Variability Of C-reactive Protein Levels Research Articles

The erratic C-reactive protein: a novel outcome measure for longitudinal disease activity in rheumatoid arthritis.

There is a relationship between both the magnitude and variability of C-reactive protein (CRP) levels and disease activity level in rheumatoid arthritis (RA). It seems that CRP levels remain low and stable in clinical remission then increase and become erratic in active disease. The purpose of this research was to determine if there is a difference in the variability of CRP levels over time in patients in clinical remission versus those with active disease. Patients with a diagnosis of RA with a minimum of 3 CRP readings in the previous 12-month period were included at a single site. At each visit the patient was evaluated by an experienced rheumatologist to determine current disease activity - remission versus active disease. The primary outcome measure was the difference between the coefficient of variation of the CRP (CRP-COV) in patients in remission versus those with active disease. 272 patients were enrolled into the study. The mean CRP and CRP-COV was significantly smaller for patients in clinical remission versus active disease, for patients in CDAI remission (<2.6), and for those who did not require a change in treatment. Smokers, on average, had higher mean CRP readings regardless of clinical status. We have identified a new clinical outcome measure of disease activity in RA that captures longitudinal variability in disease activity and identifies those patients with clinically active disease despite a "normal" CRP level due to the higher variability of CRP if not in remission.

Variability of C-reactive protein in first-generation Ecuadorian immigrants living in the United States.

Establish the variability of C-reactive protein (CRP) within a population of first-generation immigrants living in the United States. Prior work has theorized that individuals with high levels of childhood pathogen exposure may have lower CRP levels in adulthood, and therefore that for these individuals, CRP may not be as accurate an index of chronic disease risk related to low-level inflammation as is presumed based on data from wealthy populations. This potentially has major implications for the interpretation of CRP as a biomarker of chronic inflammation. This longitudinal study collected a total of 125 dried blood spot (DBS) samples from 31 participants (median 4 samples each) and CRP levels in these DBS were assayed by enzyme-linked immunosorbant assay. Surveys were administered to characterize childhood pathogen exposure, and current illness. Variance was estimated using mixed effects regression models. On average, participants were adults (mean = 41.9 years old) who had immigrated to the United States nearly 20 years prior to the study and had nearly universally experienced childhood helminth infection and other major pathogen exposures. Median serum-equivalent CRP was 0.77 mg/L. Individuals reliably differed in subacute CRP levels, and, depending on whether untransformed or log-transformed CRP was the outcome variable, 45% or 62% of variance in CRP was attributable to between-individual differences. The variability of CRP levels in individuals with relatively high childhood pathogen exposure is comparable to previously reported studies in North America and Europe. However, CRP values are relatively low. CRP is an appropriate measure of subacute inflammation in this sample.

Variability in C-reactive protein is associated with cognitive impairment in women living with and without HIV: a longitudinal study.

Despite the availability of effective antiretroviral therapies, cognitive impairment (CI) remains prevalent in HIV-infected (HIV+) individuals. Evidence from primarily cross-sectional studies, in predominantly male samples, implicates monocyte- and macrophage-driven inflammatory processes linked to HIV-associated CI. Thus, peripheral systemic inflammatory markers may be clinically useful biomarkers in tracking HIV-associated CI. Given sex differences in immune function, we focused here on whether mean and intra-individual variability in inflammatory marker-predicted CI in HIV+ and HIV- women. Seventy-two HIV+ (36 with CI) and 58 HIV- (29 with CI) propensity-matched women participating in the Women's Interagency HIV Study completed a neuropsychological battery once between 2009 and 2011, and performance was used to determine CI status. Analysis of 13 peripheral immune markers was conducted on stored biospecimens at three time points (7 and 3.5years before neuropsychological data collection and concurrent with data collection). HIV+ women showed alterations in 8 immune markers compared to HIV- women. The strongest predictors of CI across HIV+ and HIV- women were lower mean soluble tumor necrosis factor receptor I (sTNFRI) levels, higher mean interleukin (IL)-6 levels, and greater variability in C-reactive protein (CRP) and matrix metalloproteinase (MMP)-9 (p values <0.05). Stratified by HIV, the only significant predictor of CI was greater variability in CRP for both HIV+ and HIV- women (p values <0.05). This variability predicted lower executive function, attention/working memory, and psychomotor speed in HIV+ but only learning in HIV- women (p values <0.05). Intra-individual variability in CRP levels over time may be a good predictor of CI in predominately minority low-socioeconomic status midlife women.

Serum C-reactive protein increases the risk of venous thromboembolism: a prospective study and meta-analysis of published prospective evidence

Evolving debate suggests that C-reactive protein (CRP) might be associated with the development of venous thromboembolism (VTE); however, the evidence is conflicting. We aimed to assess the prospective association of CRP with VTE risk. C-reactive protein was measured in serum samples at baseline from 2420 men aged 42–61 years, from the Kuopio Ischemic Heart Disease study. Within-person variability in CRP levels was corrected for using repeat measurements of CRP taken 11 years after baseline. Incident VTE events (n = 119) were recorded during a median follow-up of 24.7 years. The age-adjusted regression dilution ratio for loge CRP was 0.57 [95% confidence interval (CIs): 0.51–0.64]. In age-adjusted Cox regression analysis, the hazard ratio (95% CIs) for VTE per 1 standard deviation (SD) increase in loge baseline CRP was 1.17 (0.98–1.40). Further adjustment for several established and emerging risk factors did not alter the association. In a meta-analysis of nine population-based studies (including the current study) comprising 81,625 participants and 2225 VTE cases, the fully-adjusted risk estimate for VTE was 1.14 (1.08–1.19) per SD increase in loge baseline CRP. In a pooled dose–response analysis, a linear association between CRP and VTE risk was suggested (P for nonlinearity = 0.272). The pooled risk estimate for VTE per 5 mg/l increment in CRP levels was 1.23 (1.09–1.38). C-reactive protein was only modestly associated with VTE risk in the primary analysis. Pooled evidence, however, suggests that elevated CRP is associated with greater VTE risk, consistent with a linear dose–response relationship.

DNA variants, plasma levels and variability of C-reactive protein in myocardial infarction survivors: results from the AIRGENE study

C-reactive protein represents the classical acute-phase protein produced in the liver in response to inflammatory stimuli. This study evaluated the association of gene polymorphisms with differences in C-reactive protein concentrations and assessed its intra-individual variability as a marker of individual response. One thousand and three myocardial infarction (MI) survivors were recruited in six European cities, and C-reactive protein concentrations were measured repeatedly during a 6-month period. We investigated 114 polymorphisms in 13 genes, all involved in the innate inflammatory pathway. We found two polymorphisms within the C-reactive protein (CRP) gene rs1800947 and rs1205, of which the minor alleles were strongly associated with lower levels of C-reactive protein (P < 10(-6)). A haplotype, identified by those two polymorphisms, was associated with the lowest C-reactive protein concentrations (P < 10(-6)). Additionally, the minor alleles of several variants were significantly associated with greater individual variability of C-reactive protein concentrations (P < 10(-3)). The present study investigated the association of polymorphisms with inter- and intra-individual variability of C-reactive protein levels. Two minor alleles of C-reactive protein variants were associated with lower C-reactive protein concentrations. Regarding intra-individual variability, we observed associations with the minor alleles of several variants in selected candidate genes, including the CRP gene itself.

Obesity is the major determinant of elevated C-reactive protein in subjects with the metabolic syndrome.

To investigate the relationship between C-reactive protein (CRP) and various characteristics of the metabolic syndrome. Population-based cross-sectional study. A total of 1929 subjects undergoing a medical examination in a preventive medicine clinic (age, 50+/-10 y; 63% males). The proportion of subjects with CRP levels above the cut point generally used to indicate an obvious source of infection or inflammation (>10 mg/l) was 3, 7, and 15% in subjects who were normal weight, overweight, and obese, respectively. Subjects with obesity had markedly higher CRP level compared to patients without obesity regardless of whether they had the metabolic syndrome. However, there was no significant difference in CRP levels between nonobese subjects without the metabolic syndrome and subjects in whom the diagnosis of the metabolic syndrome was based on criteria other than obesity (adjusted geometric mean CRP 1.75 vs 2.08 mg/l, P=0.79). Similarly, CRP levels did not differ among obese subjects with and without the metabolic syndrome (adjusted geometric mean CRP 3.22 vs 3.49 mg/l, P=0.99). There was a linear increase in CRP levels with an increase in the number of metabolic disorders (P(trend) <0.0001), which was substantially diminished after controlling for body mass index (BMI) (P(trend)=0.1). Stepwise multivariate linear regression analysis identified BMI, triglyceride levels, HDL cholesterol levels (inversely), and fasting glucose as independently related to CRP levels. However, BMI accounted for 15% of the variability in CRP levels, whereas triglycerides, HDL cholesterol and fasting glucose levels accounted for only approximately 1% of the variability in CRP levels. Obesity is the major factor associated with elevated CRP in individuals with the metabolic syndrome. CRP levels in the range suggesting a source of infection or inflammation (>10 mg/l) are more common among obese subjects than in nonobese subjects.

Markers of the acute phase response in cardiovascular disease: an update.

There is now widespread agreement that inflammation is a key component in the progression of atheromatous lesions. Inflammatory cells are present at all stages in the development of the atheromatous plaque, and gene knockout experiments in mice show that atheroma is largely prevented in the absence of the normal inflammatory mediators. In humans reduction of inflammation accompanies successful treatment strategies for atheroma. An increasing number of studies suggest that the acute phase protein, C-reactive protein, provides increased prognostic information over and above existing markers of atheroma severity or progression in healthy individuals and in the acute coronary syndromes. Recent advances in our knowledge of the normal variability of C-reactive protein levels and in precise and sensitive measurements strengthen the arguments for adding this marker to the repertoire of the routine laboratory assessment of cardiovascular disease.

Five-year intra-individual variability in C-reactive protein levels in a Japanese population-based study: the Jichi Medical School Cohort Study at Yamato, 1993-1998.

C-reactive protein (CRP) is an acute-phase reactant that is related to future cardiovascular events. However, little is known about the long-term intra-individual stability of CRP in community residents. The 5-year intra-individual correlation of CRP levels was examined in the Jichi Medical School Cohort Study in Japan. CRP measurements were obtained in 1993 and in 1998 from 388 presumptively healthy individuals aged 30-69 years at baseline. The Pearson's correlation coefficient of CRP between baseline and follow-up measurements was 0.43 (95% confidence interval (CI): 0.34-0.51). Additional analyses by sex and smoking status at baseline revealed similar coefficients. The correlation coefficient of CRP was lower than that of other classical risk factors, such as body-mass index (BMI), blood pressure, and total and high-density lipoprotein (HDL) cholesterol. A subgroup of individuals with higher levels of CRP at both baseline and follow-up measurements had higher BMI, hemoglobin Alc, and plasma fibrinogen, and lower levels of HDL-cholesterol than others, even after adjusting for age, sex, and smoking status in a multiple logistic model. In conclusion, the stability of CRP levels was statistically significant in a long-term population-based study. A subgroup with higher levels of CRP who had an aggregation of cardiovascular risk factors was identified by the 2 measurements.