osteoprotegerin and Peripheral-Arterial-Disease

Classical risk factors play a major role in the initiation and development of atherosclerosis. However, the estimation of risk for cardiovascular events based only on risk factors is often insufficient. Efforts have been made to identify biomarkers that indicate ongoing atherosclerosis. Among important circulating biomarkers associated with peripheral arterial disease (PAD) are inflammatory markers which are determined by the expression of different genes and epigenetic processes. Among these proinflammatory molecules, interleukin-6, C-reactive protein, several adhesion molecules, CD40 ligand, osteoprotegerin and others are associated with the presence and progression of PAD. Additionally, several circulating prothrombotic markers have a predictive value in PAD. Genetic polymorphisms significantly, albeit moderately, affect risk factors for PAD via altered lipoprotein metabolism, diabetes, arterial hypertension, smoking, inflammation and thrombosis. However, most of the risk variants for PAD are located in noncoding regions of the genome and their influence on gene expression remains to be explored. MicroRNAs (miRNAs) are single-stranded, noncoding RNAs that modulate gene expression at the post-transcriptional level. Patterns of miRNA expression, to some extent, vary in different atherosclerotic cardiovascular diseases. miRNAs appear to be useful in the detection of PAD and the prediction of progression and revascularization outcomes. In conclusion, taking into account one's predisposition to PAD, i.e., DNA polymorphisms and miRNAs, together with circulating inflammatory and coagulation markers, holds promise for more accurate prediction models and personalized therapeutic options.

Topics: Atherosclerosis; Biomarkers; C-Reactive Protein; CD40 Ligand; DNA; Humans; Interleukin-6; Lipoproteins; MicroRNAs; Osteoprotegerin; Peripheral Arterial Disease; Polymorphism, Genetic; Precision Medicine; Risk Factors

The aim of this study was to evaluate the association of the calcification regulators, osteopontin (OPN) and osteoprotegerin (OPG), which are involved in vascular calcification and atherosclerosis in patients with peripheral arterial disease (PAD).. A PubMed search of the English language literature was undertaken to identify articles that examine the role of the vascular calcification markers (OPN and OPG) in patients with PAD. The search retrieved 94 articles. After excluding non-relevant articles, only 11 studies qualified for review.. In 8 studies, OPG levels were correlated with the presence, severity, and progression of PAD, whereas in one article, OPG levels were not significantly elevated. In 2 studies, OPN levels were associated with PAD and vascular stiffness.. The results from clinical and experimental research regarding the role of vascular calcification markers in PAD are controversial, although most of the studies suggest a positive correlation. Larger studies are needed to determine the exact pathway of vascular calcification, mediated by calcification markers, in patients with PAD.

Topics: Biomarkers; Humans; Osteopontin; Osteoprotegerin; Peripheral Arterial Disease; Predictive Value of Tests; Prognosis; Severity of Illness Index; Vascular Calcification; Vascular Stiffness

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

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

Osteoprotegerin (OPG) and osteopontin (OPN) are vascular calcification inhibitors with a known role in the atherosclerotic and inflammatory process. We investigated their relationship with adverse outcomes (restenosis/adverse cardiovascular events) after endovascular revascularisation of patients with peripheral arterial disease (PAD).. 203 consecutive patients were enrolled in the PAD group (PADG) and 78 age and sex-matched subjects with less than two cardiovascular risk factors served as control group (COG). PADG underwent standard medical assessment at baseline and 12 months after the procedure. During follow up major adverse cardiovascular events (MACEs) including arterial restenosis with need for reintervention were documented and the PADG was divided accordingly into two subgroups.. During 12-month follow-up, 82 MACE were recorded (MACE subgroup). The rest of 124 PAD patients remained free of MACE (non-MACE subgroup). At baseline, OPG (9.89 ± 2.85 ng/ml vs 3.47 ± 1.95 ng/ml, p < 0.001) and OPN (79.99 ± 38.29 ng/ml vs 35.21 ± 14.84 ng/ml, p < 0.001) levels were significantly higher in PADG compared to COG, as well as in MACE subgroup compared to non-MACE subgroup (13.29 ± 3.23 ng/ml vs 10.86 ± 3 ng/ml and 96.45 ± 40.12 ng/ml vs 78.1 ± 38.29 ng/ml, respectively). An independent association of PAD with OPG and OPN was found in the whole patient cohort. Although OPG and OPN were significantly related to MACE incidence in the univariate analysis, multiple logistic regression analysis failed to detect any independent predictor of MACE within the PADG.. Baseline high OPG and OPN levels were independently associated with PAD presence. Even higher levels of those biomarkers were detected among PAD patients with MACE, however, their prognostic role should be further clarified.

Topics: Biomarkers; Humans; Osteopontin; Osteoprotegerin; Peripheral Arterial Disease; Risk Factors; Vascular Calcification

We hypothesized that circulating osteoprotegerin (OPG) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels could be associated with vascular calcification, which is predominant in diabetes.The study included 71 Korean participants (36 with diabetes and 35 without diabetes), who were sub-grouped according to the results of the ankle-brachial index (ABI) and/or X-ray computed tomography scan (CT scan). Serum OPG and TRAIL levels were assayed using the respective enzyme-linked immunosorbent assay kits. Statistical significance was analyzed using Student's t test between the 2 groups or analysis of variance (ANOVA) among the 4 groups.Serum OPG was up-regulated in the participants with diabetes, with peripheral arterial disease (PAD), and/or with vascular calcification. TRAIL down-regulation was more strictly controlled than OPG up-regulation; it was significantly downregulated in the participants with PAD and vascular calcification, but not in the participants with diabetes. Serum OPG and TRAIL were regulated in the participants with femoral, popliteal, and peroneal artery calcification but not in the participants with aortic calcification.OPG up-regulation and TRAIL down-regulation were found to be associated with leg lesional vascular calcification; therefore, the average OPG/TRAIL ratio was significantly increased by 3.2-fold in the leg lesional vascular calcification group.

Topics: Aortic Diseases; Biomarkers; Diabetes Complications; Humans; Leg; Osteoprotegerin; Peripheral Arterial Disease; TNF-Related Apoptosis-Inducing Ligand; Vascular Calcification

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

Osteoprotegerin plays a role in the development of several bone diseases. In addition, osteoprotegerin may contribute to the development of vascular disease. Little is known about the association between serum osteoprotegerin levels and the presence or severity of peripheral arterial disease (PAD). The aim of this study was to examine the association between serum osteoprotegerin levels and both the presence as well as the severity of lower extremity arterial disease in patients with type 2 diabetes (T2DM).. The study included 165 consecutive patients with T2DM (57 % males, mean age 65.0 ± 0.7 years). PAD was diagnosed by measurement of the toe-brachial index (TBI). Serum osteoprotegerin was measured using ELISA.. The mean osteoprotegerin level was significantly higher in patients with PAD in comparison to patients without PAD (18.2 ± 1.0 vs. 13.1 ± 2.0 pmol/L, p = 0.014). Significant univariate correlations between TBI and osteoprotegerin level (r = -0.308; p < 0.001), age, body mass index, and HDL cholesterol were observed. In the multivariate linear regression analysis, serum osteoprotegerin (β = -0.005; p = 0.020), higher age, and male gender were significant predictors of TBI. When 25(OH) vitamin D was introduced into the mentioned model, OPG was no longer a significant predictor of TBI and was replaced in the model with vitamin D (β = 0.009, p = 0.001). This finding suggests a role of OPG as a mediator of the effects of 25(OH) vitamin D.. Serum osteoprotegerin level is significantly associated with both the presence and severity of PAD in patients with T2D. Osteoprotegerin might be a biomarker for the presence of atherosclerotic disease in patients with T2DM.

Topics: Aged; Ankle Brachial Index; Biomarkers; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Osteoprotegerin; Peripheral Arterial Disease; Predictive Value of Tests; Risk Factors; Severity of Illness Index; Up-Regulation

High mobility group box-1 (HMGB-1) is a nuclear protein also acting as inflammatory mediator, whilst osteoprotegerin (OPG), member of tumor necrosis factor receptor superfamily, is indicated as marker of vascular calcification. Peripheral artery disease (PAD) and type 2 diabetes (T2D) are clinical conditions characterized by elevated serum inflammatory markers and vascular calcification enhancement. The aim of this study was to investigate the potential role of HMGB-1, OPG and several inflammatory mediators such as C-reactive protein (HsCRP), tumor necrosis factor-alpha and interleukin-6 (IL-6) on the presence and severity of peripheral artery disease in patients with T2D.. In this retrospective observational study, we have analyzed HMGB-1, OPG and inflammatory cytokines serum levels in 1393 type 2 diabetic patients with PAD and without PAD (WPAD).. HMGB-1 (7.89 ± 15.23 ng/mL), OPG (6.54 ± 7.76 pmol/L), HsCRP (15.6 ± 14.4 mg/L) and IL-6 (56.1 ± 28.6 pg/mL) serum levels were significantly higher in patients with PAD than in those WPAD (3.02 ± 8.12 ng/mL, P ˂ 0.001; 2.98 ± 2.01 pmol/L, P < 0.001; 7.05 ± 4.4 mg/L, P < 0.001; 37.5 ± 20.2 pg/mL, P < 0.001 respectively). Moreover HMGB-1 (P < 0.001), OPG (P < 0.001), HsCRP (P < 0.001) and IL-6 (P < 0.001) serum levels were positively correlated with clinical severity of PAD. HMGB-1 (adjusted OR 12.32; 95% CI 3.56-23.54, P = 0.023) and OPG (adjusted OR 3.53; 95% CI 1.54-6.15, P = 0.019) resulted independent determinants of PAD in patients with T2D after adjusting for the conventional cardiovascular risk factor and established inflammatory mediators.. In T2D patients HMGB-1 and OPG serum levels are higher in patients affected by PAD and independently associated with its occurrence and clinical severity.

Topics: Aged; Biomarkers; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; HMGB1 Protein; Humans; Male; Middle Aged; Osteoprotegerin; Peripheral Arterial Disease; Retrospective Studies; Risk Factors; Tumor Necrosis Factor-alpha; Vascular Calcification

Arterial calcification, a process that mimics bone formation, is an independent risk factor of cardiovascular morbidity and mortality, and has a significant impact on surgical and endovascular procedures and outcomes. Research efforts have focused mainly on the coronary arteries, while data regarding the femoral territory remain scarce.. Femoral endarterectomy specimens, clinical data, and plasma from a cohort of patients were collected prospectively. Histological analysis was performed to characterize the cellular populations present in the atherosclerotic lesions, and that were potentially involved in the formation of bone like arterial calcification known as osteoid metaplasia (OM). Enzyme linked immunosorbent assays and cell culture assays were conducted in order to understand the cellular and molecular mechanisms underlying the formation of OM in the lesions.. Twenty-eight of the 43 femoral plaques (65%) displayed OM. OM included osteoblast and osteoclast like cells, but very few of the latter exhibited the functional ability to resorb mineral tissue. As in bone, osteoprotegerin (OPG) was significantly associated with the presence of OM (p = .04). Likewise, a high plasma OPG/receptor activator for the nuclear factor kappa B ligand (RANKL) ratio was significantly associated with the presence of OM (p = .03). At the cellular level, there was a greater presence of pericytes in OM+ compared with OM- lesions (5.59 ± 1.09 vs. 2.42 ± 0.58, percentage of area staining [region of interest]; p = .04); in vitro, pericytes were able to inhibit the osteoblastic differentiation of human mesenchymal stem cells, suggesting that they are involved in regulating arterial calcification.. These results suggest that bone like arterial calcification (OM) is highly prevalent at femoral level. Pericyte cells and the OPG/RANK/RANKL triad seem to be critical to the formation of this ectopic osteoid tissue and represent interesting potential therapeutic targets to reduce the clinical impact of arterial calcification.

Topics: Aged; Cells, Cultured; Endarterectomy; England; Female; Femoral Artery; Humans; Male; Osteoprotegerin; Pericytes; Peripheral Arterial Disease; Plaque, Atherosclerotic; Prevalence; Prospective Studies; RANK Ligand; Vascular Calcification

Osteoprotegerin (OPG) and von Willebrand factor (VWF) form complex within endothelial cells and following secretion. The nature of blood group antigens strongly influences the levels of circulating VWF, but there is no available data concerning its ascendancy on OPG levels. We aimed to assess the relationship of AB0 blood groups with OPG, VWF levels (VWF: Ag) and collagen binding activity (VWF: CB) in peripheral arterial disease (PAD) patients.. Functional and laboratory parameters of 105 PAD patients and 109 controls were examined. Results of OPG, VWF: Ag, VWF: CB (ELISA-s) were analysed by comparative statistics, together with clinical data.. OPG levels were higher in patients than in controls (4.64 ng/mL vs. 3.68 ng/mL, p < 0.001). Among patients elevation was marked in the presence of critical limb ischemia (5.19 ng/mL vs. 4.20 ng/mL, p = 0.011). The OPG in patients correlated positively with VWF: Ag and VWF: CB (r = 0.26, p = 0.008; r = 0.33, p = 0.001) and negatively with ankle-brachial pressure index (r = -0.22, p = 0.023). Furthermore, OPG was significantly elevated in non-0 blood groups compared to 0-groups both in patients and controls (4.95 ng/mL vs. 3.90 ng/mL, p = 0.012 and 4.09 ng/mL vs. 3.40 ng/mL, p = 0.002).. OPG levels are associated to blood group phenotypes and higher in non-0 individuals. Increased OPG levels in PAD characterize disease severity. The significant correlation between OPG and VWF:CB might have functional importance in an atherothrombosis-prone biological environment.

Topics: ABO Blood-Group System; Biomarkers; Enzyme-Linked Immunosorbent Assay; Female; Humans; Incidence; Male; Middle Aged; Osteoprotegerin; Peripheral Arterial Disease; Phenotype; Risk Factors; Romania; Severity of Illness Index; Ultrasonography, Doppler, Duplex

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor superfamily and suggested as a marker of atherosclerosis. However, little is known about the association between plasma OPG levels and lower extremity arterial disease. We investigated whether plasma OPG levels were associated with the presence and severity of lower extremity arterial disease in patients with type 2 diabetes.. This was a study of 712 patients with type 2 diabetes aged 40 years or older. Plasma OPG was measured using ELISA. The lower extremity arterial disease was diagnosed by high-frequency color Doppler ultrasonic.. Of 712 patients, 505 (70.9 %) had lower extremity arterial stenosis. OPG levels were significantly increased in patients with lower extremity arterial stenosis [1.89 (1.48-2.41) vs. 2.39 (1.82-3.33) ng/mL, p < 0.001]. Plasma OPG levels increased gradually with increasing severity of lower extremity arterial stenosis (p < 0.001 for trend), after adjustment for traditional cardiovascular risk factors such as age, gender, smoking, total cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), body mass index (BMI), systolic blood pressure(SBP). The risk of lower extremity arterial disease was increased (OR = 1.17, 95 % CI 1.09 -1.28, p < 0.001) with each standard deviation (SD) higher level of OPG in patients with type 2 diabetes after adjustment for traditional CVD risk factors.. Plasma OPG levels were significantly associated with the presence and severity of lower extremity arterial disease. Our results suggest that OPG is an important plasma biomarker of lower extremity arterial disease in type 2 diabetes.

Topics: Adiponectin; Adult; Aged; C-Reactive Protein; Cohort Studies; Constriction, Pathologic; Diabetes Mellitus, Type 2; Female; Humans; Lower Extremity; Male; Middle Aged; Osteoprotegerin; Peripheral Arterial Disease; Prospective Studies; Severity of Illness Index; Ultrasonography, Doppler, Color

To identify differences in postexercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications.. We enrolled healthy control subjects and three groups of patients with type 2 diabetes mellitus: without complications, with peripheral neuropathy, and with both peripheral neuropathy and peripheral arterial disease. We used magnetic resonance spectroscopic measurements to perform continuous measurements of phosphorous metabolites (PCr and inorganic phosphate [Pi]) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements also were performed.. The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise were similar in all groups. The postexercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in diabetic patients with neuropathy and those with both neuropathy and peripheral arterial disease (P < .01 for both measurements). These two groups also had higher levels of tumor necrosis factor-α (P < .01) and granulocyte colony-stimulating factor (P < .05). Multiple regression analysis showed that only granulocyte colony-stimulating factor, osteoprotegerin, and tumor necrosis factor-α were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/PCr ratio or PCr recovery time.. Mitochondrial oxidative phosphorylation is impaired only in type 2 diabetes mellitus patients with neuropathy whether or not peripheral arterial disease is present and is associated with the increased proinflammatory state observed in these groups.

Topics: Adult; Aged; Aged, 80 and over; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Neuropathies; Exercise; Female; Granulocyte Colony-Stimulating Factor; Humans; Inflammation Mediators; Magnetic Resonance Spectroscopy; Male; Middle Aged; Mitochondria; Muscle Contraction; Muscle, Skeletal; Osteoprotegerin; Oxidative Phosphorylation; Peripheral Arterial Disease; Phosphocreatine; Time Factors; Tumor Necrosis Factor-alpha

The use of multiple biomarkers representing various etiologic pathways of atherosclerosis may improve the prediction of interindividual variation in the ankle-brachial index (ABI). To this end, we investigated associations of 47 candidate biomarkers with the ABI and presence of peripheral arterial disease (PAD) in African-Americans (AAs) and non-Hispanic whites (NHWs).. Study participants included 1,291 AAs (71.1% women, mean age, 63.4±9.3 years) and 1,152 NHWs (57.5% women, mean age 58.5±10.1 years) belonging to hypertensive sibships. Peripheral arterial disease was defined as an ABI ≤ 0.90. Circulating levels of 47 candidate biomarkers were log-transformed before analysis because of skewed distribution. Multivariate regression analyses were used to identify biomarkers associated with ABI or PAD independently of age, sex, conventional risk factors, and medication use.. After adjustment for covariates, higher levels of nine biomarkers were associated with a lower ABI in AAs (all P ≤ 0.005); these biomarkers were C-reactive protein (CRP), interleukin-6, tumor necrosis factor receptor-II (TNF-R II), lipoprotein(a), N-terminal pro-brain natriuretic peptide (NT-proBNP), pro-atrial natriuretic peptide, C-terminal pro-arginine vasopressin, osteoprotegerin, and fibrinogen. Three biomarkers - myeloperoxidase, NT-proBNP, and D-dimer - were associated with ABI in NHWs (all P ≤ 0.01). C-reactive protein, interleukin-6, TNF-R II, lipoprotein(a), NT-proBNP, pro-atrial natriuretic peptide, D-dimer, and fibrinogen were associated with PAD (all P ≤ 0.005) in AAs after adjustment for covariates. None of the biomarkers were independently associated with PAD in NHWs.. A multimarker approach improved the prediction of interindividual variation in the ABI in AAs and NHWs, and improved prediction of the presence of PAD in AAs.

Topics: Aged; Ankle Brachial Index; Biomarkers; Black or African American; C-Reactive Protein; Cross-Sectional Studies; Female; Fibrin Fibrinogen Degradation Products; Humans; Interleukin-6; Linear Models; Lipoprotein(a); Male; Middle Aged; Natriuretic Peptide, Brain; Osteoprotegerin; Peptide Fragments; Peripheral Arterial Disease; Risk Factors; White People

Cardiovascular disease (CVD) is frequent in type 2 diabetes mellitus patients due to accelerated atherosclerosis. Plasma osteoprotegerin (OPG) has evolved as a biomarker for CVD. We examined the relationship between plasma OPG levels and different CVD manifestations in type 2 diabetes.. Type 2 diabetes patients without known CVD referred consecutively to a diabetes clinic for the first time (n = 305, aged: 58.6 ± 11.3 years, diabetes duration: 4.5 ± 5.3 years) were screened for carotid arterial disease, peripheral arterial disease, and myocardial ischemia by means of carotid artery ultrasonography, peripheral ankle and toe systolic blood pressure measurements, and myocardial perfusion scintigraphy (MPS). In addition, plasma OPG concentrations and other CVD-related markers were measured.. The prevalence of carotid arterial disease, peripheral arterial disease, and myocardial ischemia was 42%, 15%, and 30%, respectively. Plasma OPG was significantly increased in patients with carotid and peripheral arterial disease compared to patients without (p < 0.001, respectively), however, this was not the case for patients with myocardial ischemia versus those without (p = 0.71). When adjusted for age, HbA1c and U-albumin creatinine ratio in a multivariate logistic regression analysis, plasma OPG remained strongly associated with carotid arterial disease (adjusted OR: 2.12; 95% CI: 1.22-3.67; p = 0.008), but not with peripheral arterial disease or myocardial ischemia.. Increased plasma OPG concentration is associated with carotid and peripheral arterial disease in patients with type 2 diabetes, whereas no relation is observed with respect to myocardial ischemia on MPS. The reason for this discrepancy is unknown.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Carotid Arteries; Carotid Artery Diseases; Diabetes Mellitus, Type 2; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Osteoprotegerin; Perfusion Imaging; Peripheral Arterial Disease; Prevalence; Retrospective Studies; Risk Factors; Ultrasonography

Peripheral arterial disease (PAD) and type 2 diabetes mellitus (DM) are both associated with excessive vascular calcification and elevated levels of inflammatory markers IL-6 and hsCRP. The recently identified Osteoprotegerin(OPG)/RANKL/TRAIL pathway has been implicated in vascular calcification, but data on levels in PAD and effect of co-existent DM are lacking.. 4 groups of patients were recruited - 26 with PAD and DM, 35 with DM alone, 22 with PAD alone, and 21 healthy individuals. Serum OPG, RANKL, TRAIL, hsCRP and IL-6 were measured using commercial ELISA assays. Presence and severity of PAD was defined using ankle brachial index (ABI).. Serum OPG (7.4±0.3 vs.5.8±0.2 pmol/l, p<0.0001), TRAIL (95.5±5.2 ng/ml vs. 76.2±4.4 ng/ml, p=0.006), hsCRP (2.6±0.3 vs. 1.8±0.3 mg/l, p=0.048), and IL-6 (4.1±0.4 vs. 2.9±0.4 pg/ml, p=0.06) were higher in patients with PAD. There was no difference in RANKL. Only OPG was significantly higher in PAD and DM (7.2±0.3 pmol/l) and PAD alone (7.7±0.4 pmol/l) compared to DM only (5.8±0.3 pmol/l) and healthy controls (5.6±0.4 pmol/l), p<0.01, but OPG was no higher in those with DM plus PAD versus those with PAD alone (p<0.3). Only OPG was associated with PAD severity, correlating negatively with ABI (r=-0.26, p=0.03), independent of age, gender, glycaemic status, hsCRP and IL-6.. PAD is associated with higher serum OPG, regardless of the co-existence of DM. This finding, in addition to its correlation with severity of PAD, suggests that OPG may be a novel marker for the presence and severity of PAD, possibly by reflecting the degree of underlying vascular calcification.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Osteoprotegerin; Peripheral Arterial Disease