High-sensitivity C-reactive Protein Assay Research Articles

Clinico Pathological Study of Rheumatoid Arthritis Association with C -Reactive Protein (CRP); a Potential Biomarker of Cartilage Damage

Objective: To explore the association between rheumatoid arthritis (RA) and C-reactive protein (CRP) levels as a potential biomarker of cartilage damage. Methodology: This case control study was done at Department of pathology Ziauddin University Clifton Campus, Karachi from June 2018 to May 2019. Patients diagnosed with rheumatoid arthritis (RA) according to established criteria, aged 18 years or older and both male and female participants were included. Clinical data was collected through medical record review and direct patient interviews. Blood samples were collected from participants for CRP measurement using standard laboratory assays. Serum CRP levels were quantified using high-sensitivity CRP assays in a certified clinical laboratory. CRP levels was defined based on established cutoff values, typically exceeding 3 mg/L. Statistical Analysis: Statistical analysis will be performed using SPSS version 26. Results: Mean age of patients was 43.38+.56 years, while control group subjects had a slightly lower mean age of 42.33+6.93 years (p = 0.412). Gender distribution showed a predominant female representation, with 76 female patients (88.4%) and 75 female controls (87.2%) (p = 0.816). There was a strong positive correlation was observed between DAS28 and CRP levels, with a Pearson correlation coefficient of r= 0.745 and (p < 0.01), indicating a significant association between disease activity and CRP concentration. Conversely, the correlation between DAS28 and ESR was weaker and not statistically significant (r = 0.123, p = 0.258). Conclusion: Study revealed that the significant elevation of serum CRP levels in RA patients compared to healthy individuals. The positive correlation between serum CRP levels and the extent of joint damage observed radiographically, suggesting CRP's potential as a biomarker for estimating disease severity and cartilage deterioration in RA.

C-Reactive Protein Levels Correlate with Measures of Dysglycemia and Gut Microbiome Profiles.

C-reactive protein (CRP) is a commonly used marker of low-grade inflammation as well as a marker of acute infection. CRP levels are elevated in those with diabetes and increased CRP concentrations are a risk factor for developing type 2 diabetes. Gut microbiome effects on metabolism and immune responses can impact chronic inflammation, including affecting CRP levels, that in turn can lead to the development and maintenance of dysglycemia. Using a high-sensitivity C-reactive protein (hsCRP) assay capable of detecting subtle changes in C-reactive protein, we show that higher hsCRP levels specifically correlate with worsening glycemia, reduced microbial richness and evenness, and with a reduction in the Firmicutes/Bacteroidota ratio. These data demonstrate a pivotal role for CRP not only in the context of worsening glycemia and changes to the gut microbiota, but also highlight CRP as a potential target for mitigating type 2 diabetes progression or as a therapeutic target that could be manipulated through the microbiome. Understanding these processes will provide insights into the etiology of type 2 diabetes in addition to opening doors leading to possible novel diagnostic strategies and therapeutics.

Ultrasensitive aptamer-functionalized Cu-MOF fluorescent nanozyme as an optical biosensor for detection of C-reactive protein

In the present work, an aptasensing method based on integration of RNA on Cu-MOF was developed for detection of C-Reactive Protein (CRP). Cu-MOF showed stimulated fluorescence and mimetic peroxidase enzymatic activity at the time and can be used as dual-signal transduction. CRP binding RNA was used as a highly selective recognition element and immobilized on the Cu-MOF. The immobilized RNA can block the peroxidase activity and fluorescence of the signal traducer probe. Adding CRP to the RNA/Cu-MOF will release RNA from the surface of Cu-MOF and recover both the stimulated fluorescence and peroxidase activity. A biosensor was built for detection of CRP using the two modes of transduction, either colorimetry or fluorometry. A dynamic linear range was obtained from 0.1 to 50 ng mL −1with a limit of detection (LOD) as small as 40 pg mL −1was calculated in fluorescence mode and 240 pg mL −1 as LOD in colorimetry mode. The LODs are lower than the LOD of nephelometric techniques used in clinical practice and is comparable to the normal clinical cutoff value in high-sensitivity CRP assays (1 μg/mL). The aptasensor was successfully applied for detection of CRP in Covid-19 patients with spike recoveries between 84 and 102% and RSD from 0.94% to 2.05%.

The monomeric C-reactive protein level is associated with the increase in carotid plaque number in patients with subclinical carotid atherosclerosis.

The high-sensitivity C-reactive protein (hsCRP) assay measures the level of the pentameric form of CRP in blood. Currently, there are no available assays measuring the level of the monomeric form of CRP (mCRP), produced at sites of local inflammation. We developed an assay measuring the mCRP level in blood plasma with functional beads for flow cytometry. The assay was used to measure the mCRP level in 80 middle-aged individuals with initially moderate cardiovascular SCORE risk. By the time of the mCRP measurement, the patients have been followed up for subclinical carotid atherosclerosis progression for 7 years. Ultrasound markers of subclinical atherosclerosis, which included plaque number (PN) and total plaque height (PH), were measured at baseline and at the 7th-year follow-up survey. Inflammatory biomarkers, including mCRP, hsCRP, inteleukin-6 (IL-6) and von Willebrand factor (VWF) level, were measured at the 7th-year follow-up survey. The median level of mCRP was 5.2 (3.3; 7.1) μg/L, hsCRP 1.05 (0.7; 2.1) mg/L, IL-6 0.0 (0.0; 2.8) pg/mL, VWF 106 (77; 151) IU/dL. In the patients with the mCRP level below median vs. the patients with the median mCRP level or higher, change from baseline in PN was 0.0 (0.0; 1.0) vs. 1.0 (1.0; 2.0) and PH 0.22 (−0.24; 1.91) mm vs. 1.97 (1.14; 3.14) mm, respectively (p < 0.05). The adjusted odds ratio for the formation of new carotid atherosclerotic plaques was 4.7 (95% CI 1.7; 13.2) for the patients with the median mCRP level or higher. The higher mCRP level is associated with the more pronounced increase in PN and PH in patients with normal level of traditional inflammatory biomarkers and initially moderate cardiovascular SCORE risk.

Prepregnancy body mass index, gestational weight gain, and maternal prepartum inflammation in normal pregnancies: findings from a Chinese cohort

BackgroundObesity has been linked to systemic inflammation in population studies.ObjectiveTo examine the associations of prepregnancy body mass index (pBMI) and total gestational weight gain (tGWG) with maternal prepartum low-grade inflammation (LGI) and clinically significant inflammation (CSI) defined by serum C-reactive protein (CRP) concentration.MethodsFive thousand four hundred seventy-six Chinese women with uncomplicated pregnancies and recorded data on pBMI and prepartum body weight were included in this study. Blood samples were drawn before delivery for high-sensitivity CRP assay. Inadequate, optimal, and excessive tGWG were defined using the Institute of Medicine's recommendation. Multivariable Poisson regressions were used to estimate relative risks (RRs) for having prepartum LGI and CSI (defined as CRP concentration 3–10 and > 10 mg/L, respectively) across pBMI and tGWG categories.ResultsThe mean pBMI, mean tGWG, and median maternal prepartum CRP concentration were 20.4 kg/m2, 13.9 kg, and 3.3 mg/L, respectively. The prevalence of prepartum CSI and LGI was 7.2% and 47.8%. The adjusted RRs (95% confidence interval) of CSI for normal (18.5–24.9 kg/m2) and high (≥ 25 kg/m2) vs. low pBMI (< 18.5 kg/m2) were 1.35 (1.05–1.74) and 2.28 (1.53–3.39), respectively. The respective adjusted RRs of LGI were 1.19 (1.11–1.28) and 1.59 (1.42–1.77). The adjusted RRs for excessive vs. optimal tGWG was 1.18 (0.94–1.48) for CSI and 1.14 (1.07–1.21) for LGI.ConclusionsPrepregnancy overweight/obesity and excessive tGWG increase the risk of maternal prepartum systemic inflammation, which further highlights the importance of weight management before and during pregnancy.

Agreement between high-sensitivity C-reactive protein and C-reactive protein assays

Abstract Background High sensitivity C-reactive protein (hs-CRP) is a biomarker used for risk prediction for cardiovascular disease (CVD) by assessing low concentrations of inflammatory markers. Measurements of regular CRP assays have become very sensitive too with a detection limit of 0.03mg/dL, while also being more available and cheaper. The aim of this study is to compare the association between CRP and hs-CRP. Methods This study compared CRP and hs-CRP serum concentrations and data acquired by medical chart review of 590 patients from 11/2017 to 10/2018 of our cardiology outpatient clinic who were divided into hs-CRP and CRP risk groups for CVD events: low&amp;lt;0.1 mg/dL, average 0.1–0.3mg/dL, high&amp;gt;0.3mg/dL. The agreement of classification in hs-CRP and CRP risk groups was assessed by kappa statistic, with Kappa coefficient of &amp;lt;0.20, 0.21–0.40, 0.41–0.60, 0.61–0.80, 0.81–0.99 interpreted as slight, fair, moderate, substantial and almost perfect agreement, respectively. Bland-Altman (BA) analysis was used to assess agreement between hs-CRP and CRP by plotting the mean of the two measurements on the x-axis against the mean difference of CRP - hs-CRP on the y-axis. Results Out of all 590 patients, 37.7% were in low risk, 33.9% in average risk and 28.5% in high risk hs-CRP group. Some group changes occurred after reclassification of the patients according to CRP measurements. Eight percent of patients reclassified into a higher risk group, 0.7% into a lower risk group, while 91.4% remained in the same risk group as determined by hs-CRP (kappa: 0.87; p&amp;lt;0.001) (Tab. 1). Important to note, there was a 100% agreement between the high-risk CRP and hs-CRP group patient classification. BA-plot displayed a fixed bias with an average difference between the two laboratory tests for CRP and hs-CRP of 0.02 mg/dL±0.09SD with only sporadic outliers (Fig. 1). The upper limit of agreement was 0.12 and lower limit of agreement was −0.07. In the lower range of CRP values, measurements were tightly clustered around the average difference. Greater variability could be observed at higher serum level of the inflammatory biomarker in the BA-plot with a bias to higher CRP concentrations than hs-CRP concentrations at values greater than 0.5mg/dL. This proportional bias, which was further demonstrated by linear regression analysis, does not affect the risk predicting qualities of hs-CRP or CRP for CVD because the cut-off values for risk groups (0.1mg/dL for low risk, 0.3mg/dL for high risk) are all below this threshold. Conclusion A close agreement between measurements of hs-CRP and CRP assays was identified, therefore regular CRP assays could replace hs-CRP for cardiac risk assessment. Benefits for clinical implementation are: First, CRP assessment is routinely available in most laboratories compared to hs-CRP. Second, CRP is less costly than hs-CRP, since no further laboratory acquisitions are necessary, which is especially relevant in regions where cost efficiency is of importance. Funding Acknowledgement Type of funding sources: None. Table 1. Kappa statisticFigure 1. Bland-Altman plot

High-Sensitivity Assays for C-Reactive Protein as a Systemic Inflammatory Marker in Assessing Asthma

Asthma is a chronic inflammatory condition, and the main features include airway hyper-responsiveness and inflammation of the airway with the accumulation of inflammatory cells. Increased level of plasma fibrinogen and serum amyloid A suggests the involvement of systemic inflammation in asthma. C-reactive protein (CRP) is an acute-phase protein that produced mainly by hepatocytes and is an inflammatory marker. CRP levels monitoring is useful in the evaluation of early inflammation and efficacy of treatment in acute-phase illnesses. Several studies show that asthma alone can cause an increase in high-sensitivity CRP (hs-CRP) when compared with the healthy controls. Besides that, steroid-naïve patients have a higher mean value of hs-CRP levels compared with those on inhaled corticosteroid. Furthermore, studies have shown that an elevated hs-CRP level has a positive correlation with non-atopic asthma but not atopic asthma. Additionally, an increase in serum hs-CRP levels correlates with the severity of asthma. Therefore, serum hs-CRP is a useful surrogate marker to predict the severity of inflammation of the bronchus in asthma and assess the asthma status.

C-reactive protein as a diagnostic and prognostic factor of endometrial cancer.

Endometrial cancer (EC) is the sixth most commonly occurring cancer in women and its morbidity and mortality are continuously increasing. Considering experience with different types of cancers, C-reactive protein (CRP) appears to be a promising diagnostic and prognostic factor. Aiming to investigate its potential in view of EC authors of this paper reviewed databases for metanalysis, randomized controlled trials and review articles. Studies indicate CRP > 3.33 mg/l correlates with the EC incidence with HR = 2.29 (p < 0.05). Moreover, High-sensitivity CRP assay allows to detect CRP in very low concentrations and distinguish patients with endometriosis, soft tissue sarcomas and possibly EC. Perioperational CRP, as well as its changes are independent prognostic factors for EC. However, CRP-to-albumin ratio as well as Glasgow Prognostic Score (GPS) have greater prognostic value that CRP alone. Additionally, CRP is possibly a mediator of carcinogenesis and cancer progression through activation of inter alia FcgRs/MAPK/ERK, FcgRs/IL-6/AKT/STAT3 and FcgRs/NF-κB/NLRP3 pathways.

Monomeric C-reactive protein as a marker of residual inflammatory risk in patients with asymptomatic carotid atherosclerosis

Background and Aims: C-reactive protein (CRP) can dissociate into monomeric subunits (mCRP) in proinflammatory milieu. The ability of mCRP to accumulate in atherosclerotic plaques and stimulate inflammatory response may enhance the progression of atherosclerosis. The aim of this study was to find whether novel mCRP or high-sensitivity CRP (hsCRP) assays correlate with plaque burden in non-obstructive asymptomatic carotid atherosclerosis (ACA).

Investigating whether a combination of higher CRP and depression is differentially associated with worse executive functioning in a cohort of 43,896 adults

Many depressed individuals experience difficulties in executive functioning that contribute substantially to functional impairment. It is unknown whether a subtype of depression characterized by chronic inflammation is differentially associated with worse executive functioning. This study examined whether the combination of depression and higher C reactive protein (CRP) is differentially associated with worse executive functioning and whether this association is stronger in older adults. This cross-sectional study analyzed data collected from a population-representative sample of 43,896 adults aged 44.13 years (SD = 13.52) who participated in the baseline assessment of the Lifelines cohort study. Multivariate regression models tested whether depressed individuals (established via structured interview) exhibiting higher levels of inflammation (indexed via high-sensitivity CRP assay following an overnight fast) performed worse on a behavioral test of executive functioning. Depression (B = −3.66, 95% CI: −4.82, −2.49, p < .001) and higher log-transformed CRP (B = −0.67, 95% CI: −0.87,-0.47, p < .001) were associated with worse executive functioning, after adjustment for age, sex, educational attainment, body mass index, smoking status, exposure to stressful life events and chronic stressors, sedentary behavior, and number of chronic medical conditions. Depressed individuals with higher log-transformed CRP exhibited differentially poorer executive functioning (B = −1.09, 95% CI: −2.07,-0.11, p < .001). This association did not differ based on age (B = 0.01, 95% CI: −0.08, 0.10, p = .82). Executive functioning is poorer in depressed individuals with higher CRP, even in early adulthood. Interventions that reduce inflammation may improve cognitive functioning in depression.

Can High-Sensitivity C-Reactive Protein Levels Predict Functional Outcome Following Epidural Steroid Injection in Patients with Lumbar Disc Disease?

Study DesignProspective cohort study.PurposeInflammatory cytokines produced at the site of disc herniation are considered as pain generators in patients with lumbar disc disease. Whether a high-sensitivity C-reactive protein (hs-CRP) assay can be used in order to predict the quantum of inflammation surrounding nerve roots is a matter of investigation. This study aimed to evaluate the association of hs-CRP level and functional outcomes measured by the Modified Oswestry Low Back Pain Disability Questionnaire (MODY) before and after epidural steroid injection (ESI) in patients with lumbar disc disease.Overview of LiteratureAlthough many studies examining the role of hs-CRP levels and lumbar pain have been published previously, the results are equivocal, and there is no clear consensus regarding which patients will benefit from an ESI.MethodsThis was a prospective study, with 77 patients in the study group and 23 participants in the control group. Baseline hs-CRP levels were obtained for both groups. Study group patients received a single ESI and were subjected to detailed pre- and post-procedure evaluation using MODY scores. For this group, hs-CRP levels were measured at 1 and 2 months after injection.ResultsOut of 77 patients, 52 had acute and 25 had chronic low back pain. Thirty-six patients with acute pain obtained significant improvement, while 16 had an insignificant response to the ESI. None of the chronic cases had a significant response. The mean baseline hs-CRP (mg/L) among the study group (29.83±10.43) was significantly higher than for the controls (10.26±2.783). The baseline hs-CRP among acute cases, where post ESI MODY score at 2 months had significant reduction, was 32.19±5.126, and those with insignificant reduction was 18.13±7.949 (p<0.001).ConclusionsBaseline hs-CRP levels can be used to prognosticate the outcome following ESI in patients with acute lumbar disc disease, with radicular pain refractory to physiotherapy and analgesics.

The Effect of Non-Surgical Periodontal Therapy on Serum Resistin Level in Chronic Periodontitis Patients with or without Type 2 Diabetes Mellitus.

Background: Resistin is a recognized marker for chronic inflammatory conditions that could be directly linked with type 2 diabetes mellitus. This study aimed to assess serum resistin level in type 2 diabetic patients with chronic periodontitis after non-surgical periodontal therapy. Methods: Forty individuals were recruited into three groups, group I consisted of 15 diabetic patients (type-2 diabetes mellitus) with moderate to severe chronic periodontitis, and 15 non-diabetic patients with moderate to severe chronic periodontitis in group II and group III consisted of 10 non-diabetic individuals with healthy periodontium. Non-surgical periodontal therapy with supra and subgingival debridement was performed for groups I and II. Gingival index, plaque index, probing pocket depth, clinical attachment loss, serum resistin and high sensitivity C-Reactive Protein assay were recorded for groups I and II before and after treatment, while HbA1c was recorded for group I. Results: Both groups showed statistically significant improvement in all clinical periodontal parameters from baseline to 3 months with no statistically significant difference when comparing both groups throughout the clinical study. A highly statistically significant decrease in mean serum levels of resistin and CRP after treatment in each group. Additionally, a statistically significant decrease in mean HbA1c level in group I was observed after treatment. Conclusion: Non-surgical periodontal therapy was effective in improving clinical periodontal parameters, serum resistin and C-reactive protein levels after 3 months for both diabetic and non-diabetic groups.

A simple aptamer-based colorimetric assay for rapid detection of C-reactive protein using gold nanoparticles

C-reactive protein (CRP) is a clinical biomarker for inflammatory diseases. In this work, we present a simple and fast colorimetric method for CRP detection that employs citrate–capped gold nanoparticles (AuNPs) and a CRP-binding aptamer as sensing elements. The aptamer consisted in a guanine rich single-stranded DNA (ssDNA) that adsorbs onto the surface of the AuNPs. In the presence of the CRP, the ssDNA releases from the AuNPs surface to interact preferentially with the protein to form guanine-quadruplexes. The exposure of the unprotected AuNPs to buffer salts leads to aggregation and subsequent color change from red-wine to blue-purple that was readily seen by the naked eye. The AuNPs aggregation was monitored using UV–Vis spectroscopy and the CRP concentration in the samples could be correlated with the aggregation ratio (A670nm/A520nm). A linear sensing range of 0.889–20.7 μg/mL was found. The detection limit (LOD) was 1.2 μg/mL which is comparable to the typical clinical cutoff concentration in high-sensitivity CRP assays (1 μg/mL) and lower than the detection limit of nephelometric methods used in clinical practice. This method can provide a fast (5 min analysis time), simple, and sensitive way for CRP detection, with negligible interference of bovine serum albumin (BSA) up to concentrations of 100 nM.

Evaluation of T-cell proliferation and immunogenicity assays with genetically engineered chondrocytes, tissuegene-c

Background & Aim Background The recognition of knee osteoarthritis as potentially mediated by the body's own immune system and inflammatory response has led to the development of non-operative biologic management modalities. TissueGene-C (TG-C), genetically engineered allogenic human chondrocytes (GEC) transduced with a retroviral vector encoding TGF-β1 (designated hChonJb#7) and non-transduced allogeneic human chondrocytes (designated hChonJ), are a more recent development that target immune-mediated pathways. Results from Phase 1, 2, and 3 trials have shown the safety and efficacy of this injection. The purpose of this study was to rule out possibility of an allogeneic response or induction of T-cells capable of responding to chondrocyte antigens or human leukocyte antigens (HLAs) in patients managed with TG-C. We evaluated: 1) T-cell proliferation assay (CD8 +, IFN-γ +); 2) T-cell proliferation assay (CD4 +, IFN-γ +); 3) Panel Reactive Antibody Test on anti-HLA antibodies; 4) Anti-TGF-β1 antibody assay; 5) High-Sensitivity C-Reactive Protein (HSCRP) assay; and 6) Cytokine Assay. Methods, Results & Conclusion Methods Between 1 May 2011 and 31 October 2012, we enrolled 102 patients into a multicenter, double-blinded, placebo-controlled, randomized study of adults with Kellgren-Lawrence grade III osteoarthritis of the knee (NCT01221441) based at 5 institutions. We injected TG-C into the intra-articular knee space. Immunogenicity was evaluated by assays targeting immune pathways. Peripheral blood mononuclear cells (PBMC) from study and control arms were isolated and challenged with TG-C for T-cell proliferation assays. Blood was analyzed for antibody formation, marker protein, and cytokines: 1) GM-CSF; 2) IL-10; 3) IL-1α; 4) IL-2; 5) IL-4; 6) IL-5; 7) IL-6; 8) Interferon (IFN)-γ and 9) TNF-α. Results Laboratory analyses revealed: no induced T-cell response; no clinically significant changes in IFN-γ producing T-cells or HSCRP levels; and no antibody formation to donor HLA and TGF-β1 proteins. No clinically significant changes were observed in the 9 cytokines assessed (GM-CSF, IL-10, IL-1a, IL-2, IL-4, IL-5, IL-6, IFN-γ and TNF-α). Conclusion These results indicate that both hChonJ or hChonJb#7 do not induce T-cell response to the previously TG-C exposed PBMCs. No evidence of immune response in Phase 2 study was noted. Patients exposed to TG-C did not respond to TG-C with in vitro exposure. It can be concluded that TG-C is not immunogenic to humans, and is therefore likely safe for repeat injections. The recognition of knee osteoarthritis as potentially mediated by the body's own immune system and inflammatory response has led to the development of non-operative biologic management modalities. TissueGene-C (TG-C), genetically engineered allogenic human chondrocytes (GEC) transduced with a retroviral vector encoding TGF-β1 (designated hChonJb#7) and non-transduced allogeneic human chondrocytes (designated hChonJ), are a more recent development that target immune-mediated pathways. Results from Phase 1, 2, and 3 trials have shown the safety and efficacy of this injection. The purpose of this study was to rule out possibility of an allogeneic response or induction of T-cells capable of responding to chondrocyte antigens or human leukocyte antigens (HLAs) in patients managed with TG-C. We evaluated: 1) T-cell proliferation assay (CD8 +, IFN-γ +); 2) T-cell proliferation assay (CD4 +, IFN-γ +); 3) Panel Reactive Antibody Test on anti-HLA antibodies; 4) Anti-TGF-β1 antibody assay; 5) High-Sensitivity C-Reactive Protein (HSCRP) assay; and 6) Cytokine Assay. Between 1 May 2011 and 31 October 2012, we enrolled 102 patients into a multicenter, double-blinded, placebo-controlled, randomized study of adults with Kellgren-Lawrence grade III osteoarthritis of the knee (NCT01221441) based at 5 institutions. We injected TG-C into the intra-articular knee space. Immunogenicity was evaluated by assays targeting immune pathways. Peripheral blood mononuclear cells (PBMC) from study and control arms were isolated and challenged with TG-C for T-cell proliferation assays. Blood was analyzed for antibody formation, marker protein, and cytokines: 1) GM-CSF; 2) IL-10; 3) IL-1α; 4) IL-2; 5) IL-4; 6) IL-5; 7) IL-6; 8) Interferon (IFN)-γ and 9) TNF-α.

Inflammatory mechanisms underlying the effects of everyday discrimination on age-related memory decline

Background/objectivesPrevious research suggests that everyday discrimination is associated with worse episodic memory and partially mediates Black-White disparities in memory aging. The biological mechanisms underlying the link between everyday discrimination and memory are unclear but may involve inflammatory processes. This study aimed to determine whether systemic inflammation, indexed by blood levels of C-reactive protein (CRP), mediates associations between everyday discrimination and episodic memory over 6 years. DesignA longitudinal mediation model quantified associations between baseline everyday discrimination, 4-year change in CRP, and 6-year change in episodic memory. SettingThe Health and Retirement Study (HRS). Participants12,624 HRS participants aged 51 and older. MeasurementsEveryday Discrimination Scale, high-sensitivity CRP assays of dried blood spots, composite scores of immediate and delayed recall of a word list. ResultsBlack participants reported greater everyday discrimination. Greater discrimination was associated with lower baseline memory and faster memory decline. Higher CRP at baseline partially mediated the negative association between discrimination and baseline memory, but CRP change did not mediate the association between discrimination and memory decline. ConclusionThis U.S.-representative longitudinal study provides evidence for deleterious effects of discrimination on subsequent episodic memory. The fact that elevated CRP only partially explained the concurrent association between discrimination and memory highlights the need for more comprehensive investigations of biological mechanisms underlying the link between social stress and age-related memory decline in order to better characterize potential intervention targets to reduce racial inequalities in memory aging.

Serum C-reactive protein in the prediction of cardiovascular diseases: Overview of the latest clinical studies and public health practice.

Cardiovascular disease is the most common cause of morbidity and mortality globally. Epidemiological studies using high-sensitivity assays for serum C-reactive protein have shown a consistent association between cardiovascular disease risk and serum C-reactive protein concentrations. C-reactive protein is a biomarker for inflammation, and has been established in clinical practice as an independent risk factor for cardiovascular disease events. There is evidence that serum C-reactive protein is an excellent biomarker of cardiovascular disease and is also an independent and strong predictor of adverse cardiovascular events. Further characterization of the impact and influence of lifestyle exposures and genetic variation on the C-reactive protein response to cardiovascular disease events may have implications for the therapeutic approaches to reduce cardiovascular disease events. This review summarizes the studies that have examined the association between serum C-reactive protein and the risk of cardiovascular disease. We also discuss the impact of independent factors and C-reactive protein genetic polymorphisms on baseline plasma C-reactive protein levels.

Home or Hospital? Point-of-Care CRP as a Triage Biomarker in the Primary Care Setting.

C-reactive protein (CRP)2 is an acute-phase reactant synthesized in the liver in response to proinflammatory signals such as interleukin-6. This biomarker is routinely used to evaluate systemic inflammatory processes, monitor response to antibiotic treatment, and for the detection of intercurrent infections. In these conditions, CRP concentrations rise rapidly and considerably (i.e., >10 mg/L). Measurement of low concentrations of CRP (between <0.3 and 0 mg/L), using high-sensitivity CRP assays, has been demonstrated to be useful for the assessment of cardiovascular disease/event risk. There are no CRP assays cleared with a waived status in the US at the time of this publication. The measurement of CRP at the point of care (POC) has been evaluated primarily in Europe as a tool to …

C-REACTIVE PROTEIN EFFECTS IN PATIENTS WITH BIPOLAR DEPRESSION TREATED WITH LURASIDONE: AN EXPLORATORY ANALYSIS OF A PLACEBO-CONTROLLED TRIAL

C-REACTIVE PROTEIN EFFECTS IN PATIENTS WITH BIPOLAR DEPRESSION TREATED WITH LURASIDONE: AN EXPLORATORY ANALYSIS OF A PLACEBO-CONTROLLED TRIAL

The Role of C-reactive Protein in Innate and Acquired Inflammation: New Perspectives

The participation of C-reactive protein (CRP) in host defense against microorganisms has been well described. More controversial has been its role in chronic conditions such as cardiovascular disease. Our recent publications explain the reasons for some of the confusion concerning CRP as a risk factor for disease and whether it is pro-inflammatory or anti-inflammatory. We found that two isoforms of CRP, pentameric (pCRP) and monomeric (mCRP), on microparticles (MPs), were not measureable by standard clinical assays. When we investigated MPs by imaging cytometry in plasma from controls versus patients with peripheral artery disease, we found that MPs from endothelial cells bearing mCRP were elevated. This elevation did not correlate with the soluble pCRP measured by high-sensitivity CRP assays. The data suggest that detection of mCRP on MPs may be a more specific marker in diagnosis, measurement of progression, and risk sensitivity in chronic disease. In an in vitro model of vascular inflammation, pCRP was anti-inflammatory and mCRP was pro-inflammatory for macrophage and T cell polarization. When we further investigated pCRP under defined conditions, we found that pCRP in the absence of a phosphocholine ligand had no inflammatory consequences. When combined with phosphocholine ligands, pCRP signaled through two Fcγ receptors (FcγRI and FcγRII) via phosphorylation of spleen tyrosine kinase (pSYK) to activate monocytes. Phosphocholine itself, when bound to pCRP, induced a congruent M2 macrophage and Th2 response. Phosphocholine is also the head group on the lipid phosphatidylcholine, which can become oxidized. Liposomes bearing oxidized phosphatidylcholine without pCRP promoted a uniform M1 macrophage and Th1 pro-inflammatory response. When oxidized liposomes were bound to pCRP, there was a disjunction in the macrophage and T cell response: monocytes matured into M2 macrophages, but the T cells polarized into a Th1 phenotype. The CRP-bound liposomes signaled monocytes via FcγRII to promote an anti-inflammatory M2 macrophage state, whereas the lack of FcγR on T cells allowed their liposome-induced polarization to a pro-inflammatory Th1 phenotype unopposed by the contribution of the pCRP/FcγR interaction. Different isoforms of CRP and its binding to complex ligands may determine its biological activities and their contribution to inflammatory states.

Effect of CPAP therapy on C-reactive protein and cognitive impairment in patients with obstructive sleep apnea hypopnea syndrome.

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with neurocognitive impairment. We examined the role of the systemic inflammatory response, measured by high-sensitivity C-reactive protein (hsCRP) assay, and the effect of CPAP treatment on hsCRP and cognitive impairment in patients with OSAHS. Eligible subjects (n = 178) were categorized into two groups: absent or mild OSAHS, and moderate to severe OSAHS. First, the Montreal Cognitive Assessment (MoCA) and serum hsCRP concentration were measured. Then, the moderate to severe OSAHS group was further divided into a conservative treatment subgroup (n = 68) and a CPAP subgroup (n = 68). After 6months of treatment, MoCA scores and hsCRP concentrations were re-measured in the moderate to severe group. Compared with the absent or mild OSAHS group, hsCRP concentration was higher (1.00 ± 1.28mg/L versus 2.71 ± 1.8, p < 0.001) and MoCA scores were significantly lower (27.4 ± 1.4 versus 26.3 ± 2.0, p < 0.001) in the moderate to severe group. After adjustment for age, education, body mass index, and neck circumference, hsCRP and MoCA scores correlated with parameters of overnight hypoxia. hsCRP and the proportion of time spent with blood oxygen saturation < 90% (T90) predicted MoCA score. hsCRP and MoCA score improved, and the subdomains of the MoCA were partially improved, in the CPAP treatment subgroup. In conservatively managed patients, hsCRP concentration increased, and there was no improvement in neurocognitive dysfunction, with the memory subdomain significantly worse. hsCRP may play a role in neurocognitive dysfunction in OSAHS. Long-term CPAP treatment could normalize the serum hsCRP concentration and partially reverse cognitive dysfunction in OSAHS.