Circulating C-reactive Protein Concentrations Research Articles

Association between active commuting and low-grade inflammation: a population-based cross-sectional study.

Prior studies suggest that physical activity lowers circulating C-reactive protein (CRP) levels. However, little is known about the association between regular active commuting, i.e. walking or cycling to work, and CRP concentrations. This study examines whether active commuting is associated with lower CRP. We conducted a cross-sectional study using population-based FINRISK data from 1997, 2002, 2007 and 2012. Participants were working adults living in Finland (n = 6208; mean age = 44 years; 53.6% women). We used linear and additive models adjusted for potential confounders to analyze whether daily active commuting, defined as the time spent walking or cycling to work, was associated with lower high-sensitivity (hs-) CRP serum concentrations compared with passive commuting. We observed that daily active commuting for 45 min or more (vs. none) was associated with lower hs-CRP [% mean difference in the main model: -16.8%; 95% confidence interval (CI) -25.6% to -7.0%), and results were robust to adjustment for leisure-time and occupational physical activity, as well as diet. Similarly, active commuting for 15-29 min daily was associated with lower hs-CRP in the main model (-7.4; 95% CI -14.1 to -0.2), but the association attenuated to null after further adjustments. In subgroup analyses, associations were only observed for women. Active commuting for at least 45 min a day was associated with lower levels of low-grade inflammation. Promoting active modes of transport may lead not only to reduced emissions from motorized traffic but also to population-level health benefits.

Abstract 6013: DNA methylation-based inflammation score is associated with hepatocellular carcinoma among people living with HIV

Abstract Background: Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide. In countries with high human immunodeficiency virus (HIV) prevalence, such as Nigeria, HIV-associated HCC causes a great health burden due to its early onset, late diagnosis, and poorer prognosis. HIV infection is involved in inflammation of the liver, which may determine an increased risk of hepatocyte neoplastic transformation. Inflammation-related DNA methylation signatures obtained in liquid biopsy, such as circulating cell-free DNA (ccfDNA) extracted from serum/plasma are promising minimally-invasive biomarkers that may inform HCC among people living with HIV. Methods: A total of 289 Nigerian participants with information on ccfDNA and other covariates were included. Participants were classified into three groups by their HCC/HIV status: 1) HCC+/HIV+ (n=28); 2) HCC-/HIV+ (n=185); and 3) HCC+/HIV- (n=76). We constructed ccfDNA methylation inflammation scores using 49 CpGs previously linked to circulating C-reactive protein (CRP) concentrations, and higher scores represented elevated CRP concentrations with lower methylation levels. To compare the ccfDNA methylation inflammation score across the groups, we performed multivariable logistic regression analyses adjusting for age, sex, alcohol consumption, smoking status, body mass index, study sites, and technical variables. Results: Participants with HCC+/HIV+ presented the highest ccfDNA methylation inflammation scores (mean=-0.03, standard deviation [SD] =0.01). Participants with HCC-/HIV+ presented the lowest scores (mean=-0.05, SD=0.01). In the multivariable logistic regressions, one SD increase of inflammation score was associated with 2.5 times higher odds of having HCC among HIV-infected participants (HCC+/HIV+ vs. HCC+/HIV-; OR=2.56, 95% CI=1.39-4.73, P=0.002). No evidence was found for the association between the inflammation score and HIV status among HCC patients (HCC+/HIV+ vs. HCC+/HIV-; OR=1.00, 95% CI=0.59-1.70, P=0.991). In the secondary analysis comparing HCC+ vs. HCC- adjusting for HIV status, one SD increase of inflammation score was associated with 3.2 times higher odds of having HCC (OR=3.22, 95% CI=1.39-7.46, P=0.006). Conclusions: We observed that ccfDNA methylation inflammation score is associated with HCC status among people with HIV. Our findings suggest that ccfDNA methylation-based inflammatory profiles may serve as a potential biomarker for early detection and risk stratification of HCC in resource-constrained countries with a high prevalence of HIV. Citation Format: Kyeezu Kim, Yinan Zheng, Claudia Hawkins, Edith Okeke, Olufunmilayo Lesi, Yishu Qu, Lewis R. Roberts, Demirkan Gursel, Fatimah B. Abdulkareem, Alani Akanmu, Godwin Imade, Jian-Jun Wei, Masha Kocherginsky, Kwang-Youn Kim, Wasiu L. Adeyemo, Firas Wehbe, Chad J. Achenbach, Atiene Sagay, Folasade T. Ogunsola, Robert L. Murphy, Lifang Hou. DNA methylation-based inflammation score is associated with hepatocellular carcinoma among people living with HIV. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6013.

The Effects of Almond Consumption on Inflammatory Biomarkers in Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Conflicting findings have been reported regarding the effects of almond consumption on inflammatory markers. This study aimed to summarize the current literature to determine whether almonds can affect inflammatory markers. A systematic search was carried out in PubMed, Scopus, and ISI Web of Science up to March 2021. Randomized clinical trials that compared almond with no almond consumption were included. The outcomes of interest were changes in circulating C-reactive protein (CRP), IL-6, TNF-α, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) concentrations. The random-effects model was used to find the mean differences. In total, 18 trials with 847 participants were eligible for the current analysis. Participants' ages ranged from 26.3 to 69.6 y. Combining 16 studies, almond consumption significantly reduced serum concentrations of CRP [weighted mean difference (WMD): -0.25mg/L; 95% CI: -0.43, -0.06 mg/L; I2=0.0%; P-heterogeneity=0.633]. However, the beneficial effect of almond intake only occurred at doses <60g/d. Pooling 11 effect sizes, almond interventions significantly decreased circulating IL-6 concentrations (WMD: -0.11 pg/mL; 95% CI: -0.21, -0.01 pg/mL; I2=19.9%; P-heterogeneity=0.254). In subgroup analyses, effects on CRP and IL-6 were nonsignificant in unhealthy participants or those with obesity. In addition, almond consumption had no significant effect on TNF-α (WMD: -0.05 pg/mL; 95% CI: -0.11, 0.01 pg/mL; I2=0.0%; P-heterogeneity=0.893; n=6), ICAM-1 (WMD: 6.39ng/mL; 95% CI: -9.44, 22.22 ng/mL; I2=66.6%; P-heterogeneity=0.006; n=7), or VCAM-1 (WMD: -8.31ng/mL; 95% CI: -35.32, 18.71 ng/mL; I2=58.8%; P-heterogeneity=0.033; n=6). In conclusion, almond consumption beneficially affects CRP and IL-6 concentrations in adults. However, it has no beneficial effect on TNF-α, ICAM-1, or VCAM-1. More trials are needed to determine the effects of almonds on inflammation.

Psychiatric symptoms are not associated with circulating CRP concentrations after controlling for medical, social, and demographic factors

Elevated serum concentrations (>3 mg/L) of the acute-phase protein, C-reactive protein (CRP), is used as a clinical marker of inflammation and is reported to be a strong risk factor for cardiovascular disease. In psychiatric populations, CRP concentration is reported to be higher in depressed versus healthy individuals. Positive associations between CRP and depression have been established in both clinical and community samples, but effect sizes are attenuated after controlling for confounding variables. Similarly, emerging research has begun to draw a link between inflammation, symptoms of anxiety, and substance abuse. Given the high level of comorbid anxiety and substance use disorders in many depressed populations, this study examined whether depression (Patient Health Questionnaire 9 [PHQ-9]) and substance use-related (Drug Abuse Screening Test [DAST]) symptoms were associated with CRP concentrations in the blood after adjusting for relevant medical, social, and demographic covariates in a large sample undergoing screening for several transdiagnostic psychiatric research studies. A total of 1,724 participants were analyzed for association of CRP with variables using multivariate linear regression. An unadjusted model with no covariates showed that PHQ-9 was significantly associated with CRP in All (β = 0.125), Female (β = 0.091), and Male (β = 0.154) participants, but DAST was significantly associated with CRP in males only (β = 0.120). For the adjusted model, in both males and females, mood-stabilizer treatment (β = 0.630), opioid medication (β = 0.360), body mass index (β = 0.244), percent body fat (β = 0.289), nicotine use (β = 0.063), and self-reported sleep disturbance (β = 0.061) were significantly associated with increased CRP concentrations. In females, oral contraceptive use (β = 0.576), and waist-to-hip ratio (β = 0.086), and in males, non-steroidal anti-inflammatory drug use (β = 0.367) were also associated with increased CRP concentrations. There was no significant association between CRP and individual depressive, anxiety, or substance use-related symptoms when covariates were included in the regression models. These results suggest that associations between circulating CRP and the severity of psychiatric symptoms are dependent on the type of covariates controlled for in statistical analyses.

Impact of Human Genetic Variation on C-Reactive Protein Concentrations and Acute Appendicitis.

BackgroundAcute appendicitis is one of the most common abdominal emergencies worldwide. Both environmental and genetic factors contribute to the disease. C-reactive protein (CRP) is an important biomarker in the diagnosis of acute appendicitis. CRP concentrations are significantly affected by genetic variation. However, whether such genetic variation is causally related to appendicitis risk remains unclear. In this study, the causal relationship between single-nucleotide polymorphisms (SNPs) associated with circulating CRP concentrations and the risk and severity of acute appendicitis was investigated.MethodsCRP concentrations in serum of appendicitis patients (n = 325) were measured. Appendicitis was categorized as complicated/uncomplicated and gangrenous/non-gangrenous. Imputed SNP data (n = 287) were generated. A genome-wide association study (GWAS) on CRP concentrations and appendicitis severity was performed. Intersection and colocalization of the GWAS results were performed with appendicitis and CRP-associated loci from the Pan-UKBB cohort. A functional-genomics approach to prioritize genes was employed.ResultsThirteen percent of significant CRP quantitative trait loci (QTLs) that were previously identified in a large cohort of healthy individuals were replicated in our small patient cohort. Significant enrichment of CRP-QTLs in association with appendicitis was observed. Among these shared loci, the two top loci at chromosomes 1q41 and 8p23.1 were characterized. The top SNP at chromosome 1q41 is located within the promoter of H2.0 Like Homeobox (HLX) gene, which is involved in blood cell differentiation, and liver and gut organogeneses. The expression of HLX is increased in the appendix of appendicitis patients compared to controls. The locus at 8p23.1 contains multiple genes, including cathepsin B (CTSB), which is overexpressed in appendix tissue from appendicitis patients. The risk allele of the top SNP in this locus also increases CTSB expression in the sigmoid colon of healthy individuals. CTSB is involved in collagen degradation, MHC class II antigen presentation, and neutrophil degranulation.ConclusionsThe results of this study prioritize HLX and CTSB as potential causal genes for appendicitis and suggest a shared genetic mechanism between appendicitis and CRP concentrations.

Examination of Cognitive Function, Neurotrophin Concentrations, and both Brain and Systemic Inflammatory Markers Following a Simulated Game of American Football.

Hoffman, JR, Ostfeld, I, Zamir, A, Amedi, R, Fonville, TR, Horstemeyer, MF, and Gepner, Y. Examination of cognitive function, neurotrophin concentrations, and both brain and systemic inflammatory markers following a simulated game of American football. J Strength Cond Res 36(3): 686-694, 2022-This investigation examined the effect of a simulated American football game on cognitive function, neurotrophin concentrations, and markers of both systemic and brain inflammation. Members of the Israel national team (6 linemen and 9 skill position players) were examined 1 week before (PRE), immediately post (IP) and 24-hour post (24P) game. Blood was obtained, and cognitive function was measured at each assessment. No head injuries to any of the players participating in the study occurred. Significant (p < 0.001) decreases in acute memory, and a trend (p = 0.066) toward a decrease in delayed memory was noted at IP. Significant negative correlations were observed between playing time (number of plays) and concentration changes from PRE to IP (r = -0.801; p = 0.001) and from PRE to 24P (r = -0.549; p = 0.034). All cognitive function measures returned to PRE levels by 24P. Increases from PRE were noted in tumor necrosis factor-alpha (TNF-α) (p = 0.041) at IP and in brain-derived neurotrophic factor (p = 0.009) and C-reactive protein (CRP) (p = 0.019) concentrations at 24P. Circulating CRP concentrations and the cytokine markers, interleukin (IL)-4, IL-6, IL-10, and TNF-α, were significantly elevated in linemen compared with skill players. Brain inflammatory markers (S100B and glial fibrillary acidic protein) and total tau protein (a marker of brain injury) were not elevated from PRE. No change from PRE was noted in either myoglobin or creatine kinase-MM concentrations. In conclusion, muscle damage and inflammatory marker responses observed from the scrimmage game were consistent with muscle desensitization associated with football participation. In addition, the systemic inflammatory marker results observed in linemen were suggestive of chronic low-grade inflammation.

Greater central adiposity resulting from increased market integration is associated with elevated C-reactive protein levels in older women from the Republic of Vanuatu

Objective: We characterized the relationship between circulating C-reactive protein (CRP) levels and nine anthropometric measures of body fat to identify the best anthropometric predictors of CRP in Ni-Vanuatu women.&#x0D; Sample and Methods: Anthropometric data and blood spot samples were collected from sixty-four Ni-Vanuatu female participants (age 35-78 years) on five islands with varying degrees of market integration, cultural change, and obesity. CRP concentration was determined with a high-sensitivity ELISA (hsCRP) assay and then compared to nine different anthropometric measurements.&#x0D; Results: BMI was significantly correlated with CRP (p=0.047). Among the eight additional anthropometrics, the suprailiac skinfold (p=0.003) and waist-circumference (p=0.009) were better predictors of CRP than BMI. Moreover, our stepwise selection model indicated that the suprailiac skinfold explained ~14% of CRP level variance.&#x0D; Conclusions: The BMI-CRP correlation coefficient for Ni-Vanuatu women falls within the range of previously reported values for East Asian populations with whom they share genetic ancestry. However, the best anthropometric predictors of CRP levels were waist circumference and suprailiac skinfold thickness. These measures capture central adiposity and are more closely associated with elevated CRP level and cardiovascular disease risk than fat distributed elsewhere on the body. Ni-Vanuatu in urban settings with high market integration are at greater risk for obesity, which is associated with elevated CRP levels. However, because nearly all Ni-Vanuatu still retain horticultural knowledge and land ownership, consumption of processed, imported foods is largely determined by degree of market integration and personal choice. Therefore, health interventions focusing on sustainable traditional food practices are feasible.

Deconstructing sex differences in C‐reactive protein trends over time

AbstractObjectivesHeightened inflammatory state, as measured by circulating C‐reactive protein (CRP) levels, can promote inflammation‐mediated disease risk. It is important to account for population fluctuation and sex variation in serum CRP concentrations on overall time trends.MethodsUsing the National Health and Nutrition Examination Survey data, we specify linear and algebraic decomposition models separately by sex to identify the drivers of the changing trends in the distribution of CRP values in the population.ResultsWe found a nonsignificant overall increase in CRP, but a significant decrease among women and increase among men, over a 10‐year period. We then used linear and algebraic decomposition techniques to identify the sources of change in CRP over time, separately for women and men. CRP increased among men mainly because lifestyle/health characteristics worsened over time, and because the size of socioeconomic/demographic groups with higher CRP increased and the size of groups with lower CRP decreased. The downward shift in CRP among women occurred because the typical woman across all cohorts had lower CRP levels.ConclusionsWe identified two fundamentally different processes of change driving the decline and rise in CRP values among women and men, respectively.

Epicardial fat, gender, and cardiovascular risk

Epicardial fat (EF) is considered an important risk factor and an active player in the pathogenesis of cardiovascular and metabolic diseases. EF is an endocrine organ that releases hormones and mediators, including the circulating C-reactive protein (CRP), and plays a vital role in modifying the vascular endothelial function and promoting the growth of coronary atherosclerosis. This study aimed to investigate the relationship between CRP concentrations and EF in a cohort of patients with metabolic syndrome at risk for coronary artery disease. In our study, carried out in primary prevention, we enrolled 36 subjects (M/F: 21/15; age: 59.3±0.79 yrs) diagnosed with metabolic syndrome. We have classified the patients into two groups: Men and Women. Besides anthropometric characterization and screening laboratory tests, the subjects performed a multidetector computed tomography scan, which allowed the EF quantification. Mean EF was 115.1 cc in the study population. The average EF of women was 111 cc; the average EF of men was 118 cc (P=0.18). CRP levels were strongly positively correlated with EF area in women (P=0.01), while the correlation was not found in men (P=0.4). Our findings suggest that, in women, the EF produces a greater amount of acute-phase proteins and increases the pro-inflammatory state in the epicardial region. For this reason, we can hypothesize, in women, a different role in the development of atherosclerotic plaque of the epicardial fat compared to men.

Role of inflammation in depression and anxiety: Tests for disorder specificity, linearity and potential causality of association in the UK Biobank.

BackgroundConcentrations of C-reactive protein (CRP), interleukin 6 (IL-6) and other inflammatory markers are elevated in people with depression and anxiety compared to controls, but evidence for disorder-specificity, linearity and potential causality is sparse.MethodsUsing population-based data from up to 144,890 UK Biobank cohort participants, we tested associations of circulating CRP concentrations with depression and anxiety symptom scores and probable diagnosis, including tests for linearity, disorder-specificity and sex difference. We examined potential causality using 1-sample and 2-sample Mendelian randomisation (MR) analyses testing associations of genetically-predicted CRP concentration and IL-6 activity with depression and anxiety. The study was conducted from June 2019 to February 2021.FindingsCRP concentration was associated with depressive and anxiety symptom scores and with probable diagnoses of depression and generalised anxiety disorder (GAD) in a dose-response fashion. These associations were stronger for depression than for anxiety, and for women than for men although less consistently. MR analyses provided consistent results suggesting that genetically predicted higher IL-6 activity was associated with increased risk for depressive symptoms, while genetically-predicted higher CRP concentration was associated with decreased risks of depressive and anxiety symptoms.InterpretationAltered activity of the IL-6/IL-6R pathway could be a risk factor for depression. The field now requires experimental studies of IL-6 modulation in humans and animal models to further examine causality, mechanisms and treatment potential. Such studies are also needed to elucidate mechanisms for divergent associations of genetically-predicted higher IL-6 activity (risk increasing) and higher CRP concentrations (protective) with depression/anxiety.FundingThis research was funded in whole, or in part, by the Wellcome Trust (grant code: 201486/Z/16/Z). For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. This work was supported by a Data Science Award from the MQ: Transforming Mental Health (grant code: MQDS17/40) to GMK and PBJ, which also supported ZY. GMK also acknowledges funding support from the Wellcome Trust (grant code: 201486/Z/16/Z), the Medical Research Council UK (grant code: MC_PC_17213 and MR/S037675/1), and the BMA Foundation (J Moulton grant 2019). NK and SM are supported by the International Max Planck Research School of Translational Psychiatry (IMPRS-TP). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1).

Genetically Predicted Circulating C-Reactive Protein Concentration and Colorectal Cancer Survival: A Mendelian Randomization Consortium Study.

A positive association between circulating C-reactive protein (CRP) and colorectal cancer survival was reported in observational studies, which are susceptible to unmeasured confounding and reverse causality. We used a Mendelian randomization approach to evaluate the association between genetically predicted CRP concentrations and colorectal cancer-specific survival. We used individual-level data for 16,918 eligible colorectal cancer cases of European ancestry from 15 studies within the International Survival Analysis of Colorectal Cancer Consortium. We calculated a genetic-risk score based on 52 CRP-associated genetic variants identified from genome-wide association studies. Because of the non-collapsibility of hazard ratios from Cox proportional hazards models, we used the additive hazards model to calculate hazard differences (HD) and 95% confidence intervals (CI) for the association between genetically predicted CRP concentrations and colorectal cancer-specific survival, overall and by stage at diagnosis and tumor location. Analyses were adjusted for age at diagnosis, sex, body mass index, genotyping platform, study, and principal components. Of the 5,395 (32%) deaths accrued over up to 10 years of follow-up, 3,808 (23%) were due to colorectal cancer. Genetically predicted CRP concentration was not associated with colorectal cancer-specific survival (HD, -1.15; 95% CI, -2.76 to 0.47 per 100,000 person-years; P = 0.16). Similarly, no associations were observed in subgroup analyses by stage at diagnosis or tumor location. Despite adequate power to detect moderate associations, our results did not support a causal effect of circulating CRP concentrations on colorectal cancer-specific survival. Future research evaluating genetically determined levels of other circulating inflammatory biomarkers (i.e., IL6) with colorectal cancer survival outcomes is needed.

Association of circulating C-reactive protein and high-sensitivity C-reactive protein with components of sarcopenia: A systematic review and meta-analysis of observational studies.

Sarcopenia, a multi-faceted skeletal muscle disorder in the older population, has poor health outcomes. Some previous observational studies investigated the association between circulating inflammatory markers and sarcopenia components to evaluate chronic inflammation as a risk factor for sarcopenia in the elderly population. Nevertheless, the association between circulating C-reactive protein (CRP) and hs-CRP, as the recognized markers of systemic inflammation and components of sarcopenia, is unclear. This meta-analysis aimed to investigate the association of muscle strength, muscle mass, and muscle function with two serum inflammatory markers, circulating C-reactive protein (CRP) and high-sensitive CRP (hs-CRP). We assessed all observational studies across different electronic databases including PubMed, Scopus, and Google Scholar using keywords such as "muscle strength", "muscle mass", "muscle function", CRP and hs-CRP from inception until the 30th of July 2019. Only studies that investigated the association between components of sarcopenia and CRP or hs-CRP levels were included. Participants' country, age, sex, BMI, and screening tool for sarcopenia were retrieved. The correlations between muscle strength, muscle mass, and muscle function with CRP, and hs-CRP were expressed as the correlation coefficient (r) with 95% confidence intervals (CIs). Begg's test and Egger's test were conducted to evaluate risk of publication bias in this study. Initially, we found fifty-nine studies for the qualitative synthesis. Ultimately, nineteen adult cross-sectional studies comprising 14,650 subjects were included in the meta-analysis. Of them, fourteen studies measured the correlation between CRP or hs-CRP and muscle strength. There were significant inverse correlation between CRP and hs-CRP concentrations with muscle strength (ES (z)=-0.22; 95% CI=-0.34 to -0.09; P<0.001), (ES (z)=-0.22; 95% CI=-0.34 to -0.09; P<0.001), respectively. No publication bias was found between muscle strength and CRP (P=0.53) or hs-CRP (P=0.62) respectively. Among diagnostic components of sarcopenia, impairment of muscle strength was independently associated with both inflammatory biomarkers. However, future cohort studies are essential to clarify the causal correlation.

C-reactive protein and temperament: An instrumental variable analysis

BackgroundTemperament is associated with circulating inflammatory biomarkers, such as C-reactive protein (CRP), which has been associated with various health conditions, including depression. This study aims to investigate whether genetic disposition for increased circulating CRP concentration may influence temperament over the life-course. MethodsUsing a longitudinal cohort that began in 1980—the Cardiovascular Risk in Young Finns Study (YFS)—we included 920 participants (59.8% female) aged 3–12 years old at baseline (childhood), and the same participants again at ages 30–39 years old (adulthood) in this study. We used both ordinary least-squares regression (OLS linear regression) and instrumental variable (IV) regression to assess associations between CRP concentration and temperament dimensions (negative emotionality, activity, and sociability). To represent genetically determined risk for increase in circulating CRP concentration, we calculated a weighted genetic risk score (GRS) which reflects risk for increased circulating CRP concentration. ResultsIn OLS linear regression analyses, we found that increased circulating CRP concentration in childhood was associated with slightly higher scores for sociability in childhood (19% increase, CI ​= ​7–32%) and adulthood (13% increase, CI ​= ​2–27%), and lower activity scores in adulthood (15% decrease, CI ​= ​3–25%). For all IV regressions, there were no apparent associations between GRS and temperament in either childhood or adulthood (all p>0.3). The Durbin-Wu-Hausman test for endogeneity produced p-values (all>0.05) that suggest there is no evidence for disagreement between the OLS and IV estimates. ConclusionsWe found no clear evidence for an association of GRS for elevated CRP with childhood or adulthood emotionality, activity, or sociability, although circulating CRP was associated with some of these traits.

Education, Smoking and CRP Genetics in Relation to C-Reactive Protein Concentrations in Black South Africans.

Because elevated circulating C-reactive protein (CRP) and low socio-economic status (SES), have both been implicated in cardiovascular disease development, we investigated whether SES factors associate with and interact with CRP polymorphisms in relation to the phenotype. Included in the study were 1569 black South Africans for whom CRP concentrations, 12 CRP single nucleotide polymorphisms (SNPs), cardiovascular health markers, and SES factors were known. None of the investigated SES aspects was found to associate with CRP concentrations when measured individually; however, in adjusted analyses, attaining twelve or more years of formal education resulted in a hypothetically predicted 18.9% lower CRP concentration. We also present the first evidence that active smokers with a C-allele at rs3093068 are at an increased risk of presenting with elevated CRP concentrations. Apart from education level, most SES factors on their own are not associated with the elevated CRP phenotype observed in black South Africans. However, these factors may collectively with other environmental, genetic, and behavioral aspects such as smoking, contribute to the elevated inflammation levels observed in this population. The gene-smoking status interaction in relation to inflammation observed here is of interest and if replicated could be used in at-risk individuals to serve as an additional motivation to quit.

C-reactive protein and ART outcomes: a systematic review.

A dynamic balance between pro- and anti-inflammatory factors contributes to regulating human female reproduction. Chronic low-grade inflammation has been detected in several female reproductive conditions, from anovulation to embryo implantation failure. C-reactive protein (CRP) is a reliable marker of inflammation that is extensively used in clinical practice. Recent studies quantified CRP in the serum of infertile women undergoing ART and suggested its potential for the prediction of ART reproductive outcomes. The first objective of this systematic review of the available literature was to evaluate the association between pre-implantation circulating CRP concentration and pregnancy rates in women undergoing ART. The second objective was to describe serum CRP concentration changes after early embryo implantation. The changes in circulating CRP throughout the ART cycle, clinical implications of CRP quantification for the management of women undergoing ART, and future therapeutic options will also be discussed. The MEDLINE database was systematically searched from inception to March 2019 using the following key words: (C-reactive protein) AND (assisted reproductive techniques OR ovulation induction OR insemination OR in vitro fertilization). Only articles in English were considered. Studies were selected based on title and abstract. The full text of potentially relevant articles was retrieved and assessed for inclusion by two reviewers (S.B. and S.H.). The protocol was registered in the International prospective register of systematic reviews (PROSPERO; registration number: CRD148687). In total, 10 studies were included in this systematic review. Most of these studies reported lower circulating CRP values before the window of implantation and higher circulating CRP values during the peri-implantation period in women with successful ART outcome (biochemical or clinical pregnancy) compared to women without a successful outcome. Several lifestyle factors and/or drugs that reduce the concentration of circulating CRP significantly improve ART outcomes. Subgroup analyses according to female BMI and baseline circulating CRP concentration are highly recommended in future analyses. These findings highlight a possible detrimental impact of preconception high circulating CRP concentration on ART outcomes. However, the biochemical or clinical pregnancy rate endpoints used in the studies examined here are insufficient (there were no data on live birth outcome), and the impact of major variables that can influence CRP and/or ART, for example maternal age, BMI, number of transferred embryos, and use of anti-inflammatory drugs, were not considered in the analyses. CRP quantification may be a potential marker of ART outcome, but its predictive value still needs to be investigated in large prospective studies. In future, the quantification of circulating CRP before starting ART could help to identify patients with a poor ART prognosis, leading to ART cycle cancellation or to preconception treatment to minimize the medical risks and costs.

Effects of a Paleolithic Diet on Cardiovascular Disease Risk Factors: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

There is some evidence supporting the beneficial effects of a Paleolithic Diet (PD) on cardiovascular disease risk factors. This diet advises consuminglean meat, fish, vegetables, fruits, and nuts and avoiding intake of grains, dairy products, processed foods, and added sugar and salt. This study was performed to assess the effects of a PD on cardiovascular disease risk factors including anthropometric indexes, lipid profile, blood pressure, and inflammatory markers using data from randomized controlled trials. A comprehensive search was performed in the PubMed, Scopus, ISI Web of Science, and Google Scholar databases up to August, 2018. A meta-analysis was performed using a random-effects model to estimate the pooled effect size. Meta-analysis of 8 eligible studies revealed that a PD significantly reduced body weight [weighted mean difference (WMD)=-2.17kg; 95% CI: -3.48, -0.87kg], waist circumference (WMD=-2.90cm; 95% CI: -4.51, -1.28 cm), body mass index (in kg/m2) (WMD=-1.15; 95% CI: -1.68, -0.62), body fat percentage (WMD=-1.38%; 95% CI: -2.08%, -0.67%), systolic (WMD=-4.24mm Hg; 95% CI: -7.11, -1.38 mm Hg) and diastolic (WMD=-2.95mm Hg; 95% CI: -4.72, -1.18 mm Hg) blood pressure, and circulating concentrations of total cholesterol (WMD=-0.22mg/dL; 95% CI: -0.42, -0.03 mg/dL), TGs (WMD=-0.23mg/dL; 95% CI: -0.46, -0.01 mg/dL), LDL cholesterol (WMD=-0.13mg/dL; 95% CI: -0.25, -0.01 mg/dL), and C-reactive protein (CRP) (WMD=-0.41mg/L; 95% CI: -0.81, -0.008 mg/L) and also significantly increased HDL cholesterol (WMD=0.05mg/dL; 95% CI: 0.005, 0.10 mg/dL). However, sensitivity analysis revealed that the overall effects of a PD on lipid profile, blood pressure, and circulating CRP concentrations were significantly influenced by removing some studies, hence the results must be interpreted with caution. Although the present meta-analysis revealed that a PD has favorable effects on cardiovascular disease risk factors, the evidence is not conclusive and more well-designed trials are still needed.

1856-P: A High Sugar (Fructose) Diet Increases C-Reactive Protein (CRP) in Rhesus Macaques: Relationships with Changes of Apolipoproteins and Adiponectin

CRP is produced by the liver in response to factors released from macrophages and adipocytes. High circulating CRP concentrations are therefore an indicator of inflammation and/or injury. We examined the effects of dietary fructose on plasma CRP concentrations in a nonhuman primate model of diet-induced metabolic syndrome. Adult male rhesus macaques 12±3 years of age, weighing 16.2±1.9 kg (n=29) maintained on chow (LabDiet 5047) ad libitum were provided with flavored fructose beverages containing 75g of fructose (300 kcal/day). Fasting plasma samples were collected at baseline and after 1 and 3 months. Indices of glucose homeostasis (insulin, glucose, HOMA-IR), adiposity/metabolic homeostasis (leptin, adiponectin) and lipid metabolism (TG, cholesterol, LDL-C, HDL-C, VLDL-C, ApoA1, ApoB, ApoC3 and ApoE) were analyzed. Fructose consumption induced weight gain +1.5±0.2 kg, and insulin resistance, accompanied by increases of plasma leptin, decreased adiponectin, hypertriglyceridemia and increases of ApoC3 and ApoE. Plasma CRP increased from 1.9±0.2 mg/l to 2.9±0.3 mg/l (%∆ = 81±13%) and 2.9±0.3 mg/l (%∆ = +91±14%; both p&amp;lt;0.001) at 1 and 3 months respectively. Bivariate correlation analysis of log-transformed data compared fructose-induced changes (Δ) of CRP with Δ’s of body weight and metabolic indices. After 1 month of fructose consumption, strong positive associations were identified between ΔCRP and ΔApoE (r=0.62, p&amp;lt;0.001), ΔApoC3 (r=0.56, p=0.002), and negatively with Δadiponectin (r=-0.49, p=0.007). After 3 months of fructose exposure, the strong associations between ΔCRP and ΔApoE (r=0.49, p=0.007) and significant relationships with ΔApoC3 (r=0.45, p=0.015) and Δadiponectin (r=-0.39, p=0.038) remained. These results support an important link between fructose diet-induced inflammation with changes of the anti-inflammatory adipocyte hormone (adiponectin) and dysregulated hepatic lipoprotein metabolism. Disclosure P.J. Havel: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. J.L. Graham: Research Support; Self; Arrowhead Research, Bristol-Myers Squibb Company, Magnamosis Inc. K.L. Stanhope: None. A. Butler: None. Funding National Institutes of Health

C-reactive protein is a significant predictor of improved survival in patients with advanced non-small cell lung cancer.

This study tries to evaluate the associations between circulating C-reactive protein (CRP) and the overall survival of patients with non-small cell lung cancer (NSCLC).One hundred ninety-two patients with advanced NSCLC who treated with chemotherapy were enrolled in this study. The cut-off value of CRP concentration was 5.0 mg/L. The patients were divided into low, intermediate and high 3 groups respectively according to the baseline level of CRP before the treatment. Kaplan–Meier analysis and Cox proportional-hazard models were used to evaluate the relationship between the CRP and overall survival time of patients.After adjusting for age, gender, smoking history, pathologic type, CRP was a significant independent impact which predicts the survival prognosis of patients with NSCLC. For all patients, the hazard ratio with high CRP levels for NSCLC-specific survival was 1.83 [95%confidenceinterval (CI) = 0.96, 3.48] compared with low CRP levels. The level of CRP was significantly correlated with survival time (hazard ratio = 1.77; 95% CI = 0.73, 4.26) for the patient with first-line chemotherapy. Patients with high level of circulating CRP also responded poorly to chemotherapy.A high level of circulating CRP was associated with a poor response and worse survival in patients with NSCLC.

Clinical validation of a non-invasive electrodermal biofeedback device useful for reducing chronic perceived pain and systemic inflammation

BackgroundThis study was performed to evaluate the potential clinical usefulness of a new non-invasive electrodermal biofeedback device in reducing perceived pain levels and chronic systemic inflammation.Materials and methodsThis multicenter study was designed and coordinated by BioTekna, included 20 general practice medical centers, took place between June 2010 and January 2011, and was validated clinically at the National and Kapodistrian University of Athens, Greece. The study participants were 1015 Caucasian men (401) and women (614), while the placebo-treated controls were 950 Caucasian men (500) and women (450). Patients were aged between 30 and 86 years (average age about 50 years) and all suffered from chronic pain and other medically unexplained symptoms (MUS). The RegMatEx electrodermal biofeedback device (brand BioTekna - Biomedical Technologies, Marcon, Venice, Italy) was used to evaluate the clinical efficacy of electrodermal biofeedback in reducing the level of pain perceived by decreasing the chronic systemic inflammation of the subjects. All subjects received 6 × 30 min sessions of electrodermal or placebo biofeedback given twice a week over 3 weeks. Perceived pain was evaluated using the Numeric Rating Scale (NRS) for pain, while systemic inflammation was examined with measurements of morning circulating C-reactive protein (CRP) concentrations.ResultsPerceived pain in the treatment group was significantly lessened in the NRS scale (p < 005), while circulating CRP concentrations were also decreased (p < 0.05). Parallel placebo studies showed no changes in perceived pain or morning serum CRP concentrations.DiscussionUse of the electrodermal biofeedback RegMatEx device was associated with reduced pain perception and decreased chronic systemic inflammation, with stability over time. This did not occur in the placebo-treated group. The symptomatology of the treated patients significantly improved in terms of pain relief as shown on the NRS scale, and this was accompanied by reported improvements in mobility, mood, and quality of life.ConclusionsThe RegMatEx electrodermal biofeedback procedure is a non-invasive and easy to use therapeutic method, free of side effects, with high patient acceptability, excellent efficacy, and duration of effect, and, hence, a valuable tool in the treatment of chronic pain and inflammation.

Mendelian randomization analysis of C-reactive protein on colorectal cancer risk.

Chronic inflammation is a risk factor for colorectal cancer (CRC). Circulating C-reactive protein (CRP) is also moderately associated with CRC risk. However, observational studies are susceptible to unmeasured confounding or reverse causality. Using genetic risk variants as instrumental variables, we investigated the causal relationship between genetically elevated CRP concentration and CRC risk, using a Mendelian randomization approach. Individual-level data from 30 480 CRC cases and 22 844 controls from 33 participating studies in three international consortia were used: the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), the Colorectal Transdisciplinary Study (CORECT) and the Colon Cancer Family Registry (CCFR). As instrumental variables, we included 19 single nucleotide polymorphisms (SNPs) previously associated with CRP concentration. The SNP-CRC associations were estimated using a logistic regression model adjusted for age, sex, principal components and genotyping phases. An inverse-variance weighted method was applied to estimate the causal effect of CRP on CRC risk. Among the 19 CRP-associated SNPs, rs1260326 and rs6734238 were significantly associated with CRC risk (P = 7.5 × 10-4, and P = 0.003, respectively). A genetically predicted one-unit increase in the log-transformed CRP concentrations (mg/l) was not associated with increased risk of CRC [odds ratio (OR) = 1.04; 95% confidence interval (CI): 0.97, 1.12; P = 0.256). No evidence of association was observed in subgroup analyses stratified by other risk factors. In spite of adequate statistical power to detect moderate association, we found genetically elevated CRP concentration was not associated with increased risk of CRC among individuals of European ancestry. Our findings suggested that circulating CRP is unlikely to be a causal factor in CRC development.