OBJECTIVE: To test whether depressive symptoms are related to subsequent C-reactive protein (CRP) levels and/or whether CRP levels are related to subsequent depressive symptoms in mid-life women. METHODS: Women enrolled in the Study of Women's Health Across the Nation (SWAN) were followed for seven years and had measures of CES-Depression scores and CRP seven times during the follow-up period. Women were pre- or early peri-menopausal at study entry and were of Caucasian, African American, Hispanic, Japanese, or Chinese race/ethnicity. Analyses were restricted to initially healthy women.
RESULTS: Longitudinal mixed linear regression models adjusting for age, race, site, time between exams, and outcome variable at year X showed that higher CES-D scores predicted higher subsequent CRP levels and vice versa over a 7-year period. Full multivariate models adjusting for body mass index, physical activity, medications, health conditions, and other covariates showed that higher CRP levels at year X predicted higher CES-D scores at year X+1, p = 0.03. Higher depressive symptoms predicted higher subsequent CRP levels at marginally significant levels, p=0.10.
CONCLUSIONS: Higher CRP levels led to higher subsequent depressive symptoms, albeit the effect was small. The study demonstrates the importance of considering bi-directional relationships for depression and other psychosocial factors and risk for heart disease.
Matthews KA, Schott LL, Bromberger JT, Cyranowski JM, Everson-Rose SA, Sowers M.
University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213
Thursday
Wednesday
C-Reactive Protein: Fitness level and body composition are associated with inflammation in non-obese children
Childhood obesity and poor fitness are associated with insulin resistance (IR), risk for coronary heart disease (CHD), and type 2 diabetes mellitus. Elevated markers of inflammation (e.g., C-reactive protein [CRP]) are independent predictors of CHD. Whether higher percent body fat and poor fitness in non-obese children are associated with evidence of inflammation and IR is unclear.
We evaluated 75 children with non-obese body mass index (BMI) for age (<95th percentile), ages 11-14 years for fasting insulin, glucose, adiponectin, CRP, body composition, and maximum oxygen-consumption (VO2max). CRP correlated positively with body composition (BMI z-score, p = 0.00062; percent body fat, p = 0.00007; and total body fat in grams, p = 0.00006) and negatively with VO2max, p = 0.036. Using multivariate analysis, VO2max and percent body fat were both independent predictors of CRP. Fasting insulin and insulin resistance as assessed by QUICKI did not correlate with CRP, fitness, or fatness in these non-obese children.
Adiponectin showed no significant correlations, and gender did not influence correlation analyses. We conclude that in non-obese children, low fitness and higher body fat are both associated with inflammation (i.e., higher levels of CRP). This observation strengthens the importance of promoting both fitness and healthy body composition in all children.
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 54650, USA.
We evaluated 75 children with non-obese body mass index (BMI) for age (<95th percentile), ages 11-14 years for fasting insulin, glucose, adiponectin, CRP, body composition, and maximum oxygen-consumption (VO2max). CRP correlated positively with body composition (BMI z-score, p = 0.00062; percent body fat, p = 0.00007; and total body fat in grams, p = 0.00006) and negatively with VO2max, p = 0.036. Using multivariate analysis, VO2max and percent body fat were both independent predictors of CRP. Fasting insulin and insulin resistance as assessed by QUICKI did not correlate with CRP, fitness, or fatness in these non-obese children.
Adiponectin showed no significant correlations, and gender did not influence correlation analyses. We conclude that in non-obese children, low fitness and higher body fat are both associated with inflammation (i.e., higher levels of CRP). This observation strengthens the importance of promoting both fitness and healthy body composition in all children.
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI 54650, USA.
Tuesday
C-Reactive Protein Is a Determinant of First-Ever Stroke: Prospective Nested Case-Referent Study
Background and Purpose: C-reactive protein ,(CRP) is a determinant of stroke, but there are no prospective studies on CRP and first ischemic stroke divided into etiologic subtypes. Our primary aim was to study C-reactive protein as a determinant of ischemic stroke, classified according to Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, and intracerebral hemorrhage (ICH) in a prospective study. A secondary aim was to study the relationship between the 1444C>T polymorphism, plasma levels of C-reactive protein and stroke. Methods: The study was a prospective population-based case-referent study nested within the Northern Sweden Cohorts. We defined 308 cases of ischemic stroke and 61 ICH. Two controls for each case were defined from the same cohort. Results: The OR for the highest (>3 mg/l) versus lowest group (<1 mg/l) of CRP was 2.58 (95% CI 1.74-3.84) for ischemic stroke and 1.63 (95% CI 0.67-3.93) for ICH. In a multivariate model including traditional risk factors, CRP remained associated with ischemic stroke (OR 2.06; 95% CI 1.29-3.29). Small-vessel disease was associated with C-reactive protein CRP in the multivariate model (OR 3.88; 95% CI 1.10-13.7). The C-reactive protein 1444 (CC/CT vs. TT) polymorphism was associated with plasma levels of C-reactive protein but neither with ischemic stroke nor with ICH. Conclusions: This prospective population-based study shows that CRP is significantly associated with the risk of having a first ischemic stroke, especially for small-vessel disease. No significant associations were found between the CRP 1444C>T polymorphism and any stroke subtype.
Jonas Sven Olof Andersson
Department of Medicine and Geriatrics
Skellefteå County Hospital
SE-931 86 Skellefteå (Sweden
Jonas Sven Olof Andersson
Department of Medicine and Geriatrics
Skellefteå County Hospital
SE-931 86 Skellefteå (Sweden
Friday
Evaluation Of C-Reactive Protein
An evaluation of the association between C-reactive protein , the change in C-reactive protein over one year, and all-cause mortality in chronic immune-mediated inflammatory disease managed in UK general practice.
Objectives. To evaluate the association between systemic inflammation , as measured by (CRP), , and all-cause mortality. To also evaluate the association between change in CRP status (sub-acute, 10 mg/l and acute >10 mg/l) and all-cause mortality.
Methods. A cohort of patients was selected from The Health Improvement Network (THIN) data set of anonymized patient-level data from UK general practice. Patients were selected if they had a diagnosis of RA, psoriasis, AS or PsA. Survival was evaluated using " Cox proportional hazards regression models (CPHMs).
Results. A total of 11 362 cases had at least one CRP measurement. Analysis grouped by each additional unit increase in log-CRP (range 1–6) across the observed range was associated with a 21% increase in the hazard ratio (HR) of death, after controlling for cardiovascular risk factors (P < 0.001). This observation was consistent in separate analysis of cases with either RA or psoriasis. Repeated CRP observations around 1 yr apart were recorded in 2802 subjects. After controlling for confounding factors, in cases whose CRP changed from sub-acute (10 mg/l) to acute (>10 mg/l), the HR for death increased 2-fold (P < 0.001) relative to cases whose CRP remained sub-acute. In comparison, among those subjects whose CRP was reduced from acute to sub-acute, the HR was virtually identical to those who stayed sub-acute (P = 0.571).
Conclusions. C-reactive protein ( level predicted all-cause mortality after standardization for traditional risk factors, as did change in CRP status from sub-acute to acute observed over 1 yr.
KEY WORDS: C-reactive protein, Systemic inflammation, Survival, Rheumatoid arthritis, Psoriasis, Ankylosing spondylitis, Psoriatic arthritis
Rheumatology 2009 48(1):78-82; doi:10.1093/rheumatology/ken415
Objectives. To evaluate the association between systemic inflammation , as measured by (CRP), , and all-cause mortality. To also evaluate the association between change in CRP status (sub-acute, 10 mg/l and acute >10 mg/l) and all-cause mortality.
Methods. A cohort of patients was selected from The Health Improvement Network (THIN) data set of anonymized patient-level data from UK general practice. Patients were selected if they had a diagnosis of RA, psoriasis, AS or PsA. Survival was evaluated using " Cox proportional hazards regression models (CPHMs).
Results. A total of 11 362 cases had at least one CRP measurement. Analysis grouped by each additional unit increase in log-CRP (range 1–6) across the observed range was associated with a 21% increase in the hazard ratio (HR) of death, after controlling for cardiovascular risk factors (P < 0.001). This observation was consistent in separate analysis of cases with either RA or psoriasis. Repeated CRP observations around 1 yr apart were recorded in 2802 subjects. After controlling for confounding factors, in cases whose CRP changed from sub-acute (10 mg/l) to acute (>10 mg/l), the HR for death increased 2-fold (P < 0.001) relative to cases whose CRP remained sub-acute. In comparison, among those subjects whose CRP was reduced from acute to sub-acute, the HR was virtually identical to those who stayed sub-acute (P = 0.571).
Conclusions. C-reactive protein ( level predicted all-cause mortality after standardization for traditional risk factors, as did change in CRP status from sub-acute to acute observed over 1 yr.
KEY WORDS: C-reactive protein, Systemic inflammation, Survival, Rheumatoid arthritis, Psoriasis, Ankylosing spondylitis, Psoriatic arthritis
Rheumatology 2009 48(1):78-82; doi:10.1093/rheumatology/ken415
Wednesday
LPS-induced MCP-1 and IL-6 production is not reversed by oestrogen in human periodontal ligament cells
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
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
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.
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