Plasma C-reactive Protein Concentrations Research Articles

The value of sepsis biomarkers and their kinetics in the prognosis of septic shock due to bacterial infections.

In this study, we aim to explore the value of procalcitonin (PCT), C-reactive protein (CRP), and serum cholinesterase (SChE) activity kinetics as useful predictors of mortality in patients with septic shock admitted to the intensive care unit (ICU). We conducted aprospective single-blinded study in the ICU of auniversity hospital during aperiod of 1 year. Were included all patients 18 years of age or older, with confirmed septic shock. For all included patients, blood samples of septic biomarkers (PCT, SChE activity, and CRP) were obtained. Serum was collected at the day of ICU admission (day 0), the day of septic shock (day 1), then 3 and 5 days after the septic shock development. During the study period, 60 patients were included. The mean age (± SD) was 47.7 ± 19 years. There were 46 male (74%) and 14 female (26%) patients. Mean SAPSII on ICU admission was 40.7 ± 16 (median: 37), and mean SOFA score on ICU admission was 16 ± 4 (median: 7). During their ICU stay, out of the 60 included patients, 37 patients died (61%). The comparison between the 2 groups (deaths and survivors) showed that the factors associated with poor outcome were age, SOFA score on ICU admission, and the need for invasive mechanical ventilation. The day of septic shock, there was no difference in the mean concentrations in those of plasma SChE activity or in the PCT and CRP plasma between survivors and non-survivors. However, the comparison of mean plasma SChE activity, and PCT and CRP plasma concentrations (on day 3 and day 5) between survivors and non-survivors, showed asignificant difference between the 2 groups. Our study suggests that, in agroup of critically ill patients with severe septic shock, arise or no change in procalcitonin and/or CRP level, and/or adecrease or no change in SChE activity should warn the clinician about the insufficiency and/or inadequacy of the therapy. However, afall in procalcitonin and/or CRP levels, and/or arise in SChE activity were associated with afavourable prognosis. Based on our study and some other data detailed above, we recommend that an estimation of SChE acti-vity, procalcitonin, and CRP on the day of septic shock, followed by estimation within the next 72-120 h, could help the prognostic assessment of critically ill patients with septic shock. Further studies are needed to define the critical values related to mortality.

Anemia and insomnia: a cross-sectional study and meta-analysis.

BackgroundSeveral recent genome-wide association studies suggested insomnia and anemia may share some common genetic components. We thus examined whether adults with anemia had higher odds of having insomnia relative to those without anemia in a cross-sectional study and a meta-analysis.MethodsIncluded in this cross-sectional study were 12,614 Chinese adults who participated in an ongoing cohort, the Kailuan Study. Anemia was defined as hemoglobin levels below 12.0 g/dL in women and 13.0 g/dL in men. Insomnia was assessed using the Chinese version of the Athens Insomnia Scale (AIS). A total AIS score ≥6 was considered insomnia. The association between anemia and insomnia was assessed using a logistic regression model, adjusting for potential confounders such as age, sex, chronic disease status, and plasma C-reactive protein concentrations. A meta-analysis was conducted using the fixed effects model to pool results from our study and three previously published cross-sectional studies on this topic in adult populations.ResultsIndividuals with anemia had greater odds of having insomnia (adjusted odds ratio [OR]: 1.32; 95% confidence interval [CI]: 1.03–1.70) compared with individuals without anemia. A significant association persisted after we excluded individuals with chronic inflammation, as suggested by C-reactive protein levels >1 mg/L (adjusted OR: 1.68; 95% CI: 1.22–2.32). The meta-analysis results, including 22,134 participants, also identified a positive association between anemia and insomnia (pooled OR: 1.39; 95% CI: 1.22–1.57).ConclusionsThe presence of anemia was significantly associated with a higher likelihood of having insomnia in adults. Due to the nature of the cross-sectional study design, results should be interpreted with caution.

246P Impact of genetically predicted elevated concentrations of C-reactive protein on ovarian cancer risk: A Mendelian randomization study

C-reactive protein (CRP) is the inflammation-responsible protein and a significant rise of the plasma concentration of CRP is pervasive in the progress of ovarian cancer. However, there are few studies that comprehensively evaluate the correlation between CRP concentrations and ovarian cancer and the causal effect remains unknown. With a Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted CRP levels and ovarian cancer risk. Utilizing 32 CRP-related single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association studies, we investigated the correlation between genetically predicted CRP and ovarian cancer risk using summary statistics from the Ovarian Cancer Association Consortium (25,509 cases and 40,941 controls). The Inverse variance weighted (IVW) method was applied to estimate the causality between genetically elevated CRP concentrations and ovarian cancer risk. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different histotypes of ovarian cancer were also conducted. An inverse association was observed between genetically predicted one-unit increase in the log-transformed CRP concentrations and ovarian cancer (OR = 0.93, 95%CI = 0.87-1.00 p = 0.047). When results were examined by histotypes, an inverse association was observed between genetically predicted one-unit increase in the log-transformed CRP concentrations and endometrioid ovarian cancer (OR = 0.80, 95%CI = 0.70-0.91 p = 0.001), low-grade serous ovarian cancer (OR = 0.70, 95%CI = 0.58-0.86 p = 0.001) and serous ovarian cancer (OR = 0.84, 95%CI = 0.74-0.96 p = 0.012). Additionally, the results demonstrated the absence of the horizontal pleiotropy. MR findings provide evidence for a causal relationship between genetically predicted one-unit increase in the log-transformed CRP concentrations and reduced ovarian cancer risk, overall and among specific histotypes. Further studies are warranted to investigate the underlying mechanism.

Microheterogeneity and preanalytical stability of protein biomarkers of inflammation and renal function

Protein biomarker microheterogeneity has attracted increasing attention in epidemiological and clinical research studies. Knowledge concerning the preanalytical stability of proteins is paramount to assess the biological significance of their proteoforms. We investigated the stability of the inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), and calprotectin (S100A8/9), and the renal function marker, cystatin C (CnC). In total 16 proteoforms were quantified by immuno-MALDI-TOF MS in EDTA plasma and serum samples from 15 healthy volunteers. Prior to analysis blood samples were stored at either room temperature from 1 h up to 8 days, or underwent up to 9 consecutive freeze/thaw cycles. Pearson's correlation coefficient and t-test, intra-class correlation coefficient (ICC), and Autoregressive Integrated Moving-Average (ARIMA) models were used to investigate the stability of proteoform concentrations and distributions in blood. Plasma and serum concentrations of CRP and SAA proteoforms were highly stable during room temperature exposure and repeated freeze/thaw cycles, demonstrating excellent reproducibility (ICC > 0.75), no serial dependency in ARIMA models, and stable distribution of proteoforms. Stability analyses for proteoforms of S100A8/9 and CnC identified only minor preanalytical changes in concentrations and distributions, and none of the proteoforms were produced during prolonged exposure to room temperature or repeated freezing/thawing. The four proteins and their proteoforms are stable during sub-optimal sample handling, and represent robust biomarker candidates for future biobank studies aimed at investigating the microheterogeneity of SAA, S100A8/9, and CnC in relation to inflammation, renal dysfunction and various clinical outcomes.

C-reactive protein for prediction of atrial fibrillation recurrence after catheter ablation

BackgroundInflammation plays an important role in the initiation and progression of atrial fibrillation (AF), but data about the relationship between subclinical inflammation and recurrence of AF after catheter ablation remains poorly studied. We aimed to assess whether plasma levels of C-reactive protein (CRP) are associated with long-term AF recurrence following catheter ablation.MethodsPrior to the intervention, plasma CRP concentrations were measured in patients who underwent first catheter ablation for AF. AF recurrence was evaluated after 12 months and defined as any AF episode longer than 30 s recorded on either 12-lead electrocardiogram, 24-h Holter or 7-day Holter monitoring. Multivariable adjusted Cox models were constructed to examine the association of CRP levels and AF recurrence.ResultsOf the 711 patients (mean age: 61 years, 25% women) included in this study, 247 patients (35%) experienced AF recurrence after ablation. Patients who were in the highest CRP quartile had a higher rate of recurrent AF compared to those who were in the lowest quartile (53.4 vs. 33.1% at 1 year of follow-up; P = 0.004). The adjusted hazard ratios (aHR) of recurrent AF across increasing quartiles of CRP were 1.0 (reference), 1.26 (95% confidence interval [CI], 0.86–1.84), 1.15 (95% CI, 0.78–1.70) and 1.60 (95% CI, 1.10–2.34) (P trend = 0.015). A similar effect was observed when CRP was analyzed as continuous variable (aHR per unit increase, 1.21; 95% CI, 1.05–1.39; P = 0.009). When a predefined CRP cut-off of 3 mg/l was applied, patients with CRP levels of 3 mg/l or above had a higher risk of AF recurrence than those with levels below (aHR, 1.44; 95% CI, 1.06–1.95; P = 0.019).ConclusionsIncreasing pre-interventional CRP levels are associated with a higher risk of AF recurrence in patients undergoing catheter ablation for AF.Trail registrationClinicalTrials.gov identifier, NCT03718364.

Skeletal muscle ferritin abundance is tightly related to plasma ferritin concentration in adults with obesity.

What is the central question of this study? Obesity is associated with complex perturbations to iron homeostasis: is plasma ferritin concentration (a biomarker of whole-body iron stores) related to the abundance of ferritin (the key tissue iron storage protein) in skeletal muscle in adults with obesity? What is the main finding and its importance? Plasma ferritin concentration was tightly correlated with the abundance of ferritin in skeletal muscle, and this relationship persisted when accounting for sex, age, body mass index and plasma C-reactive protein concentration. Our findings suggest that skeletal muscle may be an important iron store. Obesity is associated with complex perturbations to whole-body and tissue iron homeostasis. Recent evidence suggests a potentially important influence of iron storage in skeletal muscle on whole-body iron homeostasis, but this association is not clearly resolved. The primary aim of this study was to assess the relationship between whole-body and skeletal muscle iron stores by measuring the abundance of the key iron storage (ferritin) and import (transferrin receptor) proteins in skeletal muscle, as well as markers of whole-body iron homeostasis in men (n=19) and women (n=43) with obesity. Plasma ferritin concentration (a marker of whole-body iron stores) was highly correlated with muscle ferritin abundance (r=0.77, P=2×10-13 ) and negatively associated with muscle transferrin receptor abundance (r=-0.76, P=1×10-12 ). These relationships persisted when accounting for sex, age, BMI and plasma C-reactive protein concentration. In parallel with higher whole-body iron stores in our male versus female participants, men had 2.2-fold higher muscle ferritin abundance (P=1×10-4 ) compared with women. In accordance with lower muscle iron storage, women had 2.7-fold higher transferrin receptor abundance (P=7×10-10 ) compared with men. We conclude that muscle iron storage and import proteins are tightly and independently related to plasma ferritin concentration in adults with obesity, suggesting that skeletal muscle may be an underappreciated iron store.

Vitamin D status is associated with hepcidin and hemoglobin concentrations in patients with severe traumatic injury.

Severe traumatic injury leads to persistent injury-associated anemia that is associated with hypercatecholaminemia, systemic inflammation, increased hepcidin, and a functional iron deficiency. Vitamin D has been shown to reduce proinflammatory cytokines and hepcidin concentrations. This study aimed to investigate the association of vitamin D status with inflammation, iron biomarkers, and anemia following blunt trauma. A prospective observational cohort study comparing blunt trauma patients (n = 45) with elective hip replacement patients (n = 22) and healthy controls (n = 8) was performed. Bone marrow ferroportin, transferrin receptor, and erythroferrone expression was measured using quantitative polymerase chain reaction (qPCR). Plasma was assessed for systemic inflammation, erythropoietin (EPO), iron regulation, and vitamin D (25-OH) concentrations using enzyme-linked immunosorbent assay. Hemoglobin was measured on the day of discharge. Compared with hip replacement, trauma patients had higher plasma interleukin-6 (90.1 vs. 3.8 pg/mL), C-reactive protein (6,223 vs. 2,612 ng/mL), and hepcidin (79.3 vs. 21.2 ng/mL) concentrations. Trauma patients had lower vitamin D (25-OH) (12.8 vs. 18.1 ng/mL) and iron (23.5 vs. 59.9 μg/mL) levels compared with hip replacement patients. Despite the higher hepcidin EPO levels, bone marrow erythroferrone expression was increased 69% following trauma. Following elective hip replacement, patients did have anemia and impaired iron homeostasis without a significant change in inflammatory biomarkers, EPO, and vitamin D status. Vitamin D status did correlate with systemic inflammation, iron dysfunction, and persistent injury-associated anemia following severe blunt trauma. Further research is needed to determine whether supplementation with vitamin D in the trauma population could improve the persistent injury-associated anemia. Prospective study, prognostic, level III.

C-reactive Protein and Future Risk of Clinical and Molecular Subtypes of Colorectal Cancer.

Inflammation has been implicated in colorectal cancer etiology, but the relationship between C-reactive protein (CRP) and colorectal cancer risk is unclear. We aimed to investigate the association between prediagnostic plasma CRP concentrations and the risk of clinical and molecular colorectal cancer subtypes. We used prospectively collected samples from 1,010 matched colorectal cancer case-control pairs from two population-based cohorts in Northern Sweden, including 259 with repeated samples. Conditional logistic regression and linear mixed models were used to estimate relative risks of colorectal cancer, including subtypes based on BRAF and KRAS mutations, microsatellite instability status, tumor location, stage, lag time, and (using unconditional logistic regression) body mass index. CRP was not associated with colorectal cancer risk, regardless of clinical or molecular colorectal cancer subtype. For participants with advanced tumors and blood samples <5 years before diagnosis, CRP was associated with higher risk [OR per 1 unit increase in natural logarithm (ln) transformed CRP, 1.32; 95% confidence interval (CI), 1.01-1.73]. CRP levels increased over time, but average time trajectories were similar for cases and controls (P interaction = 0.19). Our results do not support intertumoral heterogeneity as an explanation for previous inconsistent findings regarding the role of CRP in colorectal cancer etiology. The possible association in the subgroup with advanced tumors and shorter follow-up likely reflects undiagnosed cancer at baseline. Future efforts to establish the putative role of chronic, low-grade inflammation in colorectal cancer development will need to address the complex relationship between systemic inflammatory factors and tumor microenvironment, and might consider larger biomarker panels than CRP alone.

Habitually skipping breakfast is associated with chronic inflammation: a cross-sectional study.

We examined whether breakfast frequency was associated with chronic inflammatory, as assessed by high-sensitivity C-reactive protein (CRP) concentration. Cross-sectional study. Kailuan community, China. Included were 70 092 Chinese adults without CVD and cancer in 2014 with CRP concentrations <10 mg/l, when breakfast frequency was assessed via a questionnaire, and plasma CRP concentration was measured. Breakfast frequency was associated with CRP concentration (P-trend < 0·001). The adjusted mean CRP was 1·33 mg/l (95 % CI 1·23, 1·44) for the 'no breakfast' group and 1·07 mg/l (95 % CI 1·0, 1·14) for the 'breakfast everyday' group (P-difference < 0·001), adjusting for age, sex, diet quality, total energy, obesity, education, occupation, marital status, smoking, alcohol consumption, blood pressure, sleep parameters, fasting blood glucose and lipid profiles. Consistently, the adjusted OR for CRP ≥ 1·0 mg/l and CRP ≥ 3·0 mg/l were 1·86 (95 % CI 1·73, 2·00) and 1·27 (95 % CI 1·15, 1·40), respectively, when comparing these two breakfast consumption groups (P-trend < 0·001 for both). The associations were more pronounced among older adults, relative to those who were younger (P-interaction < 0·001). Significant association between breakfast skipping and elevated CRP concentration was observed in those with poor diet quality, but not those with good diet quality. Habitually skipping breakfast is associated with elevated concentrations of CRP. Future prospective studies including repeated assessment of inflammatory biomarkers and a collection of detailed information on type and amount of breakfast foods are warranted.

P1279INSULIN RESISTANCE IN HEMODIALYSIS PATIENS

Abstract Background and Aims insulin resistance (IR) is a decrease in the biological response of sensitive tissues to insulin. IR is known as an adverse risk factor in cardiovascular disease, which largely determines the prognosis of patients receiving hemodialysis (HD). But this issue is not well understood. For the screening of IR, special indices have been developed that characterize the sensitivity of tissues to insulin. The aim of the study was to compare the methods of screening for IR in patients receiving HD in relation to the markers of systemic inflammation and atherogenic dyslipidemia (AtD). Method 124 patients receiving HD for 75.4 ± 44.5 months were examined including 66 men and 58 women aged 57.6 ± 13.6 years. For IR screening, the Homeostatic Model Assessment-1 and 2 indices (HOMA-1 and HOMA-2), the Quantitative Insulin Sensitivity Check Index (QUICKI) and triglycerides / glucose (Tri/G) were used. Patients were examined in accordance with the recommendations of KDIGO. Data analysis was carried out using “STATISTICA 10.0”. Results fasting insulin levels were elevated in 19% of patients. But, the calculated indices were consistent with the idea that IR is much more common. So, the IR index in the HOMA -1 model was increased in 47%, in the HOMA -2 model - in 33%, in the QUICKI model - in 36%, the TriH indicator - in 91%. The sensitivity of peripheral tissues in the HOMA-1 and HOMA-2 models was equally reduced by 35-40%. The results of the correlation analysis between indicators of IR and plasma concentration of C-reactive protein and lipid profile are presented in table 1. Informativeness of IR indicators depending on the presence of obesity is presented in table 2 We were also interested in whether insulin resistance affects the development of clinical manifestations of atherosclerosis, cardiac arrhythmias, and heart failure. An analysis of this relationship did not reveal. Only the IR index in the HOMA-1 model with a value of more than 2.7 units was associated with a 4.5-fold increase in the risk of developing clinical manifestations of atherosclerotic lesions (χ2 = 4.582 p = 0.032). Statistically significant it was only in men. Given our data, perhaps IR is one of the reasons for the higher morbidity and mortality of men at HD. Conclusion a comparison of IR models allows us to distinguish HOMA-2 as the most accurate index. The highest correlation with systemic inflammation and AtD was in the HOMA-1 and HOMA-2 indices.

Early Life Exposure to the Great Chinese Famine and Risk of Rheumatoid Arthritis in Adulthood

Abstract Objectives Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune condition. Because the immune system develops early in life, it is possible that exposure to adversity like famine in utero or during early childhood may have lifelong impacts on risk of autoimmune disease. We thus investigated whether exposure (in utero or in early life) to the Great Chinese Famine of 1959–1961 was associated with risk of RA in adulthood. Methods Included were 101,510 participants of the Kailuan Study that joined the study at baseline (2006). RA cases were confirmed by medical record review. We used logistic regression to calculate the odds ratio (OR) and 95% confidence interval (95% CI) for RA, according to famine exposure status (exposed in utero, between 0 and 3 years, between 3 and 6 years, or at 6 years or older), in comparison to participants born after 1961 (not exposed to famine). Potential confounders (e.g., sex, body mass index, smoking status, and plasma concentrations of c-reactive protein, low-density lipoprotein and high-density lipoprotein) were adjusted in the model. Results During 12 years of follow-up (2006–2018), we identified 187 RA cases. Individuals exposed to the Famine in utero or in ages 0–3 years, had a higher prevalence of RA, relative to other groups (0.24%–0.35% vs 0.08–0.20%). After adjustment for potential confounders, the OR of RA was 2.70 (95% CI: 1.40 to 5.21) for in utero famine exposed individuals, 4.44 (95% CI: 2.66 to 7.39) for those exposed in age 0–3 y, 2.50 (95% CRI: 1.40 to 4.47) for those exposed in age 3–6 y, and 2.61 (95% CI: 1.63 to 4.18) for those exposed after at least 6 years old versus individuals who were born after 1961. A similar association was observed for men and women (P-interaction = 0.86). Conclusions Individuals with exposure to famine in utero or early childhood (0–3 years), were more likely to suffer from RA in adulthood. This study reflects the importance of early life as a key developmental period for the immune system, and demonstrates that exposure to famine during this time results in increased risk of RA in adulthood. Funding Sources Study funded by start-up grant from the College of Health and Human Development and the Department of Nutritional Sciences, The Pennsylvania State University, and Natural Science Foundation of Hebei Province (H2018209318).

Quantifying the C-reactive protein concentrations of uterine lavage samples in postpartum dairy cows

Changes in the C-reactive protein (CRP) concentration, a non-specific diagnostic biomarker, in uterine lavage fluid and associations with cytological findings were examined following parturition in dairy cows. In postpartum Holstein dairy cows (n = 8), uterine lavage was performed at 3 and 6 weeks postpartum, and polymorphonuclear leukocyte (PMN) ratios to total cells (PMN:ALL) and to lymphocytes (PMN:LYM) and CRP concentrations were determined. Blood samples were collected to monitor the metabolic variables, and plasma CRP concentrations were quantified using samples collected at the same time as the uterine lavage occurred. A cytological examination was performed to determine PMN:ALL and PMN:LYM. The values for metabolic variables were within the normal range throughout the postpartum period. There was a correlation between the PMN:ALL and PMN:LYM, and both ratios were less (P < 0.05) at 6 than 3 weeks postpartum. The mean CRP concentration of the uterine lavage fluid was less at 6 (27.7 ± 9.6 ng/ml) than 3 weeks (60.8 ± 28.1 ng/ml) postpartum, whereas mean plasma CRP concentration was greater at 6 (287.4 ± 34.1 ng/ml) than 3 (254.8 ± 29.4 ng/ml) weeks postpartum. The results of the present study indicate the CRP concentration of uterine lavage fluid decreased in parallel with the frequency of PMN during uterine involution, which leads to the suggestion that uterine lavage fluid CRP concentration could be utilized as a local biomarker for evaluating uterine inflammation in cows.

The relation between healthy lifestyle changes and decrease in systemic inflammation in patients with stable cardiovascular disease

Background and aimsPharmacological lowering of inflammation has proven effective in reducing recurrent cardiovascular event rates. Aim of the current study is to evaluate lifestyle changes (smoking cessation, weight loss, physical activity level increase, alcohol moderation, and a summary lifestyle improvement score) in relation to change in plasma C-reactive protein (CRP) concentration in patients with established cardiovascular disease. MethodsIn total, 1794 patients from the UCC-SMART cohort with stable cardiovascular disease and CRP levels ≤10 mg/L, who returned for a follow-up study visit after median 9.9 years (IQR 5.4–10.8), were included. The relation between changes in smoking status, weight, physical activity, alcohol consumption, a summary lifestyle improvement score and change in plasma CRP concentration was evaluated with linear regression analyses. ResultsSmoking cessation was related to a 0.40 mg/L decline in CRP concentration (β-coefficient −0.40; 95%CI -0.73,-0.07). Weight loss (per 1SD = 6.4 kg) and increase in physical activity (per 1 SD = 48 MET hours per week) were related to a decrease in CRP concentration (β-coefficients −0.25; 95%CI -0.33,-0.16 and −0.09; 95%CI -0.17,-0.01 per SD). Change in alcohol consumption was not related to CRP difference. Every point higher in the summary lifestyle improvement score was related to a decrease in CRP concentration of 0.17 mg/L (β-coefficient −0.17; 95%CI -0.26,-0.07). ConclusionsSmoking cessation, increase in physical activity, and weight loss are related to a decrease in CRP concentration in patients with stable cardiovascular disease. Patients with the highest summary lifestyle improvement score have the most decrease in CRP concentration. These results may indicate that healthy lifestyle changes contribute to lowering systemic inflammation, potentially leading to a lower cardiovascular risk in patients with established cardiovascular disease.

Systemic inflammation is associated with incident stroke and heart disease in East Asians

Systemic inflammation, reflected by increased plasma concentrations of C-reactive protein (CRP) and fibrinogen, is associated with increased risk of coronary heart disease, but its relevance for stroke types remains unclear. Moreover, evidence is limited in non-European populations. We investigated associations of CRP and fibrinogen with risks of incident major coronary events (MCE), ischemic stroke (IS) and intracerebral hemorrhage (ICH) in a cohort of Chinese adults. A nested case-control study within the prospective China Kadoorie Biobank included 1,508 incident MCE cases, 5,418 IS cases, 4,476 ICH cases, and 5,285 common controls, aged 30–79 years. High-sensitivity CRP and low-density lipoprotein cholesterol (LDL-C) were measured in baseline plasma samples from all participants, and fibrinogen in a subset (n = 9,380). Logistic regression yielded adjusted odds ratios (ORs) per SD higher usual levels of log-transformed CRP and fibrinogen. The overall mean (SD) baseline LDL-C was 91.6 mg/dL (24.0) and geometric mean (95% CI) CRP and fibrinogen were 0.90 mg/L (0.87–0.93) and 3.01 g/L (2.98–3.03), respectively. There were approximately log-linear positive associations of CRP with each outcome, which persisted after adjustment for LDL-C and other risk factors, with adjusted ORs (95% CI) per SD higher CRP of 1.67 (1.44–1.94) for MCE and 1.22 (1.10–1.36) for both IS and ICH. No associations of fibrinogen with MCE, IS, or ICH were identified. Adding CRP to prediction models based on established risk factors improved model fit for each of MCE, IS, and ICH, with small improvements in C-statistic and correct reclassification of controls to lower risk groups. Among Chinese adults, who have low mean LDL-C, CRP, but not fibrinogen, was independently associated with increased risks of MCE and stroke.

ANRIL polymorphisms (rs1333049 and rs3217992) in relation to plasma CRP levels among in-patients with CHD

BackgroundSingle nucleotide polymorphisms (SNPs) in long non-coding RNA ANRIL (antisense noncoding RNA in the INK4 locus) were shown to be associated with coronary heart disease (CHD). The biological background for this association is not fully understood. The primary aim of this study was to investigate whether two leading ANRIL SNPs, namely, rs133049 and rs3217992, were associated with plasma levels of C-reactive protein among a large cohort of in-patients with CHD (n = 933). Material and methodsCHD was defined as previous or current detection of 50% stenosis of a main coronary artery. Severe periodontitis was diagnosed if proximal attachment loss of at least 5 mm was found in at least 30% of teeth. For genotyping rs1333049 we applied PCR using sequence-specific primers and for rs321799 restriction fragment length polymorphism analyses. C-reactive protein (CRP) plasma levels were determined using a particle-enhanced immunological turbidity test. In addition, interleukin (IL)-6, low-density lipoprotein (LDL), total cholesterol, high-density lipoprotein (HDL), triglycerides, and number of leukocytes were determined. ResultsGenotype CC of rs1333049 was significantly associated with both elevated CRP levels and decreased HDL concentrations after univariate (p = 0.028, p = 0.012) and multivariate analysis (p = 0.041, p = 0.023) stratified for age, gender, body mass index, smoking, diabetes, and severe periodontitis. Furthermore, severe periodontitis (p = 0.031), but not SNP rs3217992, was associated with CRP plasma concentrations. ConclusionsAmong patients with CHD, ANRIL SNP rs1333049 is an independent risk indicator for both elevated CRP plasma levels and reduced HDL concentrations.ClinicalTrials.gov Identifier: NCT01045070.

Association of plasma C-reactive protein with ischaemic stroke: a Mendelian randomization study.

Elevated C-reactive protein (CRP) is associated with an increased risk of ischaemic stroke (IS). However, the causality of this association is uncertain. The aim is to investigate whether genetically raised plasma CRP concentration levels are associated with IS on the basis of the Mendelian randomization method. Based on the National Center for Biotechnology Information single nucleotide polymorphism (SNP) database, the Chinese online genetic database as well as previously published studies, four CRP-associated SNP alleles (rs1130864, rs1205, rs876537 and rs3093059) with minor allele frequency ≥0.15 were selected and the concentration levels of CRP were measured in 378 first-ever IS patients and 613 healthy controls. Three SNPs were chosen and used as instrumental variables. The adjusted odds ratios (ORs) [95% confidence interval (95% CI)] of IS per addition of the modelled allele were 1.07 (0.79-1.45) for rs876537, 0.99 (0.73-1.35) for rs1205 and 1.08 (0.71-1.65) for rs3093059. The OR (95% CI) of IS for plasma CRP≥2.0mg/l was 2.19 (1.06-4.53) compared with <2.0mg/l. The adjusted OR (95% CI) of IS per genetically predicted 10% higher CRP concentration, based on the three SNPs as the instruments, was 1.02 (0.94-1.11). Furthermore, similar results were obtained with adjusted ORs (95% CI) of 1.00 (0.88-1.13) and 1.04 (0.93-1.16), respectively, for large-artery atherosclerosis and small-artery occlusion per genetically predicted 10% higher CRP concentration. This Mendelian randomization study provides no clear support that elevated CRP concentration is causally associated with the risk of IS.

Roles of C-reactive protein on the association between urinary cadmium and type 2 diabetes

Cadmium (Cd) is a toxic heavy metal that is widely distributed in the environment. However, the mechanisms linking Cd exposure and type 2 diabetes risks are not completely elucidated. In this study, we aim to investigate the roles of C-reactive protein (CRP) on the association between urinary Cd and type 2 diabetes risk. We determined urinary Cd and plasma CRP concentrations among 3,140 adults from Wuhan-Zhuhai cohort. Dose-response relationships between urinary Cd, plasma CRP, and type 2 diabetes were explored using multivariate logistic regression and linear mixed regression models. Mediation analysis was performed to investigate the role of plasma CRP in the associations between urinary Cd and type 2 diabetes risk. With adjustment for potential confounders, the odds ratios (ORs) of type 2 diabetes showed an upward trend when urinary Cd concentration gradually increased (P trend <0.01). Significantly positive dose-response relationships were observed between urinary Cd and plasma CRP, as well as between plasma CRP and type 2 diabetes risk. Compared to those when both Cd and CRP levels were low, the adjusted ORs (95%CI) of type 2 diabetes was the highest [2.053(1.395–3.020)] in individuals with high levels of urinary Cd and plasma CRP. Mediation analysis estimated that plasma CRP mediated 4.01% of the association between urinary Cd and type 2 diabetes risk [mediating effect: OR (95%CI) = 1.019(1.002–1.057)]. Individuals with high levels of urinary Cd and plasma CRP had a much higher risk of type 2 diabetes. Plasma CRP may serve as a mediator in the association between urinary Cd and type 2 diabetes risk, providing clues for further study on the biological pathway for type 2 diabetes related to Cd exposure.

Glomerular Collagen Deposition and Lipocalin-2 Expression Are Early Signs of Renal Injury in Prediabetic Obese Rats.

Feeding rats with high-fat diet (HFD) with a single streptozotocin (STZ) injection induced obesity, slightly elevated fasting blood glucose and impaired glucose and insulin tolerance, and caused cardiac hypertrophy and mild diastolic dysfunction as published before by Koncsos et al. in 2016. Here we aimed to explore the renal consequences in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9) or HFD containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four (prediabetic rats, PRED, n = 9). At week 21 blood and urine samples were taken and kidney and liver samples were collected for histology, immunohistochemistry and for analysis of gene expression. HFD and STZ increased body weight and visceral adiposity and plasma leptin concentration. Despite hyperleptinemia, plasma C-reactive protein concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while Il-1β mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret diameter, desmin protein expression, and cortical and medullary mRNA expression of TGF-β1, Nrf2, and PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation of the autophagy regulator Akt was the first sign of liver damage, while plasma lipid and liver enzyme concentrations were similar. In conclusion, glomerular collagen deposition and increased lipocalin-2 expression were the early signs of kidney injury, while most biomarkers of inflammation, oxidative stress and fibrosis were negative in the kidneys of obese, prediabetic rats with mild heart and liver injury.

C reactive protein level as a marker for dyslipidaemia, diabetes and metabolic syndrome: results from the Korea National Health and Nutrition Examination Survey

ObjectivePlasma C reactive protein (CRP) is a marker of inflammation, and increased plasma CRP is reported in many diseases, including cardiovascular disease, diabetes, metabolic syndrome, arthritis and malignancies. The aim...

Association between chronotype and body mass index: The role of C-reactive protein and the cortisol response to stress

Background: Chronotype influences several physiological systems, including the immune system and the hypothalamus-pituitary-adrenal (HPA)-axis. Previous research has shown that evening chronotype is associated with adverse metabolic health outcomes and obesity. However, the exact mechanisms underlying the observed differences in metabolic function between “morning” and “evening” types remain to be explored. Objective: To investigate the relationship of chronotype with inflammatory and neuroendocrine stress markers and to explore their mediating and moderating roles in the association between chronotype and body mass index (BMI). Methods: Twenty-eight healthy young adults (50% women), mean age 23.8 ± 3.3 (SD) years, underwent a standardized laboratory stress test (Trier Social Stress Test, TSST). Concentrations of plasma C-reactive protein (CRP) at baseline and of salivary cortisol before and after the onset of the stressor were analyzed. Heart rate was measured continuously. Chronotype was assessed with the Morningness-Eveningness Questionnaire (MEQ). Results: Lower MEQ scores (i.e. evening tendency) were associated with higher BMI (r = −.40, p < .05), elevated CRP concentrations (r = −.42, p < .05) and higher cortisol responses to acute stress (r = −.53, p < .01). The relationship between MEQ score and BMI was mediated by CRP concentrations (b = –0.03, CI 95%: –0.08 to –0.007, p < .05). In addition, we observed a moderating effect of the cortisol stress response on this mediated relationship (b = 0.005, CI 95%: 0.0002 to 0.01, p < .05), such that the mediated relationship was stronger in individuals with a higher cortisol response. Conclusion: Enhanced pro-inflammatory state and a higher cortisol response to stress may underlie the effect of evening chronotype on obesity risk and adverse metabolic health outcomes.