osteoprotegerin and Hyperlipidemias

Patients with end-stage renal disease have greatly elevated risks of atherosclerotic disease. Vascular calcification in advanced atherosclerosis is a common feature in ESRD patients. Risk factors of atherosclerosis in ESRD patients are coronary risk factors such as hypertension, diabetes and hyperlipidemia and hyperphosphatemia. Bone associated proteins including osteopontin, matrix Gla protein and osteoprotegerin may be involved in the progression of atherosclerosis.

Topics: Arteriosclerosis; Calcium-Binding Proteins; Diabetes Complications; Diabetes Mellitus; Extracellular Matrix Proteins; Glycoproteins; Humans; Hyperlipidemias; Hypertension; Kidney Failure, Chronic; Matrix Gla Protein; Osteopontin; Osteoprotegerin; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Risk Factors; Sialoglycoproteins

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

The hypothesis of this study was that the replacement of regular milk with fortified milk in hyperlipidemic adults for 1 year would improve bone biomarkers. The fortified milk contained eicosapentaenoic acid and docosahexaenoic acid from fish oils, oleic acid, vitamins A, B(6), and E, as well as folic acid. We believe that the fortified milk will improve the blood fatty acid profile and vitamin status in subjects to benefit bone health biomarkers. From the 84 patients who accepted to participate, 11 of these were excluded for the presence of metabolic diseases and 1 was excluded for noncompliance with the protocol. Seventy-two hyperlipidemic patients (35-65 years) were randomly divided between 2 study groups. The supplement group (E; n = 39) consumed 0.5 L/d of fortified milk that contained fish oil, oleic acid, and vitamins. The control group (C; n = 33) consumed 0.5 L/d of semiskimmed milk containing the same amount of total fat. Blood samples were taken at T(0), T(3), T(6), and T(12) months to determine plasma fatty acids, vitamins B(6), E, and 25-hydroxyvitamin D and serum folate, calcium, soluble osteoprotegerin (OPG), soluble receptor activator of NF-kappaB ligand (RANKL), osteocalcin, parathormone, type I collagen carboxy-terminal telopeptide, and malondialdehyde. After 1 year, the E group showed a significant increase in plasma eicosapentaenoic acid (42%), docosahexaenoic acid (60%), vitamin B6 (38%), OPG (18%), RANKL (7%), OPG/RANKL (10%), red blood cell folate (21%), serum folate (53%), calcium (4%), vitamin D (11%), and osteocalcin (22%). Dietary supplementation with the fortified milk drink improved nutritional status and bone formation markers in adult hyperlipidemic patients.

Topics: Adult; Animals; Biomarkers; Calcium; Double-Blind Method; Erythrocytes; Fatty Acids, Omega-3; Female; Folic Acid; Food, Fortified; Humans; Hyperlipidemias; Longitudinal Studies; Male; Middle Aged; Milk; Oleic Acid; Osteocalcin; Osteogenesis; Osteoprotegerin; RANK Ligand; Time Factors; Vitamin B 6; Vitamin D; Vitamins

The objective of this study is to determine whether simvastatin consumption and hyperlipidemia are associated with a worse periodontal condition and specific bone activity biomarkers.. This cross-sectional and analytic study includes 73 patients divided into three groups: 1) simvastatin-treated patients with hyperlipidemia (n = 29); 2) patients with hyperlipidemia treated by diet alone (n = 28); and 3) normolipidemic patients (controls, n = 16). The periodontal clinical variables of all participants were gathered, a blood sample was drawn from each to determine the lipid profile (total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein), serum levels of acute-phase reactants (C-reactive protein), erythrocyte sedimentation rate, and bone metabolism markers (osteoprotegerin [OPG], osteocalcin, procollagen type I N-terminal propeptide, and C-terminal telopeptide of type I collagen).. The mean ESR was higher in the diet-treated patients with hyperlipidemia than in the normolipidemic controls (P = 0.04). Serum OPG concentrations were significantly higher in the simvastatin-treated patients with hyperlipidemia than in the diet-treated patients with hyperlipidemia (P = 0.05). Multivariable linear regression analysis adjusted for age, sex, tobacco, and alcohol revealed that, compared with the normolipidemic patients, the simvastatin-treated patients with hyperlipidemia showed a mean reduction of 0.8 mm (95% confidence interval = -1.5 to 0.0, P = 0.05) in clinical attachment loss.. Within the limits of this study, the findings suggest that the intake of simvastatin is associated with increasing serum OPG concentrations, and this could have a protective effect against bone breakdown and periodontal attachment loss. The baseline systemic inflammatory state of patients with hyperlipidemia is indicated by their increased erythrocyte sedimentation rate.

Topics: Adult; Aged; Alcohol Drinking; Biomarkers; Blood Sedimentation; C-Reactive Protein; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Collagen Type I; Cross-Sectional Studies; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypolipidemic Agents; Male; Middle Aged; Osteocalcin; Osteoprotegerin; Peptide Fragments; Peptides; Periodontal Attachment Loss; Periodontal Index; Procollagen; Simvastatin; Smoking; Triglycerides

Macrophage-derived products are known to play a crucial role during atherogenesis and vascular calcification. Glucocorticoids (GC) are important modulators of immune cell functions, but their specific effects on macrophages behavior during plaque formation are not defined. The present study was therefore designed to investigate the effects of macrophage-specific deletion of the glucocorticoid receptor (GR(LysMCre)) on atherogenesis and vascular calcification in a hyperlipidemic mouse-model.. Bone marrow was isolated from GR(LysMCre) mice and wild-type controls (GR(flox)) and subsequently transplanted into lethally irradiated LDL-receptor-deficient mice. Animals were fed a Western-type diet for 15 or 24 weeks, and atherosclerotic lesions within the aortic sinus were evaluated. At both time points, no significant difference in serum lipid and corticosterone concentrations, atherosclerotic lesion size and macrophage-content within the lesions could be observed. However, GR(LysMCre) mice showed less calcification as well as a significant reduction of RANKL, BMP2, and Msx2 expression within the vasculature. In vitro studies using conditioned media from macrophages which had been stimulated with dexamethasone demonstrated a dose-dependent increase in calcium deposition by vascular smooth muscle cells.. This study demonstrates that macrophage-specific glucocorticoid receptor inactivation reduces vascular calcification without affecting atherosclerotic lesion size in LDL receptor-deficient mice.

Topics: Animals; Atherosclerosis; Bone Marrow Transplantation; Calcinosis; Calcium; Disease Models, Animal; Female; Glucocorticoids; Hyperlipidemias; Macrophages; Mice; Mice, Inbred C57BL; Mice, Knockout; Osteoprotegerin; RANK Ligand; Receptors, Glucocorticoid; Receptors, LDL; RNA, Messenger