osteoprotegerin and Stroke

Background Osteoprotegerin is a cytokine involved in bone metabolism as well as vascular calcification and atherogenesis. Although circulating osteoprotegerin levels are robustly associated with incident cardiovascular disease ( CVD ) in the general population, its relevance as a biomarker among populations at high CVD risk is less clear. Methods and Results Three independent reviewers systematically searched PubMed, EMBASE , and Web of Science to identify prospective studies that had recruited participants on the basis of having conditions related to high CVD risk. A total of 19 studies were eligible for inclusion, reporting on 27 450 patients with diabetes mellitus (2 studies), kidney disease (7 studies), preexisting heart disease (5 studies), or recent acute coronary syndromes (5 studies) at baseline. Over a mean follow-up of 4.2 years, 4066 CVD events were recorded. In a random-effects meta-analysis, the pooled risk ratio for CVD events comparing people in the top versus the bottom tertile of osteoprotegerin concentration was 1.30 (95% confidence interval, 1.12-1.50; P<0.001; I

Topics: Acute Coronary Syndrome; Angina Pectoris; Biomarkers; Cardiovascular Diseases; Comorbidity; Diabetes Mellitus; Heart Diseases; Humans; Kidney Diseases; Myocardial Infarction; Myocardial Revascularization; Osteoprotegerin; Risk; Stroke

Stroke is a major cause of mortality and morbidity around the world. Microembolic signals (MES), as the markers of unstable atherosclerotic plaque, can predict the occurrence and prognosis of ischemic stroke (IS). MES can also assess the efficacy of antithrombotic agents and predict the recurrence probability of IS. Unstable plaques are the main source of MES; thus, numerous biomarkers of atherosclerotic plaque instability are highly likely to predict the presence of MES. This study aims to review recent biomarker candidates for MES or microembolism. Current research indicates that the following are independent markers for positive MES: high level of serum soluble P-selectin, chemokine (C-X-C motif) ligand 16 (CXCL16) and fibrinogen, high neutrophil count, reduced ratio of CD4+CD25

Topics: Biomarkers; Brain Ischemia; Chemokine CXCL16; Fibrinogen; Fibrinolytic Agents; Humans; Intracranial Embolism; Neutrophils; Osteoprotegerin; P-Selectin; Plaque, Atherosclerotic; Prognosis; Recurrence; Stroke; T-Lymphocytes, Regulatory

Stroke is one of the most common causes of disability and lack of independence in activities of daily living in adults. One of the most important factors predisposing to stroke, besides hypertension and atrial fibrillation, is carotid atherosclerosis. Rupture of unstable plaque with formation of a platelet plug is the cause of about 20-25% of ischemic strokes. Osteoprotegerin (OPG) is an important regulator of bone remodeling under physiological and disease conditions, as well as the regulator of osteoclast differentiation. Elevated plasma OPG level is associated with increased risk of ischemic stroke and heart diseases, including atrial fibrillation, and is observed in patients with symptomatic carotid artery stenosis and atherosclerotic vulnerable plaques. Furthermore, the occurrence of certain genotypes of OPG is 10 times more common in people with unstable atherosclerotic plaque, making them an independent risk predictor of plaque instability. This article summarizes the current state of knowledge on the potential role of OPG as a biomarker and prognostic indicator of stroke.

Topics: Atherosclerosis; Biomarkers; Carotid Artery Diseases; Genotype; Humans; Osteoprotegerin; Plaque, Amyloid; Plaque, Atherosclerotic; Risk Assessment; Stroke

The major cause of ischemic stroke is unstable or thrombogenic atherosclerotic plaques. Vascular calcification, a process that appears crucial for plaque stability, shares common features with bone formation. Many bone turnover proteins exhibit metabolic properties, but the evidence is conflicting regarding their possible involvement in vascular disease. Antibodies against sclerostin and dickkopf-1 are currently being evaluated as potential therapy for treating bone disorders. It is important to carefully assess the cardiovascular and metabolic effects of these proteins. The aim of the present study was to explore serum levels of bone turnover markers in patients with acute noncardio-embolic ischemic stroke in comparison with healthy controls.. In a cross-sectional study, we compared 48 patients aged ≥75 years with noncardio-embolic ischemic stroke and 46 healthy controls. Serum levels of dickkopf-1, sclerostin, osteoprotegerin, osteopontin and osteocalcin were determined by Luminex technique.. We found clearly increased serum levels of osteoprotegerin, sclerostin, dickkopf-1 and osteopontin in patients with stroke compared with healthy controls. No difference was seen in serum levels of osteocalcin between the two groups.. Our findings strengthen the hypothesis of bone turnover markers being involved in vascular disease. Whether these proteins can be used as candidate markers for increased stroke risk or prognostic biomarkers remains to be further elucidated.

Topics: Adaptor Proteins, Signal Transducing; Aged; Aged, 80 and over; Biomarkers; Bone Morphogenetic Proteins; Bone Remodeling; Brain Ischemia; Female; Genetic Markers; Humans; Intercellular Signaling Peptides and Proteins; Male; Osteocalcin; Osteopontin; Osteoprotegerin; Plaque, Atherosclerotic; Stroke

High circulating levels of osteoprotegerin (OPG) carry prognostic impact in cohorts with various cardiovascular diagnoses. With the present study, we aim to investigate the role of OPG within the scale of myocardial damage.. This study includes 219 consecutive patients with acute ST-elevation myocardial infarction randomized to primary percutaneous coronary intervention (pPCI) or pPCI and remote ischemic per-conditioning. Salvage index via myocardial single-photon emission CT assessment (data available in 61% of the patients) was performed, and derived from Day 1 (myocardial area at risk) and Day 30 (final infarct size). Plasma OPG levels were measured using an in-house immunoassay. A combined end-point of all-mortality, myocardial infarction, stroke, readmission for heart failure and ischemic stroke/transient ischemic attack (Major Adverse Cardiac and Cerebrovascular Events [MACCE]) was used for follow-up; 45 (38-48 months).. High OPG levels were associated with the severity of cardiovascular disease. During follow-up, OPG was a predictor of MACCE (unadjusted, HR: 2.1, 95% CI: 1.14-3.85, P = 0.017). Adjustments for age, gender, and body mass index preserved the independent predictive power of OPG. However, OPG levels were neither associated with salvage index nor with the final infarct size. Remote ischemic per-conditioning had no effect on OPG levels.. Despite absent association between OPG levels and the scale of myocardial damage, high OPG levels predict a significantly increased risk of MACCE.

Topics: Aged; Biomarkers; Brain Ischemia; Denmark; Female; Heart Failure; Humans; Immunoassay; Ischemic Attack, Transient; Ischemic Preconditioning; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Osteoprotegerin; Patient Readmission; Percutaneous Coronary Intervention; Predictive Value of Tests; Proportional Hazards Models; Recurrence; Risk Factors; Stroke; Time Factors; Tomography, Emission-Computed, Single-Photon; Treatment Outcome; Up-Regulation; Upper Extremity

Osteoprotegerin was implicated in vascular injury and inflammatory responses, but its prognostic value in ischemic stroke remained unclear. We aimed to prospectively investigate the association between plasma osteoprotegerin and ischemic stroke prognosis combined with a Mendelian randomization analysis.. Our prospective study follows the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) reporting guideline. We measured baseline plasma osteoprotegerin levels for 3490 ischemic stroke patients recruited between August 2009 and May 2013 in 26 hospitals across China. The primary outcome was a composite outcome of death and major disability at 3 months after ischemic stroke.. Elevated plasma osteoprotegerin was associated with poor prognosis of ischemic stroke, and genetically determined high plasma osteoprotegerin was associated with an increased risk of primary outcome in Mendelian randomization analysis.. URL: https://www.. gov; Unique identifier: NCT01840072.

Topics: Biomarkers; Brain Ischemia; Humans; Ischemic Stroke; Mendelian Randomization Analysis; Osteoprotegerin; Prognosis; Prospective Studies; Risk Factors; Stroke

Osteoprotegerin (OPG), also known as osteoclastogenesis inhibitory factor, is a tumor necrosis factor receptor superfamily component. There is an established relationship between OPG and cardiovascular disease. We hypothesized that plasma OPG levels are associated with functional outcomes in acute ischemic stroke patients who have undergone endovascular thrombectomy (EVT).. From April 2014 through December 2020, a total of 360 acute ischemic stroke patients who underwent EVT were prospectively included in this retrospective observational study. Plasma OPG was measured after fasting for 12 postoperative hours after EVT. A modified Rankin Scale (mRS) was used to assess functional outcomes 3 months after index stroke occurrence. Univariate and multivariate binary logistic regression and ordinal logistic regression analyses were performed to investigate the association of plasma OPG levels with poor functional outcomes.. Overall, 145 (40.2%) patients had poor (mRS > 2) outcomes. The mean ± standard deviation plasma OPG level was 200.2 ± 74.4 pg/mL. Multivariate analysis after adjusting for sex, body mass index, and variables with. This study demonstrated that higher plasma OPG levels were associated with poor functional outcomes in acute ischemic stroke patients who underwent EVT.

Topics: Humans; Ischemic Stroke; Osteoprotegerin; Stroke; Thrombectomy; Treatment Outcome

Osteoprotegerin (OPG) is a component of the tumor necrosis factor receptor superfamily. Several studies have shown a relationship between OPG and cardiovascular disease. We investigated the association between plasma OPG levels and hemorrhagic transformation in stroke patients who received endovascular thrombectomy (EVT).. We prospectively enrolled 360 patients diagnosed with acute ischemic stroke and performed EVT from April 2014 to December 2020. Blood sampling for plasma OPG was performed after fasting for 12 h after EVT. Hemorrhagic transformation was defined using the definition and classification of the European Cooperative Acute Stroke Study-3 trial.. Of all the included patients, 130 (36.1%) experienced hemorrhagic transformation. The mean ± standard deviation of the plasma OPG concentrations was 200.2 ± 74.4 pg/mL. In multivariable analysis, after adjusting for age, sex, body mass index (BMI), and variables with p < 0.1 in univariable analysis (diabetes mellitus, atrial fibrillation, coronary artery disease, alcohol intake, current smoking, NIHSS, ASPECT score, mass effect, hemoglobin, vitamin D 25(OH)D), increased plasma OPG concentration was independently related to any hemorrhagic transformation (highest tertile vs. lowest tertile of OPG; odds ratio [OR] 2.31, 95% confidence interval [CI] (1.29-4.14), p = 0.005) and severity of hemorrhagic transformation (OR 2.92, 95% CI (1.66-5.12), p = 0.001).. Our results demonstrate that increased plasma OPG level is related to the occurrence and severity of hemorrhagic transformation in patients with cerebral infarction who receive EVT.

Topics: Brain Ischemia; Endovascular Procedures; Humans; Ischemic Stroke; Odds Ratio; Osteoprotegerin; Stroke; Thrombectomy; Treatment Outcome

Osteoprotegerin is involved in the progression of atherosclerosis. This study aimed to determine whether TNFRSF11B polymorphisms are associated with prognosis of large artery atherosclerosis (LAA) stroke. Three TNFRSF11B polymorphisms (rs2073617, rs2073618 and rs3134069) were genotyped in 1010 patients with LAA stroke. Short-term outcome was evaluated using the modified Rankin Scale score at 3-month after stroke onset. Long-term outcome was assessed using the stroke recurrence. We found that rs2073617G was associated with an increased risk of poor outcome of LAA stroke (additive model: odds ratio (OR) = 1.35, 95% confidence interval (CI) = 1.06-1.73). This association was also observed in rs3134069C (additive model: OR = 1.53, 95% CI = 1.10-2.12). Furthermore, when we combined these two polymorphisms according to the numbers of risk alleles (rs2073617G and rs3134069C), we found that the patients with 3-4 risk alleles were statistically significantly associated with an increased risk of poor outcome of LAA stroke (OR = 1.90, 95% CI = 1.10-3.28) compared with 0-2 risk alleles, and this increased risk was more evident among those with hypertension (OR = 2.02, 95% CI = 1.04-3.91), those without diabetes (OR = 2.02, 95% CI = 1.02-4.01) and those with smoking (OR = 2.43, 95% CI = 1.09-5.42). In silico analysis showed that rs2073617 and rs3134069 are located in various histone modification marked regions, DNase I hypersensitive sites and can change the binding of regulatory motifs. Moreover, rs2073617 is also located in the binding site of transcription factors. Our findings suggested that TNFRSF11B polymorphisms may be associated with an increased risk of short-term poor outcome of LAA stroke.

Topics: Alleles; Arteries; Atherosclerosis; Case-Control Studies; Computer Simulation; Disability Evaluation; Disease Progression; Female; Follow-Up Studies; Histone Code; Humans; Male; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; Prognosis; Recurrence; Stroke

Elevated circulating osteoprotegerin (OPG) level is associated with an increased risk of hospitalization for ischemic stroke and coronary artery disease. The aim of the present study was to analyze whether OPG assessment may improve the prediction of mortality in patients with stroke.. Serum OPG, fetuin A, 25-OH-D. The mean OPG serum level was 14.6 ± 6.0pmol/L (range: 3.7-43.4). There were no significant differences in the OPG values between men and women (13.9 ± 5.0 versus 15.1 ± 6.7 pmol/L; P = .12). Therefore, tertiles were calculated for the whole group. During the follow-up, 85 (35.4%) patients died and 92 (38.3%) died or had recurrent stroke. OPG level appeared a significant predictors of death and composite end-point (death/recurrent stroke), in addition to the well-established once (age, atrial fibrillation, diabetes RANKIN at admission and discharge, severity of stroke). In multivariable stepwise backward analyses, the OPG level persisted as a significant and independent predictor of death (hazard ratio [HR] = 1.084 (95% confidence intervals: 1.036-1.134)] and composite and point (HR = 1.082 [1.037-1.129]).. OPG level may be considered as a predictor of mortality in stroke patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Female; Humans; Male; Middle Aged; Osteoprotegerin; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Time Factors; Up-Regulation

Instability of atherosclerotic plaques is associated with the occurrence of stroke. Microembolic signals (MESs) are an indicator of unstable plaque. A relationship between plasma osteoprotegerin (OPG) and ischemic stroke has already been identified. The aim of this study was to investigate whether plasma OPG levels have a relationship with MESs and to evaluate the feasibility of OPG as a biomarker of stroke severity and occurrence of MESs.. Our study consisted of 127 patients with large artery atherosclerosis stroke and 56 controls. Patients were classified into subgroups based on stroke severity and the occurrence of MESs. MES-monitoring was performed for 60 min using transcranial Doppler within 72 h of stroke onset. Stroke severity at admission was assessed by the National Institutes of Health Stroke Scale.. Plasma OPG levels correlate with stroke severity and the occurrence of MESs.

Topics: Aged; Biomarkers; Brain Ischemia; Female; Humans; Intracranial Embolism; Male; Middle Aged; Osteoprotegerin; Stroke

The serum level of osteoprotegerin (encoded by OPG or TNFRSF11B) was previously shown to be increased in patients with ischemic stroke. A single nucleotide polymorphism rs3134069 in the TNFRSF11B gene was previously associated with ischemic stroke in a population of diabetic patients in Italy. It remains to be determined whether rs3134069 is associated with ischemic stroke in the general population or populations without diabetes.. We genotyped rs3134069 and performed a case-control association study to test whether rs3134069 is associated with ischemic stroke in 2 independent Chinese Han populations, including a China-Central population with 1629 cases and 1504 controls and a China-Northern population with 1206 cases and 720 controls.. This study demonstrates that rs3134069 in TNFRSF11B increases risk of ischemic stroke by decreasing TNFRSF11B expression.

Topics: Adult; Aged; Asian People; Brain Ischemia; Case-Control Studies; Chi-Square Distribution; China; Diabetes Mellitus, Type 2; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Odds Ratio; Osteoprotegerin; Phenotype; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Risk Assessment; Risk Factors; Stroke

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and is involved in the progress of atherosclerosis. We chose a gene polymorphism locus, OPG rs3102735, to explore how OPG gene polymorphisms relate to the occurrence of ischemic stroke and microembolic signals and to evaluate their relationship with the severity of neurologic deficits at admission and the degree of vascular stenosis.. We studied 251 patients diagnosed with large artery atherosclerosis (LAA) stroke and 121 controls. The LAA stroke patients were divided into clinical subgroups according to the presence of microembolic signals, severity of neurologic deficits at admission, and the degree of vascular stenosis. The OPG rs3102735 gene polymorphism was examined by polymerase chain reaction and restriction fragment length polymorphism. The microembolic signals (MES) were monitored by transcranial Doppler (TCD) for 60min within 72h of stroke onset. The severity of neurologic deficits at admission was evaluated by the National Institutes of Health Stroke Scale (NIHSS).. The CC+CT genotypes and allele C frequencies of the rs3102735 gene polymorphism were significantly higher in the LAA group than in the control group (39% vs. 25.6%, P=0.026; 21.7% vs.13.2%, P=0.006), higher in MES-positive compared to MES-negative patients (58.7% vs. 32.4%, P<0.01; 34.1% vs.17.6%, P<0.01), and higher in patients with an NIHSS Score (≥6) than in those with an NIHSS Score (<6) (46.9% vs.33.3%, P=0.031; 43.4% vs.18.3%, P=0.04). However, the genotypes and allele frequencies of SNPs in rs3102735 did not show significant differences in the degree of vascular stenosis (P>0.05).. Our findings suggest that the OPG rs3102735 gene polymorphism might be related to the occurrence of LAA ischemic stroke, microembolic signals and stroke severity and not the degree of vascular stenosis.

Topics: Acute Disease; Aged; Brain Ischemia; Carotid Stenosis; Female; Humans; Male; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; Stroke

RANKL is a member of the TNF superfamily that stimulates chemokine release, monocyte/macrophage matrix migration and matrix metalloproteinase activity and plays an important role in atherosclerosis. In our study, we have evaluated whether RANKL gene polymorphisms are involved in ischemic stroke in Italian subjects.. In a retrospective study we have included 487 patients (242 males, 245 females) with history of ischemic stroke and 543 control subjects without history of ischemic stroke (277 males, 276 females). The rs9533156, and rs2277438 gene polymorphisms of the RANKL gene were analyzed by PCR and restriction fragment length polymorphism.. We found that the rs9533156 gene polymorphism of the RANKL gene was significantly (55.0% versus 36.5%, p < 0.0001) and independently (adjusted OR 6.28 [2.34-4.21]) associated with history of ischemic stroke. No statistically significant difference was found between the two groups in our population for the rs2277438 gene polymorphism (p = 439). Furthermore, we have confirmed that rs 3134069, rs 2073617 and rs 2073618 polymorphisms of the OPG gene were significantly and independently associated with cerebrovascular disorders.. The present study identifies, for the first time, the genetic variant of RANKL as an independent risk factor for ischemic stroke.

Topics: Female; Genetic Association Studies; Humans; Italy; Male; Osteoprotegerin; Polymorphism, Single Nucleotide; RANK Ligand; Retrospective Studies; Stroke

After an acute ischaemic stroke (AIS), several inflammatory biomarkers have been investigated, but their predictive role on functional recovery remains to be validated. Here, we investigated the prognostic relevance of biomarkers related to atherosclerotic plaque calcification, such as osteopontin (OPN), osteoprotegerin (OPG) and the receptor activator of nuclear factor kappa-B ligand (RANKL) in a cohort of patients with AIS (n = 90) during 90-day follow-up.. Radiological and clinical examinations as well as blood sampling were performed at admission and at days 1, 7 and 90 from the event. Validated scores [such as modified Rankin scale (mRS) and the National Institutes of Health Stroke Scale (NIHSS)] were used to assess poststroke outcome. Serum levels of OPN, OPG and RANKL were measured by colorimetric enzyme-linked immunosorbent assay (ELISA).. When compared to the admission, OPN serum levels increased at day 7. Serum OPN levels at this time point were positively correlated with both ischaemic lesion volume and NIHSS at days 7 and 90. A cut-off of 30.53 ng/mL was identified for serum OPN by receiver operating characteristic (ROC) curve analysis. Adjusted logistic regression showed that serum OPN levels at day 7 predicted worse mRS at day 90 [OR 4.13 (95% CI 1.64-10.36); P = 0.002] and NIHSS [1.49 (95% CI 1.16-1.99); P = 0.007], independently of age, gender, hypertension and thrombolysis.. Serum levels of OPN, but not OPG and RANKL, peaked at day 7 after AIS and predicted worse neurological scores. Therefore, OPN might have a pathophysiological and clinical relevance after AIS.

Topics: Aged; Biomarkers; Brain Ischemia; Disabled Persons; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Osteopontin; Osteoprotegerin; Prognosis; Prospective Studies; RANK Ligand; Stroke; Up-Regulation

To investigate the association of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, osteoprotegerin (OPG) and death receptor 5 (DR5) with large-artery atherosclerosis (LAA) stroke and its prognosis.. We included patients with LAA stroke (n = 132) according to the TOAST classification system and controls (n = 60). To evaluate the extent and severity of cerebral atherosclerosis, the LAA stroke group was subdivided into 3 subgroups by number of cerebral arteries with atherosclerotic stenosis (≥50%): single, double and multiple (≥3). Plasma levels of TRAIL, OPG and DR5 were measured by ELISA. Ordinal logistic regression was used to analyze the association between the plasma levels of TRAIL, OPG, DR5 and the severity of cerebral atherosclerosis. Prognosis was determined by the Modified Rankin Scale at 3 months after stroke. Receiver operating characteristic (ROC) curve was used to evaluated TRAIL as a predictor of prognosis.. Plasma TRAIL level was significantly lower for LAA patients than controls (P<0.001), while plasma OPG and DR5 levels were higher (both P<0.001). Logistic regression analysis revealed that risk of severe cerebral atherosclerosis was reduced significantly with increased plasma level of TRAIL (OR 0.438; 95% CI 0.282-0.681; P<0.001), whereas increased with high plasma levels of OPG and DR5 (OR 2.707; 95% CI 1.702-4.302, P <0.001; OR 3.593; 95% CI 1.878-6.869, P <0.001). Plasma TRAIL level was negatively correlated with the prognosis (r = - 0.372, P <0.001). The optimal cut-off value of TRAIL for prognosis was 848.63 pg/mL. The sensitivity and specificity at this cut-off value were 63.1% and 86.2%, respectively. After adding the plasma TRAIL level into the multivariate model of ROC, the area under the ROC curve was increased from 0.639 to 0.785, but the change was not statistical significant (P = 0.146).. TRAIL and its receptors OPG and DR5 may be involved in LAA stroke and the plasma level of TRAIL may be a biomarker predicting the severity of cerebral atherosclerosis and the prognosis of LAA stroke.

Topics: Aged; Arteries; Atherosclerosis; Female; Humans; Middle Aged; Osteoprotegerin; Prognosis; Receptors, TNF-Related Apoptosis-Inducing Ligand; Stroke; TNF-Related Apoptosis-Inducing Ligand

Multiligand receptor for advanced glycation end products (RAGE), osteoprotegerin, and Golgb1 genes may be implicated in atherosclerosis and vascular diseases. Single nucleotide polymorphisms (SNPs) rs1035798 in RAGE gene, rs2073617 and rs2073618 in TNFRSF11B, and rs3732410 in Golgb1 will be investigated on whether there is an association with hemorrhagic stroke (HS) in Chinese population.. A total of 600 subjects including 199 HS patients and 401 controls were assayed. These samples were divided into two groups: the ≤50 year and >50 year groups. Genotyping of SNPs was determined using the SEQUENOM MassARRAY matrix-assisted laser desorption ionization-time-of-flight-mass spectrometry. The association between genotype and HS risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses.. Our data showed that in the ≤50 year group, the rs1035798 major allele homozygote C/C in RAGE gene was associated with an increased risk of HS, while Golgb1 rs3732410 minor allele homozygote G/G was associated with a decreased risk of HS. In the >50 year group, the major allele homozygote G/G of rs2073618 was found to be associated with an increased risk of HS.. The polymorphisms rs1035798 of RAGE gene, rs2073618 of TNFRSF11B, and rs3732410 of Golgb1 might be involved in the risk of HS at different stage of ages.

Topics: Adult; Aged; Alleles; Asian People; China; Female; Genetic Association Studies; Genetic Predisposition to Disease; Golgi Matrix Proteins; Homozygote; Humans; Male; Membrane Proteins; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; Receptor for Advanced Glycation End Products; Stroke

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

Osteoprotegerin (OPG) is a secretory glycoprotein that belongs to the tumor necrosis factor receptor family and plays a role in atherosclerosis. The present study aimed to evaluate whether OPG gene (TNFRSF11B) polymorphisms are involved in ischemic stroke in an Italian population with diabetes. Participants in a retrospective case-control study included 364 diabetic patients (180 males, 184 females) with history of ischemic stroke and 492 diabetic subjects without history of ischemic stroke (252 males, 240 females). The T245G, T950C, and G1181C polymorphisms of the OPG gene were analyzed by polymerase chain reaction and restriction fragment length polymorphism. We found that the T245G, T950C, and G1181C gene polymorphisms of the OPG gene were significantly (34.1 vs. 9.5 %, P < 0.0001; 30.8 vs. 6.3 %, P < 0.0001 and 26.4 vs. 11.6 % P < 0.0001, respectively) and independently (adjusted OR 5.15 [3.46-7.68], OR 6.63 [4.26-10.31], and OR 3.03 [2.04-4.50], respectively) associated with history of ischemic stroke. We also found that these three polymorphisms act synergistically in patients with stroke history. The TNFRSF11B gene polymorphisms studied are associated with history of ischemic stroke and synergistic effects between these genotypes might be potential markers for cerebrovascular disorders.

Topics: Aged; Base Sequence; Case-Control Studies; Diabetes Complications; DNA; Female; Genetic Association Studies; Humans; Italy; Male; Osteoprotegerin; Polymorphism, Single Nucleotide; Retrospective Studies; Risk Factors; Stroke

Osteoprotegerin (OPG) is known to regulate processes involved in vascular injury and inflammation. We investigated the relationship between plasma OPG levels and stroke subtype, stroke severity at admission and functional outcome at 3 months in 172 patients with acute ischaemic stroke. Patients with large artery atherosclerosis and those with multiple causes had higher plasma OPG levels than patients with lacune. Increased plasma OPG levels were independently associated with more severe stroke and poor functional outcome. These results suggest pleiotropic roles of OPG in mediating atherosclerosis and ischaemic brain injury. OPG is a potential biomarker for predicting neurologic outcome in stroke.

Topics: Acute Disease; Aged; Biomarkers; Female; Humans; Ischemia; Logistic Models; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Prognosis; Risk Factors; Severity of Illness Index; Stroke

This study investigated correlations between mortality, stroke subtype and stroke severity with serum osteoprotegerin (OPG) and S-100 protein levels prior to the treatment of patients admitted to the emergency department and diagnosed with ischaemic stroke. Pretreatment serum samples were collected from patients (n = 90) to determine OPG and S-100 protein levels. Age- and sex-matched healthy individuals (n = 16) served as controls. Compared with controls, OPG and S-100 protein levels were significantly higher in the cardioembolic and atherothrombotic stroke groups. Within the stroke group, OPG levels were significantly higher in the cardioembolic and atherothrombotic stroke groups compared with the transient ischaemic attack (TIA) group. S-100 protein levels were significantly higher in the atherothrombotic stroke group than in the lacunar stroke and TIA groups, and in the cardioembolic stroke group compared with the lacunar stroke group. Serum OPG and S-100 protein levels were significantly higher in patients who died compared with survivors. In predicting stroke subtype and severity, although both OPG and S-100 protein levels were indicators, S-100 protein was more valuable for mortality prediction.

Topics: Brain Ischemia; Case-Control Studies; Humans; Osteoprotegerin; Prospective Studies; S100 Proteins; Severity of Illness Index; Stroke

Concentrations of osteoprotegerin (OPG) have been associated with the presence of vascular and cardiovascular diseases, but the knowledge of this marker in the setting of ischaemic stroke is limited.. In 244 patients with acute ischaemic stroke (age: 69 +/- 13 years), samples of OPG were obtained serially from presentation to day 5. Patients with overt ischaemic heart disease and atrial fibrillation were excluded. The patients were followed for 47 months, with all-cause mortality as the sole end-point. Multivariable predictors of OPG values at presentation included haemoglobin (T = -2.82; P = 0.005), creatinine (T = 4.56; P < 0.001), age (T = 9.66; P < 0.001), active smoking (T = 2.25; P = 0.025) and pulse rate (T = 3.23; P = 0.001). At follow-up 72 patients (29%) had died. Patients with OPG < or =2945 pg mL(-1) at baseline had a significantly improved survival rate on univariate analysis (P < 0.0001); other time-points did not add further prognostic information. In multivariate analysis, after adjustment for age, stroke severity, C-reactive protein levels, troponin T levels, heart and renal failure concentrations of OPG independently predicted long-term mortality after stroke (adjusted hazard ratio, 2.3; 95% CI: 1.1 to 4.9; P = 0.024).. Osteoprotegerin concentrations measured at admission of acute ischaemic stroke are associated with long-term mortality.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Cause of Death; Female; Humans; Linear Models; Male; Middle Aged; Osteoprotegerin; Prognosis; Stroke

Topics: Acute Disease; Brain Ischemia; Humans; Osteoprotegerin; Stroke

Topics: Biomarkers; Brain Ischemia; Case-Control Studies; Humans; Osteoprotegerin; Predictive Value of Tests; Prospective Studies; Stroke

Several studies suggest that osteoprotegerin (OPG) concentrations may be associated with the risk of ischemic stroke, but no large prospective studies have been conducted. We conducted a nested case-control study within a large cohort to elucidate a possible relation.. The study was done within a follow-up study including 57 053 men and women. Baseline data included OPG concentrations, lifestyle factors, and medical history. Median length of follow-up was 3.1 years. We assessed the relationship between OPG and stroke risk using conditional logistic regression to adjust for known risk factors (smoking, blood pressure, cholesterol, diabetes, body mass index, alcohol use, polyunsaturated fatty acids, and education).. We identified 254 cases with verified incident acute ischemic stroke and 254 age- and sex-matched controls. Median plasma OPG concentration among cases was 1.84 microg/L (25th-75th percentile 1.45-2.30 microg/L) compared with 1.87 microg/L (1.49-2.27 microg/L) in the control group. The adjusted odds ratio was 0.87 (95% CI 0.46-1.63) comparing participants in the highest quartile of OPG concentrations with those in the lowest quartile.. These findings provide no support for the hypothesis that plasma OPG concentrations are associated with an increased risk of ischemic stroke. This result could indicate a different pathogenic process in stroke development from that in ischemic heart disease, where OPG is a strong predictor.

Topics: Acute Disease; Aged; Brain Ischemia; Case-Control Studies; Female; Humans; Male; Middle Aged; Osteoprotegerin; Predictive Value of Tests; Prospective Studies; Risk Assessment; Stroke

Osteopontin (OPN) and osteoprotegerin (OPG) are well-known vascular calcification inhibitors, which have been recently demonstrated to correlate with inflammation and cardiovascular events incidence. The aim of this cross-sectional study is to survey whether OPN and OPG are involved in carotid plaque vulnerability. For this reason, we assessed serum OPN and OPG levels in patients with carotid stenosis, and we explored their relationship with carotid plaque echogenicity and subsequent cerebrovascular ischemic events.. A total of 164 Whites were selected from a large cohort of 297 subjects to participate. In particular, 114 patients (61 men, 53 women), aged 55 to 80, had recently-diagnosed ICA stenosis higher than 50%. A group of 50 age-, sex-, and body mass index (BMI)-matched healthy individuals served as healthy controls. Patients with renal failure, hypothyroidism, osteoporosis, and lipid-lowering therapy were excluded. Images of both carotids were obtained from all participants using a high-resolution color duplex ultrasound and the gray-scale median (GSM) score was calculated. Brain computed tomography (CT), and magnetic resonance imaging (MRI) scans when CT was questionable, were performed on all patients with carotid stenosis. Clinical parameters, lipid and glycemic indexes, hsCRP, fibrinogen, white blood cells (WBC) count, OPN, and OPG were measured. Independent t test, one-way ANOVA, Pearson correlation, and multiple regression analysis were used for statistical analysis.. Among patients with carotid stenosis, 60 had history of ipsilateral stroke or TIA and positive CT or MRI findings (group A), while 54 had no neurological symptoms and negative CT and MRI scan (group B). Overall, patients with carotid stenosis showed worse lipid profile and increased waist circumference, blood pressure, hsCRP, fibrinogen, WBC count, OPN, and OPG levels compared with healthy subjects (group C) (P <.05). Statistical analysis revealed that group A had significantly lower levels of GSM than group B (57.41 +/- 38.19 vs 76.32 +/- 36.72; P = .008) and higher levels of hsCRP, OPN, and OPG than groups B and C (P < .05). Concerning the latter, biochemical markers group B showed only elevated OPG levels compared with group C (P = .038). Notably, GSM was considerably associated with serum OPN and OPG and waist circumference in patients with carotid atherosclerosis in univariate (r = -0.333; P = .032, r = -0.575; P < .001, r = -0.590; P =.006, respectively) and multiple regression analysis (R(2) = 0.445; P =.006).. The present study demonstrated elevated serum OPN and OPG levels in patients with carotid stenosis and documented an independent association between these biochemical markers, GSM and carotid-induced symptomatology. Therefore bone-matrix proteins combined with GSM could be potential markers for vulnerable carotid plaques.

Topics: Aged; Biomarkers; Blood Pressure; Body Size; C-Reactive Protein; Carotid Stenosis; Case-Control Studies; Cross-Sectional Studies; Female; Fibrinogen; Greece; Humans; Ischemic Attack, Transient; Leukocyte Count; Lipids; Logistic Models; Magnetic Resonance Angiography; Male; Middle Aged; Osteopontin; Osteoprotegerin; Stroke; Tomography, X-Ray Computed; Ultrasonography, Doppler, Color; Up-Regulation

Arterial calcification is associated with increased risk of cardiovascular events. Osteoprotegerin (OPG) is a cytokine involved in the bone metabolism and vascular calcification. Recent data support a relationship between high serum levels of OPG and increased risk for cardiovascular disease in human. The aim of this study was to evaluate the OPG serum levels in acute ischemic stroke. Our study was further designed to detect differences in serum OPG levels between subtypes of ischemic stroke.. The study consisted of 51 patients with acute ischemic stroke and 28 control subjects. Stroke subtypes were defined by the TOAST classifications. Serum OPG levels were measured with the ELISA method.. OPG serum levels were significantly higher in patients with ischemic stroke than in control subjects (p<0.001). OPG serum levels were significantly higher in large-vessel disease (LVD) subtype compared with small-vessel disease (SVD) subtype and controls (p<0.001, p<0.001). There was no significant difference in OPG serum levels between SVD group and control subjects. Serum OPG levels were correlated with age (r=0.407, p=0.005) and fasting glucose levels (r=0.542, p=0.001) in ischemic stroke group. Logistic regression analysis showed that plasma OPG levels (OR 2.1, 95% CI, 1.16 to 3.4, p=0.01) associated with presence of stroke independently of the other risk factors.. High serum OPG levels were associated with the LVD stroke subtype, suggesting that OPG levels may play role in pathogenesis of atherothrombotic stroke. The precise mechanism for the role of OPG in atherosclerosis needs to be investigated further.

Topics: Aged; Arteriolosclerosis; Atherosclerosis; Brain Infarction; Brain Ischemia; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Osteoprotegerin; Risk Factors; Stroke; Thrombosis

Arterial calcification and osteoporosis often coexist, especially in postmenopausal women. Osteoporosis associates with a substantially increased risk of stroke in elderly women, suggesting that impaired estrogen signaling may link stroke and osteoporosis. Osteoprotegerin (OPG, TNFRSF11B) and interleukin-6 (IL-6, IL6) are putative target genes for estrogen signaling and have been implicated in both cardiovascular diseases and osteoporosis. We hypothesized that specific polymorphisms in these genes may be associated with increased risk of ischemic stroke or intracerebral hemorrhage (ICH).. We performed a population-based prospective nested case-control study, in which the relationships between polymorphisms (OPG-1181G/C, OPG-950T/C and IL6-174G/C) and ischemic stroke and ICH were examined. Definitive first-ever stroke events (n = 388), i.e. ischemic stroke (n = 320), ICH (n = 61) and unspecified stroke (n = 7) cases, and controls without cardiovascular disease (n = 773), matched for age, sex and geographical region were studied. Univariate and multivariate models using conditional logistic regression, which included traditional risk factors, were used to test for association.. Carriers of the OPG-1181C/C genotype had a significantly (p = 0.018) increased risk of ICH (OR, 2.69; 95% CI, 1.19-6.12) in the univariate analysis. After adjustments (hypertension, diabetes, BMI and triglycerides), this genotype remained significantly (p = 0.005) associated with ICH (OR, 6.04; 95% CI, 1.71-21.29). By contrast, no correlations were found between this genotype and ischemic stroke, nor between the OPG-950T/C or IL6-174G/C polymorphisms and stroke subtypes.. In this population, the OPG-1181C/C genotype associates with first-ever ICH, implying that alterations in OPG-mediated signaling in the vasculature may be involved in the pathophysiology of this disease.

Topics: Adult; Aged; Brain Ischemia; Case-Control Studies; Cerebral Hemorrhage; Female; Gene Frequency; Genetic Predisposition to Disease; Health Surveys; Humans; Interleukin-6; Logistic Models; Male; Middle Aged; Odds Ratio; Osteoprotegerin; Polymorphism, Single Nucleotide; Prospective Studies; Risk Assessment; Risk Factors; Stroke; Sweden

Osteoprotegerin (OPG) and its ligand are cytokines that regulate osteoclastogenesis and that may be involved in the regulation of vascular calcification. We examined whether serum OPG levels were associated with stroke, mortality, and cardiovascular risk factors, including diabetes, as well as with bone mineral density and fractures in a sample of 490 participants in a prospective cohort of white women, at least 65 yr of age. We found that OPG levels, assayed blinded from serum obtained at baseline, were about 30% greater in women with diabetes (mean +/- SD, 0.30 +/- 0.17 ng/mL) than in those without diabetes (0.23 +/- 0.10 ng/mL; P = 0.0001). OPG levels were associated with all-cause mortality [age-adjusted odds ratio, 1.4/SD (0.11 ng/mL) increase in serum OPG level; 95% confidence interval, 1.2--1.8] and cardiovascular mortality (odds ratio, 1.4; 95% confidence interval, 1.1--1.8); these effects were not confounded by diabetes. OPG levels were not associated with baseline bone mineral density or with subsequent strokes or fractures. The association of serum OPG levels with diabetes and with cardiovascular mortality raises the possibility that OPG may be a cause of or a marker for vascular calcification.

Topics: Aged; Biomarkers; Blood Pressure; Bone Density; Cardiovascular Diseases; Cause of Death; Cohort Studies; Confidence Intervals; Diabetes Mellitus; Estrogen Replacement Therapy; Female; Fractures, Bone; Glycoproteins; Humans; Mortality; Observer Variation; Odds Ratio; Osteoprotegerin; Prospective Studies; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors; San Francisco; Smoking; Stroke; White People