thirty-five age- and sex-matched healthy individuals without any chronic metabolic or cardiovascular disease at baseline served as a healthy control group (HCG). Clinical, anthropometrical and metabolic parameters and serum fetuin-A, OPG, OPN and high-sensitivity C-reactive protein (hsCRP) levels were assayed at baseline in all participants and after 6 months only in SG patients.. Compared with HCG subjects at baseline, SG patients exhibited higher serum levels of OPG (7.39 ± 2.94 pmol/L vs 2.47 ± 1.15 pmol/L, p < 0.001), OPN (60.99 ± 17.52 ng/mL vs 45.45 ± 10.26 ng/mL, p = 0.005) and hsCRP (4.66 ± 1.74 mg/L vs 1.58 ± 0.56 mg/L, p < 0.001) as well as lower serum levels of fetuin-A (0.222 ± 0.036 μg/L vs 0.839 ± 0.092 μg/L, p < 0001). Apart from significantly reducing plasma total cholesterol and LDL, simvastatin also reduced serum levels of fetuin-A (by ~62.6 %), OPG (by ~47.2 %), OPN (by ~44.6 %) and hsCRP (by ~45.3 %) (p < 0.05) in SG patients. In standard multiple regression analysis, the simvastatin-induced reduction in fetuin-A was independently associated with changes in total cholesterol (β = -0.289, p = 0.048) and LDL (β = -0.302, p = 0.032) (R (2) = 0.305, p = 0.040).. Patients with CAD showed derangements in serum levels of all vascular calcification inhibitors compared with those in healthy controls. Simvastatin treatment for 6 months significantly decreased serum fetuin-A, OPG and OPN levels, but the clinical relevance of this requires further investigation.

Topics: Aged; alpha-2-HS-Glycoprotein; Biomarkers; Coronary Artery Disease; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; Osteopontin; Osteoprotegerin; Prospective Studies; Treatment Outcome

Over the last decades Lipocalin-type prostaglandin D synthase (L-PGDS), Osteoprotegerin (OPG), Osteopontin (OPN) and Pregnancy associated plasma protein A (PAPP-A) have been reported to be associated with coronary artery disease, and L-PGDS has been proposed as a potential new diagnostic tool in the setting of stable coronary artery disease. We set out to investigate if measurement of concentrations of these biomarkers could be used to differentiate between four groups of individuals with different atherosclerotic manifestations.. A total of 120 individuals from four equal gender- and age-matched groups were studied: (i) no previous cardiovascular disease (CVD) and no coronary calcifications [CAC-negative group], (ii) no previous CVD but evidence of severe coronary calcifications [CAC-positive group], (iii) acute coronary syndrome [ACS-group], and (iv) clinical stable patients with CVD, who were referred for cardiovascular surgery [CVD-group]. Concentrations of L-PGDS, OPG, OPN and PAPP-A were analyzed and compared between the four groups.. We did not find any significant differences in L-PGDS concentrations between the four groups (p = 0.32). OPG concentrations differed significantly (p = 0.003), with the highest concentration observed in ACS patients. Considering OPN (p = 0.12) and PAPP-A (p = 0.53) their concentrations between groups did not differ significantly.. The main message from this study is the observation that L-PGDS based on a single blood test appears to be less valuable than previously proposed in identification of patients with coronary artery disease. However, ACS patients have higher OPG concentrations than patients with different manifestations of stable atherosclerosis. Neither OPN nor PAPP-A concentrations differed between groups.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Coronary Artery Disease; Female; Humans; Intramolecular Oxidoreductases; Lipocalins; Male; Middle Aged; Osteopontin; Osteoprotegerin; Pregnancy-Associated Plasma Protein-A; Vascular Calcification

Osteoprotegerin (OPG), an inhibitor of osteoclastogenesis, has recently been under the spotlight in studies regarding the pathophysiology of atherosclerosis.. To evaluate the value of serum OPG in the diagnosis and severity in patients with stable angina pectoris (SA) and unstable angina pectoris/non ST elevation myocardial infarction.. This study involved 160 patients, SA (n = 65), acute coronary syndrome (NSTE-ACS; n = 65), and a control group (n = 30). Blood samples were collected in the first hour, after 24 hours and on the fifth day. The prevalence of coronary artery atherosclerotic lesions was determined using the Gensini scoring system.. A statistically significant difference was observed in the first hour OPG levels between the control group and both the SA and NSTE-ACS group (p < 0.001). When the cut-off value was determined as 247.71 pg/mL, the sensitivity and specificity of the first hour OPG levels indicating coronary artery disease were 91.54% and 46.67%, respectively, while the positive predictive value was 88.1% and the negative predictive value was 56%. No correlations were observed between the first, 24th hour and the fifth day OPG levels and the Gensini scores. No relation was denoted between the OPG levels and number of diseased coronary arteries.. In our study, serum OPG level seemed to be unrelated to the severity or the degree of coronary artery disease in patients with SA and unstable angina pectoris/non ST elevation myocardial infarction. OPG may only be accepted as an indicator of coronary atherosclerosis.

Topics: Acute Coronary Syndrome; Angina, Stable; Angina, Unstable; Biomarkers; Comorbidity; Coronary Angiography; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Predictive Value of Tests; Prevalence; Sensitivity and Specificity

This study evaluates the relationship of blood osteoprotegerin (OPG) and receptor activator of nuclear κ-B ligand (RANKL) levels with coronary artery calcium (CAC) and cardiovascular risk factors in two studies of postmenopausal women. OPG, a marker of bone turnover, and its ligand, RANKL, may contribute to cardiovascular disease risk.. We tested the hypothesis that serum OPG and RANKL levels were associated with CAC and cardiovascular disease risk factors among postmenopausal women in the Women On the Move through Activity and Nutrition Study (WOMAN Study; n = 86; mean [SD], age 58 [2.9] y) and replicated our findings in the Healthy Women Study (HWS; n = 205; mean [SD] age, 61 [2.3] y). Serum OPG, total RANKL, and CAC were measured at baseline and 48 months in the WOMAN Study and on the eighth postmenopausal visit in the HWS.. In the WOMAN Study, higher OPG was associated with higher CAC, and higher total RANKL was associated with lower CAC and triglycerides. In the HWS, higher total RANKL was also associated with lower CAC and triglycerides. In logistic regression models adjusted for body mass index and triglycerides, the odds ratios (95% CIs) for CAC per unit increase in OPG were 1.78 (1.17-2.73) for the WOMAN Study and 1.02 (0.84-1.24) for the HWS, and the odds ratios (95% CIs) for CAC per unit increase in log total RANKL were 0.86 (0.64-1.17) for the WOMAN Study and 0.83 (0.72-0.96) for the HWS.. The inverse association of total RANKL with CAC and triglycerides is a new finding and may have important implications given the increasing use of drugs that modify total RANKL and its receptor, receptor activator of nuclear κ-B.

Topics: Biomarkers; Calcinosis; Coronary Artery Disease; Female; Humans; Middle Aged; Osteoprotegerin; Postmenopause; Predictive Value of Tests; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Risk Factors; Triglycerides

To elucidate the prognostic power of serum osteoprotegerin (OPG) in patients with stable coronary artery disease (CAD).. Serum OPG levels were measured in the CLARICOR trial cohort of 4063 patients with stable CAD on blood samples drawn at randomization. The follow-up was 2.6 years for detailed cardiovascular events and 6 years for all-cause mortality.. OPG levels were significantly increased in non-survivors (21%) compared to survivors (median [quartiles] 2092 ng/L [1636; 2800] compared to 1695 ng/L [1322; 2193, p < 0.0001]). The 2.6-year follow-up showed that OPG adds to the prediction of both cardiovascular and all-cause mortality in combination with clinical risk factors (HR [one log10 unit increase] 6.1 [95% CI 2.4-15.6, p = 0.0001]) and HR 6.5 [95% CI 3.4-12.5, p < 0.0001], respectively). Similar, in the 6-year follow-up, OPG was found to be a strong predictor for all-cause mortality. Importantly, OPG remained an independent predictor of mortality even after adjustment for both clinical and conventional cardiovascular risk markers (HR 2.5 [95% CI 1.6-3.9, p < 0.0001]).. Serum OPG has a long-lasting independent predictive power as to all-cause mortality and cardiovascular death in patients with stable CAD.

Topics: Aged; Anti-Bacterial Agents; Clarithromycin; Coronary Artery Disease; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Osteoprotegerin; Prognosis; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors

The relationship between osteoprotegerin (OPG) a glycoprotein related to bone metabolism and the metabolic syndrome (MS) has not been established.. The aim of this study is to evaluate OPG concentration in patients with MS and its association with subclinical atherosclerosis and coronary arterial calcification (CAC).. The study included 238 asymptomatic patients. MS was diagnosed according to the NCEP/ATPIII guidelines. OPG was measured by ELISA. All subjects underwent ultrasonography of the common carotid arteries to measure intima-media thickness (IMT) and evaluate the presence of atheroma plaques. In a subgroup (n=39) CAC was quantified by ECG-triggered cardiac computed tomography. Adipose tissue was excised from 25 patients and OPG expression by RT-PCR and immunohistochemistry was studied.. Patients with the MS (n=60) had higher OPG than patients without (n=178) (p<0.05). OPG correlated with IMT (r=0.2, p=0.005) and patients with atheroma plaques had higher OPG (p=0.008) and also those with coronary artery calcification (p<0.05). OPG expression was confirmed in adipose tissue (n=12) and the expression was significantly higher in patients with MS than in those without (p=0.003).. This study shows that OPG may potentially be a biomarker for cardiovascular risk/damage in the MS and identifies adipose tissue as a potential source of OPG.

Topics: Adipose Tissue; Aged; Atherosclerosis; Biomarkers; Carotid Artery, Common; Carotid Intima-Media Thickness; Coronary Artery Disease; Female; Gene Expression; Humans; Immunohistochemistry; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Reverse Transcriptase Polymerase Chain Reaction; Vascular Calcification

Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily.Recent evidence supports a relationship between serum OPG level and atherosclerosis. The aim of this study was to evaluate the possible association of OPG with the presence of coronary artery disease (CAD), its severity and prognosis in patients with chest pain and suspected coronary stenosis.. In this cross-sectional analytic study, 180 candidates of elective coronary artery angiography were recruited. Serum level of OPG was measured by ELISA method in all patients and its relation with presence and severity of CAD based on a coronary atherosclerosis score (CAS) was assessed. Patients were followed for a mean period of about 24 ± 3.2 months and the relationship between OPG levels and future cardiac events were evaluated.. The mean serum level of OPG was 1637 ± 226 pg/mL in those with CAD and 1295 ± 185 pg/mL (nonparametric p = 0.001) in those without it. There was a significant direct correlation between the level of serum OPG and CAS (rho = 0.225, p = 0.002). The optimalcut-off point for predicting a significant coronary artery obstruction was a serum level of≥ 1412 pg/mL with a sensitivity and specificity of 60% and 57.8%, respectively. Major adversecardiac events (MACE) including cardiovascular death, admission with acute coronary syndrome,or heart failure, was significantly higher in those with higher OPG levels (22 [34.3%]vs. 15 [16%], p = 0.012).. There was a direct and significant correlation between the serum level of OPG and CAS. MACE occurred more commonly in those with higher baseline OPG levels.

Topics: Acute Coronary Syndrome; Adult; Aged; Angina Pectoris; Biomarkers; Coronary Angiography; Coronary Artery Disease; Coronary Stenosis; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Osteoprotegerin; Predictive Value of Tests; Prognosis; Risk Factors; Severity of Illness Index; Time Factors; Up-Regulation

Abdominal Aortic Aneurysm (AAA) is multifactorial disease with unknown ethiology. Among the theories on the pathogenesis of AAA are some ge. netic factors, infections, disorders in connective tissue (collagenosis), arteriosclerosis, inflammation, incorrect immune response (autoimmunity). It was discovered that crucial for AAA development is intense inflammatory reaction combined with high proteolytic activity. Recent evidence confirmed the association between osteopontin (OPN) and osteoprotegerin (OPG) levels and cardiovascular diseases and arterio. sclerosis. The aim of this work was assessment of plasma levels of OPN and OPG in the group of the patients with AAA and correlation of results with clinical parameters, "classical" risk factors for development of AAA, arteriosclerosis and morbidity. The reference group consist of the patients with Leriche Syndrome (LS). The OPG level was assessed in plasma and OPN levels were assessed in plasma and urine. Plasma OPG levels were higher in AAA group than in LS group (difference not statistically significant, p = 0.0549). It was statistically significant positive correlation between plasma OPN levels and CRP levels in the groups of AAA and LS patients. It was not any association between plasma OPG and OPN levels and abdominal aortic diameter. Plasma OPG levels correlated positively with the existence of coronary artery disease in AAA patients. Insignificant, but higher levels of this protein were found also in a group of AAA patient with myocardial infarction. In LS group we found statistically significant positive association between plasma OPG levels and patient with stroke. However, in AAA patients with incidence of stroke, we found higher plasma levels of OPN. Interestingly, there was not any association between OPN levels in the urine and clinical parameters, risk factors and morbidity, including kidney diseases. inflammatory role of OPN and depicts better reflection of inflammatory reaction of OPN than OPG in both group of patients. Plasma OPG levels in AAA patients are more associated with coronary artery disease than with peripheral artery disease, what is characteristic for LS patients. Lack of association of urine OPN levels with above mentioned parameters suggest minor importance of this urine protein in clinical condition evaluation of patients with AAA and advanced arteriosclerosis.

Topics: Aged; Aortic Aneurysm, Abdominal; Arteriosclerosis; Biomarkers; Comorbidity; Coronary Artery Disease; Female; Humans; Kidney Diseases; Male; Middle Aged; Osteopontin; Osteoprotegerin; Risk Factors; Stroke

Diabetic patients often exhibit severe, asymptomatic coronary artery disease (CAD). The relationship between osteoprotegerin (OPG), inflammatory markers and silent myocardial ischemia remains to be elucidated.. We recruited 45 type 2 diabetic patients and 33 healthy controls and assessed them for silent myocardial ischemia (SMI) by myocardial perfusion imaging. Patient blood was tested for OPG, IL-6 and leptin concentrations.. OPG, leptin and IL-6 levels were found significantly elevated in diabetic patients (p < 0.001, p < 0.01, p < 0.05). Based on our classification of presence/absence of SMI in our diabetic group, we found that there was a significant association between SMI and the biomarkers IL-6 (p < 0.001), leptin (p < 0.001) and OPG (p < 0.05). In multivariate regression analyses, OPG was found to be significantly related to diabetes mellitus and to SMI. Age, sex and smoking increased the association between OPG and SMI.. High OPG, leptin and IL-6 levels are associated with the presence and severity of SMI in type 2 diabetic patients.

Topics: Adult; Biomarkers; Case-Control Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Exercise Test; Female; Humans; Interleukin-6; Leptin; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Myocardial Perfusion Imaging; Osteoprotegerin; Regression Analysis

Osteopontin (OPN) and osteoprotegerin (OPG) have recently emerged as key factors in both vascular remodeling and development of atherosclerosis. Arterial stiffness has an independent predictive value for cardiovascular events. We evaluate the relationship between OPG, OPN serum levels and vascular function in coronary artery disease (CAD) patients.. The study population was consisted of 409 subjects (280 with CAD and 129 without CAD). Carotid-femoral pulse wave velocity (PWV) was measured as an index of aortic stiffness. OPG and OPN levels were measured, as markers of vascular remodeling and calcification, by ELISA. Gensini score was used to evaluate the extent of CAD.. CAD patients, compared to those without CAD, had higher OPG (3.91 ± 1.87 pmol/l vs. 2.88 ± 1.32 pmol/l, p<0.001) and logOPN levels (1.81 ± 0.18 ng/ml vs. 1.71 ± 0.24 ng/ml, p<0.001) and impaired PWV (8.94 ± 2.21 m/s vs. 8.28 ± 1.91 m/s, p=0.006). Furthermore, PWV was associated with serum OPG levels (r=0.19, p<0.001) and with serum logOPN levels (r=0.10, p=0.049). Multivariate linear regression analysis revealed that increased OPG (p=0.013) and logOPN (p=0.006) levels are associated with 3-vessel CAD and Gensini score (p=0.04 for OPG and p=0.09 for OPN), independently of other known cardiovascular risk factors.. The present study revealed that serum OPG and OPN levels are positively associated with arterial stiffness, and with the extent of CAD. These preliminary results suggest that OPG and OPN levels are significantly correlated with vascular function contributing to the pathogenesis of atherosclerosis in CAD. Further studies are needed to explore the mechanisms of action of OPG and OPN in CAD.

Topics: Aged; Biomarkers; Coronary Artery Disease; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Osteopontin; Osteoprotegerin; Severity of Illness Index; Vascular Stiffness

Osteoprotegerin (OPG) plays a key role in atherosclerosis progression and plaque destabilization. We investigated the relationship between intima-media thickness of the common carotid artery (CCA-IMT; an early marker of atherosclerosis) and OPG levels in patients with acute coronary syndrome (ACS) and chronic coronary artery disease (CAD).. We studied 133 consecutive patients, mean age 65 ± 9 years, referred to our department for coronary angiography. They were evaluated for cardiovascular risk factors, OPG levels and CCA-IMT and accordingly divided in two subgroups: ACS and chronic CAD.. Except for age, the two groups were similar according to conventional cardiovascular risk factors. The chronic CAD group showed a CCA-IMT lower than the ACS group (0.86 ± 0.15 vs. 0.94 ± 0.22 mm, P = 0.027); there were no differences regarding the extension of coronary atherosclerosis on angiograms. The OPG levels were higher in chronic CAD patients than in ACS patients (5.36 ± 3.06 vs. 3.85 ± 2.96 pmol/l, P = 0.004). Moreover, the CCA-IMT was significantly correlated with the age of the patients (r = 0.5; P < 0.001). OPG values were not related either to age or to the CCA-IMT. At analysis of covariance, when adjusting the groups for age, the comparison of the two groups lost statistical significance for CCA-IMT (P = 0.41), whereas the OPG values remained significant after the correction (P = 0.001).. OPG levels are higher in chronic CAD patients. CCA-IMT confirmed its importance in predicting CAD, showing significantly higher values in the patients in the ACS group as compared with those in the chronic CAD group.

Topics: Acute Coronary Syndrome; Aged; Carotid Intima-Media Thickness; Chronic Disease; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Osteoprotegerin; Risk Factors

There is an ongoing debate regarding aortic valve degenerative processes. Some markers of calcification and atherosclerosis may be potentially useful in establishing their etiology.. The aim of the study was to assess the biochemical markers of calcification and atherosclerosis in patients with degenerative aortic stenosis (AS) in relation to the aortic valve calcium score (AVCS) and concomitant coronary artery disease (CAD).. The study involved 88 patients: 68 patients with degenerative AS (group A), including 44 patients with severe AS (A1; 25 patients with CAD) and 24 patients with moderate AS (A2; 13 patients with CAD) and 20 matched subjects as controls (18 patients with CAD). In all patients, clinical data were assessed, laboratory tests were done (including the analysis of serum interleukin4 [IL-4], osteoprotegerin [OPG], and fetuin-A levels), coronary angiography was performed, and the AVCS was measured.. Study groups and subgroups had comparable serum IL-4, OPG, and fetuin-A levels. There were significant differences in the AVCS between patients with severe AS, moderate AS, and controls (3605 ± 2542 Agatston units [AU], 1390 ± 1143 AU, 100 ± 194 AU, respectively; P <0.001). There were no significant correlations between the AVCS and serum IL-4, OPG, or fetuin-A levels. In moderate AS, serum OPG levels were higher in subjects with concomitant CAD (5.84 ± 1.4 vs. 4.03 ± 1.3 pmol/l, P = 0.036). In severe AS, the mean AVCS was similar in patients with and without CAD. Higher AVCS was observed only in patients with moderate AS and coexisting CAD compared with patients without CAD (1644 ± 1285 vs. 902 ± 789 AU, P = 0.038).. There were no significant differences between patients with and without degenerative AS in selected biochemical markers. The presence of CAD in moderate AS was associated with increased AVCS and serum OPG levels suggesting the effect of atherosclerosis on early valve calcification. In patients with severe AS, there were no correlations between calcification and atherosclerotic markers.

Topics: Aged; alpha-2-HS-Glycoprotein; Aortic Valve Stenosis; Case-Control Studies; Comorbidity; Coronary Artery Disease; Female; Humans; Interleukin-4; Male; Middle Aged; Osteoprotegerin; Plaque, Atherosclerotic; Poland; Severity of Illness Index

Vascular calcification is associated with increased cardiovascular mortality in chronic hemodialysis patients. This prospective study investigated the relationship between serum osteoprotegerin, receptor activator of NF-κB ligand, inflammatory markers, and progression of coronary artery calcification score.. Seventy-eight hemodialysis patients were enrolled. Serum IL-1β, IL-6, TNF-α, osteoprotegerin, receptor activator of NF-κB, fetuin A, and bone alkaline phosphatase were measured by ELISA. Coronary artery calcification score was measured two times with 1-year intervals, and patients were classified as progressive or nonprogressive.. Baseline and first-year serum osteoprotegerin levels were significantly higher in the progressive than nonprogressive group (17.39±9.67 versus 12.90±6.59 pmol/L, P=0.02; 35.17±18.35 versus 24±11.65 pmol/L, P=0.002, respectively). The ratio of serum osteoprotegerin to receptor activator of NF-κB ligand at 1 year was significantly higher in the progressive group (0.26 [0.15-0.46] versus 0.18 [0.12-0.28], P=0.004). Serum osteoprotegerin levels were significantly correlated with coronary artery calcification score at both baseline (r=0.36, P=0.001) and 1 year (r=0.36, P=0.001). Importantly, progression in coronary artery calcification score significantly correlated with change in serum osteoprotegerin levels (r=0.39, P=0.001). In addition, serum receptor activator of NF-κB ligand levels were significantly inversely correlated with coronary artery calcification scores at both baseline (r=-0.29, P=0.01) and 1 year (r=-0.29, P=0.001). In linear regression analysis for predicting coronary artery calcification score progression, only baseline coronary artery calcification score and change in osteoprotegerin were retained as significant factors in the model.. Baseline coronary artery calcification score and serum osteoprotegerin levels were significantly associated with progression of coronary artery calcification score in hemodialysis patients.

Topics: Adult; Aged; Biomarkers; Chi-Square Distribution; Chronic Disease; Coronary Artery Disease; Disease Progression; Enzyme-Linked Immunosorbent Assay; Female; Humans; Inflammation Mediators; Kidney Diseases; Linear Models; Male; Middle Aged; Osteoprotegerin; Prospective Studies; RANK Ligand; Renal Dialysis; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Turkey; Vascular Calcification

Osteoprotegerin (OPG) and fibroblast growth factor-23 (FGF23) are recognized as strong risk factors of vascular calcifications in non dialysis chronic kidney disease (ND-CKD) patients. The aim of this study was to investigate the relationships between FGF23, OPG, and coronary artery calcifications (CAC) in this population and to attempt identification of the most powerful biomarker of CAC: FGF23? OPG?. 195 ND-CKD patients (112 males/83 females, 70.8 [27.4-94.6] years) were enrolled in this cross-sectional study. All underwent chest multidetector computed tomography for CAC scoring. Vascular risk markers including FGF23 and OPG were measured. Logistic regression analyses were used to study the potential relationships between CAC and these markers. The fully adjusted-univariate analysis clearly showed high OPG (≥10.71 pmol/L) as the only variable significantly associated with moderate CAC ([100-400[) (OR = 2.73 [1.03;7.26]; p = 0.04). Such association failed to persist for CAC scoring higher than 400. Indeed, severe CAC was only associated with high phosphate fractional excretion (FEPO(4)) (≥38.71%) (OR = 5.47 [1.76;17.0]; p = 0.003) and high FGF23 (≥173.30 RU/mL) (OR = 5.40 [1.91;15.3]; p = 0.002). In addition, the risk to present severe CAC when FGF23 level was high was not significantly different when OPG was normal or high. Conversely, the risk to present moderate CAC when OPG level was high was not significantly different when FGF23 was normal or high.. Our results strongly suggest that OPG is associated to moderate CAC while FGF23 rather represents a biomarker of severe CAC in ND-CKD patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcinosis; Coronary Artery Disease; Cross-Sectional Studies; Female; Fibroblast Growth Factor-23; Fibroblast Growth Factors; Humans; Kidney Failure, Chronic; Logistic Models; Male; Middle Aged; Osteoprotegerin; Renal Dialysis

HIV-infected individuals have an increased prevalence of coronary artery disease. Receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin have been postulated as mediators of vascular calcification. 78 HIV-infected men and 32 healthy controls without history of coronary artery disease were prospectively recruited to undergo cardiac computed tomography and computed tomography angiography to assess coronary artery calcium and plaque burden. Soluble receptor activator of nuclear factor-κB ligand was lower in HIV-infected individuals than controls [2.52 (1.08-3.98) vs. 3.33 (2.44-4.64) pg/mL, P = 0.01, median (IQR) respectively]. Soluble receptor activator of nuclear factor-κB ligand was negatively associated with the number of coronary segments with plaque (Spearman ρ = -0.41, P < 0.001) and Agatston calcium score (ρ = -0.30, P < 0.01) in HIV-infected individuals even after adjusting for traditional cardiovascular risk factors.

Topics: Case-Control Studies; CD4 Lymphocyte Count; Coronary Angiography; Coronary Artery Disease; HIV Infections; Humans; Male; Middle Aged; Osteoprotegerin; Prospective Studies; RANK Ligand

Chronic heart failure (CHF) is associated with a 4-fold increased risk for osteoporotic fractures. Therefore, we sought to identify the pathophysiological link between chronic heart failure and catabolic bone remodeling.. In a total cohort of 153 subjects (123 patients with CHF, 30 patients with coronary artery disease and preserved cardiac function) as well as mice with heart failure, bone marrow (BM) plasma levels of the catabolic receptor activator of NF-κB ligand (RANKL), and its antagonist, osteoprotegerin were measured. The osteoclast inducing activity of BM plasma was tested in cell culture. BM plasma levels of RANKL and of the ratio RANKL/osteoprotegerin were significantly elevated in patients with CHF. On multivariate regression analysis, parameters of severity and duration of heart failure were independent determinants of elevated BM plasma RANKL levels. BM plasma levels of RANKL were directly correlated with the systemic marker of bone turnover C-telopeptide of type 1 collagen (r=0.6; P<0.001). Alterations in BM plasma levels of RANKL/osteoprotegerin were confirmed in a mouse model of postinfarction heart failure. Stimulation of human mesenchymal cells with BM plasma obtained from CHF patients increased the formation of osteoclasts, and this effect was blocked by the RANKL inhibition.. CHF is associated with a profound and selective elevation of the bone resorption stimulating RANKL within the BM microenvironment. These data for the first time disclose a direct pathophysiological pathway linking CHF with catabolic bone remodeling associated with an increased osteoporotic fracture risk.. URL: http://www.clinicaltrials.gov. Unique identifiers: NCT 00289822, NCT 00284713, NCT 00326989, NCT 00962364.

Topics: Aged; Animals; Biomarkers; Bone Marrow; Bone Remodeling; Case-Control Studies; Cell Differentiation; Cells, Cultured; Chronic Disease; Cohort Studies; Collagen Type I; Comorbidity; Coronary Artery Disease; Disease Models, Animal; Female; Heart Failure; Humans; Male; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Middle Aged; Osteoclasts; Osteoporosis; Osteoprotegerin; Peptides; RANK Ligand; Regression Analysis

The aim of this prospective cohort study was to evaluate the progression of coronary artery calcification (CAC), and atherosclerosis in hemodialysis (HD) patients and to relate them to novel biomarkers, i.e. serum osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF-23).. Forty-seven HD patients were followed up for 30 months or until death. Intima media thickness (CCA-IMT), atherosclerotic plaques and CAC were assessed at baseline and after 30 months. Serum mineral parameters, lipids, OPG and plasma FGF-23 were also measured.. At baseline, 70% HD patients presented detectable CAC. The patients without calcification at baseline remained calcification free at 30 months and presented lower serum OPG and FGF-23 than those with CAC. A 64.4% progression of CAC was observed in all patients with CAC at baseline. In parallel, a 13% increase in CCA-IMT was found. Both ΔCAC and ΔCCA-IMT correlated positively with baseline and follow-up serum OPG. The patients who died had significantly higher baseline CAC and serum OPG.. The plasma level of OPG could serve as a surrogate marker of progression of atherosclerosis and calcification in patients with end-stage renal disease. Therefore, the serum OPG may be a candidate biomarker of cardiovascular complications and poor outcome among dialysis patients.

Topics: Adult; Aged; Atherosclerosis; Biomarkers; Calcinosis; Cohort Studies; Coronary Artery Disease; Disease Progression; Female; Fibroblast Growth Factor-23; Follow-Up Studies; Humans; Kidney Failure, Chronic; Male; Middle Aged; Osteoprotegerin; Predictive Value of Tests; Prospective Studies; Renal Dialysis

Plasma osteoprotegerin (P-OPG) is an independent predictor of cardiovascular disease in diabetic and other populations. OPG is a bone-related glycopeptide produced by vascular smooth muscle cells and increased P-OPG may reflect arterial damage. We investigated the correlation between P-OPG and coronary artery disease (CAD) in asymptomatic type 2 diabetic patients with microalbuminuria.. P-OPG was measured in 200 asymptomatic diabetic patients without known cardiac disease. Patients with P-NT-proBNP >45.2 ng/l and/or coronary calcium score (CCS) ≥400 were stratified as high risk of CAD (n = 133), and all other patients as low risk patients (n = 67). High risk patients were examined by myocardial perfusion imaging (MPI; n = 109), and/or CT-angiography (n = 20), and/or coronary angiography (CAG; n = 86). Significant CAD was defined by presence of significant myocardial perfusion defects at MPI and/or >70% coronary artery stenosis at CAG.. Significant CAD was demonstrated in 70 of the high risk patients and of these 23 patients had >70% coronary artery stenosis at CAG. Among high risk patients, increased P-OPG was an independent predictor of significant CAD (adjusted odds ratio [CI] 3.11 [1.01-19.54] and 3.03 [1.00-9.18] for second and third tertile vs.first tertile P-OPG, respectively) and remained so after adjustments for NT-proBNP and CCS. High P-OPG was also associated with presence of >70% coronary artery stenosis(adjusted odds ratio 14.20 [1.35-148.92] for third vs. first tertile P-OPG), and 91% of patients with low (first tertile) P-OPG did not have >70% coronary artery stenosis.. Elevated P-OPG is an independent predictor of the presence of CAD in asymptomatic type 2 diabetic patients with microalbuminuria.

Topics: Adult; Aged; Albuminuria; Biomarkers; Calcium; Comorbidity; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; Risk Factors

In patients with type 2 diabetes, high serum levels of osteoprotegerin (OPG) have been associated with a greater risk of cardiovascular events. However, it remains unclear how well OPG performs when compared with traditional biomarkers of cardiovascular risk such as high-sensitivity C-reactive protein (hsCRP). Furthermore, OPG levels are also high in the presence of diabetes-related microvascular disease, and it is unclear whether OPG can distinguish microvascular disease from large-vessel atherosclerosis. The first aim of this study was to compare OPG levels against other biomarkers of cardiovascular risk in the identification of patients with documented multivessel coronary artery disease (CAD). The second aim was to compare OPG levels in patients with microvascular complications (microalbuminuria) against those with established CAD.. Three groups of male patients with type 2 diabetes were recruited: patients without microvascular complications or large-vessel atherosclerosis (n = 24), patients with microalbuminuria only (n = 23), and patients with microalbuminuria and documented multivessel CAD (n = 25). OPG, hsCRP, interleukin 6, urate, and pulse wave velocity were measured.. Serum OPG levels were significantly higher in patients with a combination of microalbuminuria and CAD than in those with microalbuminuria alone. There were no significant differences in any of the other biomarkers between the groups.. OPG was found to be superior to the other biomarkers studied in identifying patients with documented CAD. The presence of CAD was a greater determinant of serum OPG levels than microalbuminuria in our population. These findings support the use of OPG as a biomarker of cardiovascular risk.

Topics: Aged; Biomarkers; Blood Flow Velocity; Coronary Artery Disease; Diabetes Mellitus, Type 2; Humans; Male; Middle Aged; Osteoprotegerin; Risk Factors

Because T2DM increases the risk of coronary atherosclerosis and CAD and new noninvasive techniques to assess CVD risk have gained considerable popularity, it is important to know how these tools relate to each other. The aim of this study was to evaluate the relationship between the extent of coronary artery calcification measured by MDCT, plasma OPG levels, baPWV and the established cardiovascular risk factors in Korean patients with T2DM. From November 2006 to December 2007, 110 asymptomatic Korean patients with T2DM without prior evidence of CAD were assessed (mean age 57.2 years). CAC imaging was performed using a 40-slice MDCT. Serum OPG levels were measured by an enzyme-linked immunosorbent assay (Oscotec, Korea) from the serum samples of each subject. We measured the baPWV as an index of arterial stiffness. In addition, we measured fasting glucose, HbA(1)C, hsCRP and lipid profiles. A total of 74 patients (67.3%) had minimal or insignificant CAC (<10). The CACS, OPG and baPWV showed significant positive correlations with each other. The CACS was significantly associated with the baPWV, smoking and use of a statin. The baPWV was significantly associated with age, duration of DM, total cholesterol and CACS by multiple linear regression models of the dependent variables of CACS or baPWV. CAC and baPWV were significant predictors of each other (r = 0.359, P = 0.014 and r = 0.361, P = 0.004). The results of this study showed that CAC, baPWV and serum OPG levels were significantly correlated with each other in asymptomatic Korean patients with T2DM. Furthermore, our results suggest that arterial stiffness, as determined by baPWV, may predict the extent of coronary calcification by MDCT.

Topics: Aged; Calcinosis; Coronary Artery Disease; Coronary Vessels; Diabetes Mellitus, Type 2; Humans; Male; Middle Aged; Osteoprotegerin; Republic of Korea; Vascular Resistance

Osteoprotegerin (OPG) is a secretory glycoprotein which belongs to the tumor necrosis factor receptor family. OPG immunoreactivity was demonstrated in normal blood vessels and in early atherosclerotic lesions. In a previous study, we showed that high serum OPG levels are associated with progression of coronary artery disease (CAD).. The present study was designed to assess the association between serum OPG level and long-term prognosis in patients with stable coronary artery disease.. We performed a prospective, observational cohort study in 225 subjects to examine whether serum OPG levels can predict cardiovascular mortality. The median OPG levels were 1.02 ng mL(-1) at baseline.. During the follow-up (61 + or - 25 months), 27 deaths occurred including 13 cardiovascular deaths. When the subjects were divided into three groups according to serum OPG level, the group with high serum OPG showed a higher risk for cardiovascular mortality. A Multivariate Cox proportional hazards model indicated that the higher risk of cardiovascular death in the high OPG level group remained significant (hazards ratio of 7.44, 95%CI 0.92-60.30, highest vs. lowest OPG tertile). In contrast, serum OPG levels were not associated with non-cardiovascular mortality.. Our data show that serum OPG levels are an independent predictor of cardiovascular mortality in patients with stable coronary artery disease.

Topics: Aged; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Osteoprotegerin; Prognosis; Proportional Hazards Models; Survival Analysis

Patients with inflammatory rheumatic diseases (IRDs) have a higher morbidity and mortality from accelerated atherosclerosis than the general population. We hypothesized that patients with the combination of IRD and coronary artery disease (CAD) would have a certain inflammatory phenotype compared with CAD patients without this comorbidity.. Four groups of patients were included: patients with IRD, referred to coronary artery bypass grafting (CABG) (CAD-IRD, n = 67), patients without IRD, referred to CABG (CAD, n = 52), patients with IRD without CAD (IRD, n = 32) and healthy controls (n = 30). Plasma levels of several inflammatory markers were analysed by enzyme immunoassays.. (i) Plasma levels of markers of endothelial cell activation [i.e. vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor] and osteoprotegerin (OPG) were significantly increased and plasma levels of CCL21 significantly decreased in CAD-IRD patients as compared with CAD patients without IRD. (ii) Within the CAD-IRD group, acute coronary syndrome was a significant predictor of OPG, suggesting an enhanced inflammatory response during plaque destabilization in CAD-IRD patients. (iii) Plasma levels of VCAM-1, OPG and CCL21, but not lipid parameters, IRD characteristics and several other inflammatory markers (e.g. CRP), were significant predictors of CAD-IRD as opposed to CAD in two logistic regression models.. Our findings further support a role for inflammation in the accelerated form of atherosclerosis in IRD patients, and suggest that certain inflammatory pathways, such as the enhanced endothelial cell activation and the RANK ligand/RANK/OPG system, may be of particular importance.

Topics: Aged; Biomarkers; Case-Control Studies; Chemokines; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Models, Biological; Osteoprotegerin; Regression Analysis; Rheumatic Diseases; Risk Factors

Experimental evidence identified the osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB (RANK)/RANK ligand (RANKL) pathway as a candidate system modulating vascular remodeling and cardiovascular disease (CVD).. Serum concentrations of OPG and RANKL were measured in 3250 Framingham Study participants (54% women, 61+/-9 years). During a mean follow-up of 4.6 years, 143 (of 3084 free of CVD at baseline) participants developed a first CVD event, and 235 died. In multivariable models, OPG was associated with increased hazards for incident CVD and mortality (hazard ratio, 1.27; 95% CI, 1.04 to 1.54; and hazard ratio, 1.25; 95% CI, 1.07 to 1.47, per 1-SD increment in log-OPG, respectively). Log-OPG was positively related to multiple CVD risk factors, including age, smoking, diabetes, systolic blood pressure, and prevalent CVD. In a subsample (n=1264), the prevalence of coronary artery calcification, measured by computed tomography, increased nonsignificantly with OPG quartiles. RANKL concentrations displayed inverse associations with multiple CVD risk factors, including smoking, diabetes, and antihypertensive treatment, and were not related to coronary artery calcification or incident CVD or mortality.. Our prospective data reinforce OPG as marker for CVD risk factor burden and predictor for CVD and mortality in the community.

Topics: Aged; Biomarkers; Calcinosis; Cardiovascular Diseases; Coronary Artery Disease; Female; Humans; Incidence; Logistic Models; Male; Middle Aged; Osteoprotegerin; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; RANK Ligand; Risk Assessment; Risk Factors; Time Factors; Tomography, X-Ray Computed

Osteoprotegerin (OPG) produced by cardiovascular system raising the possibility that alterations of OPG serum levels may be associated with coronary artery disease (CAD). Our aim is to assess the possible role of serum OPG and soluble tumor necrosis factor-related apoptosis-inducing ligand (s-TRAIL) in the pathology of CAD and their uses as markers of plaque stability. A total of 80 male participants were categorized into 3 groups: 28 patients with acute myocardial infarction (AMI), 32 established stable CAD, and 20 healthy controls were enrolled in this study. Acute myocardial infarction and CAD groups exhibited significantly higher OPG levels and lower s-TRAIL levels compared to the stable CAD and control participants. These results are aggravated as the number of affected coronary vessels increase in AMI and stable CAD groups.. There is an association between raised serum OPG and reduced s-TRAIL in patients with CAD. Elevation of circulating OPG levels may represent a crucial compensatory mechanism to limit further vascular damage.

Topics: Biomarkers; Coronary Artery Disease; Humans; Male; Middle Aged; Myocardial Infarction; Osteoprotegerin; TNF-Related Apoptosis-Inducing Ligand

Topics: Biomarkers; Calcinosis; Cardiovascular Diseases; Coronary Artery Disease; Humans; Incidence; Osteoprotegerin; Predictive Value of Tests; RANK Ligand; Risk Assessment; Risk Factors; Time Factors

Vascular calcifications (VCs) are important predictors of cardiovascular mortality in patients with chronic kidney disease (CKD). We have shown previously that osteoprotegerin (OPG), a potential early biomarker for VC, was an independent predictor of mortality in CKD patients. The aim of our study was to follow longitudinally coronary and aortic VCs. VCs were measured using Siemens 16 detector CT in a group of predialysis and hemodialyzed patients before and after a follow-up of 4 years. Some of these patients were transplanted in the meantime. Renal function, calcium, phosphate, iPTH, hs-CRP (high sensitive protein C reactive), and OPG serum levels were also compared. VCs progressed in predialysis, hemodialyzed, and transplanted patients but the progression was not the same in all arterial beds. A progression of coronary calcifications was observed in predialysis and transplanted patients, while aortic calcifications worsened significantly only in hemodialyzed patients. OPG serum levels and hs-CRP were significantly lower among transplanted patients. We concluded that VC depends on the severity of the kidney disease. Transplanted patients are not protected from VC, yet their OPG serum levels were significantly lower, suggesting that there is no link between between OPG levels and severity of VC. Longer follow-up of these patients would be necessary to assess whether a decline in OPG correlates with better survival.

Topics: Adult; Aged; Aortic Diseases; Belgium; Biomarkers; Calcinosis; Coronary Artery Disease; Female; Humans; Kidney Diseases; Kidney Transplantation; Least-Squares Analysis; Linear Models; Longitudinal Studies; Male; Middle Aged; Osteoprotegerin; Prognosis; Renal Dialysis; Severity of Illness Index; Time Factors; Tomography, X-Ray Computed

To analyze Osteoprotegerin (OPG), and BNP plasma levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion.. 155 CAD patients were classified in four groups: stable angina (SA n=42), unstable angina (UA n=35) non-ST elevation myocardial infarction (NSTEMI n=45) and control group (n=33), measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-,2-,3 or more vessels disease), and to the stenoses degree by Duke Jeopardy score.. OPG levels were higher in patients with CAD respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with UA and NSTEMI had higher OPG level with respect to SA patients (12.2+/-7.8 and 11.6+/-6.1 respectively pmol/l p<0.001). A positive relation was found between OPG levels and coronary plaques extension by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with UA/NSTEMI respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in patients with multi-vessels vs 1-vessel disease (p<0.001).. Patients with UA and NSTEMI show high OPG and BNP levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the CAD progression.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Case-Control Studies; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Natriuretic Peptide, Brain; Osteoprotegerin; Regression Analysis; Risk Factors; Systole

The purpose of this study was to examine the association between serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) and future coronary artery disease (CAD) in apparently healthy individuals. The identification of OPG as a novel cardiovascular risk marker suggests an association between mediators of bone homeostasis and cardiovascular disease.. Serum levels of OPG and RANKL were analyzed in a prospective case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC-Norfolk) study, a cohort study of 25 663 men and women, where 951 apparently healthy individuals who developed a coronary event during 6 years' follow-up were matched by sex and age with 1705 healthy controls. Baseline OPG, but not RANKL, was higher in cases than in controls, and OPG was higher in women than in men. Both men and women in the highest OPG quartile had a higher risk for future CAD. These associations were independent of established cardiovascular risk factors, and when using OPG as a continuous variable, also after adjustment for CRP. In contrast, RANKL showed no association with coronary events.. OPG is associated with the risk of future CAD in apparently healthy men and women, independent of established cardiovascular risk factors.

Topics: Aged; Case-Control Studies; Coronary Artery Disease; England; Female; Humans; Male; Middle Aged; Osteoprotegerin; Population Surveillance; Prospective Studies; RANK Ligand; Risk Assessment; Risk Factors; Time Factors

Vascular calcification is frequently accompanied by intima-media thickening, but the associations among these atherosclerotic features and bone-related peptides in diabetic patients are unclear. We enrolled 168 type 2 diabetic patients and 40 non-diabetic subjects consecutively admitted to our hospital. Mean intima-media thickness (mean-IMT) in common carotid arteries was measured by B-mode ultrasonography. Agatston coronary artery calcium score (CACS) was obtained using multidetector-row computed tomography (MDCT). Plasma bone-related peptides osteopontin and osteoprotegerin levels were measured. Diabetic patients had higher mean-IMT (p=0.0002) and log(CACS+1) (p<0.0001) and similar bone-related peptides compared to non-diabetic subjects. In diabetic patients classified into tertiles according to their CACS levels, those with the highest scores showed the highest mean-IMT (p=0.0004) and bone-related peptides (p<0.05) among the groups. log(CACS+1) and mean-IMT were associated (p<0.0001) and were positively correlated with osteopontin (p<0.01) and osteoprotegerin (p<0.01) in diabetic patients. Multivariate analyses revealed that the significant independent determinants of log(CACS+1) were age, duration of diabetes and osteopontin (p<0.0001) and those of mean-IMT were age, hypertension, osteopontin and osteoprotegerin (p<0.0001), respectively. We have demonstrated that vascular calcification in type 2 diabetic patients is frequently accompanied by intima-media thickening, and osteopontin may act as a vascular calcification inhibitor by increasing intima-media thickness.

Topics: Adult; Age of Onset; Aged; Atherosclerosis; Calcinosis; Coronary Artery Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Multivariate Analysis; Osteopontin; Osteoprotegerin; Tomography, X-Ray Computed

Expression of bone proteins resulting from transdifferentiation of vascular smooth muscle cells into osteoblasts suggests that vascular calcifications are a bioactive process. Osteoprotegerin (OPG) could play a key role in bone-vascular calcification imbalance and could be a marker of vascular calcification extent and progression. The purpose of this study was to evaluate relationships between vascular risk biomarkers (including classic risk factors and OPG) and coronary artery calcification (CAC) extent in chronic kidney disease (CKD) patients and to establish within the markers the appropriate cut-off value to predict CAC.. A total of 133 non-dialyzed CKD patients at various stages of kidney disease [75 males/58 females, median age: 69.9 (27.4-94.6)] were enrolled, excluding extrarenal replacement therapy patients. All underwent chest multidetector computed tomography for CAC scoring. Blood samples were collected for measurement of vascular risk markers (kidney disease, inflammation, nutrition, calcium phosphate and OPG). A potential relationship between CAC and these biological markers was investigated, and a receiver-operating characteristic (ROC) curve was designed thereafter to identify a cut-off value of involved markers that best predicted the presence of CAC.. After adjustment for age, diabetes, smoking and gender, among biological markers, only low-estimated glomerular filtration rate using Modification of Diet in Renal Disease [OR = 3.63 (1.10-12.02)], high FEPO(4) [OR = 3.99 (1.17-13.6)] and high OPG levels [OR = 8.54 (2.14-34.11)] were associated with the presence of CAC. A protective effect of 1.25(OH)(2) vitamin D [OR = 0.20 (0.05-0.79)] and LDL cholesterol [OR = 0.27 (0.08-0.94)] on CAC was also observed. ROC curve analysis showed that the OPG best cut-off value predicting CAC was 757.7 pg/mL.. These results suggest that a CAC increase is strongly associated with a plasma OPG increase in CKD patients. The values of OPG >757.7 pg/mL allow us to predict the presence of CAC in these patients.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcinosis; Chronic Disease; Coronary Artery Disease; Female; Glomerular Filtration Rate; Humans; Kidney Diseases; Male; Middle Aged; Osteoprotegerin; Predictive Value of Tests; Risk Factors; ROC Curve

Cardiovascular disease is the major cause of morbidity and mortality in chronic kidney disease (CKD) and early biomarkers are required which can predict disease and death in such patients. The aim of our study was to investigate if osteoprotegerin (OPG) could be a predictor of coronary artery calcification (CAC) and mortality in CKD.. A total of 77 outpatients (32 with pre-dialysis CKD and 45 undergoing hemodialysis) were followed-up during 2 years. Measurements of CAC were performed using Siemens Multidetector CT software and calcium scores were measured according to the Agatston method.. OPG was an independent predictor of the Agatston score for CAC and correlated with the degree of CAC in pre-dialysis patients. A two-sample t-test characterized survivors as having a better glomerular filtration rate, lower Agatston scores, and lower serum levels of OPG. Kaplan-Meier survival curves separated survivors from non-survivors at plasma OPG cut-off levels of <3.1 ng/mL. A multivariable logistic regression analysis showed that OPG was an independent predictor of mortality from all causes in CKD patients.. OPG predicted mortality in CKD patients and could be a valuable biomarker in early detection of CAC in these patients.

Topics: Adult; Aged; Biomarkers; Chronic Disease; Coronary Artery Disease; Female; Humans; Kidney Diseases; Male; Middle Aged; Osteoprotegerin; Predictive Value of Tests; Risk Factors; Survival Rate

We prospectively assessed the evolution of coronary artery calcification (CAC) and osteoprotegerin (OPG) levels after renal transplantation (RT). Eighty-three recipients were followed-up prospectively during 1 year. Blood was collected before (baseline) and after RT for determination of mineral metabolism parameters including OPG. CAC was measured by multidetector computed tomography at transplantation (baseline) and 1 year later. Progression of CAC was defined as a difference between the follow-up square-root transformed volume (SRV) and the baseline SRV >or= 2.5. By multivariate analysis, baseline OPG level, age and low LDL levels were significantly associated with baseline CAC. RT was accompanied by mineral metabolism improvement with a decrease of OPG from 955 [395-5652] to 527 [217-1818] pg/mL and parathyroid hormone from 94 [1-550] to 62 [16-410] pg/mL. Thirty-one percent of patients did not exhibit CAC at baseline. CAC diminished in 14.5%, stabilized in 59.2% and progressed in 26.3% of patients. Baseline CAC was associated with progression (OR 2.92 [1.02-8.36]). No significant association was found between OPG and CAC progression despite a higher baseline OPG level in progressors (1046 [456-3285]) vs. non-progressors (899 [396-5952] pg/mL). CAC at baseline, but not 1 year after RT, is independently associated with baseline OPG; posttransplant CAC progression is predicted by baseline CAC score.

Topics: Adult; Aged; Calcinosis; Coronary Artery Disease; Disease Progression; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Kidney Transplantation; Logistic Models; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Parathyroid Hormone; Predictive Value of Tests; Prospective Studies; Risk Factors; ROC Curve; Young Adult

Although cardiovascular disease is a principal cause of death in patients with chronic kidney disease (CKD), it is often asymptomatic in diabetic patients. The coronary artery calcification score (CACS) measured by multidetector computed tomography (MDCT) is useful for screening ischemic heart disease in the general population. We investigated which clinical parameters predict high CACS in predialysis diabetic nephropathy (DN). Participants were 85 patients with DN. Nobody had any history of coronary angioplasty or coronary bypass surgery. We measured blood counts, blood chemistry, bone alkaline phosphatase, intact-PTH, interleukin-6, osteoprotegerin (OPG), hemoglobin A1c, 25-hydroxyvitamin D (25(OH)D) and fetuin-A. CACS and bone mineral density (BMD) were measured by a single 16-slice MDCT and DEXA, respectively. The median value of CACS equaled 256 Agatston units (range 0-4494 units). Stepwise increase in CACS with CKD stage progression was observed (p<0.01 for trend). Simple regression analyses showed that Log (CACS+1) was positively correlated with age, systolic blood pressure, phosphorus and OPG. In addition, it was negatively correlated with nutritional parameters, such as body mass index, albumin, total-cholesterol and 25(OH)D. Fetuin-A and BMD had no impact on CACS. Multiple regression analyses showed that low albumin and high OPG were associated with high CACS. The sensitivity of OPG for detecting CACS>200 was 80%, when the cut-off value was 1.2 ng/mL. In conclusion, CACS increased with CKD stage progression in predialysis DN patients. Serum OPG was positively associated with high CACS and can be a useful screening tool for severe coronary calcification, whereas no association between fetuin-A and CACS was found.

Topics: Adult; Aged; Aged, 80 and over; Calcinosis; Coronary Artery Disease; Cross-Sectional Studies; Diabetic Nephropathies; Female; Humans; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Renal Dialysis; Risk Factors

The objective of this study was to explore the relationship between increased plasma osteoprotegerin (OPG) levels and acute coronary syndrome (ACS).. Plasma OPG levels from 85 subjects undergoing coronary artery angiography in three different groups, including ACS (n=45), stable angia pectoris (SAP) (n=20) and normal coronary artery (NCA) (n=20), were detected by ELISA. Twenty-two ascending aorta specimens were surgically taken from 8 ACS, 7 SAP and 7 NCA patients, and OPG mRNA expression in the specimens was detected by RT-PCR. In addition, 10 coronary artery sections each were selected from autopsy archives for the presence of vulnerable atherosclerosis plaques (VP), stable plaques (SP) or no plaques (NP) and OPG protein expression in the sections was detected by immunohistochemistry.. Plasma OPG concentrations in the ACS group were significantly higher than those in the SAP or NCA group.The levels of plasma OPG in the 1-, 2- and 3-vessel disease subgroups of ACS were increasingly higher (P < 0.05 or 0.01). Multiple logistic regression analyses revealed a significant independent relation between plasma OPG concentration and the presence of ACS (P = 0.032, odd ratio = 1.006).Ascending aorta specimens from the ACS group had a greater OPG mRNA expression than those from the NCA or SAP group (P < 0.01). Sections with VP had a markedly higher OPG expression than sections with SP or NP (P < 0.05 and P < 0.01, respectively).. Increased plasma osteoprotegerin levels are associated with the presence and severity of acute coronary syndrome.

Topics: Acute Coronary Syndrome; Angina Pectoris; Biomarkers; Coronary Artery Disease; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Logistic Models; Male; Middle Aged; Osteoprotegerin; Pilot Projects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Severity of Illness Index

Accumulating evidence indicates that vascular and bone mineralization may be related, although the exact mechanism remains unknown.. Our objective was to investigate whether an observed inverse association between bone mineral density (BMD) and coronary artery calcification (CAC) in postmenopausal women currently taking estrogen therapy is mediated by osteoprotegerin (OPG) or receptor activator of nuclear factor-kappaB ligand (RANKL).. Participants were 92 postmenopausal women (aged 58-81 yr) taking estrogen therapy who had hip and spine BMD assessed by dual-energy x-ray absorptiometry and CAC measured by electron-beam computed tomography in 1998-2002 and serum RANKL and OPG levels measured in samples collected in 1997-1999. Total CAC score was dichotomized as none/minimal (10).. OPG serum levels were higher in women who had some CAC compared with those who had none/minimal (126.8 +/- 1.08 vs. 102.9 +/- 1.07 pg/ml, respectively, P = 0.03); these differences became nonsignificant after adjustment for age and other risk factors (P = 0.51). A 1 sd increase in hip BMD was associated with significantly lower odds of having CAC > 10 (odds ratio = 0.52; 95% confidence interval = 0.29-0.93) independent of age, fat-free mass, high-density lipoprotein cholesterol, current smoking, and use of cholesterol-lowering medications. Other skeletal sites demonstrated a similar pattern. Addition of RANKL and/or OPG to the model had minimal effect on the magnitude or statistical significance of the BMD-CAC association. Additionally, a test of interaction indicated that RANKL and OPG are not significant effect modifiers.. Serum OPG and RANKL do not account for the observed association between bone and coronary artery calcification among postmenopausal women using hormone therapy.

Topics: Aged; Aged, 80 and over; Bone Density; Calcinosis; Coronary Artery Disease; Estrogen Replacement Therapy; Female; Humans; Middle Aged; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B

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.

Topics: Adult; Aged; Biomarkers; Calcinosis; Coronary Artery Disease; Coronary Vessels; Female; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Middle Aged; Osteoprotegerin; Risk Factors; Texas; Tomography, X-Ray Computed

Osteoprotegerin (OPG), a soluble decoy receptor for receptor activator of nuclear factor kappaB ligand, is implicated in the pathogenesis of atherosclerosis. Patients with rheumatoid arthritis (RA) have inflammation and increased atherosclerosis. We examined the hypothesis that OPG concentrations are increased in patients with RA and are associated with coronary-artery atherosclerosis. Serum OPG concentrations were measured by ELISA and coronary-artery calcification by electron-beam computer tomography in 157 patients with RA and 87 control subjects. OPG concentrations were higher in patients with long-standing RA (n=67) [median (interquartile range)]: [1895 (1337-2847) pg/mL, and early RA (n=90): [1340 (1021-1652) pg/mL, than controls 1068 (692-1434) pg/mL; (p<0.001)]. In patients with RA, OPG concentrations were associated with erythrocyte sedimentation rate (p<0.001), homocysteine (p=0.001), disease duration (p=0.02), coronary calcium score (p=0.03), and cumulative dose of corticosteroids (p=0.04) after adjustment for age and sex. In patients with long-standing RA, OPG was associated with coronary-artery calcification independently of cardiovascular risk factors and disease activity [OR for every increase in 500 pg/mL of OPG=2.22 (1.43-3.34), p<0.001]. In conclusion, OPG concentrations are increased in patients with RA and are associated with inflammation. In patients with long-standing disease, OPG is independently associated with coronary-artery calcification.

Topics: Adult; Aged; Arthritis, Rheumatoid; Biomarkers; Calcinosis; Case-Control Studies; Coronary Artery Disease; Female; Humans; Male; Middle Aged; Osteoprotegerin; Radiography; Time Factors

Topics: Biomarkers; Coronary Artery Disease; Humans; Osteoprotegerin; Vascular Diseases

This study prospectively evaluated the relationship between cardiovascular risk factors, selected biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, and osteoprotegerin [OPG]), and the progression of coronary artery calcification (CAC) in type 2 diabetic subjects.. Coronary artery calcification is pathognomonic of coronary atherosclerosis. Osteoprotegerin is a signaling molecule involved in bone remodeling that has been implicated in the regulation of vascular calcification and atherogenesis.. Three hundred ninety-eight type 2 diabetic subjects without prior coronary disease or symptoms (age 52 +/- 8 years, 61% male, glycated hemoglobin [HbA(1)c] 8 +/- 1.5) were evaluated serially by CAC imaging (mean follow-up 2.5 +/- 0.4 years). Progression/regression of CAC was defined as a change > or =2.5 between the square root transformed values of baseline and follow-up volumetric CAC scores. Demographic data, risk factors, glycemic control, medication use, serum hs-CRP, IL-6, and plasma OPG levels were measured at baseline and follow-up.. Two hundred eleven patients (53%) had CAC at baseline. One hundred eighteen patients (29.6%) had CAC progression, whereas 3 patients (0.8%) had regression. Age, male gender, hypertension, baseline CAC, HbA(1)c >7, waist-hip ratio, IL-6, OPG, use of beta-blockers, calcium channel antagonists, angiotensin-converting enzyme (ACE) inhibitors, statins, and Framingham/UKPDS (United Kingdom Prospective Diabetes Study) risk scores were univariable predictors of CAC progression. In the multivariate model, baseline CAC (odds ratio [OR] for CAC >400 = 6.38, 95% confidence interval [CI] 2.63 to 15.5, p < 0.001), HbA(1)c >7 (OR 1.95, CI 1.08 to 3.52, p = 0.03), and statin use (OR 2.27, CI 1.38 to 3.73, p = 0.001) were independent predictors of CAC progression.. Baseline CAC severity and suboptimal glycemic control are strong risk factors for CAC progression in type 2 diabetic subjects.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcinosis; Cohort Studies; Coronary Artery Disease; Diabetes Mellitus, Type 2; Disease Progression; Female; Glycated Hemoglobin; Humans; Interleukin-6; Male; Middle Aged; Osteoprotegerin; Risk Factors; Severity of Illness Index; Tomography, X-Ray Computed

Topics: Aged; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Japan; Male; Middle Aged; Osteoprotegerin; Polymorphism, Genetic; Regression Analysis

This study sought to prospectively evaluate the relationship between plasma osteoprotegerin (OPG), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], coronary artery calcification (CAC), and cardiovascular events in patients with type 2 diabetes.. Arterial calcification is a prominent feature of atherosclerosis and is associated with an increased risk of cardiovascular events. Osteoprotegerin is a cytokine that has recently been implicated in the regulation of vascular calcification.. A total of 510 type 2 diabetic patients (53 +/- 8 years; 61% male) free of symptoms of cardiovascular disease were evaluated by CAC imaging. Risk factors, hs-CRP, IL-6, and OPG levels were measured. Patients were followed up for cardiovascular events (cardiac death, myocardial infarction, acute coronary syndrome, late revascularization, and nonhemorrhagic stroke).. Significant CAC (>10 Agatston units) was seen in 236 patients (46.3%); OPG was significantly elevated in patients with increased CAC. In multivariable analyses, OPG retained a strong association with elevated CAC scores after adjustment for age, gender, and other risk factors (odds ratio = 2.84, 95% confidence interval 2.2 to 3.67; p < 0.01). Sixteen cardiovascular events occurred during a mean follow-up of 18 +/- 5 months. The waist-to-hip ratio, United Kingdom Prospective Diabetes Study (UKPDS) risk score, OPG level, and CAC score were significant predictors of time to cardiovascular events in a univariate Cox proportional hazards model. In the multivariate model, the CAC score was the only independent predictor of adverse events. Levels of hs-CRP and IL-6 were related to neither the extent of CAC nor short-term events.. A high proportion of asymptomatic diabetic patients have significant subclinical atherosclerosis. Of the biomarkers studied, only OPG predicted both subclinical disease and near-term cardiovascular events. Therefore, measurement of OPG merits further investigation as a simple test for identifying high-risk type 2 diabetic patients.

Topics: Biomarkers; C-Reactive Protein; Calcinosis; Cardiovascular Diseases; Coronary Artery Disease; Diabetes Mellitus, Type 2; Female; Glycoproteins; Humans; Interleukin-6; Male; Middle Aged; Osteoprotegerin; Prognosis; Proportional Hazards Models; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors; Sensitivity and Specificity; Survival Rate

Emerging evidence from in vitro studies and mouse genetics attributes to osteoprotegerin (OPG), a member of the tumor necrosis factor receptor family, an important role in vascular biology. We evaluated serum levels of OPG in a group of children with Kawasaki disease (KD), before immunoglobulin (IVIG) infusion and at 3-month followup.. Fifty patients (38 boys, 20 girls, median age 3.6 yrs, range 4 mo-7.4 yrs) fulfilling criteria for the diagnosis of KD, 30 febrile controls with infectious diseases, 18 patients with juvenile systemic lupus erythematosus (JSLE), and 40 healthy controls were enrolled. All KD patients received IVIG treatment within the first 10 days of illness, and aspirin. Coronary artery abnormalities (CAA) were reported in 6 out of 58 patients; all were male and younger than 5 years. Serum OPG was measured by ELISA in patients with KD before IVIG and at 3-month followup (median time 3.2 mo, range 3-3.5).. At baseline and at the 3-month followup, KD patients had significantly higher OPG serum levels than febrile controls (p < 0.001 and p < 0.004, respectively), JSLE patients (p < 0.0001), and healthy controls (p < 0.0001). At baseline, KD patients who developed CAA had higher OPG serum levels than those without CAA (p = 0.0001); this difference was not present at 3-month followup. The optimal OPG cutoff value of 123.2 pg/ml was a significant predictor for CAA, with a sensitivity of 100% (6/6), a specificity of 96% (50/52), and a positive predictive value of 75% (6/8).. High OPG levels might be the result of compensatory production during acute and subacute phases of KD. OPG assay might be an additional clinically useful marker to monitor and differentiate patients who develop, from those who do not develop, such coronary artery abnormalities.

Topics: Biomarkers; Child; Child, Preschool; Cohort Studies; Coronary Artery Disease; Female; Glycoproteins; Humans; Immunoglobulins, Intravenous; Infant; Male; Mucocutaneous Lymph Node Syndrome; Osteoprotegerin; Predictive Value of Tests; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Sensitivity and Specificity

Topics: Coronary Artery Disease; Glycoproteins; Humans; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor

Topics: Carrier Proteins; Coronary Artery Disease; Glycoproteins; Humans; Male; Membrane Glycoproteins; Middle Aged; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor

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).. 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 0.94+/-0.34, 1.04+/-0.38, 1.19+/-0.38, and 1.44+/-0.54 ng/mL (medians 0.91, 0.99, 1.09, and 1.37) for the subjects with normal coronary arteries or luminal irregularities, 1-vessel disease, 2-vessel disease, and 3-vessel disease, respectively. Multivariate logistic regression analysis revealed that serum OPG levels were significantly associated with the presence of CAD [odds ratio, 5.2; 95% confidence interval, 1.7 to 16.0].. Our data show that serum OPG levels are associated with the presence and severity of CAD, suggesting that OPG may be involved in the progression of CAD.

Topics: Adult; Aged; Coronary Angiography; Coronary Artery Disease; Disease Progression; Female; Glycoproteins; Humans; Male; Middle Aged; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors