osteoprotegerin and Coronary-Disease

Initially described as key regulators in metabolic bone disease osteoprotegerin (OPG), receptor activator of nuclear factor kappa B (RANK) and RANK ligand (RANKL) have also been discriminated as regulators in immunologic function. Cardiovascular diseases (CVD) develop over many years in life and are often triggered by inflammatory processes within the vessel wall that lead to vascular remodeling. Recently some study groups have described OPG as a prognostic parameter for mortality and morbidity in cardiovascular patients.

Topics: Adult; Age Factors; Aged; Arteriosclerosis; Bone Density; Bone Resorption; Cardiovascular Diseases; Coronary Disease; Female; Gonadal Steroid Hormones; Heart Failure; Humans; Male; Middle Aged; Osteoclasts; Osteoporosis; Osteoprotegerin; Prognosis; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Sex Factors; Ventricular Dysfunction, Left; Young Adult

Vascular calcification is an important problem in the patients with diabetes and chronic kidney disease (CKD) , and contributes to the increased risk of cardiovascular events by a variety of mechanisms, including an increase in arterial stiffness by medial calcification or an increase in plaque vulnerability by a specific type of atherosclerotic calcification. Coronary calcification is a marker of atherosclerosis and evaluation of coronary artery calcium (CAC) score by cardiac MDCT has been recognized as the useful strategies to initiate or intensify appropriate treatment to slow the progression of atherosclerosis. Besides the risk of coronary heart disease, CAC has been demonstrated to be associated with the risk of complication during PCI, including arterial perforation and dissection, stent malapposition, and resultant late stent thrombosis. Increasing evidence demonstrates that both types of vascular calcification are active and tightly regulated by a process similar to bone formation.

Topics: Animals; Bone Morphogenetic Protein 2; Calcium; Core Binding Factor Alpha 1 Subunit; Coronary Disease; Coronary Vessels; Humans; Mice; Osteoprotegerin; Phosphorus; Plaque, Atherosclerotic; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Notch; Risk; Vascular Calcification

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

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

To observe the correlation of osteoprotegerin, soluble receptor activator of nuclear factor-κB ligand (sRANKL), inflammatory factors and epicardial adipose tissue volume (EATV) with the severity of coronary heart disease (CHD).. We studied 390 patients who were admitted to the Department of Cardiology of our hospital because of chest pain and underwent coronary angiography (CAG) from August 2018 to December 2019. According to CAG, 209 patients had non-CHD and 181 patients had CHD. Demographic data, biochemical indicators including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), lipoprotein a (Lp(a)), apolipoprotein B (apoB), apolipoprotein AI (apoAI), creatine kinase isoenzyme (CK-MB), osteoprotegerin, sRANKL, inflammatory factors (hs-CRP, FIB and IL-6), and EATV were collected.. The number of males, age, diabetes and hypertension in the CHD group was higher than those in the non-CHD group (P < .05). LDL-C, TC and apoB in the two groups were not significantly different (P > .05); HDL-C and apoAI in the CHD group were lower than those in the non-CHD group, and Lp(a) and CK-MB were higher than those in the control group (P < .05). Osteoprotegerin, IL-6, hs-CRP, EATV and FIB in the CHD group were higher than those in the non-CHD group, while sRANKL was lower than that in the control group (P < .05). Pearson correlation analysis showed that osteoprotegerin, sRANKL, inflammatory factors (hs-CRP, FIB and IL-6) and EATV were correlated with the severity of CHD (P < .05). Multivariate logistic regression analysis showed that CK-MB, osteoprotegerin, sRANKL, inflammatory factors (hs-CRP, FIB and IL-6) and EATV were risk factors for CHD, while HDL-C, Lp(a), apoAI were protective factors.. Osteoprotegerin, sRANKL, inflammatory factors and EATV were positively correlated with the severity of CHD, which had certain value for the diagnosis of CHD.

Topics: Adipose Tissue; Coronary Disease; Humans; Male; Osteoprotegerin; Pericardium; RANK Ligand

To explore the polymorphisms of T149C and T950C gene in osteoprotectin (OPG) promoter sites and the levels of serum OPG and soluble nuclear factor-ΚB receptor activator ligand (sRANKL) and the incidence of coronary heart disease (CHD).. 528 patients in Tianjin suspected of CHD and underwent coronary angiography (CAG) who admitted to the department of cardiology of Tianjin Chest Hospital from April 2017 to December 2018 were enrolled. According to the CAG results, they were divided into two groups: CHD group (n = 302) and non-CHD group (n = 226). The gender, age, history of hypertension, family history of CHD, diabetes, levels of blood lipid parameters in serum and other clinical data of patients were recorded. The levels of serum OPG and sRANKL were measured by enzyme-linked immunosorbent assay (ELISA). T149C and T950C gene polymorphisms were analyzed by polymerase chain reaction-restriction endonuclease fragment length polymorphism (PCR-RFLP) methods. Hardy-Weinberg genetic balance test was performed for alleles. Binomial classification multivariate non-conditional Logistic regression method was used to analyze the relationship between T149C and T950C gene polymorphisms, serum levels of OPG and sRANKL and CHD.. All patients were enrolled in the final analysis. The serum level of OPG in CHD group was significantly higher than that in non-CHD group (μg/L: 1.76±0.49 vs. 1.47±0.29, P < 0.01), the serum level of sRANKL was significantly lower than that in non-CHD group (ng/L: 342.14±121.38 vs. 376.63±108.66, P < 0.05). Logistic regression analysis showed that after adjusting for age, gender, blood lipid parameters, diabetes and other factors, the increase in serum OPG level was an independent risk factor for CHD [odds ratio (OR) = 1.995, 95% confidence interval (95%CI) = 1.935-2.066, P = 0.012]. PCR-RFLP results showed that TT, TC and CC genotypes were found in T149C and T950C of OPG promoter. According to Hardy-Weinberg equilibrium test, the polymorphisms of OPG T149C and T950C accorded with Hardy-Weinberg law, achieving genetic balance with representative of the population. The frequencies of TT, TC, CC and alleles T and C in T149C genotypes of non-CHD group were 53.5%, 42.9%, 3.6%, 75.0% and 25.0%, respectively, and they were 43.1%, 50.3%, 6.6%, 68.2% and 31.8%, respectively in CHD group. There were statistically significant differences in genotype and allele frequencies between the two groups (all P < 0.05). It was shown by Logistic regression analysis that the risk of CHD in TC+CC genotype of T149C was 1.86 of TT genotype (OR = 1.86, 95%CI = 1.24-2.78, P = 0.003). It was suggested that C allele might be a susceptible gene for CHD. In non-CHD group, the frequencies of TT, TC, CC, and alleles T and C in T950C genotypes were 39.8%, 46.5%, 13.7%, 63.1% and 36.9%, respectively. They were 39.4%, 43.4%, 17.2%, 61.1% and 38.9%, respectively in CHD group. There were no significant differences in genotype and allele frequencies between the two groups (all P > 0.05). Logistic regression analysis showed that TC+CC genotype of T950C was not related with CHD.. The increased level of serum OPG was closely related with CHD and could be used as a risk factor for CHD. The cases carried OPG T149C TC+CC genotype might have the risk suffering CHD. C allele is might be a susceptible gene.

Topics: China; Coronary Disease; Female; Humans; Male; Osteoprotegerin; Polymorphism, Genetic; Promoter Regions, Genetic; Risk Factors

Topics: Coronary Disease; Female; Humans; Male; Osteoprotegerin

Topics: Coronary Disease; Female; Humans; Male; Osteoprotegerin

This study aimed to explore serum adiponectin and osteoprotegerin levels in patients with coronary heart disease (CHD) and their correlation with inflammatory and ischemia factors. From September 2010 to Augest 2010, 347 CHD patients were enrolled for a retrospective analysis. Serum lipoprotein phospholipase A2 (Lp-PLA2), hypersensitive C-reactive protein (hs-CRP), ischemia modified albumin (IMA), and adiponectin and osteoprotegerin levels were detected and analyzed. Serum adiponectin levels (ng/mL, CV was 4.3% at 250 ng/mL) were found to be negatively correlated with Lp-PLA2 (r = -0.958, P = 0.014) and hs-CRP (r = -0.958, P = 0.015) and positively correlated with IMA (r = 0.962, P = 0.025). Serum osteoprotegerin levels were positively correlated with Lp-PLA2 (r = 0.933, P = 0.027) and hs-CRP (r = 0.932, P = 0.022) and negatively correlated with IMA (r = -0.924, P = 0.017). In addition, serum adiponectin levels negatively correlated with osteoprotegerin levels. In conclusion, serum adiponectin level was negatively correlated with CHD progression, whereas serum osteoprotegerin level was positively correlated with CHD progression. Combined detection of adiponectin and osteoprotegerin levels may be of potential value in the clinical determination of CHD severity.

Topics: Adiponectin; Aged; Base Sequence; Biomarkers; Coronary Disease; Female; Humans; Male; Middle Aged; Osteoprotegerin; Severity of Illness Index

To determine the serum level of cytokines in women with coronary heart disease (CHD) concurrent with osteoporosis (OP) and in those with isolated CHD; to assess a relationship of the levels of cytokines, osteoprotegerin (OPG), and transforming growth factor-β (TGF-β) to the ten-year absolute risk of osteoporotic fractures, the presence of fractures in the history, and that of CHD; and to establish the role of elevated cytokine levels in the development of future fractures.. A cross-sectional cohort study included 98 women (mean age, 71.2?8.6 years) with CHD. Forty-eight patients had CHD concurrent with severe OP. The Fracture Risk Assessment Tool (FRAX) was applied to estimate a ten-year absolute risk for fractures in all the patients. The serum levels of OPG, TGF-β, interleukin (IL)-1β, IL-4, IL-6, IL-8, and IL-10, and tumor necrosis factor-a (TNF-α) were measured by enzyme immunoassay.. The women with comorbidity were found to have higher levels of OPG, TGF-β, IL-6, IL-8, IL-10, and TNF-α than those with isolated CHID. There was a direct correlation between fractures, CHID, and IL-10 and TNF-α levels and an inverse relationship between fractures, CHD, and IL-8; between CHD and OPG levels. Conclusion. The women with comorbidity were noted to have elevated levels of proinflammatory cytokines and OPG; a correlation was between cytokine levels and fractures and CHD. Increased OPG and IL-6 levels are independent predictors of fractures.. Цель исследования. Определить содержание цитокинов в сыворотке крови у женщин с сочетанием ишемической болезни сердца (ИБС) и остеопороза (ОП) и женщин с изолированной ИБС; оценить взаимосвязь уровней цитокинов, остеопротегерина (OPG), трансформирующего β-фактора роста (ТФР-β), с показателем абсолютного 10-летнего риска остеопоротических переломов, наличием переломов в анамнезе, наличием ИБС; установить роль повышенных уровней цитокинов в развитии будущих переломов. Материалы и методы. В одномоментном когортном исследовании приняли участие 98 женщин ИБС, средний возраст 71,2±8,6 года. У 48 пациенток имелось сочетание ИБС и тяжелого ОП. Всем пациенткам оценивали абсолютный 10-летний риск переломов по FRAX, определяли уровень OPG, ТФР-β, интерлейкинов-1β, 4, 6, 8, 10, α-фактора некроза опухоли (α-ФНО) в сыворотке крови методом иммуноферментного анализа. Результаты. Выявлено, что у женщин, имеющих сочетанную патологию, уровень OPG, ТФР-β, ИЛ-6, ИЛ-8, ИЛ-10 и α-ФНО, выше чем у женщин с изолированной ИБС. Установлена прямая корреляция между наличием переломов, ИБС и уровнем ИЛ-10 и α-ФНО, а также обратная связь между наличием переломов, ИБС и ИЛ-8; наличием ИБС и уровнем OPG. Заключение. У женщин с сочетанной патологией отмечено повышение уровня провоспалительных цитокинов и OPG, установлена корреляция между уровнем некоторых цитокинов и наличием переломов и ИБС. Повышение уровней OPG и ИЛ-6 являются независимыми предикторами переломов.

Topics: Aged; Bone Density; Cohort Studies; Coronary Disease; Female; Humans; Interleukins; Middle Aged; Osteoporosis, Postmenopausal; Osteoprotegerin; Russia; Severity of Illness Index; Statistics as Topic; Transforming Growth Factors; Tumor Necrosis Factor-alpha

Osteoprotegerin (OPG), a key factor in bone remodeling and vascular calcification, has been suggested to be associated with cardiovascular events. This study sought to assess the relationship between plasma OPG, anthropometric, metabolic status, severity and extent of coronary artery calcification, and the two-year recurrence risk of coronary event in patients with coronary heart disease (CHD).. A total of 155 consecutive patients with symptoms suggestive of CHD were enrolled in this cross-sectional study. Blood samples were taken for laboratory tests. Coronary angiography and cardiac CT scan were performed to assess the severity and extent of involved vessels. Two-year risk of subsequent CHD was estimated based on the computational Framingham risk prediction model.. OPG level was in direct linear association with age (β = 0.38, p < 0.001), waist to hip ratio (β = 0.17, p < 0.05), hs-CRP (β = 0.17, p < 0.05), systolic and diastolic blood pressure (β = 0.17, p < 0.05; β = 0.23, p < 0.01), and HbA1c (β = 0.17, p < 0.05). After age-sex adjustment, only HbA1c (β = 0.15, p < 0.05) was a significant indicator of serum OPG. OPG showed significant linear association with the coronary calcium score (CCS), and the number of involved vessels even after adjustment for age, sex, diabetes, blood pressure, and markers of bone-calcium metabolism (β = 0.27, P < 0.05; β = 29, P < 0.01). There is a significant positive association between two-year risk of subsequent CHD and serum OPG in females (β = 0.45, P < 0.01) but not in males.. Increased OPG is independently associated with the severity and extent of CHD. This study also proposes OPG as a potential marker in predicting the risk of subsequent CHD, in females.

Topics: Coronary Angiography; Coronary Disease; Cross-Sectional Studies; Female; Heart; Humans; Male; Middle Aged; Osteoprotegerin; Risk Factors; Severity of Illness Index; Sex; Tomography, X-Ray Computed; Waist-Hip Ratio

Inflammatory biomarkers are reported as risk factors for atrial fibrillation (AF), but their impact is uncertain.. We investigated the associations between inflammatory biomarkers and future AF in a large general cohort.. Available markers were white blood cells (WBCs) with subgroups, fibrinogen, high-sensitivity C-reactive protein (hs-CRP), and osteoprotegerin (OPG). A total of 6315 men and women from a population survey in Tromsø, Norway in 1994 to 1995 were followed for a mean of 10.9 years. Mean age at baseline was 60 years. Measurements of height, weight, blood pressure, heart rate, total cholesterol, high-density lipoprotein (HDL) cholesterol, WBC count, and information on diabetes, angina, myocardial infarction, and antihypertensive treatment, were obtained at baseline. Fibrinogen, hs-CRP, and OPG were obtained at a follow-up visit. The outcome measure was first-ever AF, documented on an electrocardiogram. The Cox proportional hazards regression model was used to estimate hazard ratios of AF.. In the multivariable analysis, adjusted for traditional cardiovascular risk factors and other inflammatory biomarkers, hs-CRP was associated with AF in men only (hazard ratio = 1.14 for a 1 SD increase; 95% CI, 1.02-1.28). There was a significant increase in AF across quartiles of WBCs in men (P = 0.007) and in the total study population (P = 0.004). OPG was associated with AF in patients free of coronary heart disease at baseline. Fibrinogen and subgroups of WBCs showed no significant association with AF.. This population-based cohort study showed that hs-CRP was independently associated with AF in men, but apparently not in women, and that patients with WBCs in the upper quartile had increased risk of AF.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; C-Reactive Protein; Coronary Disease; Electrocardiography; Female; Fibrinogen; Humans; Inflammation; Leukocyte Count; Male; Middle Aged; Multivariate Analysis; Norway; Osteoprotegerin; Proportional Hazards Models; Prospective Studies; Risk Factors; Sex Factors

This study was designed to evaluate the biological significance of simultaneous changes in the circulating levels of osteoprotegerin (OPG) and TNF-related apoptosis inducing ligand (TRAIL) in patients with coronary artery disease (CAD), and, in particular, with acute myocardial infarction (AMI).. Total levels of OPG and TRAIL were measured by ELISA in patients with AMI (n=113), unstable angina (UA, n=21) and healthy controls (n=120).. Since OPG was elevated during the acute phase (first 12-24-48h) after AMI and in patients with UA with respect to healthy controls, while TRAIL was decreased in acute AMI patients, CAD patients were characterized by an increased OPG/TRAIL ratio. Moreover, the OPG/TRAIL ratio was significantly (p<0.05) higher in the acute AMI patients who developed heart failure (HF) than in those who did not develop HF in the follow-up.. An impaired OPG/TRAIL ratio after AMI is related to a higher risk of HF.

Topics: Angina, Unstable; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Female; Heart Failure; Humans; Male; Myocardial Infarction; Osteoprotegerin; TNF-Related Apoptosis-Inducing Ligand

Osteoprotegerin (OPG) inhibits interaction of the receptor-activator of nuclear factor-kappaB (RANK) ligand (RANKL) with its receptor RANK, which is expressed on osteoclasts. OPG appeared to accelerate vascular calcification in vitro by the inhibition of vascular osteoclast-like cells. On the contrary, early-onset arterial calcification was observed in OPG-deficient mice. We measured the coronary artery calcification score (CACS) and abdominal aortic calcification score (AAoCS) by multi-detector computed tomography in 30 pre-dialysis CKD patients (eGFR 20 mL/min on average). Biomarkers were measured, including serum OPG, soluble RANKL (sRANKL) and tartrate-resistant acid phosphatase (TRACP) -5b (the biomarker of osteoclasts independent of renal function). The median values of CACS and AAoCS were 54.4 and 1,088 Agatston units (AU), respectively. Serum OPG was increased and serum sRANKL was decreased. In a multivariate logistic regression analysis using CACS > or = 100 AU as the outcome variable, CACS was found to be positively correlated with serum corrected Ca x iP product and serum OPG, though it was not correlated with serum TRACP-5b. ROC curve analysis showed that the serum OPG cutoff value predicting CACS > or = 100 AU was 5.2 pmol/L (624 pg/mL). In a stepwise regression analysis, log (AAoCS + 1) was positively correlated with serum OPG alone, but it was not correlated with age, eGFR, serum albumin and bone alkaline phosphatase (BAP). No correlation was found between serum OPG and serum TRACP-5b. In conclusion, vascular calcification in pre-dialysis CKD patients was correlated with an increase in OPG, but was independent of serum TRACP-5b. The decrease in serum sRANKL may have been caused by the increase in OPG production.

Topics: Acid Phosphatase; Aorta, Abdominal; Aortic Diseases; Biomarkers; Calcinosis; Coronary Disease; Coronary Vessels; Dialysis; Female; Humans; Isoenzymes; Logistic Models; Male; Osteoclasts; Osteoprotegerin; RANK Ligand; Tartrate-Resistant Acid Phosphatase

Vascular calcifications in CKD are now linked to serum alterations of both divalent ions and calcification inhibitory proteins. Due to possible biochemical differences between dialysis (D) and transplantation (Tx), we examined the entity and severity of these biochemical modifications and of coronary artery calcium score separately in these two populations. We assayed, besides standard markers of inflammation, divalent ions and serum levels of fetuin, matrix Gla protein (MGP) and osteoprotegerin (OPG), in 51 Tx patients (age 45 +/- 12 years; 30 males, 21 females; previous D duration 4.8 +/- 4.2 years; Tx since 6.6 +/- 5.5 years; Cr 1.8 +/- 0.6 mg/dl) and in 49 D patients (age 49 +/- 14 years; 30 males,19 females; D duration 5.6 +/- 4.8 years). Additionally, coronary calcium score (AS) was evaluated by cardiac multi-slice CT. Compared with D patients, Tx patients had better values of divalent ions and inflammation markers, and lower prevalence (65 vs. 86%; p < 0.02) and severity (AS = 570 +/- 1,637 vs. 1,311 +/- 3,128; p < 0.008) of coronary calcification. In addition, a tendency toward normalization for all of the three calcification inhibitory proteins was evident. In both Tx and D, AS correlated with age and OPG (Tx: r(s) = 0.439, p < 0.001, and r(s) = 0.510, p < 0.0001; D: r(s) = 0.471, p < 0.001, and r(s) = 0.403, p < 0.005, respectively); in D patients, a correlation was present also with D duration (r(s) = 0.435; p < 0.002), other markers of inflammation and, notably, fetuin (r(s) = -0.442; p < 0.002). Regression analysis selected previous time on D in Tx patients (r(m) = 0.400; p < 0.004), and C-reactive protein and OPG in D patients (r(m) = 0.518; p < 0.004) as the most predictive parameters of AS. Discriminant analysis confirmed the major role of age and D duration in the appearance of AS and evidenced male gender as a distinct risk condition. At variance, Tx duration was never associated with AS. In conclusion, as compared to D, renal Tx patients show serum levels of calcification inhibition proteins and of divalent ions closer to normal. As this is associated with a lower prevalence and severity of AS, it is suggested that Tx antagonize the accelerating role of D in the progression of vascular calcification. Assessment of both coronary calcifications and serum levels of calcification inhibitory proteins may be of value to identify those subjects at higher risk of development and progression of vascular lesions, among whom males have the highest

Topics: 1-Carboxyglutamic Acid; alpha-Fetoproteins; Biomarkers; Calcinosis; Calcium; Calcium-Binding Proteins; Coronary Disease; Enzyme-Linked Immunosorbent Assay; Extracellular Matrix Proteins; Female; Follow-Up Studies; Humans; Kidney Failure, Chronic; Kidney Transplantation; Male; Matrix Gla Protein; Middle Aged; Osteoprotegerin; Prognosis; Renal Dialysis; Severity of Illness Index; Tomography, X-Ray Computed

Topics: Calcinosis; Coronary Disease; Estrogen Replacement Therapy; Estrogens; Female; Humans; Middle Aged; Osteoporosis, Postmenopausal; Osteoprotegerin

We investigated whether osteoprotegerin (OPG), an important regulator in the genesis of arteriosclerosis and bone formation, is able to identify patients at risk for perioperative myocardial infarction measured as cardiac troponin I (cTNI) and signs of myocardial ischemia in the electrocardiogram after coronary artery bypass grafting (CABG).. Observational study.. Post-surgical intensive care unit of a tertiary care center.. Ninety-seven patients undergoing elective CABG.. None.. OPG and cTNI were measured before and 24 hrs after CABG. Additionally, cTNI was measured after 12 hrs. Electrocardiography was done before and immediately after CABG. OPG before CABG (OPGpre) measurements correlated with cTNI measurements after 12 hrs (cTNI12) (r = 0.56; p < .0001) and with cTNI measurements after 24 hrs (cTNI24) (r = 0.77; p < .0001). OPGpre measurements correlated with electrocardiographic findings after surgery (r = 0.65; p < .0001). There was a positive correlation between OPGpre value and the number of bypasses (r = 0.95; p < .0001). A strong correlation was found between OPGpre and homocysteine (r = 0.96; p < .0001). The median OPG presurgical level for the four patients with cardiac complications was found to be notably elevated (28.1 [26.6/31.0] pmol/L) in comparison with that for patients without complications (10.2 [3.7/16.9] pmol/L).. OPG appears to be a useful marker for estimating risk for perioperative myocardial infarction in patients undergoing CABG, as demonstrated by signs of ischemia on electrocardiography.

Topics: Aged; Biomarkers; Cohort Studies; Confidence Intervals; Coronary Artery Bypass; Coronary Disease; Female; Glycoproteins; Graft Rejection; Graft Survival; Humans; Male; Middle Aged; Osteoprotegerin; Perioperative Care; Postoperative Complications; Predictive Value of Tests; Probability; Prognosis; Radiography; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Treatment Outcome

Topics: Animals; Calcinosis; Coronary Disease; Glycoproteins; Humans; Muscle, Smooth, Vascular; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Sodium-Phosphate Cotransporter Proteins

The relationship between osteoprotegerin (OPG) and lipid profile, insulin sensitivity, adipocytokines and sex steroids has been poorly studied and subject to controversy. The purpose of this study was to look at the correlates of OPG in an elderly male population.. One hundred and fifty-one nondiabetic, elderly Lebanese men (age range 50-83) were recruited in this cross-sectional study based on voluntary enrolment.. In all the subjects, serum OPG levels were measured and related to clinical parameters (age, waist, body mass index (BMI), systolic and diastolic blood pressure), as well as to metabolic and hormonal parameters. The following fasting laboratory measurements were performed: plasma glucose and insulin levels, total cholesterol, triglycerides and HDL cholesterol, adiponectin, leptin, as well as sex steroids (testosterone, SHBG, free androgen index, ooestradiol, DHEAS), GH and IGF-1. QUICKI index was calculated as a measure of insulin sensitivity.. OPG levels were significantly correlated with age (r = 0.28, P < 0.0001) but not with BMI, waist, systolic or diastolic blood pressure. There was a trend towards higher OPG levels in subjects without, compared to subjects with the metabolic syndrome (3.58 +/- 1.28 vs. 3.26 +/- 1.04 pmol/l, P = 0.09). OPG was negatively correlated with fasting glucose and triglyceride levels (r = -0.18, P = 0.031 and r = -0.19, P = 0.02, respectively) and positively correlated with the QUICKI index (r = 0.17, P = 0.033), HDL cholesterol (r = 0.21, P = 0.009) and adiponectin levels (r = 0.27, P = 0.001). No significant correlations were reported with total or LDL cholesterol levels and with leptin levels. After adjustment for age, OPG is still correlated with triglycerides (r = -0.19, P = 0.02), glucose (r = -0.21, P = 0.011) and adiponectin (r = 0.19, P = 0.02). Finally, OPG was positively associated with SHBG (r = 0.31, P < 0.001) and negatively associated with free androgen index (r =-0.346, P < 0.001); both correlations persisted after adjustment for age (r = 0.21, P = 0.009 and r = -0.23, P = 0.005, respectively). No significant correlation was found between OPG and oestradiol levels while a weak negative correlation was demonstrated with DHEAS (r = -0.18, P = 0.025). Also, no significant correlation was found between OPG and GH or IGF-1 values. In a multiple regression analysis with a stepwise model, the main determinants of OPG were free androgen index and adiponectin (P < 0.0001 and P = 0.015, respectively).. Our results show that circulating OPG levels are favourably associated with some components of the metabolic syndrome. Also, for the first time, an association between OPG and adiponectin is described. Finally, the negative correlation we found between OPG and free androgen index may suggest a potential role of OPG in the increase in cardiovascular disease related to ageing and sex steroid deficiency.

Topics: Adiponectin; Aged; Biomarkers; Coronary Disease; Glycoproteins; Gonadal Steroid Hormones; Humans; Insulin Resistance; Lipids; Male; Metabolic Syndrome; Middle Aged; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Regression Analysis

Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of the NF-kappaB ligand (RANKL). OPG has been shown to be an important inhibitor of osteoclastogenesis and arterial calcification in animal models. OPG has been proposed as a link molecule between osteoporosis and arterial calcification, but the relationship between the OPG gene and the cardiovascular system in human populations is unclear. Thus, the aim of this study was to investigate the relationship between OPG gene polymorphisms and aortic calcification or coronary artery disease in Koreans.. Genotyping of four polymorphisms, A163G, G209A, T245G and T950C, in the promoter region of the OPG gene was performed in 251 healthy Korean women (mean age 51.3 +/- 6.9 years) and in a second study population consisting of 100 patients who underwent coronary angiography (mean age 57.0 +/- 11.9 years), by allelic discrimination using the 5' nuclease polymerase chain reaction assay. Cardiovascular risk factors and serum OPG levels were measured and aortic calcification in thoracic and abdominal aorta was examined by simple radiological methods.. In the first study population, the prevalence of aortic calcification increased significantly as the subjects grew older. The frequencies of mutant alleles were significantly higher in the subjects with aortic calcification compared with those without aortic calcification in G209A and T950C polymorphisms, although these significances were lost after adjustment for age. No significant relationship was found between OPG gene polymorphisms and serum OPG levels or cardiovascular risk factors. In the second study group, there were no associations between OPG promoter genotypes and aortic calcification, serum OPG levels, or coronary artery disease.. We observed that the four polymorphisms in the promoter region of the OPG gene were not associated with aortic calcification or coronary artery disease in Koreans. Further studies are needed to clarify this relationship.

Topics: Adult; Aged; Analysis of Variance; Aorta; Calcinosis; Coronary Angiography; Coronary Disease; Female; Glycoproteins; Humans; Korea; Middle Aged; Osteoprotegerin; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors

OPG (osteoprotegerin) is an inhibitor of osteoclastogenesis and recent work suggests it has a role in atherosclerosis. Therefore we measured serum OPG levels in patients with coronary artery disease, compared the serum OPG levels among the different groups according to the number of stenotic vessels and determined whether there was any correlation with aortic calcification, LV (left ventricular) mass index and serum CRP (C-reactive protein) levels. Subjects (n=100; mean age, 57 years) who underwent coronary angiograms were enrolled. Blood pressure, body mass index, fasting blood glucose, lipid profiles and CRP levels were measured and the LV mass indices were calculated using ECGs. Serum OPG levels were measured by ELISA. The presence of calcification in the aortic notch was checked by a chest X-ray. The subjects were divided into four groups according to the number of stenotic vessels. The mean serum OPG levels increased significantly as the number of stenotic vessels increased, and the mean serum OPG levels were higher in the group with three-vessel disease compared with the groups with no- or one-vessel disease. The mean serum CRP level was significantly higher in the group with three-vessel disease compared with the groups with no-, one- and two-vessel disease. Age and LV mass index showed significant positive correlations with serum OPG levels, although significance was lost after an adjustment for age. Serum CRP levels were positively correlated with serum OPG levels even after an adjustment for age. There were no differences in serum OPG levels according to the presence of fasting hyperglycaemia or aortic calcification. In conclusion, serum OPG level was related to the severity of stenotic coronary arteries and serum CRP levels. LV mass indices showed no significant correlation with OPG levels. The precise mechanism for the role of OPG in atherosclerosis needs to be investigated further.

Topics: Aged; Aortography; Biomarkers; C-Reactive Protein; Calcinosis; Coronary Angiography; Coronary Disease; Disease Progression; Electrocardiography; Enzyme-Linked Immunosorbent Assay; Glycoproteins; Humans; Hypertrophy, Left Ventricular; Middle Aged; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor

OPG (osteoprotegerin) has been suggested to have an important role in atherogenesis and vascular calcification. In the present study, we have investigated serum OPG and RANKL (receptor activator of nuclear factor kappaB ligand) concentrations in patients with ST elevation AMI (acute myocardial infarction) and established CAD (coronary artery disease). OPG and RANKL were measured in 58 male patients hospitalized in the coronary care unit with ST elevation AMI, in 52 asymptomatic male patients with an established diagnosis of CAD and in 52 healthy male controls. These last two groups were matched with the AMI patients for age and body mass index. OPG was significantly (P<0.05) higher in patients with AMI at 1 h after AMI (8.04+/-4.86 pmol/l) than in both patients with established CAD (4.92+/-1.65 pmol/l) and healthy subjects (3.15+/-1.01 pmol/l). Subjects with established CAD had significantly (P<0.05) increased OPG levels compared with controls. RANKL levels in patients with established CAD (0.02+/-0.05 pmol/l) and with AMI (0.11+/-0.4 pmol/l) were significantly (P<0.05) lower compared with controls (0.32+/-0.35 pmol/l). In the AMI group, OPG decreased significantly (P<0.05) at 1 and 4 weeks after infarction (8.04+/-4.86 compared with 6.38+/-3.87 and 6.55+/-2.6 pmol/l respectively), but OPG levels, either at 1 h or 1-4 weeks after AMI, remained significantly (P<0.05) higher compared with established CAD (4.92+/-1.65 pmol/l) and controls (3.15+/-1.01 pmol/l). Our data show for the first time that OPG levels are increased in ST elevation AMI within 1 h of infarction. Whether the increase in OPG is a consequence or a causal factor of plaque destabilization deserves further investigation.

Topics: Aged; Biomarkers; Body Mass Index; Carrier Proteins; Coronary Disease; Electrocardiography; Follow-Up Studies; Glycoproteins; Humans; Ligands; Male; Membrane Glycoproteins; Middle Aged; Myocardial Infarction; Osteoprotegerin; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor

Osteoprotegerin (OPG) is an inhibitor of osteoclastogenesis, which has been recently involved in atherosclerosis. The relationship between coronary atherosclerosis and OPG has never been studied in asymptomatic type 2 diabetic patients.. This is a nested case-control study; 162 asymptomatic type 2 diabetic patients were evaluated for silent myocardial ischemia using stress myocardial perfusion imaging; of 50 patients with positive results, 37 underwent coronary angiography, 20 of whom showed significant coronary artery disease (CAD group). Of 112 patients without silent myocardial ischemia, 20 subjects (NO-CAD group) were selected and matched by age and sex to patients with CAD. OPG, C-reactive protein, adiponectin, lipoprotein(a), albuminuria, and classical risk factors were measured.. The percentages of subjects with OPG levels above median and with nephropathy were higher in the CAD group than in the NO-CAD group (70 vs. 25%, P = 0.004 and 50 vs. 5%, P = 0.001, respectively). LDL cholesterol levels were higher and HDL cholesterol levels lower in the CAD compared with the NO-CAD group (P = 0.033 and P = 0.005, respectively). No other variables were associated with CAD. Logistic regression analysis showed that OPG values above median (odds ratio 8.31 [95% CI 1.18-58.68], P = 0.034) and nephropathy (21.98 [1.24-388.36], P = 0.035) were significant independent predictors of asymptomatic CAD in type 2 diabetic patients.. Our investigation reports the first evidence of an independent association of OPG with asymptomatic CAD in type 2 diabetic patients. The results of this nested case- control study with 20 cases need to be confirmed in a larger population.

Topics: Adrenergic beta-Agonists; Aged; Biomarkers; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dipyridamole; Electrocardiography; Exercise Test; Female; Glycated Hemoglobin; Glycoproteins; Humans; Lipids; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Platelet Aggregation Inhibitors; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors

Osteoprotegerin (OPG) antagonizes receptor activator of nuclear factor-kappaB ligand (RANKL), the principal regulator of osteoclasts. Of note, OPG-deficient mice display osteoporosis and arterial calcification. Recently, OPG gene polymorphisms have been associated with osteoporosis and early predictors of cardiovascular disease. In this study, we examined OPG gene polymorphisms in 468 men who had absence of coronary artery disease (CAD) or single-, double-, or triple-vessel disease on coronary angiography. Denaturing gradient gel electrophoresis followed by DNA sequencing revealed nucleotide substitutions 149 T-->C, 163 A-->G, 209 G-->A, 245 T-->G, 950 T-->C (all promoter), 1181 G-->C (exon 1), and 6890 A-->C (intron 4), respectively. Although single polymorphisms were not associated with CAD, linkage of polymorphisms 950 and 1181 revealed that haplotypes were overrepresented in men with CAD (chi(2) = 17.05; P = 0.03) with an increased risk of CAD in carriers of genotypes 950 TC/1181 GC and 950 CC/1181 CC (odds ratio, 1.67; 95% confidence interval, 1.02-2.72; P = 0.04). Furthermore, serum OPG levels were correlated with the presence of a C allele at position 950 (P = 0.02). In summary, linkage of genetic variations of the OPG gene at positions 950 and 1181 may confer an increased risk of CAD in Caucasian men.

Topics: Alleles; Cohort Studies; Coronary Disease; DNA; Electrophoresis; Genetic Linkage; Glycoproteins; Humans; Logistic Models; Male; Osteoprotegerin; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; Promoter Regions, Genetic; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor

Osteoprotegerin (OPG) regulates osteoclast and immune functions and appears to represent a protective factor for the vascular system. However, the role of OPG in human atherosclerosis has not been evaluated. In this study, we assessed OPG serum levels in 522 age-matched men who, on the basis of coronary angiography, had either absence of coronary artery disease (CAD) or presence of single-vessel disease, double-vessel disease, or severe triple-vessel disease. OPG serum levels were positively correlated with age (r = 0.28; P < 0.001) and were higher in men with diabetes mellitus (P < 0.01). OPG serum levels in men without CAD were 5.4 +/- 2.0 pmol/liter, compared with 6.1 +/- 2.1 pmol/liter in single-vessel disease (P < 0.005), 5.9 +/- 2.4 in double-vessel disease (P < 0.05), and 6.3 +/- 2.3 pmol/liter in triple-vessel disease (P < 0.001). Moreover, OPG serum levels were positively correlated with the severity of CAD as determined by a CAD scoring system (r = 0.17; P < 0.01). In conclusion, our data underline that OPG serum levels are associated with the severity of CAD and are increased in elderly men and patients with diabetes mellitus. We conclude that increased OPG serum levels may reflect advanced cardiovascular disease in men.

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