Objective
Periodontal ligament (PDL) cells express oestrogen receptors but the functional importance of oestrogen in PDL cells exposed to bacterial endotoxins is not known. Here we investigate if the inflammation promoter lipopolysaccharide (LPS) affects PDL cell production of interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) and/or normal functional PDL cell characteristics such as collagen synthesis and cell proliferation and if oestrogen modulates the effects of LPS.
Methods
PDL cells were obtained from periodontal ligament of premolars. PDL cells were treated with Escherichia coli LPS in the absence or presence of oestrogen (17β-oestradiol, E2). Cellular concentration of IL-6, MCP-1 and CRP was determined by enzyme-linked immunosorbent assay (ELISA). Collagen synthesis was determined by l-[3H]proline incorporation. Cell proliferation was assessed by DNA synthesis measurement using [3H]thymidine incorporation.
Results
Stimulation with LPS (500 ng/ml to 10 μg/ml) increased IL-6 production in a concentration-dependent manner. Lower concentration (100 ng/ml) of LPS had no effect. LPS-induced stimulation of IL-6 was not reversed by a physiologically high concentration (100 nM) of E2. LPS increased also MCP-1 production which was unaffected by E2. Treatment with E2 alone had no effect on either IL-6 or MCP-1. Stimulation with LPS had no effect on CRP. LPS did not affect collagen synthesis and cell proliferation, reflecting normal physiological properties of PDL cells.
Conclusions
LPS stimulates PDL cell IL-6 and MCP-1 production but has no effect on the normal physiological properties of PDL cells. LPS-induced IL-6 and MCP-1 is not reversed by oestrogen suggesting that oestrogen exerts no anti-inflammatory effect via this mechanism.
ARTICLE
Wednesday
Tuesday
The Utility of Serum C-Reactive Protein in Differentiating Bacterial from Nonbacterial Pneumonia in Children: A Meta-Analysis of 1230 Children.
Background:
Differentiating bacterial from nonbacterial community-acquired pneumonia in children is difficult. Although several studies have evaluated serum concentrations of C-reactive protein (CRP) as a predictor of bacterial pneumonia in this patient population, the utility of this test remains unclear.
Objective:
The purpose of this meta-analysis was to quantitatively define the utility of serum CRP as a predictor of bacterial pneumonia in acutely ill children.
Methods:
Multiple databases were searched, bibliographies reviewed, and 2 authorities in the field were queried. Studies were included if: (1) the patient population was between 1 month and 18 years of age; (2) C-reactive protein (CRP) was quantified in all subjects as part of the initial evaluation of a suspected, infectious, pulmonary process; (3) a cutoff serum CRP concentration between 30 and 60 mg/dL was used to distinguish nonbacterial from bacterial pneumonia; (4) some criteria were applied to differentiate bacterial from nonbacterial or viral pneumonia; (5) all patients were acutely ill; and (6) a chest radiograph was obtained as part of the initial evaluation. The quality of each included study was determined across 4 metrics: diagnostic criteria; study design; exclusion of chronically ill or human immunodeficiency virus infected subjects; and exclusion of patients who recently received antibiotics. Data was extracted from each article; the primary outcome measure was the odds ratio of patients with bacterial or mixed etiology pneumonia and serum CRP concentrations exceeding 30-60 mg/L. Heterogeneity among the studies was determined by Cochran's Q statistic; the methods of both Mantel and Haenszel, and DerSimonian and Laird were used to combine the study results.
Results:
Eight studies fulfilled inclusion criteria. Combining all of the studies demonstrated a pooled study population of 1230 patients with the incidence of bacterial infection of 41%. Children with bacterial pneumonia were significantly more likely to have serum C-reactive protein (CRP) concentrations exceeding 35-60 mg/L than children with nonbacterial infections (odds ratio = 2.58, 95% confidence interval = 1.20-5.55). Sensitivity analysis demonstrated that this difference was robust. There was significant heterogeneity among the 8 studies (Q = 37.7, P < 0.001, I2 = 81.4) that remained throughout the sensitivity analysis.
Differentiating bacterial from nonbacterial community-acquired pneumonia in children is difficult. Although several studies have evaluated serum concentrations of C-reactive protein (CRP) as a predictor of bacterial pneumonia in this patient population, the utility of this test remains unclear.
Objective:
The purpose of this meta-analysis was to quantitatively define the utility of serum CRP as a predictor of bacterial pneumonia in acutely ill children.
Methods:
Multiple databases were searched, bibliographies reviewed, and 2 authorities in the field were queried. Studies were included if: (1) the patient population was between 1 month and 18 years of age; (2) C-reactive protein (CRP) was quantified in all subjects as part of the initial evaluation of a suspected, infectious, pulmonary process; (3) a cutoff serum CRP concentration between 30 and 60 mg/dL was used to distinguish nonbacterial from bacterial pneumonia; (4) some criteria were applied to differentiate bacterial from nonbacterial or viral pneumonia; (5) all patients were acutely ill; and (6) a chest radiograph was obtained as part of the initial evaluation. The quality of each included study was determined across 4 metrics: diagnostic criteria; study design; exclusion of chronically ill or human immunodeficiency virus infected subjects; and exclusion of patients who recently received antibiotics. Data was extracted from each article; the primary outcome measure was the odds ratio of patients with bacterial or mixed etiology pneumonia and serum CRP concentrations exceeding 30-60 mg/L. Heterogeneity among the studies was determined by Cochran's Q statistic; the methods of both Mantel and Haenszel, and DerSimonian and Laird were used to combine the study results.
Results:
Eight studies fulfilled inclusion criteria. Combining all of the studies demonstrated a pooled study population of 1230 patients with the incidence of bacterial infection of 41%. Children with bacterial pneumonia were significantly more likely to have serum C-reactive protein (CRP) concentrations exceeding 35-60 mg/L than children with nonbacterial infections (odds ratio = 2.58, 95% confidence interval = 1.20-5.55). Sensitivity analysis demonstrated that this difference was robust. There was significant heterogeneity among the 8 studies (Q = 37.7, P < 0.001, I2 = 81.4) that remained throughout the sensitivity analysis.
Serum C-Reactive Protein at Admission Predicts In-Hospital Mortality in Medical Patients
Background
Previous studies have examined the role of inflammatory markers in patients with coronary heart disease, stroke, chronic renal failure and other selected patient populations. The aim of this study was to assess the clinical utility of serum C-reactive protein (CRP) at admission in predicting outcome in hospitalized medical patients.
Methods
All patients admitted to our medical department were eligible to be included in the study. At the time of admission, demographic and clinical information was obtained. CPR was measured within 12 h of hospitalization. The results were analyzed using Cox proportional hazards multiple regression model.
Results
Three hundred eighty-two patients were included in the study (186 males and 196 females). Age (mean ± standard deviation) was 70.8 ± 15.7 years. Serum CRP [median (interquartile range) at admission was 29.7 mg/l (6.6–114.3). Serum CRP at admission was independently associated with in-hospital death. Levels above 120 mg/l increased the probability of fatal outcome three fold (hazard ratio = 2.98, 95% confidence interval: 1.35–6.58). In patients older than 80 years, CRP at admission was a stronger predictor of in-hospital death (hazard ratio = 5.41, 95% confidence interval: 1.38–21.26).
Conclusions
Serum CRP at admission is an independent predictor of mortality in hospitalized patients, particularly in the elderly. Admission CRP higher than 120 mg/l was associated with increased probability of in-hospital death (three fold in the overall population and five fold in the elderly subgroup) compared with lower levels.
Previous studies have examined the role of inflammatory markers in patients with coronary heart disease, stroke, chronic renal failure and other selected patient populations. The aim of this study was to assess the clinical utility of serum C-reactive protein (CRP) at admission in predicting outcome in hospitalized medical patients.
Methods
All patients admitted to our medical department were eligible to be included in the study. At the time of admission, demographic and clinical information was obtained. CPR was measured within 12 h of hospitalization. The results were analyzed using Cox proportional hazards multiple regression model.
Results
Three hundred eighty-two patients were included in the study (186 males and 196 females). Age (mean ± standard deviation) was 70.8 ± 15.7 years. Serum CRP [median (interquartile range) at admission was 29.7 mg/l (6.6–114.3). Serum CRP at admission was independently associated with in-hospital death. Levels above 120 mg/l increased the probability of fatal outcome three fold (hazard ratio = 2.98, 95% confidence interval: 1.35–6.58). In patients older than 80 years, CRP at admission was a stronger predictor of in-hospital death (hazard ratio = 5.41, 95% confidence interval: 1.38–21.26).
Conclusions
Serum CRP at admission is an independent predictor of mortality in hospitalized patients, particularly in the elderly. Admission CRP higher than 120 mg/l was associated with increased probability of in-hospital death (three fold in the overall population and five fold in the elderly subgroup) compared with lower levels.
Phosphoethanolamine-complexed C-reactive protein: A pharmacological-like macromolecule that binds to native low-density lipoprotein in human serum
Background
C-reactive protein (CRP) is an acute phase plasma protein. An important binding specificity of CRP is for the modified forms of low-density lipoprotein (LDL) in which the phosphocholine-binding sites of CRP participate. CRP, however, does not bind to native LDL.
Methods
We investigated the interaction of CRP with native LDL using sucrose density gradient ultracentrifugation.
Results
We found that the blocking of the phosphocholine-binding sites of CRP with phosphoethanolamine (PEt) converted CRP into a potent molecule for binding to native LDL. In the presence of PEt, CRP acquired the ability to bind to fluid-phase purified native LDL. Because purified native LDL may undergo subtle modifications, we also used whole human serum as the source of native LDL. In the presence of PEt, CRP bound to native LDL in serum also. The effect of PEt on CRP was selective for LDL because PEt-complexed CRP did not bind to high-density lipoprotein in the serum.
Conclusions
The pharmacologic intervention of endogenous CRP by PEt-based compounds, or the use of exogenously prepared CRP-PEt complexes, may turn out to be an effective approach to capture native LDL cholesterol in vivo to prevent the development of atherosclerosis.
ARTICLE
C-reactive protein (CRP) is an acute phase plasma protein. An important binding specificity of CRP is for the modified forms of low-density lipoprotein (LDL) in which the phosphocholine-binding sites of CRP participate. CRP, however, does not bind to native LDL.
Methods
We investigated the interaction of CRP with native LDL using sucrose density gradient ultracentrifugation.
Results
We found that the blocking of the phosphocholine-binding sites of CRP with phosphoethanolamine (PEt) converted CRP into a potent molecule for binding to native LDL. In the presence of PEt, CRP acquired the ability to bind to fluid-phase purified native LDL. Because purified native LDL may undergo subtle modifications, we also used whole human serum as the source of native LDL. In the presence of PEt, CRP bound to native LDL in serum also. The effect of PEt on CRP was selective for LDL because PEt-complexed CRP did not bind to high-density lipoprotein in the serum.
Conclusions
The pharmacologic intervention of endogenous CRP by PEt-based compounds, or the use of exogenously prepared CRP-PEt complexes, may turn out to be an effective approach to capture native LDL cholesterol in vivo to prevent the development of atherosclerosis.
ARTICLE
Researcher Identifies Protein That Helps Predict Prostate Cancer Survival
An Oregon Health & Science University Cancer Institute researcher has identified a protein that is a strong indicator of survival for men with advanced prostate cancer. The C-reactive protein , also known as CRP, is a special type of protein produced by the liver that is elevated in the presence of inflammation.
"This could mean that a simple blood test that is already available could help in clinical decision making and patient counseling. Patients and doctors would know better what to expect from the prostate cancer they are facing," said Tomasz Beer, M.D., director of the Prostate Cancer Research Program at the OHSU Cancer Institute, associate professor of medicine (hematology/medical oncology), OHSU School of Medicine.
Beer's research will be published online in the journal Cancer on Monday, April 21.
Past research has shown that cancer causes an inflammatory response. This research also suggests that inflammation may play an important role in driving prostate cancer progression and resistance to therapy. Inflammatory cells are attracted to cancer sites and this local inflammation can lead to a release of inflammatory markers, like CRP.
"While inflammation may sometimes slow the progression of the cancer, an increasing body of evidence suggests that cancer can actually take advantage of the inflammatory response, and the reaction of the immune system may fuel cancer progression. To the extent that our hypothesis proves true, C-reactive protein may be reflecting the overall intensity of the inflammation," Beer said.
The finding that higher CRP is associated with shorter survival and a lower probability of response to chemotherapy is a result of a secondary analysis of inflammatory markers in patients enrolled in the ASCENT study, a large Phase 2 clinical trial that evaluated treatment with docetaxel and DN-101, a high dose formulation of calcitriol or docetaxel with placebo. This analysis included patients from both groups. The analyses were supported by Novacea Inc., the sponsor of the ASCENT study. This new finding was in collaboration with Novacea.
Because this is the first time CRP has been linked with both response and survival in study subjects with advanced prostate cancer receiving chemotherapy, it will be important to confirm this finding in an independent data set before this can become a routine blood test for men with advanced prostate cancer, Beer explained.
“If confirmed, besides providing useful information for the patient, this finding could also provide us with vital insight into the fundamental role of inflammation in the progression of advanced prostate cancer. A better understanding of this process could provide us with novel therapeutic interventions for control of this disease and its symptoms,” Beer said.
OHSU and Beer have significant financial interest in Novacea Inc., a company that has a commercial interest in the results of this research and technology. This potential conflict was reviewed, and a management plan approved by the OHSU Conflict of Interest in Research Committee and the Integrity Program Oversight Council was implemented.
"This could mean that a simple blood test that is already available could help in clinical decision making and patient counseling. Patients and doctors would know better what to expect from the prostate cancer they are facing," said Tomasz Beer, M.D., director of the Prostate Cancer Research Program at the OHSU Cancer Institute, associate professor of medicine (hematology/medical oncology), OHSU School of Medicine.
Beer's research will be published online in the journal Cancer on Monday, April 21.
Past research has shown that cancer causes an inflammatory response. This research also suggests that inflammation may play an important role in driving prostate cancer progression and resistance to therapy. Inflammatory cells are attracted to cancer sites and this local inflammation can lead to a release of inflammatory markers, like CRP.
"While inflammation may sometimes slow the progression of the cancer, an increasing body of evidence suggests that cancer can actually take advantage of the inflammatory response, and the reaction of the immune system may fuel cancer progression. To the extent that our hypothesis proves true, C-reactive protein may be reflecting the overall intensity of the inflammation," Beer said.
The finding that higher CRP is associated with shorter survival and a lower probability of response to chemotherapy is a result of a secondary analysis of inflammatory markers in patients enrolled in the ASCENT study, a large Phase 2 clinical trial that evaluated treatment with docetaxel and DN-101, a high dose formulation of calcitriol or docetaxel with placebo. This analysis included patients from both groups. The analyses were supported by Novacea Inc., the sponsor of the ASCENT study. This new finding was in collaboration with Novacea.
Because this is the first time CRP has been linked with both response and survival in study subjects with advanced prostate cancer receiving chemotherapy, it will be important to confirm this finding in an independent data set before this can become a routine blood test for men with advanced prostate cancer, Beer explained.
“If confirmed, besides providing useful information for the patient, this finding could also provide us with vital insight into the fundamental role of inflammation in the progression of advanced prostate cancer. A better understanding of this process could provide us with novel therapeutic interventions for control of this disease and its symptoms,” Beer said.
OHSU and Beer have significant financial interest in Novacea Inc., a company that has a commercial interest in the results of this research and technology. This potential conflict was reviewed, and a management plan approved by the OHSU Conflict of Interest in Research Committee and the Integrity Program Oversight Council was implemented.
Maternal serum C-reactive protein concentrations in early pregnancy and subsequent risk of preterm delivery
OBJECTIVE: To examine the relation between maternal early pregnancy serum C-reactive protein (CRP) and preterm delivery (PTD).
DESIGN AND METHODS: Women were recruited before 20 weeks gestation and were followed up until delivery. Maternal serum C-reactive protein CRP was measured by competitive immunoassay . Logistic regression procedures were used to calculate adjusted odds ratio (OR) and 95% confidence intervals (95%CI).
RESULTS: Elevations in CRP ( concentrations were associated with the risk of PTD overall. After adjusting for confounding, the OR for highest quartile (> or = 7.5 vs. < 2.0 mg/L) of C-reactive protein ( was 2.04 (95%CI: 1.13-3.69). Stratified analyses indicated that elevated CRP was associated with an increased risk of spontaneous preterm labour (OR=2.15, 95%CI: 0.85-5.42), medically indicated preterm delivery (OR=3.29, 95%CI: 0.98-11.02), and very preterm delivery (OR=20.6, 95%CI: 2.53-168.03), but not with preterm premature rupture of membranes (OR=1.48, 95%CI: 0.56-3.86).
CONCLUSIONS: Elevated C-reactive protein ( concentrations in early pregnancy are associated with an increased risk of PTD, particularly medically indicated PTD and very PTD.
Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University , Bangkok
DESIGN AND METHODS: Women were recruited before 20 weeks gestation and were followed up until delivery. Maternal serum C-reactive protein CRP was measured by competitive immunoassay . Logistic regression procedures were used to calculate adjusted odds ratio (OR) and 95% confidence intervals (95%CI).
RESULTS: Elevations in CRP ( concentrations were associated with the risk of PTD overall. After adjusting for confounding, the OR for highest quartile (> or = 7.5 vs. < 2.0 mg/L) of C-reactive protein ( was 2.04 (95%CI: 1.13-3.69). Stratified analyses indicated that elevated CRP was associated with an increased risk of spontaneous preterm labour (OR=2.15, 95%CI: 0.85-5.42), medically indicated preterm delivery (OR=3.29, 95%CI: 0.98-11.02), and very preterm delivery (OR=20.6, 95%CI: 2.53-168.03), but not with preterm premature rupture of membranes (OR=1.48, 95%CI: 0.56-3.86).
CONCLUSIONS: Elevated C-reactive protein ( concentrations in early pregnancy are associated with an increased risk of PTD, particularly medically indicated PTD and very PTD.
Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University , Bangkok
Rheumatoid Arthritis Linked To Early Death From Cardiovascular Disease
People with rheumatoid arthritis (RA), an inflammatory autoimmune disease, tend to die younger and, largely from cardiovascular disease (CVD). One explanation for this increasingly recognized fact is that inflammation promotes atherosclerosis. A marker of inflammation, elevation of the C-reactive protein (CRP) level has been shown to predict CVD in the general population. However, other highly inflammatory diseases--Crohn's, for example--do not carry the same high risk of premature death from heart disease.
To identify other possible suspects, researchers in the United Kingdom investigated whether genetic variants linked to the likelihood of developing RA might also make patients more likely to die from CVD. Led by Dr. Tracey M. Farragher at the University of Manchester and funded by the Arthritis Research Campaign (arc), the study focused on two genes--HLA-DRB1and PTPN22--and their interactions with known RA risk factors. The evidence implicates
HLA-DRB1 genotypes , already associated with RA susceptibility and severity, as a predictor of premature death from CVD for inflammatory arthritis patients. For RA patients in particular, having the shared epitope (SE)--a group of HLA-DRB1 alleles with kindred amino acid traits--plus anti-cyclic citrullinated peptide (anti-CCP) antibodies and current smoking is an especially deadly combination.
The study focused on 1,022 patients with inflammatory polyarthritis (IP) recruited from a primary-care-based register of adults. The subjects were all white and nearly 65 percent female, with a mean age of 54 at the onset of symptoms. Starting anywhere between 1989 and 1994, data on file for each participant included the results of blood tests for rheumatoid factor (RF), elevation of the C-reactive protein ((CRP), and anti-CCP antibodies; evaluations of joint pain and functional disability; smoking habits; and, when applicable, the cause and date of death. DNA samples were also available. 751 of the total patients met the American College of Rheumatology criteria for RA.
HLA-DRB1 and PTPN22 genotyping was performed on every patient's DNA. Using Cox proportional hazards regression models, researchers assessed the association of each gene family with the risk of death from all causes and from cardiovascular disease. They also examined the interactions between SE presence, anti-CCP status, and smoking history, adjusted by patient sex and age at symptom onset.
In the years between the register's inception and the study's completion, 242 (24 percent) of the patients died. CVD was named as the cause of death for 76 (31.4 percent) of the deceased. Based on the researchers' analyses, having two copies of the SE alleles increased the risk of death from all causes and from CVD. For individuals with the HLA-DRB1 combination, the risk of death from CVD was increased more than 3-fold. The fatal impact was independent of RF and C-reactive protein ( levels. It was aggravated, however, by the interaction of SE, anti-CCP antibodies, and smoking. Current smokers who carried 2 SE alleles and had anti-CCP antibodies had the highest risk of dying from all causes, as well as a substantially higher risk of dying early from CVD. In calculations focusing on RA patients only, this finding remained consistent. Researchers found no evidence of any association between the PTPN22 gene and the risk of death.
This study is the first to link the HLA-DRB1 genotype with premature death, particularly from cardiovascular disease, for those afflicted with any form of inflammatory arthritis, including RA. As Dr. Farragher stresses, the results "raise the possibility of a targeted strategy to prevent CVD in these patients," while reinforcing the lethal danger of smoking for anyone with a genetic predisposition for arthritis.
Journal article: "Association of the HLA-DRB1 Gene With Premature Death, Particularly From Cardiovascular Disease, in Patients With Rheumatoid Arthritis and Inflammatory Polyarthritis," Tracey M. Farragher, Nicola J. Goodson, Haris Naseem, Alan J. Silman, Wendy Thomson, Deborah Symmons, and Anne Barton, Arthritis & Rheumatism, February 2008; 58:2, pp. 359-369.
To identify other possible suspects, researchers in the United Kingdom investigated whether genetic variants linked to the likelihood of developing RA might also make patients more likely to die from CVD. Led by Dr. Tracey M. Farragher at the University of Manchester and funded by the Arthritis Research Campaign (arc), the study focused on two genes--HLA-DRB1and PTPN22--and their interactions with known RA risk factors. The evidence implicates
HLA-DRB1 genotypes , already associated with RA susceptibility and severity, as a predictor of premature death from CVD for inflammatory arthritis patients. For RA patients in particular, having the shared epitope (SE)--a group of HLA-DRB1 alleles with kindred amino acid traits--plus anti-cyclic citrullinated peptide (anti-CCP) antibodies and current smoking is an especially deadly combination.
The study focused on 1,022 patients with inflammatory polyarthritis (IP) recruited from a primary-care-based register of adults. The subjects were all white and nearly 65 percent female, with a mean age of 54 at the onset of symptoms. Starting anywhere between 1989 and 1994, data on file for each participant included the results of blood tests for rheumatoid factor (RF), elevation of the C-reactive protein ((CRP), and anti-CCP antibodies; evaluations of joint pain and functional disability; smoking habits; and, when applicable, the cause and date of death. DNA samples were also available. 751 of the total patients met the American College of Rheumatology criteria for RA.
HLA-DRB1 and PTPN22 genotyping was performed on every patient's DNA. Using Cox proportional hazards regression models, researchers assessed the association of each gene family with the risk of death from all causes and from cardiovascular disease. They also examined the interactions between SE presence, anti-CCP status, and smoking history, adjusted by patient sex and age at symptom onset.
In the years between the register's inception and the study's completion, 242 (24 percent) of the patients died. CVD was named as the cause of death for 76 (31.4 percent) of the deceased. Based on the researchers' analyses, having two copies of the SE alleles increased the risk of death from all causes and from CVD. For individuals with the HLA-DRB1 combination, the risk of death from CVD was increased more than 3-fold. The fatal impact was independent of RF and C-reactive protein ( levels. It was aggravated, however, by the interaction of SE, anti-CCP antibodies, and smoking. Current smokers who carried 2 SE alleles and had anti-CCP antibodies had the highest risk of dying from all causes, as well as a substantially higher risk of dying early from CVD. In calculations focusing on RA patients only, this finding remained consistent. Researchers found no evidence of any association between the PTPN22 gene and the risk of death.
This study is the first to link the HLA-DRB1 genotype with premature death, particularly from cardiovascular disease, for those afflicted with any form of inflammatory arthritis, including RA. As Dr. Farragher stresses, the results "raise the possibility of a targeted strategy to prevent CVD in these patients," while reinforcing the lethal danger of smoking for anyone with a genetic predisposition for arthritis.
Journal article: "Association of the HLA-DRB1 Gene With Premature Death, Particularly From Cardiovascular Disease, in Patients With Rheumatoid Arthritis and Inflammatory Polyarthritis," Tracey M. Farragher, Nicola J. Goodson, Haris Naseem, Alan J. Silman, Wendy Thomson, Deborah Symmons, and Anne Barton, Arthritis & Rheumatism, February 2008; 58:2, pp. 359-369.
What is High Sensitivity C-reactive Protein (HS-CRP)?
CRP is short for "C-reactive protein " a protein found in the blood. C-Reactive Protein is what we call a marker for inflammation , meaning its presence indicates a heightened state of inflammation in the body. Inflammation is a normal response to many physical states including fever, injury and infection. Inflammation is now believed to play a role in the initiation and progression of cardiovascular disease .
Is HS-C-reactive protein a real risk factor, like cholesterol or smoking?
In studies involving large numbers of patients, C-Reactive Protein levels seem to be correlated with levels of cardiac risk . In fact, CRP seems to be at least as predictive of cardiac risk as cholesterol levels. Data from the Physicians Health Study , a clinical trial involving 18,000 apparently healthy physicians, found that elevated levels of C-Reactive Protein were associated with a threefold increase in the risk of heart attack.
In the Harvard Women's Health Study , results of the CRP test were more accurate than cholesterol levels in predicting coronary problems. Twelve different markers of inflammation were studied in healthy, postmenopausal women . After three years, CRP was the strongest predictor of risk. Women in the group with the highest C Reactive Protein CRP levels were more than four times as likely to have died from coronary disease, or suffered a nonfatal heart attack or stroke. This group was also more likely to have required a cardiac procedure such as angioplasty or bypass surgery than women in the group with the lowest levels.
Elevated hs-CRP is related to increased risk for heart attack, restenosis of coronary arteries after angioplasty, stroke, and peripheral vascular disease (PVD).
So how can I be tested?
A simple blood test can be done at the same time as a cholesterol screening. The high-sensitivity C-reactive protein (hs-CRP) test, helps determine heart disease risk and is widely available. Patients should ask their doctors about hs-CRP specifically.
It is important to remember that the usefulness of knowing hs- C-Reactive Protein levels in a particular individual is still unknown. For the time being, The American Heart Association recommends hs- C-Reactive Protein as part of routine screening for those who are at intermediate risk for heart disease. HS-CRP results in that risk group can help the physician determine additional testing and treatment. The American Heart Association adds that patients at low risk probably do not need their hs-CRP tested and those at high risk should be treated agressively regardless of their CRP test results. Certain medical centers, including The Cleveland Clinic Foundation, are investigating what the exact role of hs- C-Reactive Protein measurement should be in a physician's daily clinical practice.
What can I do if my HS-CRP level is high?
Inflammation should be treated by lifestyle change, such as losing weight, exercising, controlling diabetes, stopping smoking, controlling high blood pressure, and reducing alcohol intake. Antithrombotic medications such as aspirin or clopidogrel may provide protection. Cholesterol-lowering statin drugs and ACE inhibitors may also reduce CRP. Your doctor will prescribe the correct medications and dosage to treat your condition.
Source of this article:
Preventive Cardiology and Rehabilitation Program
The Cleveland Clinic Foundation, Desk C5
9500 Euclid Avenue
Cleveland, OH 44195
Is HS-C-reactive protein a real risk factor, like cholesterol or smoking?
In studies involving large numbers of patients, C-Reactive Protein levels seem to be correlated with levels of cardiac risk . In fact, CRP seems to be at least as predictive of cardiac risk as cholesterol levels. Data from the Physicians Health Study , a clinical trial involving 18,000 apparently healthy physicians, found that elevated levels of C-Reactive Protein were associated with a threefold increase in the risk of heart attack.
In the Harvard Women's Health Study , results of the CRP test were more accurate than cholesterol levels in predicting coronary problems. Twelve different markers of inflammation were studied in healthy, postmenopausal women . After three years, CRP was the strongest predictor of risk. Women in the group with the highest C Reactive Protein CRP levels were more than four times as likely to have died from coronary disease, or suffered a nonfatal heart attack or stroke. This group was also more likely to have required a cardiac procedure such as angioplasty or bypass surgery than women in the group with the lowest levels.
Elevated hs-CRP is related to increased risk for heart attack, restenosis of coronary arteries after angioplasty, stroke, and peripheral vascular disease (PVD).
So how can I be tested?
A simple blood test can be done at the same time as a cholesterol screening. The high-sensitivity C-reactive protein (hs-CRP) test, helps determine heart disease risk and is widely available. Patients should ask their doctors about hs-CRP specifically.
It is important to remember that the usefulness of knowing hs- C-Reactive Protein levels in a particular individual is still unknown. For the time being, The American Heart Association recommends hs- C-Reactive Protein as part of routine screening for those who are at intermediate risk for heart disease. HS-CRP results in that risk group can help the physician determine additional testing and treatment. The American Heart Association adds that patients at low risk probably do not need their hs-CRP tested and those at high risk should be treated agressively regardless of their CRP test results. Certain medical centers, including The Cleveland Clinic Foundation, are investigating what the exact role of hs- C-Reactive Protein measurement should be in a physician's daily clinical practice.
What can I do if my HS-CRP level is high?
Inflammation should be treated by lifestyle change, such as losing weight, exercising, controlling diabetes, stopping smoking, controlling high blood pressure, and reducing alcohol intake. Antithrombotic medications such as aspirin or clopidogrel may provide protection. Cholesterol-lowering statin drugs and ACE inhibitors may also reduce CRP. Your doctor will prescribe the correct medications and dosage to treat your condition.
Source of this article:
Preventive Cardiology and Rehabilitation Program
The Cleveland Clinic Foundation, Desk C5
9500 Euclid Avenue
Cleveland, OH 44195
Thursday
The Utility of Serum C-Reactive Protein in Differentiating Bacterial from Nonbacterial Pneumonia in Children: A Meta-Analysis of 1230 Children.
Background: Differentiating bacterial from nonbacterial community-acquired pneumonia in children is difficult. Although several studies have evaluated serum concentrations of C-reactive protein (CRP) as a predictor of bacterial pneumonia in this patient population, the utility of this test remains unclear.
Objective: The purpose of this meta-analysis was to quantitatively define the utility of serum CRP as a predictor of bacterial pneumonia in acutely ill children.
Methods: Multiple databases were searched, bibliographies reviewed, and 2 authorities in the field were queried. Studies were included if: (1) the patient population was between 1 month and 18 years of age; (2) CRP was quantified in all subjects as part of the initial evaluation of a suspected, infectious, pulmonary process; (3) a cutoff serum CRP concentration between 30 and 60 mg/dL was used to distinguish nonbacterial from bacterial pneumonia; (4) some criteria were applied to differentiate bacterial from nonbacterial or viral pneumonia; (5) all patients were acutely ill; and (6) a chest radiograph was obtained as part of the initial evaluation. The quality of each included study was determined across 4 metrics: diagnostic criteria; study design; exclusion of chronically ill or human immunodeficiency virus infected subjects; and exclusion of patients who recently received antibiotics. Data was extracted from each article; the primary outcome measure was the odds ratio of patients with bacterial or mixed etiology pneumonia and serum CRP concentrations exceeding 30-60 mg/L. Heterogeneity among the studies was determined by Cochran's Q statistic; the methods of both Mantel and Haenszel, and DerSimonian and Laird were used to combine the study results.
Results: Eight studies fulfilled inclusion criteria. Combining all of the studies demonstrated a pooled study population of 1230 patients with the incidence of bacterial infection of 41%. Children with bacterial pneumonia were significantly more likely to have serum C-reactive protein (CRP) concentrations exceeding 35-60 mg/L than children with nonbacterial infections (odds ratio = 2.58, 95% confidence interval = 1.20-5.55). Sensitivity analysis demonstrated that this difference was robust. There was significant heterogeneity among the 8 studies (Q = 37.7, P < 0.001, I2 = 81.4) that remained throughout the sensitivity analysis.
Conclusions: In children with pneumonia, serum CRP concentrations exceeding 40-60 mg/L weakly predict a bacterial etiology.
(C) 2008 Lippincott Williams & Wilkins, Inc
ARTICLE
Objective: The purpose of this meta-analysis was to quantitatively define the utility of serum CRP as a predictor of bacterial pneumonia in acutely ill children.
Methods: Multiple databases were searched, bibliographies reviewed, and 2 authorities in the field were queried. Studies were included if: (1) the patient population was between 1 month and 18 years of age; (2) CRP was quantified in all subjects as part of the initial evaluation of a suspected, infectious, pulmonary process; (3) a cutoff serum CRP concentration between 30 and 60 mg/dL was used to distinguish nonbacterial from bacterial pneumonia; (4) some criteria were applied to differentiate bacterial from nonbacterial or viral pneumonia; (5) all patients were acutely ill; and (6) a chest radiograph was obtained as part of the initial evaluation. The quality of each included study was determined across 4 metrics: diagnostic criteria; study design; exclusion of chronically ill or human immunodeficiency virus infected subjects; and exclusion of patients who recently received antibiotics. Data was extracted from each article; the primary outcome measure was the odds ratio of patients with bacterial or mixed etiology pneumonia and serum CRP concentrations exceeding 30-60 mg/L. Heterogeneity among the studies was determined by Cochran's Q statistic; the methods of both Mantel and Haenszel, and DerSimonian and Laird were used to combine the study results.
Results: Eight studies fulfilled inclusion criteria. Combining all of the studies demonstrated a pooled study population of 1230 patients with the incidence of bacterial infection of 41%. Children with bacterial pneumonia were significantly more likely to have serum C-reactive protein (CRP) concentrations exceeding 35-60 mg/L than children with nonbacterial infections (odds ratio = 2.58, 95% confidence interval = 1.20-5.55). Sensitivity analysis demonstrated that this difference was robust. There was significant heterogeneity among the 8 studies (Q = 37.7, P < 0.001, I2 = 81.4) that remained throughout the sensitivity analysis.
Conclusions: In children with pneumonia, serum CRP concentrations exceeding 40-60 mg/L weakly predict a bacterial etiology.
(C) 2008 Lippincott Williams & Wilkins, Inc
ARTICLE
Usefulness of C-Reactive Protein and Left Ventricular Diastolic Performance for Prognosis in Patients With Left Ventricular Systolic Heart Failure
High-sensitivity C-reactive protein (hs-CRP) is a hepatocyte-derived inflammatory cytokine shown to be increased in the setting of acute heart failure (HF), particularly with increased intracardiac filling pressures. In the chronic HF setting, the relation between hs-CRP and echocardiographic indexes of left ventricular (LV) diastolic performance has not been examined. We measured plasma hs-CRP levels using a particle-enhanced immunonephelometry assay (Dade Behring, Inc., Deerfield, Illinois) in 136 subjects with chronic HF (LV ejection fraction [EF] ≤35%, New York Heart Association functional classes II to IV). We performed echocardiography, including color M-mode and tissue Doppler methods. We prospectively examined subjects’ death, cardiac transplantation, and HF hospitalization status over 33 ± 17 months. In our study cohort (mean LVEF 26 ± 6%, median plasma hs-CRP 3.19 mg/L), plasma hs-CRP levels progressively increased with worsening LV diastolic dysfunction. In particular, plasma hs-CRP levels correlated with mitral E/A wave ratio (Spearman r = 0.25, p = 0.004), mitral deceleration time (r = −0.28, p = 0.002), pulmonary vein systolic wave/diastolic wave ratio (r = −0.32, p <0.001), mitral E wave/color M-mode velocity of propagation ratio (r = 0.28, p = 0.001), and mitral E wave/tissue Doppler septal E′ wave ratio (r = 0.28, p = 0.001). Plasma hs-CRP levels independently predicted adverse clinical events even after adjustment for LVEF and mitral E wave/tissue Doppler septal E′ wave ratio (hazard ratio 2.28, 95% confidence interval 1.18 to 4.39). In conclusion, in patients with chronic systolic HF, expression of circulating CRP was associated with increasing echocardiographic indexes of diastolic dysfunction. High plasma hs-CRP levels portend poor long-term outcomes, particularly in those with severe concomitant systolic and diastolic dysfunctions.
W.H. Wilson Tang, MDa, Kevin Shrestha, ABa, Frederick Van Lente, PhDb, Richard W. Troughton, MBBSc, Maureen G. Martin, RDCSa, Allen G. Borowski, RDCSa, Sue Jasper, RN, BSNa, Allan L. Klein, MDa
W.H. Wilson Tang, MDa, Kevin Shrestha, ABa, Frederick Van Lente, PhDb, Richard W. Troughton, MBBSc, Maureen G. Martin, RDCSa, Allen G. Borowski, RDCSa, Sue Jasper, RN, BSNa, Allan L. Klein, MDa
Tuesday
InfectCheck CRP Barcode-Style Lateral Flow Assay for Semi-Quantitative Detection of C-reactive Protein in Distinguishing between Bacterial and Viral..
In the present study, we describe an InfectCheck barcode-style lateral flow assay for semi-quantitative detection of C-Reactive Protein in distinguishing between bacterial and viral infections. The severity of bacterial infection can be assessed by simply counting the number of red lines developed at the CRP test zone of the test device. If only one visible line appeared at the CRP test zone, it represents a low or mild inflammation with C-Reactive Protein levels < 10 mg/L. Two and three visible lines mean moderate (≥ 10–25 mg/L) and severe (≥ 25–50 mg/L) inflammations respectively while four visible lines stand for a very severe inflammation (≥ 50–100 mg/L). If the visible lines become faint and the intensity of the first line is weaker than that of the control line and may even disappear, this outcome corresponds to the stage of having super severe inflammation (≥ 100 mg/L). A total of 500 patients admitted to hospital through the Accident and Emergency Unit at the Prince of Wales Hospital were examined. The InfectCheck CRP barcode-style rapid test gave a high sensitivity of 88.7% and a high negative predictive value of 93.8%. This result indicates that the rapid test is reliable to exclude non-infected patients. The calculated intra- and inter-assay coefficient of variation for the five C-Reactive Protein concentration ranges was both within 20.0%. It is a one-step whole blood rapid test without any sample pre-treatment and the result is available within 20 min. This user friendly diagnostic tool can allow self-testing by interested individuals without any expensive reading device.
Leung W, Chan CP, Rainer TH, Ip M, Cautherley GW, Renneberg R.
Leung W, Chan CP, Rainer TH, Ip M, Cautherley GW, Renneberg R.
Human C-Reactive Protein Activates Monocyte-Derived Dendritic Cells and Induces Dendritic Cell-Mediated T-Cell Activation
OBJECTIVE: Recent studies proposed a pathogenic role for C-reactive protein (CRP), an independent predictor of cardiovascular disease (CVD), in atherosclerosis. Therefore, we tested whether CRP may modulate dendritic cell (DC) function, because these professional antigen-presenting cells have been implicated in atherogenesis .
METHODS AND RESULTS: Human monocyte-derived immature DCs were cultured with human CRP (0 to 60 microg/mL) for 24 hours. Thereafter, activation markers were measured by flow-cytometry and DCs were cocultured with CFSE-labeled lymphocytes to measure T-cell proliferation and interferon (IFN)-gamma secretion after 8 days. Exposure to 60 microg/mL CRP (n=5) induced an activated cell morphology and significant (CD40 increase MFI 5.23+/-0.28, P<0.01 paired t test; CD80 6.18+/-0.51, P<0.01) to modest (CD83 1.38+/-0.17, P<0.05, CCR7 1.60+/-0.29, P=0.05) upregulation of DC activation markers. The expression of CD86 and HLA-DR was high, but not affected. T-lymphocytes incubated with CRP-pulsed DCs displayed increased IFN-gamma secretion and proliferation (P<0.001). DC activation was concentration-dependent and detected from 2 microg/mL CRP; the maximum effect was equivalent to that seen with 0.1 microg/mL lipopolysaccharide (LPS). Polymyxin B abolished the LPS response, without influencing CRP effects. Finally, immunohistochemistry could demonstrate DC/CRP colocalization in human atherosclerotic lesions .
CONCLUSIONS: These findings suggest that CRP in plaques or found circulating in CVD patients can influence DC function during atherogenesis.
source: Departments of Cardiology, and Pharmacology, University of Antwerp , Wilrijk, Belgium and the Centre for Regenerative Medicine and Cell Therapy, Departments of Cardiology, and Experimental Haematology, University Hospital of Antwerp, Edegem, Belgium
METHODS AND RESULTS: Human monocyte-derived immature DCs were cultured with human CRP (0 to 60 microg/mL) for 24 hours. Thereafter, activation markers were measured by flow-cytometry and DCs were cocultured with CFSE-labeled lymphocytes to measure T-cell proliferation and interferon (IFN)-gamma secretion after 8 days. Exposure to 60 microg/mL CRP (n=5) induced an activated cell morphology and significant (CD40 increase MFI 5.23+/-0.28, P<0.01 paired t test; CD80 6.18+/-0.51, P<0.01) to modest (CD83 1.38+/-0.17, P<0.05, CCR7 1.60+/-0.29, P=0.05) upregulation of DC activation markers. The expression of CD86 and HLA-DR was high, but not affected. T-lymphocytes incubated with CRP-pulsed DCs displayed increased IFN-gamma secretion and proliferation (P<0.001). DC activation was concentration-dependent and detected from 2 microg/mL CRP; the maximum effect was equivalent to that seen with 0.1 microg/mL lipopolysaccharide (LPS). Polymyxin B abolished the LPS response, without influencing CRP effects. Finally, immunohistochemistry could demonstrate DC/CRP colocalization in human atherosclerotic lesions .
CONCLUSIONS: These findings suggest that CRP in plaques or found circulating in CVD patients can influence DC function during atherogenesis.
source: Departments of Cardiology, and Pharmacology, University of Antwerp , Wilrijk, Belgium and the Centre for Regenerative Medicine and Cell Therapy, Departments of Cardiology, and Experimental Haematology, University Hospital of Antwerp, Edegem, Belgium
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