Plasma C-reactive Protein Concentrations Research Articles

Association between Inflammatory and Metabolic Biomarkers and Common Mental Disorders among Adults: 2015 Health Survey of São Paulo, SP, Brazil.

Recent studies suggest that plasma inflammatory biomarker concentrations may represent valuable indicators for the diagnosis and prognosis of mental disorders. At the same time, metabolic alterations may contribute to the development and progression of systemic low-grade inflammation. Background/Objectives: This study evaluated the association between plasma inflammatory biomarkers and common mental disorders (CMD), exploring the relationship between metabolic biomarkers, metabolic syndrome (MetS), and inflammatory biomarkers in younger and older adults. Methods: This cross-sectional study used data from the 2015 Health Survey of São Paulo with a Focus on Nutrition Study. The occurrence of CMD was assessed through the Self-Reporting Questionnaire (SRQ-20). Blood samples were used to measure plasma concentrations of inflammatory and cardiometabolic biomarkers. MetS was defined according to the International Diabetes Federation Consensus. The Mann-Whitney test compared inflammatory biomarker concentrations across CMD groups and cardiometabolic conditions, and logistic regression models explored associations between inflammatory biomarker concentration and CMD. Results: The sample included 575 participants, 22.6% (n = 130) of whom had CMD. Concentrations of plasminogen activator inhibitor 1, C-reactive protein (CRP), and the systemic low-grade inflammation score varied significantly among CMD groups. CRP concentrations were positively associated with the presence of CMD, independent of confounding factors. Participants with insulin resistance, dyslipidemia, and MetS exhibited significantly higher CRP concentrations than individuals without these conditions. Conclusions: The findings suggest that increased plasma CRP concentrations may be a potential risk factor for CMD. Higher CRP concentrations were observed in individuals with insulin resistance, dyslipidemia, and MetS. Future interventional studies should explore these hypotheses in diverse populations.

Possibility of correction of the blood-heart barrier damage as a consequence of the impact of the SARS-CoV-2 virus on the cardiovascular system in patients with coronary artery disease in combination with COVID-19.

damage to the blood-heart barrier (BHB) and endothelial dysfunction is a characteristic feature of congestive (cardiopulmonary) chronic heart failure (CHF), the main cause of death in elderly people with CHF caused by new coronavirus variants (SARS-CoV-2), but the mechanism of this phenomenon remains unclear. The aim of this project is to determine the mechanism of BHB damage in coronary artery disease (CAD) with COVID-19, as well as the possibility of its correction with the use of sulodexide. The endocardial endothelium (EE) is a barrier that prevents blood leakage from the endocardium to the interstitium; however, this barrier is impaired during the course of COVID-19 in patients with CAD. Previous studies have shown that one of the pathophysiological mechanisms is the activation of matrix metalloproteinases (MMPs) in CAD with CHF. MMP-9 degrades connexins, which leads to EE dysfunction. One study [Rubens P. et al. 2021] found a juxtacrine connection of EE with the myocyte and mitochondria (Mito), but how this works is still an open question. Materials and methods. We examined 65 patients with coronary artery disease diagnosed with COVID-19. Patients were divided into two groups: Group I (n=35) - patients who had been taking sulodexide at a dose of 500 LE x 2p/day for 6 months against the background of standard therapy of coronary artery disease; Group II (n=30) - patients without sulodexide. Echocardiography and laser Doppler flowmetry were performed at baseline and 6 months later. Echocardiography at the time of inclusion in the study revealed that 30 (50%) patients in group I and 14 (47%) patients in group II had reduced left ventricular ejection fraction (LV EF) values of 40 to 50%. After 6 months of treatment with sulodexide, a tendency to improve LV systolic function and decrease in left ventricular myocardial mass index (LFMMI) was noted in patients of group I. There were no differences between the groups at the time of inclusion in the study in terms of the level of the capillary flow reserve – occlusion test (CFRo) and the capillary flow reserve – nitroglycerin test (CFRn). A repeated study of CFR revealed a significant increase in CFRo and CFRn levels only in group I. In patients of group II, no significant changes in CFRo and CFRn were found. An inverse relationship between the level of CFRo and C-reactive protein (CRP) was found in patients of group I (r=0.52, p<0.05). After 6 months of treatment, plasma CRP concentrations decreased significantly: from 17.7 [1.3; 50.1] to 5.7 [1.0; 12.0] mg/L in group I (p=0.01) and from 14.2 [1.2; 27.0] to 4.2 [1.0; 11.0] mg/L in group II (p=0.01). No significant correlations between CRP level and CFRo after 6 months of treatment were found. There were correlations of CFRo and CFRn with left ventricular systolic function, as well as inverse relationships with the size of the left and right ventricles and systolic pressure in the pulmonary artery. There was a tendency to improve systolic and diastolic left ventricular function in the first group, where sulodexide was used, and no significant changes in echocardiography were noted in the second group. At the initial examination of patients, the ratio of CFRo and CFRn had no significant differences. After 6 months of treatment, a significant increase in the ratio of CFRo and CFRn was observed only in patients taking sulodexide, and no positive dynamics of this ratio was observed in group II. The results indicate that MMP-9 activation, endothelial damage, endothelial-myocyte (E-M) uncoupling, and mitochondrial-myocyte uncoupling in heart failure in patients with CAD combined with COVID-19 were detected to a significant extent; however, treatment with sulodexide successfully mitigated the destructive changes in the heart in CAD with CHF. The results obtained are directly relevant to the range of cardiac manifestations and phenotypes arising from COVID-19 complications in people with CAD. Conclusion. The obtained results confirm the improvement of microcirculation, as well as a tendency to improve systolic function and left ventricular myocardial mass index after 6 months of sulodexide treatment in patients with coronary artery disease with preserved and moderately reduced left ventricular ejection fraction (LV EF) who have undergone COVID-19. The described effects of improving endothelial function, as well as improving the state of the blood-brain barrier due to the use of sulodexide, make it possible to recommend the use of this drug in the category of patients with CAD to reduce the negative impact of COVID-19 on the cardiovascular system.

Methylglyoxal mediates the association between 2-hour plasma glucose and HbA1c with inflammation: The Maastricht Study.

Glucose excursions in persons with diabetes may drive chronic inflammation. Methylglyoxal (MGO) is formed from glucose, is elevated in persons with diabetes, and is a potent glycating agent linked with inflammation. We investigated whether glucose excursions are associated with low-grade inflammation and whether MGO mediates this association. We used data from The Maastricht Study, an extensive phenotyping study into the etiology of type 2 diabetes and its complications. Data of 3017 participants, who underwent an oral glucose tolerance test and where data on MGO levels and inflammation were available, were used. Linear regression analyses, adjusted for potential confounders, evaluated associations between fasting plasma glucose (FPG), 2-hours plasma glucose (2h-PG) and HbA1c and low-grade inflammation (stdβ, [95% confidence interval]), calculated from plasma concentrations of C-reactive protein, serum amyloid A, interleukin-6, interleukin-8, tumor necrosis factor and soluble intercellular adhesion molecule-1. Mediation analyses investigated whether MGO mediated these associations. 2h-PG (0.172 [0.110; 0.234]) and HbA1c (0.148 [0.101; 0.196]), but not FPG (0.049 [-0.002; 0.100]), were associated with low-grade inflammation. 2h-PG and HbA1c were also associated with 2h-MGO (0.471 [0.407; 0.534], and 0.244 [0.195; 0.294], respectively). Furthermore, 2h-MGO was independently and positively associated with low-grade inflammation (0.078 [0.037, 0.120]). 2h-MGO mediated 23% of the association between 2h-PG and inflammation, and 16% of the association between HbA1c and inflammation. MGO mediates the association between post-load glucose excursions and HbA1c with inflammation, providing evidence for a role of postprandial MGO formation to hyperglycemia-induced low-grade inflammation.

Effect of the Japanese herbal medicine Hochuekkito for systemic inflammation, prognostic nutrition index, and body composition status in patients with gastrointestinal cancer

A systemic inflammatory response via host-tumor interactions is a cancer hallmark that plays a pivotal role in the pathogenesis of malnutrition and sarcopenia in patients with malignancies. Hochuekkito (TJ-41) is a traditional Japanese herbal medicine that modulates inflammation in patients with various chronic inflammatory diseases. However, the clinical efficacy of TJ-41 in patients with malignancies remains unclear. We systemically analyzed chronological changes in levels of systemic inflammatory parameters, nutrition-related parameters, and body composition status in 99 patients who received TJ-41 treatment for more than 3 months. The cohort comprised 56 patients with gastrointestinal cancer (Cancer Cohort) and 43 with other diseases (Other Disease Cohort). We also performed invivo experiments in mice to validate the clinical findings. Despite no significant changes in serum albumin concentration and prognostic nutrition index, the serum C-reactive protein (CRP) concentration significantly decreased in a time-dependent manner in all patients. However, the serum CRP concentration significantly decreased during TJ-41 treatment in the Cancer Cohort but not the Other Disease Cohort. Furthermore, downregulation of CRP during TJ-41 treatment occurred only in patients with metastases. The psoas muscle index, as a muscle quantity marker, was significantly lower in the CRP-increased group compared with the CRP-decreased group during TJ-41 treatment. Invivo experiments using a Colon-26 syngeneic model showed that the plasma CRP, amyloid A, and interleukin-6 concentrations were significantly lower in the TJ-41 group than the control group. TJ-41 might be useful as part of multimodality therapy for gastrointestinal cancer, especially in patients with metastases.

Inflammatory Biomarkers in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Faction.

To verify the relationship between gene polymorphisms of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) with inflammation markers and codependent metabolic variables in patients with type 2 diabetes mellitus and chronic heart failure (CHF). This study included 154 patients (mean age, 69.1±3.2 years). The control group consisted of 47 patients with metabolic syndrome (MS) without CHF; the 2nd group included 56 patients with CHF with preserved ejection fraction (CHFpEF); and the 3rd group consisted of 51 patients with CHF with reduced ejection fraction (CHFrEF). The rs1800629 polymorphism of the TNF-α gene (TNF-α: G308A) was studied in real time by the polymerase chain reaction (PCR) method and the rs1800795 polymorphism of the IL-6 gene (IL-6: 174 G>C) was studied by PCR with the electrophoretic detection. The frequencies of polymorphic alleles were compared with the clinical blood test results, plasma concentrations of C-reactive protein (CRP), TNF-α, leptin, and fibrinogen. Differences between the groups were determined using the F test. Relationships between individual studied parameters were identified using the regression analysis. In most patients, the occurrence of gene polymorphisms was eident as increased plasma concentrations of biomarkers. An association was found between the TNF-α gene polymorphism (G308A) and an increase in plasma TNF-α and between the IL-6 gene polymorphism (174 C>G) and an increase in plasma CRP. In the CHFpEF group, the rs1800629 gene polymorphism was observed in 55% of patients, among whom 93% had increased TNF-α. The rs1800795 gene polymorphism was observed in 82% of CHFpEF patients, among whom 21% had increased CRP. In the CHFrEF group, the G308A transition in the TNF-α gene was observed in 53% of patients; an increase in the respective cytokine was noted in 67% of patients; the IL-6 gene polymorphism 174 C>G was found in 78%, however, only 14% of patients with this polymorphism had also increased CRP. In the control group, the TNF-α G308A gene polymorphism was found in 30% of patients, while an increase in free TNF-α was associated with this polymorphism in 50% of patients; the IL-6 174 C>G gene polymorphism was detected in 78%, while no increase in the CRP level was observed in this group. This demonstrates a high probability of the TNF-α G308A gene polymorphism occurrence in patients with CHF. Inflammatory markers are important predictors of CHF. The most significant predictor was the TNF-α G308A gene polymorphism, which was observed in more than 50% of patients, the majority of whom had an increase in plasma TNF-α.

Baseline C-reactive Protein as a Risk Factor for Cryptococcal Meningitis and Death in HIV-associated Cryptococcal Antigenemia With CrAg Titer as an Effect Modifier.

Persons with HIV and cryptococcal antigenemia are at high risk of progression to cryptococcal meningitis or death. Baseline cryptococcal antigen (CrAg) plasma titer ≥1:160 is a known risk factor for poor outcomes, but other risk factors are unknown. In HIV-associated cryptococcal meningitis, baseline serum C-reactive protein (CRP) concentrations are positively associated with increased mortality. We hypothesized that CRP might also be associated with meningitis or death in persons with cryptococcal antigenemia. We measured plasma CrAg titers and CRP concentrations on cryopreserved serum from prospectively enrolled persons with HIV and cryptococcal antigenemia. Using time-to-event analyses, we compared 24-week meningitis-free survival in persons with normal CRP (<8 mg/L) and elevated CRP (≥8 mg/L). Logistic regression was used to assess how CRP concentration and CrAg titer might interact as covariates. Of the 94 persons with elevated CRP, 19 (20.2%) developed meningitis or death, whereas of the 88 persons with normal CRP, 8 (9.1%) developed meningitis or death (P = .035). Persons with CrAg titer <1:160 and normal CRP had an ∼5% (3/61) event rate, whereas those with CrAg titer <1:160 but elevated CRP had an ∼20% (12/59) event rate. Importantly, we identified a statistically significant interaction effect between CrAg titer and CRP groups, in which elevated CRP increased risk in the low CrAg titer group (odds ratio, 1.54; 95% confidence interval, 1.16-2.04), but this effect was not present in high CrAg titer group (odds ratio, 0.78; 95% confidence interval, .53-1.15). Our findings demonstrate that CrAg titer may modify the direction of effect of CRP with meningitis-free survival; future studies should account for this interaction.

Elevated Plasma C-reactive Protein Related to Iron Overload in Maintenance Hemodialysis Patients with Anemia: A Cross-Sectional Observational Study in Vietnam

Background: Iron overload in MHD patients is associated with many factors, including inflammation. Objectives: We conducted this study to determine the ratio of iron overload and its relationship with elevated plasma C-reactive protein (CRP) concentration in maintenance hemodialysis (MHD) patients with anemia. Methods: A cross-sectional observational study was conducted on 103 MHD patients with anemia. Plasma iron, ferritin, total iron-binding capacity (TIBC), and CRP concentrations were measured in all patients. Transferrin saturation (TSAT) was calculated based on plasma ferritin and TIBC concentrations. Patients with plasma ferritin &gt; 800 ng/mL and/or TSAT &gt; 50% were determined to have iron overload. Results: The proportion of iron overload was 51.5% (53/103 patients). The median CRP concentration in the iron overload group was 3.15 (1.66 - 6.67) mg/L, higher than that of the non-iron overload group [1.5 (0.78 - 3.24) mg/L], P &lt; 0.001. Plasma CRP was an independent factor associated with iron overload (P = 0.003). It was also a valuable predictor for iron overload in MHD patients with anemia (AUC = 0.703; P &lt; 0.001). Conclusions: Plasma CRP was a good predictor of iron overload in maintenance hemodialysis patients with anemia.

Prognostic value of laboratory markers in patients with acute pulmonary embolism

BackgroundAcute pulmonary embolism (APE) is a serious illness. Identifying prognostic factors for APE may help in the management of those patients. This study’s objective was to evaluate the prognostic value of laboratory markers in predicting right ventricular dysfunction (RVD) and 30-day mortality in pulmonary embolism patients.MethodsEighty patients with APE were enrolled and followed up for 30 days. Detailed echocardiography was done to evaluate RVD. All patients were subjected to arterial blood gas analysis, complete blood count (CBC), plasma concentration of C-reactive protein (CRP), serum D-dimer level, and serum troponin I level, and the following ratio were calculated: neutrophil-to-lymphocytic ratio (NLR), platelet to lymphocytic ratio (PLR), red cell distribution width (RDW), mean platelet volume (MPV), and alveolar to arterial gradient.ResultsOur results analysis revealed significantly elevated levels of median NLR, PLR, CRP, D-dimer, and troponin in both the RVD and non-survivor groups (P value < 0.001). The blood markers that showed the highest predictive ability for right ventricular dysfunction (RVD) and 30-day mortality, as determined by receiver operating characteristic (ROC) analysis and logistic regression, were A-a O2 gradient, serum troponin, CRP, D-dimer, NLR, and PLR (P value < 0.001).ConclusionEvaluation of different serum markers including NLR, PLR, RDW, CRP, D-dimer, troponin, and A-a O2 gradient is a simple and available marker for predicting right ventricular dysfunction (RVD) and 30-day mortality in patients with APE.Trial registrationClinicalTrials.gov ID: NCT04237974.

Selenomethionine Supplementation Contributes to Reducing Oxidative Stress and Inflammation Markers following Exercise-Induced Muscle Damage

Background. Exercise-induced muscle damage (EIMD) is a temporary response to intense or prolonged exercise that can cause muscle pain, inflammation, and impaired muscle function. Antioxidant supplementation is a proposed strategy to reduce EIMD symptoms by targeting reactive oxygen and nitrogen species (RONS) involved in the process. Objective. The study aimed to investigate the effect of Selenomethionine supplementation on malondialdehyde (MDA) and C-reactive protein (CRP) levels resulting from Exercise-Induced Muscle Damage (EIMD). Materials and methods. This study used a randomized pretest-posttest control group design, involving a total of 32 male recreational students from the State University of Surabaya (Indonesian: Universitas Negeri Surabaya), (age 19.25 ± 0.76 years, body mass 63.16 ± 3.38 kg, height 167.28 ± 4.54 cm, body fat 19.60% ± 4.57%). The participants were randomly assigned to the selenomethionine group (SEM, 100 µg/day) or placebo group (PLA, corn starch 100 mg/day) for a period of 28 days (4 weeks). On days 1 (baseline) and 29, participants underwent a single bout of EIMD. Blood samples were collected 24 hours post-EIMD to measure MDA and CRP concentrations in plasma. The statistical analysis was conducted using paired sample t-test. Results. The placebo group experienced a significant increase in plasma MDA and CRP concentrations after EIMD compared with baseline values (p &lt; 0.05). However, the SeMet group showed lower plasma MDA and CRP levels than the placebo group. Conclusions. Daily Selenomethionine supplementation for 28 days has been found to reduce oxidative stress by lowering MDA levels in the blood and to decrease inflammation by reducing CRP levels post-exercise-induced muscle damage. This indicates a lower risk of EIMD due to reduced oxidative stress and inflammation.

Palliative effects of carnosol on lung-deposited pollutant particles-induced thrombogenicity and vascular injury in mice.

The toxicity of inhaled particulate air pollution perseveres even at lower concentrations than those of the existing air quality limit. Therefore, the identification of safe and effective measures against pollutant particles-induced vascular toxicity is warranted. Carnosol is a bioactive phenolic diterpene found in rosemary herb, with anti-inflammatory and antioxidant actions. However, its possible protective effect on the thrombotic and vascular injury induced by diesel exhaust particles (DEP) has not been studied before. We assessed here the potential alleviating effect of carnosol (20 mg/kg) administered intraperitoneally 1 h before intratracheal (i.t.) instillation of DEP (20 μg/mouse). Twenty-four hours after the administration of DEP, various parameters were assessed. Carnosol administration prevented the increase in the plasma concentrations of C-reactive protein, fibrinogen, and tissue factor induced by DEP exposure. Carnosol inhibited DEP-induced prothrombotic effects in pial microvessels invivo and platelet aggregation invitro. The shortening of activated partial thromboplastin time and prothrombin time induced by DEP was abated by carnosol administration. Carnosol inhibited the increase in pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor α) and adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and P-selectin) in aortic tissue. Moreover, it averted the effects of DEP-induced increase of thiobarbituric acid reactive substances, depletion of antioxidants and DNA damage in the aortic tissue. Likewise, carnosol prevented the decrease in the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) caused by DEP. We conclude that carnosol alleviates DEP-induced thrombogenicity and vascular inflammation, oxidative damage, and DNA injury through Nrf2 and HO-1 activation.

Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies

ObjectiveTo investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related.Research design and methodsObservational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC.ResultsObservationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10− 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (−0.04 (−0.12, 0.32) and − 0.03 (−0.13, 0.06)), nor of glucose on CRP (−0.01 (−0.08, 0.07) and − 0.00 (−0.14, 0.13)).ConclusionsElevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.

Admission plasma concentration of neutrophil gelatinase-associated lipocalin and -C-reactive protein have additive prognostic value in patients with STEMI

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): This work was supported by Righospitalets Forskningsfond (07IO) Lundbeck Foundation (R186-2015-2132). Background Inflammation plays an apparent critical role in patients with acute coronary syndrome (ACS) and is associated with mortality. However, the complex process is poorly understood. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel biomarker originating from mature neutrophils and renal tubular cells. It has previously been shown to be associated with mortality and acute kidney injury in ACS patients. In this study we sought to assess the potential additive prognostic value of NGAL and its relation to other markers of inflammation. Methods In 1556 consecutive ST-elevation myocardial infarction (STEMI) patients, NGAL and C-reactive protein (CRP) plasma concentration were measured at hospital admission, before acute coronary angiography. Patients were stratified to plasma concentration of both biomarkers &amp;gt;/&amp;lt; the median concentration into 4 groups (low NGAL/ low CRP (group 1), low NGAL/high CRP (2), high NGAL/low CRP (3), high NGAL/high CRP(4)). Primary outcome was 30-day all-cause mortality. Results In total, 477 (31%), 324 (21%), 316 (20%), and 439 (28%) patients were stratified in group 1-4, respectively. With 0, 1, or 2 biomarker plasma concentration above the median (group 1 – 4), patients were older (61 – 67 years old, p&amp;lt;0.0001), had more comorbidity (hypertension (40 – 53%), p=0.002; previous stroke (4.0 – 9.9%), p=0.007; peripheral arterial disease (PAD) (2.6 – 10%), p&amp;lt;0.0001; chronic kidney dysfunction (CKD) (0.6 – 11%), p&amp;lt;0.0001) and more critical per-infarction circumstances (time from symptom debut to angiography (170 – 229 minutes), p&amp;lt;0.0001; cardiogenic shock (1.3 – 14%), p&amp;lt;0.0001, cardiac arrest (0.8 – 3.4%), p=0.0002) and lower left ventricular ejection fraction (LVEF) (48 – 43%, p&amp;lt;0.0001). Increased NGAL and CRP was associated with 30-day all-cause mortality (Figure A). Only high NGAL/high CRP was independently associated with 30-day mortality in a cox proportional hazard model when adjusting for age, hypertension, previous stroke, CKD, LVEF, and cardiogenic shock (HR (95% CI) 5.19 (1.20 – 22.52), p=0.03). Both CRP and NGAL had significant predictive value of 30-day mortality (AUC ROC 0.67, p&amp;lt;0.0001 and 0.78, p&amp;lt;0.0001, respectively). Combining NGAL and CRP did, however, not increase the predictive value of NGAL alone (AUC ROC 0.77, p=0.86) (Figure B). Conclusion Combined admission NGAL and CRP plasma concentration was independently associated with 30-day all-cause mortality in STEMI patients. Adding CRP to NGAL did, however, not increase the predictive value.Figure AFigure B

Systemic inflammation, lifestyle behaviours and dementia: A 10-year follow-up investigation

ObjectivesLifestyle behaviours have been linked to dementia incidence, but their cumulative impact on dementia and the underlying mechanisms remain poorly understood. This study investigated the association of co-occurring lifestyle behaviours with dementia incidence and the mediating role of systemic inflammation in this association. MethodsThe sample comprised 3131 participants (55.2% female) from the English Longitudinal Study of Ageing aged 52–92 years at baseline (2008/09). Self-reported baseline lifestyle behaviours (alcohol intake, fruit and vegetable consumption, smoking, physical activity, sleep duration, social engagement, and cognitive activity) were summed to derive an index of lifestyle behaviours, ranging from 0 to 7, with higher scores denoting a higher number of health-risk behaviours. Incident dementia cases (n = 130, 4.2%) were identified through doctor-diagnosed dementia, informant interviews, and health records between 2014/15 and 2018/19. Systemic inflammation was measured through fasting plasma concentrations of C-reactive protein in 2012/13. ResultsBinary logistic regression models indicated that the odds of subsequent dementia increased by 1.19 for each additional health-risk behaviour (95% confidence intervals: 1.04, 1.37, p = 0.014) after adjusting for age, sex, ethnicity, wealth, education, marital status, body mass index, coronary heart disease, hypertension, stroke, and depression. However, this association was not mediated by C-reactive protein. ConclusionsCo-occurring health-risk behaviours were associated with higher dementia incidence up to 10 years later, underscoring the importance of modifying health-risk behaviours for the prevention of dementia. Systemic inflammation did not explain the association between behaviours and dementia.

C-reactive protein, cardiovascular issues of an acute-phase protein: an update for theclinician

Inflammation is an important pathogenic factor for the development of atherosclerotic cardiovascular disease. Currently, the most frequently used biomarker reflecting systemic inflammation is C-reactive protein (CRP), an acute-phase protein produced primarily by hepatocytes under the influence of interleukin-6, interleukin-1 beta, and tumor necrosis factor. Growing evidence from epidemiological studies has shown a robust association between elevated serum or plasma CRP concentrations and the incidence of a first cardiovascular adverse event (including acute myocardial infarction, ischemic stroke, and sudden cardiac death) in the general population, as well as recurrence of major adverse cardiovascular events among patients with established disease. The additive value that CRP measurement gives to traditional risk factors is reflected in novel cardiovascular risk calculators and in current intervention regimens, which already consider CRP as a target therapeutic. However, the variations in CRP levels, that depend on sex, ethnicity, hormonal status, and some peculiarities of the measurement assays, must be taken into consideration when deciding to implement CRP as a useful biomarker in the study and treatment of atherosclerotic cardiovascular disease. This review aims to offer an updated vision of the importance of measuring CRP levels as a biomarker of cardiovascular risk beyond the traditional factors that estimate the risk of atherosclerotic disease.

A combination nutritional supplement reduces DNA methylation age only in older adults with a raised epigenetic age

An increase in systemic inflammation (inflammaging) is one of the hallmarks of aging. Epigenetic (DNA methylation) clocks can quantify the degree of biological aging and this can be reversed by lifestyle and pharmacological intervention. We aimed to investigate whether a multi-component nutritional supplement could reduce systemic inflammation and epigenetic age in healthy older adults.We recruited 80 healthy older participants (mean age ± SD: 71.85 ± 6.23; males = 31, females = 49). Blood and saliva were obtained pre and post a 12-week course of a multi-component supplement, containing: Vitamin B3, Vitamin C, Vitamin D, Omega 3 fish oils, Resveratrol, Olive fruit phenols and Astaxanthin. Plasma GDF-15 and C-reactive protein (CRP) concentrations were quantified as markers of biological aging and inflammation respectively. DNA methylation was assessed in whole blood and saliva and used to derive epigenetic age using various clock algorithms.No difference between the epigenetic and chronological ages of participants was observed pre- and post-treatment by the blood-based Horvath or Hannum clocks, or the saliva-based InflammAge clock. However, in those with epigenetic age acceleration of ≥ 2 years at baseline, a significant reduction in epigenetic age (p = 0.015) and epigenetic age acceleration (p = 0.0058) was observed post-treatment using the saliva-based InflammAge clock. No differences were observed pre- and post-treatment in plasma GDF-15 and CRP, though participants with CRP indicative of an elevated cardiovascular disease risk (hsCRP ≥ 3µg/ml), had a reduction in CRP post-supplementation (p = 0.0195).Our data suggest a possible benefit of combined nutritional supplementation in individuals with an accelerated epigenetic age and inflammaging.

Prognostic Value of Pretreatment Plasma C-Reactive Protein in Patients with Early-Stage Breast Cancer.

Breast cancer incidence is now the highest among all cancers and accountable for 6.6% of all cancer-related deaths worldwide. Studies of the prognostic utility of plasma C-reactive protein (CRP) measurement in early-stage breast cancer have given discrepant results. We identified 6,942 patients in the Danish Breast Cancer Cooperative Group database with early-stage breast cancer diagnosed between 2002 and 2016 who had a measure of pretreatment plasma CRP. Outcomes were recurrence-free interval and survival for a period up to 10 years. We analyzed associations with plasma CRP using Fine-Gray proportional subdistribution hazards model with recurrence-free interval. Data on plasma CRP were analyzed per doubling of concentration and in relation to CRP levels of <3 mg/L, 3 to 10 mg/L, and >10 mg/L and stratified according to standard clinical parameters in sensitivity analyses. A doubling of the plasma CRP concentration was associated with increased risk of recurrence (multivariate adjusted HR, 1.05; 95% CI, 1.01-1.08) and shorter survival (HR, 1.13; 95% CI, 1.09-1.16) in multivariate analyses. Survival was shorter in patients with plasma CRP levels of 3 to 10 and >10 mg/L versus <3 mg/L, with multivariate adjusted HRs of 1.30; 95% CI, 1.17-1.45 and 1.65; 95% CI, 1.39-1.95, respectively. Elevated plasma CRP measured before treatment in patients with early-stage breast cancer is an independent biomarker of increased risk of recurrence and early death. CRP measures before treatment might be used to individualize follow-up of patients with early-stage breast cancer.

Inflammation, the kynurenines, and mucosal injury during human experimental enterotoxigenic Escherichia coli infection

Enterotoxigenic Escherichia coli (ETEC) is an important cause of diarrhea in children and travelers, especially in low- and middle-income countries. ETEC is a non-invasive gut pathogen colonizing the small intestinal wall before secreting diarrhea-inducing enterotoxins. We sought to investigate the impact of ETEC infection on local and systemic host defenses by examining plasma markers of inflammation and mucosal injury as well as kynurenine pathway metabolites. Plasma samples from 21 volunteers experimentally infected with ETEC were collected before and 1, 2, 3, and 7 days after ingesting the ETEC dose, and grouped based on the level of intestinal ETEC proliferation: 14 volunteers experienced substantial proliferation (SP) and 7 had low proliferation (LP). Plasma markers of inflammation, kynurenine pathway metabolites, and related cofactors (vitamins B2 and B6) were quantified using targeted mass spectrometry, whereas ELISA was used to quantify the mucosal injury markers, regenerating islet-derived protein 3A (Reg3a), and intestinal fatty acid-binding protein 2 (iFABP). We observed increased concentrations of plasma C-reactive protein (CRP), serum amyloid A (SAA), neopterin, kynurenine/tryptophan ratio (KTR), and Reg3a in the SP group following dose ingestion. Vitamin B6 forms, pyridoxal 5'-phosphate and pyridoxal, decreased over time in the SP group. CRP, SAA, and pyridoxic acid ratio correlated with ETEC proliferation levels. The changes following experimental ETEC infection indicate that ETEC, despite causing a non-invasive infection, induces systemic inflammation and mucosal injury when proliferating substantially, even in cases without diarrhea. It is conceivable that ETEC infections, especially when repeated, contribute to negative health impacts on children in ETEC endemic areas.

P951 Efficacy and safety of tofacitinib for the treatment of moderate- severe ulcerative colitis in biologic naïve patients

Abstract Background To assess the rates of clinical response at week 8, biochemical response, steroid-free clinical remission, endoscopic healing and safety data at week 26 of tofacitinib in biologic naive patients with moderate-severe ulcerative colitis (UC). Methods This was a retrospective analysis of prospectively collected data extracted from the notes of biologic naïve patients with moderate-severe UC who were treated with tofacitinib in the last 3 years in 5 Greek IBD centers and who had a follow up of at least 26 weeks after initiation of treatment. Tofacitinib was administered at a dose of 10 mg bid for 8 or 16 weeks followed by a maintenance dose of 5mg bid thereafter. Week-8 or -16 clinical response was defined as the reduction in the partial Mayo score of at least 2 points, without concomitant use of any steroid preparation [budesonide, prednis(ol)one, or methylprednisolone]. Steroid free clinical remission at week 26 was defined as a partial Mayo score of ≤1 points without concomitant use of any steroid preparation. Biochemical response at week 26 was defined as any reduction in fecal calprotectin or plasma C-reactive protein concentrations as compared to their baseline levels.Mucosal healing at week 26 was defined as Mayo endoscopic sub-score of ≤1. A safety list of all reported adverse events was completed. Treatment discontinuation due to adverse events was considered as treatment failure, whereas patients needing escalation of the maintenance dose were also considered as non-responders. Results Overall, 41 patients (26 males), aged (mean, SD) 35.2 (12.7) years and disease duration of mean (SD) 6.5 (4.8) years were included. UC was extensive in 22, left-sided in 17, and proctitis in 2 patients. Clinical response was seen in 31 (75.6%) and 34 (82.9%) patients at week 8 and 12 respectively.Biochemical response and steroid free clinical remission at week 26 were seen in 35 (85.4%) patients. Endoscopic healing was seen in 29 (70.7%) patients. Adverse events,which did not lead to treatment discontinuation, occurred in 5 patients (hyperlipidemia n=3, elevated liver enzymesn=1, herpes zoster n=1). Conclusion In this retrospective real-world ongoing cohort study, tofacitinib demonstrated clinical response at week 8 or 16 and steroid free clinical remission at week 26 in more than 75% of biologic naïve patients with moderate-severe UC with a good safety profile.

Zinc status and indicators of intestinal health in enterotoxigenic Escherichia coli F18 challenged newly weaned pigs fed diets with different levels of zinc.

This study investigated the impact of an enterotoxigenic Escherichia coli (ETEC) F18 challenge on newly weaned pigs when fed one of three Zn levels (150, 1,400, or 2,500ppm) on performance, Zn status, ETEC shedding, and diarrhea. The ETEC challenge was hypothesized to have a more pronounced negative impact on pigs fed a diet containing 150ppm Zn compared to 1,400 or 2,500ppm Zn for 14 d after weaning. The study included 72 ETEC F18 susceptible pigs weaned at ~28 d of age (d 0 of the study). The pigs were distributed according to initial weight and litter to one of the three dietary Zn levels. Half of the pigs were challenged with ETEC on d 1 and 2. The challenge reduced (P ≤ 0.03) feed intake and average daily gain (ADG) during d 3 to 5. Challenged pigs fed 150ppm Zn had lower (P = 0.01) ADG during d 5 to 7 compared to those fed 1,400 or 2,500ppm Zn, whereas control pigs' ADG were not affected by dietary Zn content. Challenged pigs fed 150ppm Zn also showed lower (P < 0.01) fecal dry matter (DM) on d 5 compared to control pigs fed 150ppm Zn and challenged pigs fed 1,400 or 2,500ppm Zn. Challenge increased (P < 0.01) ETEC shedding in all groups, but challenged pigs fed 150ppm Zn showed higher (P ≤ 0.05) fecal shedding of ETEC and toxins than when fed 1,400 or 2,500ppm. On d 3, C-reactive protein concentration in plasma was lower (P < 0.03) for pigs fed 1,400 and 2,500 compared to 150ppm Zn. Plasma haptoglobin and pig major acute phase protein were unaffected by dietary Zn content. On d 0, the serum Zn concentration was 586 ± 36.6 µg/L, which pigs fed 150ppm Zn maintained throughout the study. The serum Zn concentration increased (P ≤ 0.07) in pigs fed 1,400 or 2,500ppm Zn. The challenge decreased (P < 0.01) the serum Zn concentration in pigs fed 2,500ppm Zn. On d 5 and 7, serum Zn concentration was similar for challenged pigs fed 1,400 and 2,500ppm Zn, while control pigs fed 2,500ppm Zn had higher (P < 0.01) serum Zn concentration than 1,400ppm Zn. On d 7, serum Zn concentration tended (P = 0.08) to be lower for pigs with diarrhea (fecal DM ≤ 18%). In summary, these results indicate that newly weaned pigs fed 150ppm Zn are more susceptible to ETEC F18 colonization and its adverse consequences such as diarrhea and reduced growth, even though challenge did not increase acute phase proteins.

Association of systemic inflammation with shock severity, 30-day mortality, and therapy response in patients with cardiogenic shock

BackgroundMortality in cardiogenic shock (CS) remains high even when mechanical circulatory support (MCS) restores adequate circulation. To detect a potential contribution of systemic inflammation to shock severity, this study determined associations between C-reactive protein (CRP) concentrations and outcomes in patients with CS.MethodsUnselected, consecutive patients with CS and CRP measurements treated at a single large cardiovascular center between 2009 and 2019 were analyzed. Adjusted regression models were fitted to evaluate the association of CRP with shock severity, 30-day in-hospital mortality and treatment response to MCS.ResultsThe analysis included 1116 patients [median age: 70 (IQR 58–79) years, 795 (71.3%) male, lactate 4.6 (IQR 2.2–9.5) mmol/l, CRP 17 (IQR 5–71) mg/l]. The cause of CS was acute myocardial infarction in 530 (48%) patients, 648 (58%) patients presented with cardiac arrest. Plasma CRP concentrations were equally distributed across shock severities (SCAI stage B–E). Higher CRP concentrations were associated with 30-day in-hospital mortality (8% relative risk increase per 50 mg/l increase in CRP, range 3–13%; p < 0.001), even after adjustment for CS severity and other potential confounders. Higher CRP concentrations were only associated with higher mortality in patients not treated with MCS [hazard ratio (HR) for CRP > median 1.50; 95%-CI 1.21–1.86; p < 0.001], but not in those treated with MCS (HR for CRP > median 0.92; 95%-CI 0.67–1.26; p = 0.59; p-interaction = 0.01).ConclusionElevated CRP concentrations are associated with increased 30-day in-hospital mortality in unselected patients with cardiogenic shock. The use of mechanical circulatory support attenuates this association.Graphical abstract