Showing papers on "C-reactive protein published in 2017"

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Abstract: BackgroundExperimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. MethodsWe conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. ResultsAt 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in t...

Peripheral inflammatory markers in Alzheimer’s disease: a systematic review and meta-analysis of 175 studies

Abstract: Objectives Increasing evidence suggests that inflammation is involved in Alzheimer’s disease (AD) pathology. This study quantitatively summarised the data on peripheral inflammatory markers in patients with AD compared with healthy controls (HC). Methods Original reports containing measurements of peripheral inflammatory markers in AD patients and HC were included for meta-analysis. Standardised mean differences were calculated using a random effects model. Meta-regression and exploration of heterogeneity was performed using publication year, age, gender, Mini-Mental State Examination (MMSE) scores, plasma versus serum measurements and immunoassay type. Results A total of 175 studies were combined to review 51 analytes in 13 344 AD and 12 912 HC patients. Elevated peripheral interleukin (IL)-1β, IL-2, IL-6, IL-18, interferon-γ, homocysteine, high-sensitivity C reactive protein, C-X-C motif chemokine-10, epidermal growth factor, vascular cell adhesion molecule-1, tumour necrosis factor (TNF)-α converting enzyme, soluble TNF receptors 1 and 2, α1-antichymotrypsin and decreased IL-1 receptor antagonist and leptin were found in patients with AD compared with HC. IL-6 levels were inversely correlated with mean MMSE scores. Conclusions These findings suggest that AD is accompanied by a peripheral inflammatory response and that IL-6 may be a useful biological marker to correlate with the severity of cognitive impairment. Further studies are needed to determine the clinical utility of these markers.

Inflammatory Biomarkers Interleukin‐6 and C‐Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial

Abstract: BackgroundEvaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfu...

No Beneficial Effects of Resveratrol on the Metabolic Syndrome: A Randomized Placebo-Controlled Clinical Trial.

Abstract: Context Low-grade inflammation is associated with obesity and the metabolic syndrome (MetS). Preclinical evidence suggests that resveratrol (RSV) has beneficial metabolic and anti-inflammatory effects that could have therapeutic implications. Objective To investigate effects of long-term RSV treatment on inflammation and MetS. Setting and Design A randomized, placebo-controlled, double-blind, parallel group clinical trial conducted at Aarhus University Hospital. Participants Middle-aged community-dwelling men (N = 74) with MetS, 66 of whom completed all visits (mean ± standard error of the mean): age, 49.5 ± 0.796 years; body mass index, 33.8 ± 0.44 kg/m2; waist circumference, 115 ± 1.14 cm. Intervention Daily oral supplementation with 1000 mg RSV (RSVhigh), 150 mg RSV, or placebo for 16 weeks. Main outcome measures Plasma levels of high-sensitivity C-reactive protein (hs-CRP), circulating lipids, and inflammatory markers in circulation and adipose/muscle tissue biopsy specimens; glucose metabolism; and body composition including visceral fat and ectopic fat deposition. Results RSV treatment did not lower circulating levels of hs-CRP, interleukin 6, or soluble urokinase plasminogen activator receptor in plasma, and inflammatory gene expression in adipose and muscle tissues also remained unchanged. RSV treatment had no effect on blood pressure, body composition, and lipid deposition in the liver or striated muscle. RSV treatment had no beneficial effect on glucose or lipid metabolism. RSVhigh treatment significantly increased total cholesterol (P < 0.002), low-density lipoprotein (LDL) cholesterol (P < 0.006), and fructosamine (P < 0.013) levels compared with placebo. Conclusion RSV treatment did not improve inflammatory status, glucose homeostasis, blood pressure, or hepatic lipid content in middle-aged men with MetS. On the contrary, RSVhigh significantly increased total cholesterol, LDL cholesterol, and fructosamine levels compared with placebo.

Systemic inflammation as a novel QT-prolonging risk factor in patients with torsades de pointes.

Abstract: Objective Increasing evidence indicates systemic inflammation as a new potential cause of acquired long QT syndrome (LQTS), via cytokine-mediated changes in cardiomyocyte ion channels. Torsade de pointes (TdP) is a life-threatening polymorphic ventricular tachycardia occurring in patients with LQTS, usually when multiple QT-prolonging factors are simultaneously present. Since classical risk factors cannot fully explain TdP events in a number of patients, we hypothesised that systemic inflammation may represent a currently overlooked risk factor contributing to TdP development in the general population. Methods Forty consecutive patients who experienced TdP (TdP cohort) were consecutively enrolled and circulating levels of C-reactive protein (CRP) and proinflammatory cytokines (interleukin-6 (IL-6), tumour necrosis factor alpha (TNFα), interleukin-1 (IL-1)) were compared with patients with active rheumatoid arthritis (RA), comorbidity or healthy controls. An additional 46 patients with different inflammatory conditions (acute infections, n=31; immune-mediated diseases, n=12; others, n=3) and elevated CRP (inflammatory cohort) were prospectively enrolled, and corrected QT (QTc) and cytokine levels were measured during active disease and after a CRP decrease of >75% subsequent to therapy. Results In the TdP cohort, 80% of patients showed elevated CRP levels (median: ~3 mg/dL), with a definite inflammatory disease identifiable in 18/40 cases (acute infections, n=12; immune-mediated diseases, n=5; others, n=1). In these subjects, IL-6, but not TNFα and IL-1, was ~15–20 times higher than in controls, and comparable to RA patients. In the inflammatory cohort, where QTc prolongation was common (mean values: 456.6±30.9 ms), CRP reduction was associated with IL-6 level decrease and significant QTc shortening (−22.3 ms). Conclusion The data are first to show that systemic inflammation via elevated IL-6 levels may represent a novel QT-prolonging risk factor contributing to TdP occurrence in the presence of other classical risk factors. If confirmed, this could open new avenues in antiarrhythmic therapy.

Reduction of inflammation after administration of interleukin-1 receptor antagonist following aneurysmal subarachnoid hemorrhage: results of the Subcutaneous Interleukin-1Ra in SAH (SCIL-SAH) study.

Abstract: OBJECTIVE Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating cerebrovascular event with long-term morbidity and mortality. Patients who survive the initial bleeding are likely to suffer further early brain injury arising from a plethora of pathological processes. These may result in a worsening of outcome or death in approximately 25% of patients and may contribute to longer-term cognitive dysfunction in survivors. Inflammation, mediated by the cytokine interleukin-1 (IL-1), is an important contributor to cerebral ischemia after diverse forms of brain injury, including aSAH. Its effects are attenuated by its naturally occurring antagonist, IL-1 receptor antagonist (IL-1Ra [anakinra]). The authors hypothesized that administration of additional subcutaneous IL-1Ra would reduce inflammation and associated plasma markers associated with poor outcome following aSAH. METHODS This was a randomized, open-label, single-blinded study of 100 mg subcutaneous IL-1Ra, administered twice daily in patients with aSAH, starting within 3 days of ictus and continuing until 21 days postictus or discharge from the neurosurgical center, whichever was earlier. Blood samples were taken at admission (baseline) and at Days 3-8, 14, and 21 postictus for measurement of inflammatory markers. The primary outcome was difference in plasma IL-6 measured as area under the curve between Days 3 and 8, corrected for baseline value. Secondary outcome measures included similar area under the curve analyses for other inflammatory markers, plasma pharmacokinetics for IL-1Ra, and clinical outcome at 6 months. RESULTS Interleukin-1Ra significantly reduced levels of IL-6 and C-reactive protein (p < 0.001). Fibrinogen levels were also reduced in the active arm of the study (p < 0.002). Subcutaneous IL-1Ra was safe, well tolerated, and had a predictable plasma pharmacokinetic profile. Although the study was not powered to investigate clinical effect, scores of the Glasgow Outcome Scale-extended at 6 months were better in the active group; however, this outcome did not reach statistical significance. CONCLUSIONS Subcutaneous IL-1Ra is safe and well tolerated in aSAH. It is effective in reducing peripheral inflammation. These data support a Phase III study investigating the effect of IL-1Ra on outcome following aSAH. Clinical trial registration no.: EudraCT: 2011-001855-35 ( www.clinicaltrialsregister.eu ).

The subgingival microbiome, systemic inflammation and insulin resistance: The Oral Infections, Glucose Intolerance and Insulin Resistance Study

Abstract: Background Inflammation might link microbial exposures to insulin resistance. We investigated the cross-sectional association between periodontal microbiota, inflammation and insulin resistance. Methods The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 152 diabetes-free adults (77% female) aged 20-55 years (mean = 34 ± 10). Three hundred and four subgingival plaque samples were analysed using the Human Oral Microbe Identification Microarray to measure the relative abundances of 379 taxa. C-reactive protein, interleukin-6, tumour necrosis factor-α and adiponectin were assessed from venous blood and their z-scores were summed to create an inflammatory score (IS). Insulin resistance was defined via the HOMA-IR. Associations between the microbiota and both inflammation and HOMA-IR were explored using multivariable linear regressions; mediation analyses assessed the proportion of the association explained by inflammation. Results The IS was inversely associated with Actinobacteria and Proteobacteria and positively associated with Firmicutes and TM7 (p-values Conclusion Bacterial measures were related to inflammation and insulin resistance among diabetes-free adults.

Serum IL-1β and IL-17 levels in patients with COPD: associations with clinical parameters.

Abstract: COPD is a chronic airway inflammatory disease characterized mainly by neutrophil airway infiltrations. Interleukin (IL)-1β and IL-17 are the key mediators of neutrophilic airway inflammation in COPD. This study was undertaken to evaluate the serum IL-1β and IL-17 levels and associations between these two key mediators with clinical parameters in COPD patients. Serum samples were collected from 60 COPD subjects during the acute exacerbation of COPD, 60 subjects with stable COPD and 40 healthy control subjects. Commercial enzyme-linked immunosorbent assay kits were used to measure the serum IL-1β and IL-17 concentrations. The association between serum IL-1β and IL-17 with FEV1% predicted, C-reactive protein, neutrophil percentage and smoking status (pack-years) was assessed in the COPD patients. We found that serum IL-1β and IL-17 levels in acute exacerbation of COPD subjects were significantly higher than that in stable COPD or control subjects and were positively correlated to serum C-reactive protein levels, neutrophil % and smoking status (pack-years) but negatively correlated with FEV1% predicted in COPD patients. More importantly, serum IL-1β levels were markedly positively associated with serum IL-17 levels in patients with COPD (P=0.741, P<0.001). In conclusion, elevated serum IL-1β and IL-17 levels may be used as a biomarker for indicating persistent neutrophilic airway inflammation and potential ongoing exacerbation of COPD.

Serum inflammatory markers and colorectal cancer risk and survival

Abstract: Inflammation has been linked with development of some cancers. We investigated systemic inflammation in relation to colorectal cancer incidence and subsequent survival using common serum inflammatory markers A cohort of men and women aged 20 years and older in greater Stockholm area with serum C-reactive protein (CRP) and albumin measured between 1986 and 1999 were included (n=325 599). A subset of these had baseline measurements of haptoglobin and leukocytes. Multivariable Cox regression was performed to assess risk of colorectal cancer by levels of inflammatory markers, adjusting for potential confounders. Analyses were stratified by circulating glucose, total cholesterol and triglycerides. Overall and CRC-specific death following diagnosis were assessed as secondary outcomes. A total of 4764 individuals were diagnosed with colorectal cancer. A positive association between haptoglobin and colorectal cancer incidence was found (hazard ratio (HR): 1.17; 95% CI: 1.06–1.28). A positive association was also observed with leukocytes (HR: 1.21; 95% CI: 1.03–1.42). No evidence of association was noted between CRP and colorectal cancer risk. Higher risks of all-cause death were seen with haptoglobin and leukocytes levels. Higher haptoglobin levels were linked with an increased risk of colorectal cancer death (HR: 1.19; 95% CI: 1.01–1.41). Prediagnostic systemic inflammation may impact colorectal cancer incidence and survival; therefore, prompting investigations linking inflammatory pathways preceding colorectal cancer with disease severity and progression.

Immunoanalytical characteristics of C-reactive protein and high sensitivity C-reactive protein.

Abstract: C-reactive protein (CRP) is a polypeptide molecule belonging to the family of pentraxins. It has a molecular mass of 120,000 daltons and consists of five identical sub-units that contain each 206 amino acids. CRP is synthesized primarily by the liver in response to certain pro-inflammatory cytokines. It plays an important role in innate immunity, opsonization by its properties, complement activation and immunoglobulins receptor binding. CRP is a protein of the acute systemic inflammation and is, therefore, a prime marker of inflammation. As atherosclerosis has an inflammatory component, CRP can appreciate cardiovascular risk when analysed by more sensitive assays, that are able to measure extremely low concentrations of CRP, called high sensitivity CRP (hs-CRP). The CRP is quantified by immunonephelometry or immunoturbidimetry. There is no standard technique. The hs-CRP quantification is based on immunonephelemetry sensitized techniques called "immunolatex". We present in this paper the main biochemical and physiological data related to CRP, explaining the need for its quantification, the problems encountered in immunoassay and the interpretation of results.

C-reactive protein levels predict systolic heart failure and outcome in patients with first ST-elevation myocardial infarction treated with coronary angioplasty.

Abstract: INTRODUCTION There is growing evidence that inflammation plays a pivotal role in the etiology and progression of atherosclerosis. High C-reactive protein (CRP) levels have been associated with high mortality in patients with acute myocardial infarction (AMI). Furthermore, in animal models CRP has been found to significantly increase infarct size. So there is growing evidence that CRP is not only a marker for cardiovascular disease but also might be pathogenic. The aim of our study was to test the hypothesis that peak CRP levels could predict heart failure (HF) in ST-elevation myocardial infarction (STEMI) patients. MATERIAL AND METHODS Eighty-one consecutive patients with STEMI were prospectively enrolled in the study. C-reactive protein concentrations were measured on admission and after 6, 12, 24, 30, 48, 72 and 96 h. We assessed the association between the elevation of CRP, heart failure and cardiovascular mortality following the first 12 months after STEMI. RESULTS C-reactive protein levels reached a peak after 48 h. Patients with STEMI and signs of HF showed significantly higher peak CRP levels. We found a positive correlation between maximum CK levels and peak CRP and a negative correlation between left ventricular ejection fraction (EF) and peak CRP. One year total mortality and HF mortality rates were found to be higher in patients with peak CRP > 47.5 mg/l than in those with CRP below that level (p < 0.001). CONCLUSIONS Peak CRP levels in STEMI patients predict emergence of HF. Peak CRP is also a strong predictor of global and cardiovascular mortality during the following year after STEMI.

Does statins promote vascular calcification in chronic kidney disease

Abstract: Background In end-stage renal disease (ESRD), coronary artery calcification (CAC) and inflammation contribute to cardiovascular disease (CVD). Statins do not improve survival in patients with ESRD, and their effect on vascular calcification is unclear. We explored associations between CAC, inflammatory biomarkers, statins and mortality in ESRD. Materials and methods In 240 patients with ESRD (63% males; median age 56 years) from cohorts including 86 recipients of living donor kidney transplant (LD-Rtx), 96 incident dialysis patients and 58 prevalent peritoneal dialysis patients, associations of CAC score (Agatston Units, AUs), interleukin-6 (IL-6) with high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor (TNF), use of statins and all-cause mortality were analysed. Cardiac CT was repeated in 35 patients after 1·5 years of renal replacement therapy. In vitro, human vascular smooth muscle cells (hVSMCs) were used to measure vitamin K metabolism. Results Among 240 patients, 129 (53%) had a CAC score > 100 AUs. Multivariate analysis revealed that independent predictors of 1-SD higher CAC score were age, male gender, diabetes and use of statins. The association between CAC score and mortality remained significant after adjustment for age, gender, diabetes, CVD, use of statins, protein-energy wasting and inflammation. Repeated CAC imaging in 35 patients showed that statin therapy was associated with greater progression of CAC. In vitro synthesis of menaquinone-4 by hVSMCs was significantly impaired by statins. Conclusion Elevated CAC score is a mortality risk factor in ESRD independent of inflammation. Future studies should resolve if statins promote vascular calcification and inhibition of vitamin K synthesis in the uremic milieu.

Both antenatal and postnatal inflammation contribute information about the risk of brain damage in extremely preterm newborns

Abstract: BackgroundPreterm newborns exposed to intrauterine inflammation are at an increased risk of neurodevelopmental disorders. We hypothesized that adverse outcomes are more strongly associated with a combination of antenatal and postnatal inflammation than with either of them alone.MethodsWe defined antenatal inflammation as histologic inflammation in the placenta. We measured the concentrations of seven inflammation-related proteins in blood obtained on postnatal days 1, 7, and 14 from 763 infants born before 28 weeks of gestation. We defined postnatal inflammation as a protein concentration in the highest quartile on at least 2 days. We used logistic regression models to evaluate the contribution of antenatal and postnatal inflammation to the risk of neurodevelopmental disorders.ResultsThe risk of white matter damage was increased when placental inflammation was followed by sustained elevation of C-reactive protein or ICAM-1. We found the same for spastic cerebral palsy when placental inflammation was followed by elevation of TNF-α or IL-8. The presence of both placental inflammation and elevated levels of IL-6, TNF-α, or ICAM-1 was associated with an increased risk for microcephaly.ConclusionCompared with a single hit, two inflammatory hits are associated with stronger risk for abnormal cranial ultrasound, spastic cerebral palsy, and microcephaly at 2 years.

CANTOS Trial Validates the Inflammatory Pathogenesis of Atherosclerosis Setting the Stage for a New Chapter in Therapeutic Targeting

Abstract: > Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning . > > —Winston Churchill The CANTOS trial (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) provides intriguing support for the inflammatory hypothesis of atherosclerosis and cancer in man, demonstrating diverse clinical benefits of inhibiting IL (interleukin)-1β for cardiovascular events and lung cancer. Limited effects on cardiovascular mortality and safety concerns raised by a higher incidence of fatal infection warrant further studies to identify patient subgroups which profit most from anti-inflammatory therapy and a careful pursuit of alternative targets. Abundant evidence from experimental and clinical studies has lend strong support to the hypothesis that inflammation contributes to the pathogenesis of atherosclerotic disease in conjunction with or beyond elevated lipid levels; however, ultimate proof by selective anti-inflammatory treatment in a clinical trial remained elusive for decades. This has now changed with the results of the CANTOS, a double-blind trial involving high-risk patients with prior myocardial infarction (MI) and a residual inflammatory response (defined by hsCRP [high-sensitivity C-reactive protein] levels >2 mg/L despite intensive statin therapy), who were randomized to canakinumab (50, 150, or 300 mg every 3 months) or placebo.1 Canakinumab, a human monoclonal antibody targeting IL-1β as the master cytokine of innate immunity, dose dependently reduced hsCRP and IL-6 levels by ≤43% from baseline. At 150 mg (but not the other doses), canakinumab significantly lowered the risk for the primary (MI, stroke, cardiovascular death) and secondary end points (hazard ratio [HR], 0.85 and 0.83, respectively). Adversely, canakinumab was associated with leukopenia and a higher incidence of fatal infection. Whereas no significant difference in all-cause or cardiovascular mortality was observed, canakinumab strikingly reduced cancer mortality (exploratory results indicating HR 0.23, for lung cancer), supporting a role of inflammation in cancer progression. …

Evaluation of C-Reactive Protein and Fibrinogen in Patients with Chronic and Aggressive Periodontitis: A Clinico-Biochemical Study.

Abstract: INTRODUCTION Periodontal disease is characterised by chronic infection and inflammation in periodontal tissues leading to destruction of alveolar bone with subsequent tooth loss. Periodontal infections are the result of an interaction between tooth associated microbial biofilms and the host defences. Periodontal pathogens can affect local and systemic immune and inflammatory responses. AIM The aim of the present study was to evaluate serum C-Reactive Protein (CRP), plasma fibrinogen and peripheral blood levels in healthy subjects, chronic and aggressive periodontitis patients. MATERIALS AND METHODS A total of 55 subjects, 27 males and 28 females were selected for the study. Blood samples were taken from healthy controls (n=20) and patients with chronic periodontitis (n=20) and aggressive periodontitis (n=15). The periodontal status of each patient was assessed by recording Oral Hygiene Index-Simplified (OHI-S), Bleeding Index (BI), Probing Pocket Depth (PPD) and Clinical Attachment Level (CAL). The levels of serum CRP were measured using high sensitivity Enzyme Linked Immunosorbent Assay (ELISA) and levels of plasma fibrinogen were measured using Quantitative Immunoturbidimetric assay. Data description was done in the form of mean and standard deviation and analysis of data was done using one way ANOVA (Analysis of Variance) and Students t-test to test the statistical significance between groups. RESULTS The levels of serum CRP and plasma fibrinogen was increased in patients with chronic and aggressive periodontitis when compared to healthy controls (p<0.001). A positive correlation was found to exist between levels of clinical parameters like OHI-S, BI, PPD and CAL when compared with CRP and fibrinogen as well as with the study groups. CONCLUSION The finding of the present study suggests the role of serum as a diagnostic marker in inflammatory conditions and indicates that levels of CRP and fibrinogen may serve as important biomarkers for evaluating the association between periodontitis and cardiovascular diseases.

Hypoxia and inflammation indicate significant differences in the severity of obstructive sleep apnea within similar apnea-hypopnea index groups.

Abstract: We determined whether hypoxia parameters are associated with C-reactive protein (CRP), mean platelet volume (MPV), white matter hyperintensity (WMH), and the severity of obstructive sleep apnea (OSA), and also evaluated whether hypoxia parameters, CRP, MPV, and WMH differ in patients with similar apnea-hypopnea index (AHI) scores. A total of 297 patients, who were evaluated using polysomnography, were assessed retrospectively. The measured hypoxia parameters included total sleep time with oxygen saturation 0.05). Above the hypoxia threshold (CT90 ≥ 10%) of CRP, MPV increased significantly and the presence of WMH increased twofold. These data suggest that increased hypoxia severity may mediate increased inflammation and activation of platelets and contribute to the pathogenesis of WMH in patients with OSA. In addition, patients with severe OSA may show significant variability in inflammation and vascular risk. Further prospective data are needed.

Serum osteopontin: a biomarker of disease activity and predictor of relapsing course in patients with giant cell arteritis. Potential clinical usefulness in tocilizumab-treated patients

Abstract: Background Osteopontin (OPN) is a glycoprotein involved in Th1 and Th17 differentiation, tissue inflammation and remodelling. We explored the role of serum OPN (sOPN) as a biomarker in patients with giant cell arteritis (GCA). Methods sOPN was measured by immunoassay in 76 treatment-naive patients with GCA and 25 age-matched and sex-matched controls. In 36 patients, a second measurement was performed after 1 year of glucocorticoid treatment. Baseline clinical and laboratory findings, as well as relapses and glucocorticoid requirements during follow-up, were prospectively recorded. sOPN and C reactive protein (CRP) were measured in 32 additional patients in remission treated with glucocorticoids or tocilizumab (interleukin 6 (IL-6) receptor antagonist). In cultured temporal arteries exposed and unexposed to tocilizumab, OPN mRNA expression and protein production were measured by reverse transcription polymerase chain reaction (RT-PCR) and immunoassay, respectively. Results sOPN concentration (ng/mL; mean±SD) was significantly elevated in patients with active disease (116.75±65.61) compared with controls (41.10±22.65; p Conclusions sOPN is a marker of disease activity and a predictor of relapse in GCA. Since OPN is not exclusively IL-6-dependent, sOPN might be a suitable disease activity biomarker in tocilizumab-treated patients.

Salivary and serum adiponectin and C-reactive protein levels in acute myocardial infarction related to body mass index and oral health.

Abstract: Background and Objective Adiponectin is produced by adipose cells and is considered an anti-inflammatory molecule. In contrast, C-reactive protein (CRP) has been identified as a hallmark of systemic inflammation and used as a risk marker of cardiovascular disease (CVD). Of interest was the relationship of these two biomarkers to oral health and CVD risk. Material and Methods This investigation examined these two molecules in serum and unstimulated whole saliva of patients within 48 h of an acute myocardial infarction (AMI) compared to control subjects. We hypothesized a differential response in these biomolecules resulting from the heart attack that would be affected by both the body mass index and oral health characteristics of the individuals. Results Significantly lower adiponectin levels were observed in the serum of patients with AMI. Serum adiponectin in both groups and salivary adiponectin in patients with AMI decreased with increasing body mass index. Oral health was significantly worse in patients with AMI, and both serum and salivary adiponectin were elevated with better oral health in control subjects. Serum CRP levels were increased in patients with AMI regardless of their oral health, and both serum and salivary CRP were significantly elevated in S-T wave elevated patients with MI. Conclusions These initial data provide evidence relating obesity and oral health to salivary and serum analyte levels that occur in association with cardiac events. Relationships have been described between CVD risk and periodontal disease. Additionally, various systemic inflammatory biomarkers appear to reflect both the CVD risk and the extent/severity of periodontitis. Our findings indicated that oral health and obesity contribute to altering levels of these salivary and serum analytes in association with cardiac events. The potential that serum and/or salivary biomarkers could aid in evaluating CVD risk requires knowledge regarding how the oral health of the individual would impact the effectiveness of these biological measures.

C-reactive protein upregulates the whole blood expression of CD59 - an integrative analysis.

Abstract: Elevated C-reactive protein (CRP) concentrations in the blood are associated with acute and chronic infections and inflammation. Nevertheless, the functional role of increased CRP in multiple bacterial and viral infections as well as in chronic inflammatory diseases remains unclear. Here, we studied the relationship between CRP and gene expression levels in the blood in 491 individuals from the Estonian Biobank cohort, to elucidate the role of CRP in these inflammatory mechanisms. As a result, we identified a set of 1,614 genes associated with changes in CRP levels with a high proportion of interferon-stimulated genes. Further, we performed likelihood-based causality model selection and Mendelian randomization analysis to discover causal links between CRP and the expression of CRP-associated genes. Strikingly, our computational analysis and cell culture stimulation assays revealed increased CRP levels to drive the expression of complement regulatory protein CD59, suggesting CRP to have a critical role in protecting blood cells from the adverse effects of the immune defence system. Our results show the benefit of integrative analysis approaches in hypothesis-free uncovering of causal relationships between traits.

Independent and Combined Effects of Serum Albumin and C-Reactive Protein on Long-Term Outcomes of Patients Undergoing Percutaneous Coronary Intervention.

Abstract: BACKGROUND Both inflammation and malnutrition have been reported to be closely linked to atherosclerosis, especially in patients with chronic kidney disease (CKD). The combined effects of serum albumin and C-reactive protein (CRP) on clinical outcomes after percutaneous coronary intervention (PCI) were investigated.Methods and Results:A total of 2,164 all-comer patients with coronary artery disease who underwent their first PCI and had data available for preprocedural serum albumin and hs-CRP levels between 2000 and 2011 were studied. Patients were assigned to 4 groups according to their median serum albumin and CRP levels (4.1 g/dL and 0.10 mg/dL, respectively). The incidence of major adverse cardiac events (MACE), including all-cause death and non-fatal myocardial infarction (MI), was evaluated. During a median follow-up period of 7.5 years, 331 cases of MACE (15.3%), including 270 deaths and 61 non-fatal MIs, occurred. Kaplan-Meier curves showed that the rates of MACE differed significantly among the groups (log-rank P<0.0001), even stratified by with or without CKD (both log-rank P<0.0001). After adjustment for established cardiovascular risk factors, low serum albumin with high CRP levels was associated with adverse cardiac events (hazard ratio 2.55, 95% confidence interval 1.72-3,88, P<0.0001, high albumin/low CRP group as reference). CONCLUSIONS The presence of both low serum albumin and high CRP levels conferred a synergistic adverse effect on the risk for long-term MACE in patients undergoing PCI.