Differences In C-reactive Protein Concentrations Research Articles

Maternal and fetal C-reactive protein genotype and first trimester CRP concentrations in maternal plasma

Maternal plasma CRP concentrations in pregnancy are increased over pre-pregnancy values and high concentrations have been associated with adverse obstetrical outcomes. The objective of this study was to explore the relationship between maternal and fetal variation in C-reactive protein (CRP) genotype and maternal plasma CRP concentrations in the first trimester in low risk patients. DNA was extracted from maternal and cord blood of subjects in a prospective observational cohort. Single-nucleotide polymorphism (SNP) selection was made using a linkage disequilibrium bin approach. CRP concentrations were measured in first trimester maternal plasma using an enzyme-linked immunosorbent assay (ELISA) kit. Kruskal–Wallis rank testing was used to analyze genetic and clinical determinants of CRP concentrations. Genotype results were available in 190 mother–baby pairs. There was no significant difference in CRP concentration among maternal or fetal CRP genotypes. Thus, first trimester concentrations of maternal plasma CRP in low risk subjects do not appear to be significantly associated with CRP genotype. Instead, differences in clinical factors probably have more influence on baseline maternal CRP concentrations.

Ethnic Differences in C-Reactive Protein Concentrations

Limited data exist regarding the ethnic differences in C-reactive protein (CRP) concentrations, an inflammatory marker associated with risk of cardiovascular disease (CVD). We hypothesized that known CVD risk factors, including anthropometric characteristics, would explain much of the observed ethnic variation in CRP. We performed a cross-sectional analysis of 3154 women, without known CVD and not receiving hormone therapy, enrolled in the Study of Women's Health Across the Nation (SWAN), a multiethnic prospective study of pre- and perimenopausal women. The study population was 47.4% white, 27.7% African-American, 8.5% Hispanic, 7.7% Chinese, and 8.6% Japanese; mean age was 46.2 years. African-American women had the highest median CRP concentrations (3.2 mg/L), followed by Hispanic (2.3 mg/L), white (1.5 mg/L), Chinese (0.7 mg/L), and Japanese (0.5 mg/L) women (all pairwise P < 0.001 compared with white women). Body mass index (BMI) markedly attenuated the association between ethnicity and CRP. After adjusting for age, socioeconomic status, BMI, and other risk factors, African-American ethnicity was associated with CRP concentrations >3 mg/L (odds ratio 1.37, 95% CI 1.07-1.75), whereas Chinese and Japanese ethnicities were inversely related (0.58, 0.35-0.95, and 0.43, 0.26-0.72, respectively). Modifiable risk factors, particularly BMI, account for much but not all of the ethnic differences in CRP concentrations. Further study is needed of these ethnic differences and their implications for the use of CRP in CVD risk prediction.

When do social inequalities in C-reactive protein start? A life course perspective from conception to adulthood in the Cardiovascular Risk in Young Finns Study

It is unclear when in the life course do social inequalities in inflammation emerge. We examined whether the association between socioeconomic position (SEP) and C-reactive protein (CRP) is determined at conception, in childhood, adolescence or adulthood in 1484 participants from the population-based Cardiovascular Risk in Young Finns Study. Five variants of the CRP gene were used to investigate whether SEP differences in CRP levels are determined at conception. SEP and serum CRP were assessed in childhood (age 3-9), adolescence (age 12-18) and in adulthood (age 24-39). SEP was measured using parental education and occupational status in childhood and adolescence, and participants' own education and occupational status in adulthood. Participants with CRP > 10 mg/l were excluded. All CRP gene variants were associated with circulating CRP concentrations in childhood, but there were no differences in the distribution of these variants by SEP. No strong evidence was found of associations between parental SEP and CRP. A graded association between higher SEP and lower CRP was observed in adulthood for education (P = 0.0005) but not for occupational status. Trajectories that led to high educational achievement both in the participants and their parents were associated with lower (P <or= 0.047) CRP levels in adulthood. Excluding participants with infectious diseases, pregnant or lactating women and women using oral contraceptives did not change the findings. In this cohort, SEP differences in CRP concentrations seen in adulthood appear not to be determined at conception or evident in childhood or adolescence.

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.

Relationship of IgG and IgM autoantibodies to oxidized low density lipoprotein with coronary artery disease and cardiovascular events

The relationship between autoantibodies to oxidized low density lipoprotein (OxLDL) and coronary artery disease (CAD) remains controversial. IgM and IgG OxLDL autoantibodies to malondialdehyde (MDA)-modified LDL, copper oxidized low density lipoprotein (CuOxLDL), and oxidized cholesterol linoleate (OxCL), as well as apolipoprotein B-100 immune complexes (apoB-ICs), were measured in 504 patients undergoing clinically indicated coronary angiography. Patients were followed for cardiovascular events for a median of 4 years. In univariate analysis, IgM OxLDL autoantibodies and IgM apoB-ICs were inversely associated with the presence of angiographically determined CAD, whereas IgG OxLDL autoantibodies and IgG apoB-ICs were positively associated. In logistic regression analysis, compared with the first quartile, patients in the fourth quartile of IgM OxLDL autoantibodies and apoB-ICs showed a lower probability of angiographically determined CAD (>50% diameter stenosis). Odds ratios and (95% confidence intervals) were as follows: MDA-LDL, 0.51 (0.32-0.82; P = 0.005); CuOxLDL, 0.63 (0.39-1.01; P = 0.05); OxCL, 0.63 (0.39-1.01; P = 0.05); and apoB-IC, 0.55 (0.34-0.88; P = 0.013). These relationships were accentuated in the setting of hypercholesterolemia, with the highest IgM levels showing the lowest risk of CAD for the same level of hypercholesterolemia. Multivariable analysis revealed that neither IgM or IgG OxLDL autoantibodies nor apoB-ICs were independently associated with angiographically determined CAD or cardiovascular events. In conclusion, IgG and IgM OxLDL biomarkers have divergent associations with CAD in univariate analysis but are not independent predictors of CAD or clinical events.

Additive effect of interleukin-6 and C-reactive protein ( CRP) single nucleotide polymorphism on serum CRP concentration and other cardiovascular risk factors

Background Serum C-reactive protein (CRP) levels, closely associated with cardiovascular disease (CVD) risk are influenced by CRP or interleukin-6 ( IL-6) single nucleotide polymorphism (SNPs). However, it is still controversial. Therefore, we investigated the association of IL-6/CRP SNPs and serum CRP levels or other CVD risk factors in healthy adult Korean men. Methods In healthy adult men (age ≥ 20 years, n = 677), we genotyped IL-6−572C > G and CRP SNPs (− 717G > A, 1444C > T, 2147A > G) and measured anthropometric parameters, lipid profile, serum levels of CRP and IL-6 and insulin resistance. Results At IL-6−572C > G ( n = 677), subjects with G/G genotype ( n = 42) showed higher concentrations of CRP ( P = 0.027) and IL-6 ( P = 0.028) as compared with C allele carriers after age-adjustment (C/C: n = 371, C/G: n = 264). Fasting insulin and homeostatis model assessment insulin resistance (HOMA-IR) were also higher in G/G genotype. However, there were no significant differences in other metabolic biomarkers. Among 677 study subjects, 676 were genotyped at CRP−717G > A (G/G: n = 513, G/A: n = 150, A/A: n = 13), 672 at CRP+1444C > T (C/C: n = 580, C/T: n = 85, T/T: n = 7), and 668 at CRP+2147A > G (A/A: n = 273, A/G: n = 296, G/G: n = 99). There were no significant differences in CRP concentrations and other markers related to CVD risk according to each CRP SNP genotype. However, we could find the additive gene–gene interaction between IL-6−572C > G and CRP SNPs on CRP concentration; subjects with the ‘G/G’ at IL-6−572 showed the highest CRP levels when they have variant allele at CRP SNPs after adjusted for age, body mass index, cigarette smoking and alcohol drinking (− 717G > A: F = 7.806, P = 0.005; CRP + 1444C > T: F = 8.398, P = 0.004; and CRP + 2147A > G: F = 7.564, P = 0.006, respectively) Particularly, G allele carriers at CRP+2147A > G in subjects with IL-6−572G/G showed highest HOMA-IR ( F = 9.092, P = 0.003). Conclusion The present data showed that serum CRP levels and other CVD risk factors appeared more influenced by IL-6−572C > G rather than CRP SNPs (− 717G > A, 1444C > T, and 2147A > G), however CRP levels and insulin resistance may be additively affected by IL-6−572 and CRP SNP, particularly when subjects with G/G genotype at IL-6−572 have allele variant at CRP SNPs.

Insight into the nature of the CRP–coronary event association using Mendelian randomization

It is unclear wheather the association between C-reactive protein (CRP) and incident coronary events is free from bias and confounding. Individuals homozygous for a +1444C>T polymorphism in the CRP gene have higher circulating concentrations of CRP. Since the distribution of this polymorphism occurs at random during gamete formation, its association with coronary events should not be biased or confounded. We calculated the weighted mean difference in CRP between individuals with variants of the +1444C>T polymorphism in the CRP gene among 4,659 European men from six studies (genotype-intermediate phenotype studies). We used this difference together with data from previous observational studies to compute an expected odds ratio (OR) for non-fatal myocardial infarction (MI) among individuals homozygous for the T allele. We then performed four new genetic association studies (6,201 European men) to obtain a summary OR for the association between the +1444C>T polymorphism and non-fatal MI (genotype-disease studies). CRP was 0.68 mg/l [95% confidence interval (95% CI) 0.31-1.10; P = 0.0001] higher among subjects homozygous for the +1444-T allele, with no confounding by a range of covariates. The expected ORs among TT subjects for non-fatal MI corresponding to this difference in CRP was 1.20 (95% CI 1.07-1.38) using the Reykjavik Heart study data and 1.25 (1.09-1.43) for all observational studies to 2004. The estimate for the observed adjusted-OR for non-fatal MI among TT subjects was 1.01 (95% CI 0.74-1.38), lower than both expected ORs. A common CRP gene polymorphism is associated with important differences in CRP concentrations, free from confounding. The null association of this variant with coronary events suggests possible residual confounding (or reverse causation) in the CRP-coronary event association in observational studies, though the confidence limits are still compatible with a modest causal effect. Additional studies of genotype (or haplotype) and coronary events would help clarify whether or not the link between CRP and coronary events in observational studies is causal.

C-Reactive Protein Concentration is More Strongly Related to Metabolic Syndrome in Women Than in Men-The Minoh Study-

The gender differences in the association between C-reactive protein (CRP) and features of the metabolic syndrome (MS) need to be elucidated among Japanese. The study population included 715 men and 988 women aged 40-69 years who were not taking anti-hypertensive, lipid-lowering, hypoglycemic, anti-thrombotic, or non-steroidal anti-inflammation medications, and did not have a past history of cardiovascular disease or CRP concentration >10 mg/L. Except for high-density lipoprotein cholesterol, the unadjusted correlation between CRP and each MS component, including body mass index (BMI), systolic and diastolic blood pressures, triglycerides, fasting glucose, fasting insulin, and uric acid, was greater in women than in men. With adjustment for age, smoking status, and drinking status, the differences in CRP concentrations between those with the MS components of BMI, triglycerides, and uric acid and those without were greater in women than in men. Results of stratified analyses by the number of components of the MS of 0, 1, 2, 3, and > or = 4 revealed that an increase in CRP concentrations was greater in women than men with an increased number of components of the MS (gender interaction, p = 0.005). This tendency was observed in non-smokers, but not in current smokers (gender interaction, p = 0.013 and = 0.513, respectively). CRP concentrations are closely related to the MS-like state in both sexes, but an increase in CRP concentration associated with risk factor-clustering is more pronounced in women, particularly non-smokers.

C-reactive protein (+1444C > T) polymorphism influences CRP response following a moderate inflammatory stimulus

Elevations in C-reactive protein (CRP) concentration are associated with an increased risk of future coronary events in prospective studies and it has been suggested that CRP could be used to aid risk prediction. A +1444C > T polymorphism in the CRP gene has been associated with differences in CRP concentration. We investigated the effect of this polymorphism on the CRP response to periodontal therapy, an intermediate inflammatory stimulus. Clinical parameters, CRP, and interleukin-6 (IL-6) concentrations were evaluated in 55 consecutive patients suffering from periodontitis at baseline, 1, 7 and 30 days after an intensive course of periodontal treatment. In a multivariate analysis individuals homozygous for the +1444T allele showed higher CRP concentrations (day 1, 21.10 ± 4.81 mg/L and day 7, 4.89 ± 0.74 mg/L) compared with C-allele carriers (day 1, 12.37 ± 1.61 mg/L and day 7, 3.08 ± 2.00 mg/L). This effect was independent of conventional cardiovascular risk factors and inflammatory factors known to affect CRP concentrations. CRP genotype may need to be considered when CRP values are used in coronary risk prediction.

Gender difference in C-reactive protein concentrations in individuals with atherothrombotic risk factors and apparently healthy ones

Recent studies have shown that C-reactive proteins have a pathogenetic role in atherothrombosis and concentrations of these substances could be used as a marker for future vascular events. The objective of this study was to determine gender differences in highly sensitive C-reactive protein (hs-CRP) in individuals with atherothrombotic risk factors and apparently healthy ones. We have presently matched 469 females and 469 males having the same age and body mass index (BMI). Of these, 210 men and 210 women had no atherothrombotic risk factors. In this group the hs-CRP concentrations were 1.6±3.4 mg l−1 in women and 1.0±2.7 mg l−1 in men (p<0.0005). These values were 2.1±3.4 mg l−1 and 1.5±2.8 mg l−1, respectively, in the entire cohort (p<0.0005), which included also individuals with atherothrombotic risk factors. We conclude that significant gender differences exist in hs-CRP concentrations despite perfect matching for age and BMI. These differences should be reflected in guidelines that suggest hs-CRP cut-off points for the stratification of vascular risk.

C-Reactive Protein, Insulin Resistance, Central Obesity, and Coronary Heart Disease Risk in Indian Asians From the United Kingdom Compared With European Whites

Indian Asians in the United Kingdom have increased coronary heart disease (CHD) mortality compared with European whites, but the causes are not well understood. Increased circulating concentrations of C-reactive protein (CRP) are an independent risk factor for CHD. Therefore, we investigated this marker of inflammation in healthy UK Indian Asian and European white men. Methods and Results-- We measured serum CRP concentrations and conventional CHD risk factors in 1025 healthy male subjects (518 Indian Asians and 507 European whites) aged 35 to 60 years who were recruited at random from general practitioner lists. The geometric mean CRP concentration was 17% higher (95% confidence interval, 3% to 33%) in Indian Asians compared with European whites. CRP values were strongly associated with conventional CHD risk factors, measures of obesity, and metabolic disturbances associated with insulin resistance in both racial groups. The difference in CRP concentrations between Indian Asians and European whites remained after adjustment for conventional CHD risk factors but was eliminated by an adjustment for central obesity and insulin resistance score in Asians. On the basis of these results, we estimate that the processes underlying elevated CRP and/or increased CRP production itself are associated with an approximately 14% increase in population CHD risk among Indian Asians compared with European whites. CRP concentrations are higher in healthy Indian Asians than in European whites and are accounted for by greater central obesity and insulin resistance in Indian Asians. Our results suggest that inflammation or other mechanisms underlying elevated CRP values may contribute to the increased CHD risk among Indian Asians.

C-reactive protein measured in dried blood spots from patients with cystic fibrosis

There was no significant difference in C-reactive protein concentration determined in paired serum and eluates from dried spots blood spolleted on Guthrie cards; mean difference 0.6 μg/ml (95% CI −3.3−2.2 μg/ml; n=101). Dried blood spot samples were stable for up to 21 days and were unaffected by posting to the laboratory. In eight patients with cystic fibrosis undergoing specific antibiotic treatment for Pseudomonas aeruginosa pulmonary infection the fall in C-reactive protein concentration was not significantly different between serum and dried whole blood spot specimens. This method could be used to monitor infection and the response to antibiotic treatment.

Value of C-reactive protein in reflecting the magnitude of complement activation in children undergoing open heart surgery

The kinetics of C-reactive protein (CRP) were studied prospectively in 30 children (aged 21 days - 16 years) undergoing open heart surgery. CRP was related to the kinetics of total haemolytic complement, complement C3a and postoperative complications. Two (7%) patients died and ten (33%) had postoperative complications. The patients with complications were younger (p less than 0.035), underwent longer perfusions (p less than 0.001) and had longer aortic cross-clamping times (p less than 0.003). The mean peak CRP level after surgery (108 mg/l) was reached, on the average, in 43 h. No statistical difference in CRP concentrations was found between the complication and non-complication groups. Extensive complement activation was seen in every patient. CRP did not reflect the magnitude of complement activation induced by cardiopulmonary bypass. The patient sample was too small to draw reliable conclusions about the value of CRP in detecting postoperative complications after open heart surgery in children.

The Concentration of C-Reactive Protein in Sera from Healthy Individuals

C-reactive protein (CRP) in a concentration of 0.02-13.5 mg/l was regularly demonstrated in sera obtained from apparently healthy children and adults of both sexes. CRP must therefore be considered a normal constituent of serum. A weak positive correlation was found between CRP concentration and age. No significant difference in CRP concentration was demonstrable between men and non-pregnant women. Neither was any such difference found between females using oral contraceptives and controls.