106 resultados para c-reactive protein


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OBJECTIVE: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. ANIMALS: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. PROCEDURE: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. RESULTS: Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.

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AIM Assess the ability of a panel of gingival crevicular fluid (GCF) biomarkers as predictors of periodontal disease progression (PDP). MATERIALS AND METHODS In this study, 100 individuals participated in a 12-month longitudinal investigation and were categorized into four groups according to their periodontal status. GCF, clinical parameters and saliva were collected bi-monthly. Subgingival plaque and serum were collected bi-annually. For 6 months, no periodontal treatment was provided. At 6 months, patients received periodontal therapy and continued participation from 6 to 12 months. GCF samples were analysed by ELISA for MMP-8, MMP-9, Osteoprotegerin, C-reactive Protein and IL-1β. Differences in median levels of GCF biomarkers were compared between stable and progressing participants using Wilcoxon Rank Sum test (p = 0.05). Clustering algorithm was used to evaluate the ability of oral biomarkers to classify patients as either stable or progressing. RESULTS Eighty-three individuals completed the 6-month monitoring phase. With the exception of GCF C-reactive protein, all biomarkers were significantly higher in the PDP group compared to stable patients. Clustering analysis showed highest sensitivity levels when biofilm pathogens and GCF biomarkers were combined with clinical measures, 74% (95% CI = 61, 86). CONCLUSIONS Signature of GCF fluid-derived biomarkers combined with pathogens and clinical measures provides a sensitive measure for discrimination of PDP (ClinicalTrials.gov NCT00277745).

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AIMS Vent-HeFT is a multicentre randomized trial designed to investigate the potential additive benefits of inspiratory muscle training (IMT) on aerobic training (AT) in patients with chronic heart failure (CHF). METHODS AND RESULTS Forty-three CHF patients with a mean age of 58 ± 12 years, peak oxygen consumption (peak VO2 ) 17.9 ± 5 mL/kg/min, and LVEF 29.5 ± 5% were randomized to an AT/IMT group (n = 21) or to an AT/SHAM group (n = 22) in a 12-week exercise programme. AT involved 45 min of ergometer training at 70-80% of maximum heart rate, three times a week for both groups. In the AT/IMT group, IMT was performed at 60% of sustained maximal inspiratory pressure (SPImax ) while in the AT/SHAM group it was performed at 10% of SPImax , using a computer biofeedback trainer for 30 min, three times a week. At baseline and at 3 months, patients were evaluated for exercise capacity, lung function, inspiratory muscle strength (PImax ) and work capacity (SPImax ), quality of life (QoL), LVEF and LV diameter, dyspnoea, C-reactive protein (CRP), and NT-proBNP. IMT resulted in a significantly higher benefit in SPImax (P = 0.02), QoL (P = 0.002), dyspnoea (P = 0.004), CRP (P = 0.03), and NT-proBNP (P = 0.004). In both AT/IMT and AT/SHAM groups PImax (P < 0.001, P = 0.02), peak VO2 (P = 0.008, P = 0.04), and LVEF (P = 0.005, P = 0.002) improved significantly; however, without an additional benefit for either of the groups. CONCLUSION This randomized multicentre study demonstrates that IMT combined with aerobic training provides additional benefits in functional and serum biomarkers in patients with moderate CHF. These findings advocate for application of IMT in cardiac rehabilitation programmes.

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OBJECTIVE The knowledge on the level of systemic inflammation in peripheral artery disease (PAD) is less well established than that in coronary artery disease (CAD). Systemic inflammation frequently coincides with atherosclerosis, but also with various traits of the metabolic syndrome (MetS). The individual contribution of CAD, PAD, and the MetS to inflammation is not known. METHODS We enrolled a total of 1396 patients, 460 patients with PAD Fontaine stages IIa-IV verified by duplex ultrasound (PAD group) and 936 patients free of limb claudication undergoing coronary angiography, of whom 507 had significant CAD with coronary stenoses ≥50% (CAD group), and 429 did not have significant CAD at angiography (control group). RESULTS C-reactive protein (CRP) was significantly higher in the PAD than in the CAD or in the control group (0.86 ± 1.85 mg/dl versus 0.44 ± 0.87 mg/dl and 0.39 ± 0.52 mg/dl, respectively, p < 0.001 for both comparisons). These significant differences were confirmed when patients with and subjects without the MetS were analyzed separately. In particular, within the PAD group, CRP was significantly higher in patients with the MetS than in subjects without the MetS (1.04 ± 2.01 vs. 0.67 ± 1.64 mg/dl; p = 0.001) and both, the presence of PAD and the MetS proved to be independently associated with CRP in analysis of covariance (F = 31.84; p < 0.001 and F = 10.52; p = 0.001, respectively). CONCLUSION Inflammatory activity in PAD patients is higher than in CAD patients and is particularly high in PAD patients affected by the MetS. Low grade systemic inflammation is independently associated with both the MetS and PAD.

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BACKGROUND Vascular Ehlers-Danlos syndrome (VEDS) causes reduced life expectancy because of arterial dissections/rupture and hollow organ rupture. Although the causative gene, COL3A1, was identified >20 years ago, there has been limited progress in understanding the disease mechanisms or identifying treatments. METHODS AND RESULTS We studied inflammatory and transforming growth factor-β (TGF-β) signaling biomarkers in plasma and from dermal fibroblasts from patients with VEDS. Analyses were done in terms of clinical disease severity, genotype-phenotype correlations, and body composition and fat deposition alterations. VEDS subjects had increased circulating TGF-β1, TGF-β2, monocyte chemotactic protein-1, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and leptin and decreased interleukin-8 versus controls. VEDS dermal fibroblasts secreted more TGF-β2, whereas downstream canonical/noncanonical TGF-β signaling was not different. Patients with COL3A1 exon skipping mutations had higher plasma intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and VEDS probands had abnormally high plasma C-reactive protein versus affected patients identified through family members before any disease manifestations. Patients with VEDS had higher mean platelet volumes, suggesting increased platelet turnover because of ongoing vascular damage, as well as increased regional truncal adiposity. CONCLUSIONS These findings suggest that VEDS is a systemic disease with a major inflammatory component. C-reactive protein is linked to disease state and may be a disease activity marker. No changes in downstream TGF-β signaling and increased platelet turnover suggest that chronic vascular damage may partially explain increased plasma TGF-β1. Finally, we found a novel role for dysregulated TGF-β2, as well as adipocyte dysfunction, as demonstrated through reduced interleukin-8 and elevated leptin in VEDS.

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BackgroundAcute cough is a common problem in general practice and is often caused by a self-limiting, viral infection. Nonetheless, antibiotics are often prescribed in this situation, which may lead to unnecessary side effects and, even worse, the development of antibiotic resistant microorganisms worldwide. This study assessed the role of point-of-care C-reactive protein (CRP) testing and other predictors of antibiotic prescription in patients who present with acute cough in general practice.MethodsPatient characteristics, symptoms, signs, and laboratory and X-ray findings from 348 patients presenting to 39 general practitioners with acute cough, as well as the GPs themselves, were recorded by fourth-year medical students during their three-week clerkships in general practice. Patient and clinician characteristics of those prescribed and not-prescribed antibiotics were compared using a mixed-effects model.ResultsOf 315 patients included in the study, 22% were prescribed antibiotics. The two groups of patients, those prescribed antibiotics and those treated symptomatically, differed significantly in age, demand for antibiotics, days of cough, rhinitis, lung auscultation, haemoglobin level, white blood cell count, CRP level and the GP¿s license to self-dispense antibiotics. After regression analysis, only the CRP level, the white blood cell count and the duration of the symptoms were statistically significant predictors of antibiotic prescription.ConclusionsThe antibiotic prescription rate of 22% in adult patients with acute cough in the Swiss primary care setting is low compared to other countries. GPs appear to use point-of-care CRP testing in addition to the duration of clinical symptoms to help them decide whether or not to prescribe antibiotics.

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Inflammation is one possible mechanism underlying the associations between mental disorders and cardiovascular diseases (CVD). However, studies on mental disorders and inflammation have yielded inconsistent results and the majority did not adjust for potential confounding factors. We examined the associations of several pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and high sensitive C-reactive protein (hsCRP) with lifetime and current mood, anxiety and substance use disorders (SUD), while adjusting for multiple covariates. The sample included 3719 subjects, randomly selected from the general population, who underwent thorough somatic and psychiatric evaluations. Psychiatric diagnoses were made with a semi-structured interview. Major depressive disorder was subtyped into "atypical", "melancholic", "combined atypical-melancholic" and "unspecified". Associations between inflammatory markers and psychiatric diagnoses were assessed using multiple linear and logistic regression models. Lifetime bipolar disorders and atypical depression were associated with increased levels of hsCRP, but not after multivariate adjustment. After multivariate adjustment, SUD remained associated with increased hsCRP levels in men (β = 0.13 (95% CI: 0.03,0.23)) but not in women. After multivariate adjustment, lifetime combined and unspecified depression were associated with decreased levels of IL-6 (β = -0.27 (-0.51,-0.02); β = -0.19 (-0.34,-0.05), respectively) and TNF-α (β = -0.16 (-0.30,-0.01); β = -0.10 (-0.19,-0.02), respectively), whereas current combined and unspecified depression were associated with decreased levels of hsCRP (β = -0.20 (-0.39,-0.02); β = -0.12 (-0.24,-0.01), respectively). Our data suggest that the significant associations between increased hsCRP levels and mood disorders are mainly attributable to the effects of comorbid disorders, medication as well as behavioral and physical CVRFs.

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AIMS/HYPOTHESIS Plasminogen activator inhibitor-1 (PAI-1) has been regarded as the main antifibrinolytic protein in diabetes, but recent work indicates that complement C3 (C3), an inflammatory protein, directly compromises fibrinolysis in type 1 diabetes. The aim of the current project was to investigate associations between C3 and fibrinolysis in a large cohort of individuals with type 2 diabetes. METHODS Plasma levels of C3, C-reactive protein (CRP), PAI-1 and fibrinogen were analysed by ELISA in 837 patients enrolled in the Edinburgh Type 2 Diabetes Study. Fibrin clot lysis was analysed using a validated turbidimetric assay. RESULTS Clot lysis time correlated with C3 and PAI-1 plasma levels (r = 0.24, p < 0.001 and r = 0.22, p < 0.001, respectively). In a multivariable regression model involving age, sex, BMI, C3, PAI-1, CRP and fibrinogen, and using log-transformed data as appropriate, C3 was associated with clot lysis time (regression coefficient 0.227 [95% CI 0.161, 0.292], p < 0.001), as was PAI-1 (regression coefficient 0.033 [95% CI 0.020, 0.064], p < 0.05) but not fibrinogen (regression coefficient 0.003 [95% CI -0.046, 0.051], p = 0.92) or CRP (regression coefficient 0.024 [95% CI -0.008, 0.056], p = 0.14). No correlation was demonstrated between plasma levels of C3 and PAI-1 (r = -0.03, p = 0.44), consistent with previous observations that the two proteins affect different pathways in the fibrinolytic system. CONCLUSIONS/INTERPRETATION Similarly to PAI-1, C3 plasma levels are independently associated with fibrin clot lysis in individuals with type 2 diabetes. Therefore, future studies should analyse C3 plasma levels as a surrogate marker of fibrinolysis potential in this population.

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OBJECTIVES To evaluate possible differences in periodontal inflammatory, microbiological and clinical parameters between women with preterm premature rupture of membranes (PPROM) and controls with uncomplicated pregnancies. MATERIALS AND METHODS Fifty-six women (32 test (PPROM) and 24 controls (uncomplicated pregnancies)) were examined at three time-points (T1: gestational weeks 20-35, T2: within 48 h after parturition, T3: 4-6 weeks after parturition). The examinations included assessment of the Periodontal Screening Index, collection of gingival crevicular fluid (GCF) and subgingival as well as vaginal bacterial sampling. RESULTS Periodontal inflammation was found to be higher in the test compared with the control group (p < 0.05) and decreased over time in both groups (p < 0.05). Microbiological outcomes showed no intergroup differences (p > 0.05) in prevalence of bacteria, but a decrease in subgingival periodontopathogens from T1 to T2 in the test group (p < 0.05) was observed. Interleukin (IL)-1β levels in GCF at T2 were not different between groups (p > 0.05). In women with PPROM, GCF levels of IL-8 (p < 0.05) and C-reactive protein (p < 0.05) were lower and IL-10 levels higher (p < 0.05) compared with controls. CONCLUSIONS Periodontal inflammation is elevated during pregnancy and seems to be more pronounced in women with PPROM. CLINICAL RELEVANCE The findings of the present study revealed an association between periodontal inflammation and PPROM, thus emphasizing the importance of optimizing self-performed oral hygiene in pregnant women.

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OBJECTIVES Pre-antiretroviral therapy (ART) inflammation and coagulation activation predict clinical outcomes in HIV-positive individuals. We assessed whether pre-ART inflammatory marker levels predicted the CD4 count response to ART. METHODS Analyses were based on data from the Strategic Management of Antiretroviral Therapy (SMART) trial, an international trial evaluating continuous vs. interrupted ART, and the Flexible Initial Retrovirus Suppressive Therapies (FIRST) trial, evaluating three first-line ART regimens with at least two drug classes. For this analysis, participants had to be ART-naïve or off ART at randomization and (re)starting ART and have C-reactive protein (CRP), interleukin-6 (IL-6) and D-dimer measured pre-ART. Using random effects linear models, we assessed the association between each of the biomarker levels, categorized as quartiles, and change in CD4 count from ART initiation to 24 months post-ART. Analyses adjusted for CD4 count at ART initiation (baseline), study arm, follow-up time and other known confounders. RESULTS Overall, 1084 individuals [659 from SMART (26% ART naïve) and 425 from FIRST] met the eligibility criteria, providing 8264 CD4 count measurements. Seventy-five per cent of individuals were male with the mean age of 42 years. The median (interquartile range) baseline CD4 counts were 416 (350-530) and 100 (22-300) cells/μL in SMART and FIRST, respectively. All of the biomarkers were inversely associated with baseline CD4 count in FIRST but not in SMART. In adjusted models, there was no clear relationship between changing biomarker levels and mean change in CD4 count post-ART (P for trend: CRP, P = 0.97; IL-6, P = 0.25; and D-dimer, P = 0.29). CONCLUSIONS Pre-ART inflammation and coagulation activation do not predict CD4 count response to ART and appear to influence the risk of clinical outcomes through other mechanisms than blunting long-term CD4 count gain.

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Chinese Shar-Pei dogs have a high prevalence of hypocobalaminemia and are commonly presented with clinical signs suggestive of severe and long-standing gastrointestinal disease such as diarrhea, vomiting, and/or weight loss. The aim of the current study was to evaluate serum concentrations of inflammatory markers, markers for intestinal disease, and immunological markers in Shar-Peis with hypocobalaminemia or normocobalaminemia (serum cobalamin concentrations within the reference interval). Serum samples from Shar-Peis were collected from various parts of the United States. Serum concentrations of inflammatory markers (i.e., C-reactive protein [CRP], calprotectin [CP], and S100A12), hyaluronic acid (HA, a marker for cutaneous mucinosis), and analytes commonly altered in chronic intestinal diseases (i.e., albumin, zinc, alpha1-proteinease inhibitor [α1PI], immunoglobulin [Ig]A, and IgM) were compared between Shar-Peis with hypocobalaminemia and Shar-Peis with normocobalaminemia. Serum concentrations of CRP, CP, S100A12, HA, zinc, and cα1-PI concentrations did not differ between hypocobalaminemic and normocobalaminemic Shar-Peis (P > 0.05). Serum concentrations of albumin were significantly lower in hypocobalaminemic Shar-Peis (median: 2.5 g/dl) than in normocobalaminemic Shar-Peis (median: 2.9 g/dl; P < 0.0001). Higher serum IgA concentrations and lower serum IgM concentrations were observed in hypocobalaminemic Shar-Peis (median: 1.7 g/l and 0.8 g/l, respectively) than in normocobalaminemic Shar-Peis (median: 0.7 g/l and 1.9 g/l, respectively; both P < 0.0001). In conclusion, no difference was found in serum concentrations of CRP, CP, S100A12, and HA between hypocobalaminemic and normocobalaminemic Shar-Peis whereas some differences were observed in analytes (e.g., albumin, IgA, and IgM) that may be altered in patients with chronic enteropathies.

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This article gives a review of the classification, diagnostic procedures and treatment of idiopathic inflammatory myopathies from a neurological point of view. The myositis syndromes can be subdivided into four groups, polymyositis (PM), dermatomyositis (DM), inclusion body myositis (IBM) and necrotizing myopathy (NM), which substantially differ clinically and pathophysiologically. Myositis may also occur in association with cancer or autoimmune systemic diseases (overlap syndrome). Diagnosis of inflammatory myopathies is based on clinical symptoms, determination of creatine phosphokinase and acute phase parameters in blood (e.g. C-reactive protein and erythrocyte sedimentation rate), electromyography results and findings of magnetic resonance imaging (MRI) in muscle. A muscle biopsy is mandatory to confirm the diagnosis. High quality randomized controlled trials of treatment regimens for inflammatory myopathies are sparse; however, empirical experience indicates a clear effectiveness of immunosuppressive treatment of PM, DM and NM.

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AIMS Proprotein convertase subtilisin kexin 9 (PCSK9) is an emerging target for the treatment of hypercholesterolaemia, but the clinical utility of PCSK9 levels to guide treatment is unknown. We aimed to prospectively assess the prognostic value of plasma PCSK9 levels in patients with acute coronary syndromes (ACS). METHODS AND RESULTS Plasma PCSK9 levels were measured in 2030 ACS patients undergoing coronary angiography in a Swiss prospective cohort. At 1 year, the association between PCSK9 tertiles and all-cause death was assessed adjusting for the Global Registry of Acute Coronary Events (GRACE) variables, as well as the achievement of LDL cholesterol targets of <1.8 mmol/L. Patients with higher PCSK9 levels at angiography were more likely to have clinical familial hypercholesterolaemia (rate ratio, RR 1.21, 95% confidence interval, CI 1.09-1.53), be treated with lipid-lowering therapy (RR 1.46, 95% CI 1.30-1.63), present with longer time interval of chest pain (RR 1.29, 95% CI 1.09-1.53) and higher C-reactive protein levels (RR 1.22, 95% CI 1.16-1.30). PCSK9 increased 12-24 h after ACS (374 ± 149 vs. 323 ± 134 ng/mL, P < 0.001). At 1 year follow-up, HRs for upper vs. lower PCSK9-level tertiles were 1.13 (95% CI 0.69-1.85) for all-cause death and remained similar after adjustment for the GRACE score. Patients with higher PCSK9 levels were less likely to reach the recommended LDL cholesterol targets (RR 0.81, 95% CI 0.66-0.99). CONCLUSION In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

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OBJECTIVE The aim of this study was to investigate the occurrence of subclinical atherosclerosis and underlying mechanisms in men with newly diagnosed diabetes and established diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS In a population-based study of 61-year-old Caucasian men (n = 271) with established diabetes (n = 50) and newly diagnosed diabetes (n = 24) and healthy control subjects (n = 197), standard risk factors and highly sensitive (hs) C-reactive protein (CRP) were measured. Ultrasound measurements of intima-media thickness (IMT) were performed bilaterally in the common carotid artery, and a composite measure was calculated from common carotid and carotid bulb IMT (composite IMT). The plaque status was assessed. RESULTS Composite IMT and carotid plaque size increased gradually among the healthy control subjects, newly diagnosed diabetic patients, and established diabetic patients (P for trend < or =0.001, respectively). CRP was higher in newly and established diabetes (NS between diabetes groups) compared with healthy control subjects (P < 0.001). Total cholesterol levels were lower in newly diagnosed diabetes (5.51 +/- 1.13 mmol/l, P < 0.05) and established diabetes (5.45 +/- 1.15 mmol/l, P < 0.01) compared with those of healthy control subjects (5.77 +/- 1.03 mmol/l). In men with diabetes (n = 74), diabetes onset status (newly diagnosed versus established), waist-to-hip ratio (WHR), and serum triglycerides, but not CRP, explained 16% of the variance in composite IMT. CONCLUSIONS This is the first study to show increased preclinical atherosclerotic changes (IMT and plaque size) and increased inflammation (hs-CRP) in men with newly diagnosed diabetes as well as in patients with established diabetes compared with healthy control subjects. WHR, diabetes onset status (newly diagnosed versus established), and triglycerides, but not CRP, were independent correlates of carotid artery IMT in men with diabetes.

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OBJECTIVES The aim of the study was to test the hypothesis that circulating markers of inflammation (high-sensitive C-reactive protein, hsCRP) and oxidative modification of lipids (oxidized low-density lipoprotein, oxLDL) were associated with the occurrence of echolucent rather than echogenic femoral artery plaques in a cross-sectional population based cohort of 513, 61-year-old men. BACKGROUND The relationships between circulating oxLDL, hsCRP and the occurrence of echolucent plaques in the femoral artery have not previously been investigated. METHODS The levels of circulating oxLDL and hsCRP were determined in plasma by ELISA. Plaque occurrence, size and echogenicity were measured by B-mode ultrasound in the right femoral artery. Assessment of plaque echogenicity was based on the classification (grades 1-4) proposed by Gray-Weale et al. RESULTS A higher frequency of echolucent femoral plaques was observed in subjects with the metabolic syndrome and current smokers (p=0.01 and p<0.001, respectively) as well as with increasing levels of oxLDL and hsCRP (p=0.002 and p=0.005, respectively). In a multiple logistic regression analysis oxLDL and current smokers turned out to be independent associated with the presence of echolucent femoral artery plaques. CONCLUSIONS The results of the present study support our hypothesis that circulating oxLDL is a marker of an unstable echolucent plaque phenotype in the femoral artery in man.