Conventional C-reactive Protein Research Articles

VARIATIONS IN SERUM CONCENTRATIONS OF Hs-CRP IN PERIODONTITIS AND HEALTHY SUBJECTS

CRP is a plasma protein that measures the acute phase response to systemic inflammation and is one of the markers of choice in monitoring numerous chronic diseases. Patients with periodontitis have specific haematological variations, such as higher C-reactive protein (CRP) levels and elevated pro-inflammatory mediator levels. This study aims to quantify Hs-CRP levels in periodontally healthy and diseased subjects and evaluate the relationship between periodontitis and Hs-CRP levels. This Case-control study recruited 120 patients from two study groups—60 cases of chronic periodontitis (moderate to severe) and 60 controls. Periodontitis is assessed by three different index scores, namely: Community periodontal index score (CPI), Clinical attachment level (CAL) and periodontal probing depth (PPD). The Hs-CRP is measured due to its high sensitivity to assess systemic inflammation, making it more effective than conventional CRP tests. Our study results indicate that Hs-CRP levels increase subsequently with the severity of the periodontal disease. Moreover, Clinical attachment level (CAL) is the most significant indicator of Periodontitis that correlates with systemic inflammation in the body. Hence, concluding that periodontitis, being an oral condition, can have a massive impact on general systemic health, and elevated Hs-CRP levels, considered a biomarker of chronic systemic inflammation, can be a future risk to several fatal systemic diseases.

Significance of Serum Leucine-rich Alpha-2 Glycoprotein as a Diagnostic Marker in Pediatric Inflammatory Bowel Disease.

Serum leucine-rich alpha-2 glycoprotein (LRG) has been utilized for adult inflammatory bowel disease (IBD); however, its efficacy in pediatric IBD remains unknown. The aim of this study was to compare the diagnostic accuracy of serum LRG for pediatric IBD with that of current inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). This retrospective case-control study included pediatric patients, aged <16 years, who underwent colonoscopy and/or esophagogastroduodenoscopy between April 2017 and March 2022. All eligible patients were divided into two groups: patients with IBD, diagnosed with ulcerative colitis and Crohn's disease, and non-IBD controls. The optimal cut-off value of serum LRG for IBD diagnosis was determined from receiver operating characteristic analysis, and diagnostic accuracy of serum LRG was compared to serum ESR and CRP. A total of 53 patients (24 with IBD and 29 non-IBD controls) met the inclusion criteria. The cut-off value of serum LRG for IBD diagnosis was determined to be 19.5 μg/ml. At this cut-off value, serum LRG had a positive predictive value (PPV) of 0.80 and negative predictive value (NPV) of 0.88. In contrast, PPV and NPV were 0.78 and 0.70 for serum ESR and 0.82 and 0.72 for serum CRP, respectively. Serum LRG can be a potential diagnostic marker for pediatric IBD, with higher diagnostic accuracy than that of the conventional serum markers ESR and CRP.

Prognostic value of neutrophil- lymphocyte count ratio (NLCR) among adult ICU patients in comparison to APACHE II score and conventional inflammatory markers: a multi center retrospective cohort study

BackgroundNeutrophil-lymphocyte count ratio (NLCR) has been reported as better indicator of bacteremia than procalcitonin (PCT), and more precise predictor of mortality than C-reactive protein (CRP) under various medical conditions. However, large controversy remains upon this topic. To address the discrepancy, our group has compared the efficiency of NLCR with conventional inflammatory markers in predicting the prognosis of critical illness.MethodsWe performed a multi-center retrospective cohort study involving 536 ICU patients with outcomes of survival, 28- and 7-day mortality. NLCR was compared with conventional inflammatory markers such as PCT, CRP, serum lactate (LAC), white blood cell, neutrophil and severity score APACHE II (Acute Physiology and Chronic Health Evaluation II) to evaluate the potential outcomes of critical illness. Then, receiver operating characteristics (ROC) curves were constructed to assess and compare each marker’s sensitivity and specificity respectively.ResultsNLCR values were not different between survival and mortality groups. Meanwhile, remarkable differences were observed upon APACHE II score, CRP, PCT and LAC levels between survival and death groups. ROC analysis revealed that NLCR was not competent to predict prognosis of critical illness. The AUROCs of conventional markers such as CRP, PCT, LAC and APACHE II score were more effective in predicting 28- and 7-day mortality.ConclusionsNLCR is less reliable than conventional markers CRP, PCT, LAC and APACHE II score in assessing severity and in predicting outcomes of critical illness.

Combination of Highly Sensitive C-Reactive Protein with R-ISS Is a Novel and Powerful Staging System in Multiple Myeloma

Introduction: Multiple myeloma (MM) is a hematological malignancy characterized by proliferation of abnormal plasma cells in bone marrow. Revised-International Staging System (R-ISS) is generally used as a predictor in newly diagnosed MM (NDMM) since 2015. R-ISS combines ISS with chromosomal abnormalities (CA) and serum lactate dehydrogenase (LDH). R-ISS I is defined as ISS I without high risk CA and normal LDH, R-ISS III is defined as ISS III with high risk CA or high level LDH, and R-ISS II includes all of the other possible combinations. Therefore, about 60% of NDMM are classified to R-ISS II. However, MM is a highly heterogeneous disease, so the clinical outcome of MM with R-ISS II also must be heterogeneous. Therefore, factors stratifying the majority of MM is needed. C-reactive protein (CRP) is a commonly used inflammatory marker. In particular, highly sensitive (hs) CRP detects lower concentration of CRP as compared with the conventional method, and has been reported to be associated with mortality of lung, breast, and renal cell cancers. In this study, we evaluated the predicting potential of hs-CRP in MM in the novel agent era to see if hs-CRP can develop the stratifying power of R-ISS. Materials and Methods: The retrospective study examined 80 patients with symptomatic NDMM who had been diagnosed at our institution between April 2006 and September 2019. Patients with infection and/or amyloidosis were excluded. Linkable anonymizing data, including age, gender, immunoglobulin type, symptoms, R-ISS, hs-CRP at diagnosis, time to next treatment (TNT) of the initial treatment, and overall survival (OS) were collected. The concentration of hs-CRP was measured by quantitative latex agglutination turbidimetric immunoassay. The lower detection limit of hs-CRP is 0.01 mg/dL, while that of conventional CRP was 0.10 mg/dL. We analyzed these data using the Kaplan-Meier method, Fisher's exact, multivariate cox proportional hazard models, and log-rank test. P-values ≤0.05 was considered to be statistically significant. This retrospective study was approved by institutional review board in University of Fukui, Japan (No. 20190101). Results: Among 80 patients, 39 (48.8%) were male. Median age at diagnosis was 71 years (range: 36-89 years). IgG, IgA, and BJP types were 56.8%, 25.9%, and 17.3%, respectively. Median follow-up was 29 months (range: 1-120 months). All of the patients were treated with bortezomib and/or lenalidomide-based regimens throughout their clinical courses. R-ISS I, II, and III were 7.3%, 76.4%, and 16.4%, and median OS in patients with R-ISS I, II, and III were unreached, 67, and 15 months, respectively (p&amp;lt;0.0001). Median hs-CRP was 0.10 mg/dL (range: 0.01-8.86 mg/dL), and the patients were divided into 2 groups according to median hs-CRP, consisting of low hs-CRP group (≤0.1 mg/dL, n=42) and high hs-CRP groups (&amp;gt;0.1 mg/dL, n=38). No significant difference in gender, age, immunoglobulin type was observed between 2 groups according to Fisher's exact test. The levels of hs-CRP appeared to be associated with the presence of bone lesions, not hypercalcemia, renal dysfunction, and anemia. There was not significant correlation between hs-CRP and TNT of the initial treatment, due to the variation of the used regimens. However, Kaplan-Meier curves showed that low hs-CRP group had significantly better OS than high hs-CRP group (64 months vs. 54 months, p=0.0116). Multivariate analysis indicated that both R-ISS (hazard ration (HR), 6.19) and hs-CRP (HR, 7.03) were independent prognostic factors for OS. Moreover, comparing the patients with R-ISS II divided by median hs-CRP, OS was significantly longer in R-ISS II with low hs-CRP than R-ISS II with high hs-CRP (median OS: 81 months vs. 54 months, p=0.0009) (Figure 1). Similarly, in the patients with R-ISS III, OS tended to be longer in low hs-CRP group than high hs-CRP group (median OS: 21 months vs. 5.5 months). All the patients with R-ISS I survived within the follow-up period. Conclusions: Hs-CRP enabled to detect 0.01-0.1 mg/dL, that is not measured by the conventional CRP method. The superiority of hs-CRP contributes to the role as a powerful predictor in MM. The novel staging system that combines hs-CRP and R-ISS may establish better understanding of prognosis in NDMM. Disclosures Yamauchi: Pfizer: Honoraria, Research Funding; Otsuka: Research Funding; Chugai: Honoraria; Abbie: Research Funding; Solasia Pharma: Research Funding; Daiichi Sankyo: Research Funding; Ono Pharmaceutical: Honoraria; Astellas: Research Funding.

Contribution of Presepsin, Procalcitonin and C-reactive protein to the SOFA Score in Early Sepsis Diagnosis in Emergency Abdominal Surgical Patients

Purpose: This study examined whether the addition of biomarkers presepsin (PSEP), procalcitonin (PCT) and C-reactive pro-tein (CRP) to the initial SOFA (iSOFA) score can improve diagnostic accuracy of early sepsis diagnosis in emergency ab-dominal surgery patients.Materials and Methods: Seventy-two study subjects had diagnosis of acute abdomen due to gastrointestinal disturbances.&nbsp;The study evaluated diagnostic accuracy and predictive value of two models (iSOFA only and iSOFA combined with three bio-markers) for sepsis diagnosis.Results:&nbsp;The AUC value for the iSOFA was highest, followed by the AUC value obtained for PSEP, PCT and CRP (0.989, 0.738, 0.694 and 0.606, respectively).The logistic regression analysis of the two mod-els showed for the first model that patients with a higher iSOFA score are almost two times more likely to suffer from sepsis. In the second model, patients with a higher iSOFA score and a higher level of biomark-ers are three times more likely to have sep-sis.Conclusions: Although the SOFA score is known to be the best diagnostic tool for sepsis diagnosis, it seems that among the three investigated markers PSEP and PCT– although not contributing to the iSOFA score– are good independent markers with significantly higher levels in septic than in non-septic patients. PSEP has the highest diagnostic accuracy for sepsis. Only the conventional marker CRP provides certain added value to the iSOFA score for sepsis prediction.&nbsp;Further investigations should be per-formed to study the possible diagnostic value of dynamic changes of the three ex-amined markers in prediction and early diagnosis of sepsis.

Value of Hepcidin as a diagnostic biomarker of sepsis in critically ill adults

To investigate the diagnostic value of Hepcidin as a sepsis biomarker in critically ill adults. An observational study was conducted. The patients with suspected or proven infection admitted to intensive care unit (ICU) of Zhoupu Hospital Affiliated to Shanghai University of Medicine and Health Sciences from March 2016 to November 2017 were enrolled. According to the third international consensus definitions for sepsis and septic shock (Sepsis-3), the patients were divided into non-sepsis group and sepsis group, and the septic patients were subdivided into general sepsis subgroup and septic shock subgroup according to the severity of disease. The differences in serum Hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), neutrophil granulocytes (NEUT) and lactic acid (Lac) within 1 hour after ICU admission between non-sepsis and sepsis groups and among the sepsis subgroups were compared. The acute physiology and chronic health evaluation II (APACHE II) within 24 hours after ICU admission and sequential organ failure score (SOFA) were recorded, and the mortality rate was followed up for 28 days. Receiver operation characteristic curve (ROC) was used to evaluate and compare the diagnostic value of Hepcidin and PCT, CRP, WBC for sepsis. Logistic regression model was used to estimate the association between Hepcidin and sepsis. Spearman correlation analysis was used to analyze the correlation between Hepcidin and other parameters of sepsis patients. A total of 183 patients were enrolled, 93 in the non-sepsis group and 90 in the sepsis group (48 with general sepsis and 42 with septic shock). (1) The levels of Hepcidin, IL-6, TNF-α, PCT, Lac in serum, and APACHE II and SOFA scores in the sepsis group were significantly higher than those in the non-sepsis group. ROC analysis showed that the area under the ROC curve (AUC) of Hepcidin and PCT for sepsis diagnosis were 0.865 [95% confidence interval (95%CI) = 0.807-0.911] and 0.848 (95%CI = 0.788-0.897), respectively, without statistical significance (Z = 0.443, P = 0.657). Furthermore, the AUC of Hepcidin for sepsis diagnosis was significantly higher than that of the conventional biomarkers CRP and WBC [AUC was 0.530 (95%CI = 0.455-0.604) and 0.527 (95%CI = 0.452-0.601), respectively] with statistical significance (both P < 0.01). When Hepcidin > 54.00 μg/L, its sensitivity for sepsis diagnosis was 95.56%, specificity was 66.67%, positive and negative predictive value was 73.51% and 93.94%, respectively. Parallel test was conducted for combination of Hepcidin and PCT, which showed that the AUC was 0.885, and the sensitivity and negative predictive value was significantly improved to 98.96% and 98.36%, respectively. Logistic regression analysis demonstrated that after adjusted for PCT, Hepcidin > 54.00 μg/L was also associated with sepsis independently, with odds ratio (OR) of 1.011 (95%CI = 1.008-1.015, P < 0.001), indicating that Hepcidin and PCT were not completely overlapped in the diagnosis of sepsis. (2) With the increase in infection severity, serum Hepcidin, PCT, IL-6, TNF-α, Lac, APACHE II, SOFA score and 28-day mortality all showed an increasing trend in patients. There was a significantly positive correlation between Hepcidin and IL-6, TNF-α, PCT, APACHE II, and SOFA in the sepsis patients (r value was 0.526, 0.449, 0.591, 0.359, and 0.374, respectively, all P < 0.01), but no correlation was found between Hepcidin and Lac (r = 1.104, P > 0.05). Serum Hepcidin is a useful biomarker for the diagnosis of sepsis, and it is correlated to the severity of the sepsis. The combination of Hepcidin and PCT can improve the accuracy of diagnosis of sepsis. China Clinical Trial Registration Center, ChiCTR-DDD-16008522.

CRP-Based Cardiovascular Risk Assessment: New Conventional CRP Assay Fit for Purpose?

Subclinical inflammation was shown to play a role in the context of cardiovascular disorder processes. American College of Cardiology/American Heart Association guidelines on cardiovascular risk assessment in specific clinical contexts recommend the use of C-reactive protein (CRP) measurement with high sensitive (hs)-CRP assays that meet the precision requirements for values <2 mg/L. Until now, only hs-CRP assays reached the required limit of quantification. However, new regular CRP assays allow measuring CRP down to 0.6 mg/L. A multisite comparative study between hs-CRP and a new conventional CRP assay (Tina-quant) was performed to evaluate the possibility of using regular CRP assays for cardiovascular risk assessment. A satisfactory concordance was observed between regular CRP assays and the hs-CRP assay. Both assays met the analytical precision requirements at the different cutpoints tested (1.00, 2.00, and 3.00 mg/L). These results suggest that this new regular CRP assay can be used for cardiovascular risk assessment, which is expected to provide substantial operational and financial advantages when compared with hs-CRP assays.

Effects of Statin Therapy in Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is associated with a significant risk of cardiovascular mortality. The use of statins for lipid modulation and the prevention of cardiovascular disease in this population also may impart pleiotropic anti-inflammatory and immunomodulatory effects. Our aim was to identify studies that compared the use of statins and placebo or no statin therapy in patients with SLE. A meta-analysis was conducted on the follow-up measures of serum lipid levels, inflammatory markers, and disease activity, which was measured using the SLE Disease Activity Index (SLEDAI) score. The mean difference (MD) was calculated by the inverse variance method under a fixed or random-effects model, as appropriate. A total of eight studies met our inclusion criteria, including five randomized controlled trials. The total number of patients was 814 (statins 446, placebo/no statins 368), and follow-up ranged from 1 month to 7 years. The total cholesterol (MD -23.48 mg/dL, 95% confidence interval [CI] -34.57 to -12.39, P < 0.0001), low-density lipoprotein (MD -20.7 mg/dL, 95% CI -30.51 to -10.89, P < 0.0001), and high-sensitivity C-reactive protein (MD -0.40 mg/dL, 95% CI -0.64 to -0.16, P = 0.001) levels were significantly reduced by statin therapy. There was no change with statin use in serum levels of high-density lipoprotein and conventional C-reactive protein, and there was no difference in the SLEDAI score. The use of statins in SLE reduced the serum lipid and high-sensitivity C-reactive protein levels, which suggests a role for the primary prevention of cardiovascular disease. Statins did not affect the SLEDAI score, and therefore their use for modifying SLE disease activity levels is not presently supported.

PTU-242 Diagnostic accuracy of serial complement protein analysis in acute appendicitis: c3, c4, ic3b and tcc

Introduction White cell count (WCC) and C-reactive protein (CRP) use in the diagnosis of acute appendicitis (AA) lacks sufficient sensitivity and specificity. The aim of this study was to assess the diagnostic accuracy of admission and serial plasma Complement proteins C3, C4, iC3b and TCC in AA. Method A prospective observational study was undertaken between February 2012 and December 2013. Patients aged ≥18 years presenting with right iliac fossa pain with suspected AA were recruited. AA was defined histologically in operatively managed patients or on CT in conservatively managed cases. Plasma C3, C4, iC3b and TCC were measured on admission and at 4 and 8 h. The change (∆) in biomarker over 4 and 8 h was calculated by subtracting the concentration at admission from that at each time point to give ∆ 4 and ∆ 8 , respectively. Admission and ∆ values were compared in AA and all other conditions (non-AA) and the diagnostic efficacy was assessed using Receiver Operating Characteristic (ROC) curves. Results 74 patients were recruited to the study, 26 participants were male (35%) with a median age of 33 years (range 18–84). Blood samples were obtained at 4 h and 8 h after admission in 43 and 28 patients, respectively. 31 patients underwent appendicectomy. AA was diagnosed in 22 cases (one case being diagnosed by CT and treated conservatively). Isolated admission C3, C4, iC3b and TCC did not discriminate between AA and non-AA. TCC∆ 4 was diagnostic with a ROC Area Under Curve (AUC) of 0.84 (95% C. I 0.69–0.99). Admission WCC, Absoulte Neutrophil Count (ANC) and CRP demonstrated ROC AUCs of 0.75 (0.62–0.88), 0.76 (0.63–0.89) and 0.78 (0.67–0.88), respectively. Conclusion TCC∆ 4 demonstrates good diagnostic accuracy in AA superior to admission conventional biomarkers WCC, ANC and CRP. TCC∆ 4 could be used as a four hourly blood test in the Emergency Department to stratify patient risk for admission or further investigation. Further validation in a prospective observational study is required. Disclosure of interest None Declared.

FRI0126 The Ankylosing Spondylitis Disease Activity Score (ASDAS): Defining the Best Calculation Method When the Conventional C-Reactive Protein (CRP) is below the Threshold of Detection - Results from the DESIR Cohort

BackgroundThe Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new Assessment of SpondyloArthritis international Society (ASAS) and Outcomes in Rheumatology (OMERACT)-endorsed measure of disease activity in axial spondyloarthritis (SpA). The...

SAT0243 Endothelial dysfunction reflected by high S-ICAM-1 and VWF levels accelerates coronary atherosclerosis in systemic lupus erythematosus patients

BackgroundConventional risk factors of coronary artery disease fail to explain accelerated atherosclerosis in systemic lupus erythematosus (SLE) patients. Clinical and experimental studies shows that soluble intercellular adhesion molecule 1 (sICAM-1)...

Accuracy of symptoms, signs, and C-reactive protein for early chronic obstructive pulmonary disease

Guidelines recommend detection of early chronic obstructive pulmonary disease (COPD), but evidence on the diagnostic work-up for COPD only concerns advanced and established COPD. To quantify the accuracy of symptoms and signs for early COPD, and the added value of C-reactive protein (CRP), in primary care patients presenting with cough. Cross-sectional diagnostic study of 73 primary care practices in the Netherlands. Four hundred primary care patients (182 males, mean age 63 years) older than 50 years, presenting with persistent cough (>14 days) without established COPD participated, of whom 382 completed the study. They underwent a systematic diagnostic work-up of symptoms, signs, conventional laboratory CRP level, and hospital lung functions tests, including body plethysmography, and an expert panel decided whether COPD was present (reference test). The independent value of all items was estimated by multivariable logistic regression analysis. According to the expert panel, 118 patients had COPD (30%). Symptoms and signs with independent diagnostic value were age, sex, current smoking, smoking more than 20 pack-years, cardiovascular comorbidity, wheezing complaints, diminished breath sounds, and wheezing on auscultation. Combining these items resulted in an area under the receiver operating characteristic curve (ROC area) of 0.79 (95% confidence interval = 0.74 to 0.83) after internal validation. The proportion of subjects with elevated CRP was higher in those with early COPD, but CRP added no relevant diagnostic information above symptoms and signs. In subjects presenting with persistent cough, the CRP level has no added value for detection of early COPD.

Influence of chronic inflammation and autoimmunity on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients

ObjectiveConventional risk factors for coronary artery disease fail to explain the increased frequency or cardiovascular morbidity in systemic lupus erythematosus (SLE) patients. This study was conducted to determine the possible influence of autoimmune and inflammatory phenomena markers on coronary artery calcifications and myocardial perfusion abnormalities in SLE patients.Materials and methodsMulti-detector computed tomography (MDCT)-based coronary calcium scoring and single photon emission computerized tomography (SPECT) studies (Tc-99m sestamibi) were performed in 60 SLE patients in stable clinical condition, without a prior history of coronary artery disease. Laboratory evaluation included serum C-reactive protein (CRP), complement C3c and C4 components and antiphospholipid antibodies (aPL). The latter included anticardiolipin (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibodies, of both IgG and IgM classes, and lupus anticoagulant (LA) in plasma.ResultsSPECT revealed persistent perfusion defects in 22 (36.7%) patients and exercise-induced defects in eight (13.3%), while MDCT revealed coronary calcifications in 15 (25%). Calcium scores ranged from 1 to 843.2 (mean 113.5 ± 259.7). No association was found between conventional coronary artery disease risk factors (obesity, hypertension, tobacco use, hyperlipidaemia, diabetes) nor CRP, C3c or C4 levels and coronary calcifications or myocardial perfusion defects. On the contrary, in patients with these pathologies, augmented autoimmunization was found, reflected by increased aCL IgG and antiβ2GPI IgG levels. In patients with aCL IgG >20 RU/ml or antiβ2GPI IgG >3 RU/ml, the relative risk of coronary calcification formation was 4.1 compared to patients with normal values. Accordingly, in LA-positive patients the relative risk of coronary calcification formation was 4.4 compared to LA-negative patients.ConclusionsConventional risk factors for coronary artery disease as well as markers of an ongoing inflammation did not show any association with perfusion defects and/or coronary artery calcifications in SLE patients. On the contrary, calcified atherosclerotic plaques and myocardial perfusion defects were observed mainly in patients with elevated levels of anticardiolipin and aβ2GPI antibodies of the IgG class. It might be speculated that coronary artery calcifications and perfusion defects are a result of antiphospholipid antibodies-induced coronary artery microthrombosis.

Mild depression versus C-reactive protein as a predictor of cardiovascular death: a three year follow-up of patients with stable coronary artery disease

Objective:Depression is common in patients with coronary artery disease (CAD) and is associated with higher risk of cardiovascular adverse events. We aimed to explore the prognostic role of mild depression on cardiovascular mortality and compare its prognostic value with C-reactive protein (CRP) levels in patients with stable CAD.Research design and methods:We initially recruited 523 consecutive patients with stable CAD. Glucose, lipids and CRP levels were measured and an echocardiographic study was performed. In addition, depressive symptomatology was assessed with the Zung Depression Rating Scale (ZDRS, range 20–80). Patients on antidepressant treatment or with ZDRS score ≥60 were excluded. Patients were followed up at 6 month intervals (median 33 months, interquartile range 24–40 months) by telephone interview.Results:Follow-up data were obtained from 485 patients (92.7%). Nineteen patients with baseline CRP levels >10 mg/L and eight with non-cardiovascular death were excluded from analysis. Of the remaining 458 patients 113 (24.7%) presented cardiac events. Of them 21 died (4.6%), 42 developed acute coronary syndrome (9.2%), 27 (5.9%) had a revascularization procedure due clinical deterioration, two had a stroke (0.44%) and 21 (4.6%) an arrhythmic event. Multivariate Cox regression analysis showed that ZDRS score was independent predictor of cardiovascular death (hazard ratio [HR]: 1.104 with 95% confidence interval [CI]: 1.039–1.172, p = 0.001) after adjustment for conventional risk factors and CRP. The Wald test statistic of CRP was 2.59, whereas the Wald test statistic of ZDRS score was 3.23, indicating better predictability of ZDRS score. ZDRS score was also independent predictor of both cardiovascular death and arrhythmic event (HR: 1.102 with 95% CI: 1.051–1.156, p < 0.001) after adjustment for conventional risk factors and CRP levels. The main limitations of our study were the evaluation of depression at one point in time and the assessment of inflammatory burden by measuring only CRP levels.Conclusions:Mild depression is associated with increased cardiovascular mortality and is a better predictor than CRP levels in patients with stable CAD.

Use of Highly Sensitive C-Reactive Protein for Followup of Wegener’s Granulomatosis

Since Wegener's granulomatosis (WG) represents a relapsing disease, efforts have been made to reliably predict relapses using blood tests. Followup measures such as conventionally determined C-reactive protein (CRP), antineutrophil cytoplasmic antibody (C-ANCA) titer, and proteinase-3 (PR3) ELISA are applied. We evaluated whether during remission elevated highly sensitive CRP (hsCRP) precedes relapse as a marker of subclinical inflammation and thus might improve clinical assessment. We investigated 227 sera of 57 patients with WG: 74 sera collected from patients in remission who subsequently relapsed (before relapse), 30 sera collected during relapse, and 123 sera from patients in remission without relapse. We also distinguished between major and minor relapse. hsCRP, conventionally determined CRP (CRP), C-ANCA, PR3-ELISA, and erythrocyte sedimentation rate (ESR) were measured using commercial kits, and levels were correlated to clinical status. Only hsCRP and ANCA titer, but not CRP levels, were higher in sera from patients who subsequently relapsed versus those who did not, indicating patients at risk. Levels of hsCRP, CRP, and ESR were higher in sera collected during relapse than in the sera before relapse. hsCRP, conventional CRP, and ESR were also higher in samples collected during major relapse than before major relapse. Looking at the levels just before relapse compared to previous levels during remission, none of these measures rose directly before the clinical manifestation of the relapse. Our study provides evidence for an additional value of hsCRP in the clinical assessment of patients with WG.

A pilot study on potential new plasma markers for diagnosis of acute appendicitis

Background Diagnosis of acute appendicitis (AA) remains a surgical dilemma, with negative appendectomy rates of 5% to 40% and perforation suggestive for late operative intervention in 5% to 30%. The aim of this study is to evaluate new plasma markers, representing early neutrophil activation, to improve diagnostic accuracy in patients suspected for AA. Materials and Methods Fifty-one patients who underwent surgery for AA were included (male-female = 28:23), and blood was sampled. Plasma concentrations of 2 neutrophil proteins were measured: lactoferrin (LF) and calprotectin (CP). Controls consisted of 27 healthy volunteers. C-reactive protein (CRP) and white blood cell count (WBC) concentrations were measured for routine patient care. Results Median plasma concentrations for LF and CP were significantly higher in 51 patients with proven AA (665 and 766 ng/mL, respectively) than in 27 healthy volunteers (198 and 239 ng/mL, respectively, P < .001). No clinically relevant correlation exists between the plasma levels of LF and CP and the conventional laboratory tests for CRP and WBC. Conclusions Circulating LF and CP levels are significantly elevated in patients with appendicitis and are detectable in plasma using relatively simple and low-cost enzyme-linked immunosorbent assays. Furthermore, plasma levels of LF and CP give additional information to conventional markers WBC and CRP, making them potential new markers for AA diagnosis.

Evaluation of Analytical Measurement Ranges of Three Full Range C-Reactive Protein Tests Using Immunoturbidimetric Assay

Recently developed full-range C-reactive protein (CRP) tests, which are based on the immunoturbidimetric method, have wider analytical measurement ranges (AMR) than previously used tests. We evaluated the AMR of 3 full-range CRP tests-2 new and 1 previously used test. We analyzed the precision and AMR of 2 full-range CRP tests (Sekisui, Nanopia CRP, N-CRP and Iatron, IATRO CRP-EX, I-CRP) and compared the values obtained for these tests with those obtained for the conventional full-range CRP test (Sekisui, PureAuto S CRP, P-CRP). We evaluated the tests for the limit of quantification and for linearity. We also compared these results of these tests by using the comparative test (Dade Behring, cCRP) for cardiovascular risk assessment. Coefficients of variation (CVs) of all the full-range CRP tests were less than 10% for concentrations greater than 0.6 mg/L, and CVs of N-CRP and I-CRP were lower than those of P-CRP for concentrations less than 1 mg/L. N-CRP (0.1-467 mg/L) and I-CRP (0.1-280 mg/L) had wider AMR than P-CRP (3-233 mg/L). All the full-range CRP tests showed more than 90% agreement with the cCRP values for the assessment of cardiovascular risk. The 3 full-range CRP tests, by virtue of their wide AMR, may be used for the detection of acute inflammation as well as for the assessment of cardiovascular risk. N-CRP and I-CRP may be more useful than P-CRP for determining the CRP concentration, especially for the detection of concentrations close to the lower or upper limit of the analytical range, without the need for repetition of the test.

High sensitivity C-reactive protein: Its correlation with sputum cell counts in bronchial asthma

Two major acute-phase proteins were identified in human, C-reactive protein and serum amyloid A. There are 3 types of C-reactive protein assays: conventional C-reactive protein, high sensitivity C-reactive protein and cardiac C-reactive protein. High sensitivity C-reactive protein assays can detect minor inflammatory changes that could be missed by other indices of inflammation. Induced sputum cell counts are relatively non-invasive, safe and reliable method for identifying the presence and type of airway inflammation in asthmatic patients. This study was designed to detect the role of serum levels of high sensitivity C-reactive protein in asthmatic patients with or without inhaled corticosteroids treatment. Also to determine the relationship of serum high sensitivity C-reactive protein levels to clinical indices of asthma and inflammatory cell counts in induced sputum. Serum high sensitivity C-reactive protein level, pulmonary function tests, body mass index and induced sputum cell counts were estimated in 50 asthmatic patients (26 steroid inhaled and 24 steroid naïve). Fifteen healthy volunteers, who matched in age and sex with the other groups, were used as a control group. There was an increase of high sensitivity C-reactive protein in asthmatic patients among both steroid inhaled and steroid naïve patients compared to the healthy controls. Serum high sensitivity C-reactive protein correlated negatively with pulmonary function tests and positively with sputum eosinophil % in both inhaled steroid and steroid naïve groups. High sensitivity C-reactive protein is one of the markers of systemic inflammation that can be indirectly reflecting the degree of severity of airway inflammation in bronchial asthma.

Association of serum osteoprotegerin with ankle-brachial index and urine albumin: Creatinine ratio in African-Americans and non-Hispanic whites

Osteoprotegerin (OPG), a member of tumor necrosis factor receptor superfamily, has been implicated in vascular disease. We investigated the association of serum OPG with the ankle-brachial index (ABI) and urine albumin:creatinine ratio (UACR), in a bi-ethnic cohort of 1324 African-Americans (mean age 64 years, 71% women) and 1237 non-Hispanic whites (mean age 59 years, 57% women) belonging to hypertensive sibships. Serum levels of OPG were measured by solid phase sandwich immunoassay. ABI was measured using a standard protocol and peripheral arterial disease (PAD) defined as ABI < 0.90. UACR was expressed as mg albumin/gm creatinine. Multivariable regression analysis using generalized estimating equations (GEE) were performed to assess whether serum OPG levels were associated with ABI and UACR. After adjustment for conventional risk factors (age, sex, diabetes, waist circumference, history of smoking, total and HDL cholesterol, hypertension), prior history of myocardial infarction or stroke, and medication (renin–angiotensin–aldosterone system inhibitors, statins, aspirin, estrogen) use, higher OPG levels were significantly associated with lower ABI and higher UACR in African-Americans ( P = 0.001 and P < 0.0001, respectively) and non-Hispanic whites ( P = 0.017 and P = 0.002, respectively); the association remained significant after further adjustment for plasma C-reactive protein (CRP) in both ethnic groups. In multivariable logistic regression analysis, higher OPG levels were associated with PAD in African-Americans, independent of the covariates listed above ( P = 0.026); the association remained significant after additional adjustment for plasma CRP ( P = 0.047). In non-Hispanic whites, the association of higher OPG levels with PAD was of borderline significance after adjustment for the relevant covariates ( P = 0.106). We conclude that higher OPG levels are associated with lower ABI and higher UACR, independent of conventional risk factors and plasma CRP.

Relationship of socioeconomic status to C-reactive protein and arterial stiffness in urban Japanese civil servants

This study investigates whether the two socioeconomic status indicators, educational level and employment grade, are associated with C-reactive protein (CRP) levels and arterial stiffness among Japanese urban civil servants. Brachial-ankle pulse-wave velocity (baPWV) as an indicator of arterial stiffness, CRP, occupational stress and conventional risk factors were evaluated in 3412 men and 854 women. Although the socioeconomic gradient showed a significant association with the CRP levels in men after adjustment for age, the significance disappeared after multivariate adjustment, whereas in women, the socioeconomic gradient showed no significant association with the CRP levels. In men, educational level was significantly associated with the baPWV value after adjustment for conventional risk factors, CRP and occupational stress (P for trend <0.0001). With regards to employment grade, only low-level non-manual workers had a significantly lower baPWV value as compared to manual workers at a fully adjusted model, and trend significance disappeared. However, in women, neither educational level nor employment grade was associated with the baPWV value. In summary, the socioeconomic gradient, especially the educational level, was significantly inversely related to the baPWV value in men. In women, the socioeconomic gradient was not related to the baPWV value. An inverse relationship between the socioeconomic gradient and CRP levels was found in men only after age adjustment. We suggest that because the educational level is an important aspect in the adolescent environment and hence might influence the future lifestyle, early health education should be provided to prevent an unfavourable lifestyle and atherosclerotic diseases in later life.