Marker Of Low-grade Inflammation Research Articles

Assessment of Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio as Inflammatory Markers among Sudanese Patients with Chronic Kidney Disease in Kordofan state- 2024

Background and Objective: Low grade chronic inflammation is one of the central pathophysiological factors in chronic kidney disease (CKD). The complete blood count is a routine, inexpensive and easy test that provides information about formed blood contents. Neutrophil/lymphocyte ratio) NLR) and platelet lymphocyte ratio (PLR) are simple parameters and novel inflammatory marker, which may be used in many diseases for predicting inflammation. The aim of this study is to assess the utilization of NLR And PLR as inflammatory markers in patient with CKD. Methods: A cross- sectional descriptive study including 59 participants at different stage of CKD which was conducted. CKD was assessed based on glomerular filtration rate (GFR). Quantitative C-reactive protein (CRP) was analyzed by a fluorescence immunochromatographic methods as the bench inflammatory marker. NLR and PLR were calculated after complete blood count was performed. Results: Based on CRP value the participants were subdivided into two groups the first is group without inflammation (CRP <1) and the second with inflammation (CRP > 1). The study revealed the mean of NLR was slightly higher (3.08) in the group that had inflammation, unlike other (2.78). while the mean PLR within normal range in two groups (inflamed = 132.5, non-inflamed = 151.7). our study was showing positive correlation between NLR and CRP (R= 0.05, P= 0.000). with regards to PLR and CRP the correlation was not significant. Conclusion: Depending of these results, it can be concluded that NLR, together with CRP, may serve as a marker of systemic low-grade inflammation in patients with CKD. Larger prospective cohort studies in various ethnic groups are required to assess the possibility of using NLR as an alternative marker for CRP in patients with CKD.

From geriatric assessment to inflammation. A pilot, observational, study about frailty components in older patients with persistent atrial fibrillation

BackgroundAtrial fibrillation (AF) is the most common arrhythmia diagnosed at an older age. AF is associated with frailty, a condition possibly justifying the higher rate of complications and mortality in aged individuals. This study was aimed at describing the characteristics correlated to frailty in older AF subjects. MethodsAfter having excluded a < 3 months major surgery procedure, cancer or other conditions associated with activation of inflammation, and a life expectancy < 12 months, we consecutively enrolled patients ≥ 65 years with persistent AF. They underwent a Comprehensive Geriatric Assessment evaluation. In particular, Mini-Mental State Examination, 15-item Geriatric Depression Scale and Short-Physical Performance Battery (SPPB) described, respectively, cognitive profile, depressive symptoms and physical performance. A venous blood sample was collected to measure interleukin-6 (IL-6; marker of low-grade inflammation) and acylcarnitines, expression of mitochondrial dysfunction and abnormal energy production. ResultsOverall, 49 patients (mean age: 76 ± 6 years; women 30.6 %) were studied. Cluster analysis described two different patterns; the second (N = 18, 36.7 %), when compared to the first one (N = 31, 63.3 %), was characterized by a worse phenotype, identified by the simultaneous presence of lower body mass index, higher CHA2DS2-VASc score (index of clinical complexity), worse SPPB functional performance, and high IL-6 levels. Second cluster patients had a higher concentration of 13 of the 35 acylcarnitines evaluated and increased 5-year mortality. All these features can outline a frail condition. ConclusionsBody size, clinical complexity, physical performance and low-grade inflammation seem to rapidly and adequately describe frailty.

Examining systemic inflammation as a pathway linking peer victimization to depressive symptoms in adolescence.

Adolescents exposed to victimization are at an increased risk for a variety of adverse mental health outcomes, including depressive symptoms. Yet, the biological pathways underlying these associations remain poorly understood. Focusing on within-person processes, we examined whether low-grade systemic inflammation mediated the longitudinal associations between peer victimization and depressive symptoms in adolescence. 207 adolescents (at baseline Mage = 12.69 years; SD = 0.49; 43.5% female) participated in a multi-wave longitudinal study, with assessments repeated every 6 months over 1.5 years. At each assessment wave, participants self-reported their peer victimization experiences and depressive symptoms. Dried blood spots were collected at each wave using a finger prick procedure to assay a key marker of low-grade systemic inflammation, interkeukin-6 (IL-6). Data were analyzed using random-intercept cross-lagged panel models. The cross-lagged paths from IL-6 to depressive symptoms were significant across all models and waves (β12 = .13; β23 = .12; β34 = .08), indicating that when adolescents' levels of low-grade systemic inflammation were above their person-specific average, they reported increased levels of depressive symptoms in the subsequent months. However, no significant cross-lagged within-person associations emerged between peer victimization and either IL-6 or depressive symptoms. The findings provide no evidence for the hypothesized mediating role of inflammation in the within-person associations between peer victimization and depressive symptoms. Nevertheless, they extend prior research by indicating that elevated levels of low-grade systemic inflammation predict the development of depressive symptoms in adolescence.

Dissecting depression symptoms: Multi-omics clustering uncovers immune-related subgroups and cell-type specific dysregulation

In a subset of patients with mental disorders, such as depression, low-grade inflammation and altered immune marker concentrations are observed. However, these immune alterations are often assessed by only one data type and small marker panels. Here, we used a transdiagnostic approach and combined data from two cohorts to define subgroups of depression symptoms across the diagnostic spectrum through a large-scale multi-omics clustering approach in 237 individuals. The method incorporated age, body mass index (BMI), 43 plasma immune markers and RNA-seq data from peripheral mononuclear blood cells (PBMCs). Our initial clustering revealed four clusters, including two immune-related depression symptom clusters characterized by elevated BMI, higher depression severity and elevated levels of immune markers such as interleukin-1 receptor antagonist (IL-1RA), C-reactive protein (CRP) and C-C motif chemokine 2 (CCL2 or MCP-1). In contrast, the RNA-seq data mostly differentiated a cluster with low depression severity, enriched in brain related gene sets. This cluster was also distinguished by electrocardiography data, while structural imaging data revealed differences in ventricle volumes across the clusters. Incorporating predicted cell type proportions into the clustering resulted in three clusters, with one showing elevated immune marker concentrations. The cell type proportion and genes related to cell types were most pronounced in an intermediate depression symptoms cluster, suggesting that RNA-seq and immune markers measure different aspects of immune dysregulation. Lastly, we found a dysregulation of the SERPINF1/VEGF-A pathway that was specific to dendritic cells by integrating immune marker and RNA-seq data. This shows the advantages of combining different data modalities and highlights possible markers for further stratification research of depression symptoms.

Soluble and Cellular Inflammatory Predictive Markers Associated with Recurrent Pregnancy Loss Among Kazakhstani Women: a Pilot Study

&lt;b&gt;Background:&lt;/b&gt; Recurrent pregnancy loss (RPL) is a common complication of pregnancy globally, characterized by multiple miscarriages but with poorly explained etiologies. Insofar as a state of low-grade inflammation (LGI) accompanies RPL, this study explores the link between RPL and markers of LGI among Kazakhstani women.&lt;br /&gt; &lt;b&gt;Methods: &lt;/b&gt;The retrospective study was conducted on 112 Kazakh women, comprising 64 with a confirmed diagnosis of RPL and 48 women with two or more uncomplicated pregnancies serving as controls. Statistical analysis was performed on SPSS 29 software.&lt;br /&gt; &lt;b&gt;Results:&lt;/b&gt; All tested blood analytes, including CRP, glucose, cholesterol, LDL-cholesterol, Hemoglobin, and RBC counts, were negatively associated with RPL. The only exception was neutrophil values having a positive association with RPL despite a lack of significant correlation between groups.&lt;br /&gt; &lt;b&gt;Conclusion:&lt;/b&gt; The study shows a marginal association between the LGI biomarkers considered and the overall risk factors of RPL in Kazakh women, which is in apparent contradiction with earlier studies. The absence of parallel studies in Central Asian countries hampers the analysis of study trends in related communities. Future case-control studies with more sample sizes are needed to explore the RPL biomarkers in depth.

Associations of fruit intake with adiposity and cardiometabolic biomarkers in UK Biobank

BackgroundFruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress.MethodsThe main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake.ResultsFruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations.ConclusionsWe observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.

Low-grade systemic inflammation links heavy metal exposures to mortality: A multi-metal inflammatory index approach

Certain heavy metals have been correlated to an elevated risk of inflammation-related diseases and mortality. Nevertheless, the intricate relationships between metal exposure, inflammation and mortality remain unknown. We included 3741 adults with measurements of ten urinary heavy metals in the National Health and Nutritional Examination Survey (NHANES) 2005–2010, followed up to December 31, 2019. Low-grade systemic inflammation was evaluated by various markers, including C-reactive protein (CRP) and ratios derived from regular blood tests. We assessed associations between heavy metal and all-cause mortality using multivariate COX regressions. Then we assessed the mediation effect of low-grade systemic inflammation on the associations via Sobel Test. To gauge the systemic inflammatory potential of the multi-metal mixture and its correlation with all-cause mortality, a Metal Mixture Inflammatory Index (MMII) was developed using reduced rank regression (RRR) models. The association between MMII and all-cause mortality was explored via multivariate COX regressions. Cadmium, antimony and uranium displayed positive associations with mortality, with hazard ratios (HR) ranging from 1.18 to 1.46 (all P-FDR < 0.05). Mediation analyses revealed that the associations between specific heavy metals (cadmium and antimony) and mortality risk were slightly mediated by the low-grade systemic inflammation markers, with mediation proportions ranging from 3.11 % to 5.38 % (all P < 0.05). MMII, the weighted sum of 9 heavy metals, significantly predicted platelet-to-lymphocyte ratio (PLR) and CRP (β = 0.10 and 1.16, all P < 0.05), was positively associated with mortality risk (HR 1.28, 95 % CI 1.14 to 1.43). Exposure to heavy metals might increase all-cause mortality, partly mediated by low-grade systemic inflammation. MMII, designed to assess the potential systemic inflammatory effects of exposure to multiple heavy metals, was closely related to the all-cause mortality risk. This study introduces MMII as an approach to evaluating co-exposure and its potential health effects comprehensively.

Novel low-grade inflammation markers in children with attention deficit hyperactivity disorder

Novel low-grade inflammation markers in children with attention deficit hyperactivity disorder

Markers of chronic low-grade inflammation and serum cytokine levels in patients with type 1 diabetes: associations with time in ranges and glucose variability

BACKGROUND: Increased glucose variability is recognized as a risk factor for vascular diabetic complications. It is assumed that deteriorating effect of GV on blood vessels can be realized through the activation of inflammatory signaling pathways.AIM: to determine associations of low-grade inflammation markers and serum cytokines with time in ranges and GV parameters derived from continuous glucose monitoring (CGM) in patients with type 1 diabetes (T1D).MATERIALS AND METHODS: In 470 adult patients with T1D, high-sensitivity C-reactive protein (hsCRP) and fibrinogen was measured, neutrophil-lymphocyte ratio (NLR) and the Systemic Immune-inflammation Index (SII) were calculated. In a sample of 130 patients and 20 healthy individuals (control), serum concentrations of interleukins (IL-1β, IL-4, IL-6, sIL-6Rα, IL-19, IL-20, IL-22, IL-26, IL-27, IL-28A, IL-29, IL-32, IL-34, IL-35) were assessed by multiplex analysis. Time in the ranges and GV parameters: Coefficient of Variability (CV), Mean Amplitude of Glycemic Excursions (MAGE), and Mean Absolute Glucose rate of changes (MAG) were derived from CGM data.RESULTS: Patients with Time In Range (TIR) &lt;70% had higher concentrations of hs-CRP and fibrinogen, higher SII values, and demonstrated a trend toward higher TIR compared with those with TIR ≥70% (p=0.018, p=0.026, p=0.037, p=0.101, respectively). Patients with T1D, when compared to control, demonstrated increased concentrations of IL-1β (p&lt;0.0001), IL-6 (p&lt;0.0001), decreased levels of IL-4 (p=0.002), and a tendency to decrease IL-22 and IL-29 (p=0.1). Patients with TIR&gt;70% had higher levels of IL-4 (p=0.02) as well as lower concentrations of IL-1β (p=0.0003) and IL-6 (p=0.007) than patients with TIR≤70%. In a multivariate stepwise regression analysis including clinical data and CGM parameters as independent variables, body mass index was positive predictor of hsCRP and fibrinogen levels, TIR was negatively associated with IL-20 and IL-34, time above range was associated positively with IL-1β, MAGE showed positive association with SII, IL-26 and IL28A, while MAG was positively associated with IL-29.CONCLUSION: T1D patients with non-target TIR (&lt;70%) have higher levels of low-intensity inflammatory markers and serum pro-inflammatory cytokines than patients with TIR&gt;70%. Both hyperglycemia and increased GV are associated with intensity of low-grade inflammation in T1D.

Association of inflammatory markers and ultrasonographic indicators of endothelial (dys)function in humans

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The Austrian Science Fund (FWF) Introduction It has been widely known that chronic inflammation is a crucial factor in the process of atherogenesis and atherosclerosis. Also, endothelial dysfunction presents the first and still reversible step of that process.(1) It is a challenge to find a laboratory marker whose levels would be informative about the extent of endothelial dysfunction and atherogenesis in humans. Purpose The aim of the present study was to determine associations between markers of chronic, low-grade inflammation and ultrasonographic indicators of endothelial (dys)function in healthy volunteers (H) and in patients with metabolic syndrome (MS). Methods Any kind of clinically manifest acute inflammatory or infectious disease, as well as chronic inflammatory, autoimmune or malignant disease was an exclusion criterion for participation. Serum levels of C-reactive protein (CRP) were measured using standard clinical chemistry analyser, and serum levels of interleukin-6 (IL-6) using electro-chemiluminescence immunoassay. Blood vessel wall function was quantified as flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD), which were measured automatically and continuously using the ultrasound device with linear probe (10 MHz) and the software for ultrasound blood vessel diameter analysis,(2) following currently valid guidelines.(3,4,5) Results A total of 130 individuals were enrolled in the study (65 H and 65 MS), with a median age of 56 (IQR 50.0, 60.0) years and 47.7% women in each group. CRP and IL-6 levels, although being very low and within the intervals that are considered normal in everyday clinical practice for both groups [CRP - H: 1.2 (0.6, 2.3), MS: 2.4 (1.2, 5.5) μg/mL; IL-6 - H: 2.3 (1.7, 3.0), MS: 4.1 (2.7, 6.8) pg/mL], were significantly higher in the MS compared to H (both p&amp;lt;0.001). The MS group also had significantly lower FMD (p=0.013) and NMD (p=0.033) compared to H. In H, IL-6 levels were significantly negatively correlated with FMD (r=-0.46, p&amp;lt;0.001), but not with NMD; whereas no significant associations of IL-6 levels with FMD or NMD were observed in the MS group. CRP levels were not significantly associated with FMD or NMD in neither the H nor MS group. Conclusion Higher IL-6 serum levels in the absence of acute inflammatory or infectious disease are significantly associated with lower FMD values among individuals with low risk for cardiovascular diseases, who are still considered healthy. Direct correlation is attenuated and lost among individuals with developed clinical signs of metabolic syndrome, probably due to its complex pathophysiology, as well as redundant and interdependent mechanisms contributing to the occurrence of endothelial dysfunction in such an environment. Further investigation on larger cohorts is needed to determine whether IL-6 serum levels could serve as a marker of endothelial dysfunction in individuals without clinically developed traditional risk factors and symptoms of cardiovascular disease.

#1815 The neutrophil/lymphocyte, neutrophil/HDL-cholesterol, and monocyte/HDL-cholesterol ratios as simple markers of low-grade inflammation in CKD patients

Abstract Background and Aims Chronic kidney disease (CKD) has been associated with inflammation and oxidative stress, as well as with high cardiovascular (CV) morbidity and mortality. The neutrophil/lymphocyte (NLR), neutrophil/HDL-cholesterol (NHR), and monocyte/HDL-cholesterol (MHR) ratios have been linked both to inflammation and increased CV risk in a variety of diseases. The aim of this study was to investigate changes in these ratios in CKD patients of stage 2-5 without any clinical and laboratory signs of inflammation, and to compare these indicators with those in healthy volunteers. Method A retrospective cross-sectional study was conducted in 88 healthy volunteers and 187 CKD patients (50 of stage 2, 44 of stage 3a, 45 of stage 3b and 48 of stage 4-5). Patients with acute renal impairment, nephrotic proteinuria, infections, systemic inflammation, malignancies and hematologic diseases were excluded, as were those receiving hypolipidemic, corticosteroid, immunosuppressive or immunostimulant drugs. The whole blood samples were collected and the absolute numbers of neutrophils, lymphocytes, and monocytes were used for calculation of NLR, NHR and MHR, respectively. Serum creatinine, HDL-cholesterol, C-reactive protein (CRP) and albumin were measured and eGFR calculated according to the CKD EPI equation. Statistical analysis was performed with the Mann-Whitney, Shapiro–Wilk, Kruskal-Wallis, and Spearman's correlation tests using the SPSS software. Results The NLR, NHR and MHR were higher in CKD patients when compared to healthy volunteers (P &amp;lt; 0,001), but only NLR and NHR increased significantly across CKD stages (P &amp;lt; 0,01). The ratio differences between CKD stages were more evident for NHR which was also in best correlation with eGFR (ρ = −0,406, P &amp;lt; 0,001). The CRP values increased across CKD stages as well (P &amp;lt; 0,01) although remaining within the reference range. The NLR, NHR and MHR were significantly related to CRP with NHR providing the best correlation (ρ = 0,289, P &amp;lt; 0,001). Conclusion This study showed that NLR and NHR increased across CKD stages 2-5 and could be used to identify low-grade inflammation in this population even within normal CRP values.

ASSOCIATION OF SUBCLINICAL INFLAMMATION MARKERS WITH PRIMARY HYPERTENSION IN CHILDREN - A SYSTEMATIC REVIEW WITH META-ANALYSIS

Objective: Primary hypertension (PH) is a growing threat to children's health. The pathogenesis of this phenomenon is not fully known, and subclinical inflammation and activation of the immune system are potential explanations. This systematic review and meta-analysis aimed to systematically determine whether there is an association between low–grade inflammation markers and PH in children. Design and method: The MEDLINE, EMBASE, and Cochrane databases were searched up to March 2023, with no language restrictions, for cohort, cross-sectional, and case-control studies; additional references were obtained from reviewed articles. The included studies needed to investigate an association between any inflammation markers and PH defined by the authors. Participants of the study were children (&lt;18 years old) with PH and healthy controls. The main outcome measured was the concentration of any subclinical inflammation markers in children with PH and in healthy controls. This meta-analysis included 12 studies published between 2005 and 2022, enrolling 1220 patients (689 with PH and 531 healthy controls). The data were analyzed using Review Manager. Pooled mean difference (MD) with 95% confidence interval (95% CI) was used to assess the differences in inflammation markers levels. All analyses were based on the random-effect model. The risk of bias was assessed using the Newcastle-Ottawa Scale. Results: There was a significant difference between hypertensive and control groups in high-sensitivity C-reactive protein (hsRCP) concentration (MD: 0.07 95%CI [0.04,0.09]), intercellular adhesion molecule 1 (ICAM-1) (MD: 85.28 95%CI: [50.57-119.99]), vascular cell adhesion molecule 1 (VCAM-1) (MD: 259.78 95%CI: [22.65-496.91]), neutrophil count (MD: 0.80 95%CI [0.53-1.07]), monocyte count (MD: 0.07 95%CI: [0.02-0.12]), and neutrophil-to-lymphocyte ratio (NLR) (MD: 0.49 95%CI: [0.32-0.65]). There was no difference in terms of interleukin 6 (IL-6), lymphocyte count, platelet count, mean platelet volume (MPV), as well as in platelet-to-lymphocyte (PLR) and monocyte-to-lymphocyte (MLR) ratios. Conclusions: Some easily accessible markers of low-grade inflammation might be used as an additional tool for diagnosis and screening for hypertension in pediatric patients. These promising results should be validated in large and well-conducted studies.

Feasibility and Preliminary Efficacy of American Elderberry Juice for Improving Cognition and Inflammation in Patients with Mild Cognitive Impairment.

Despite data showing that nutritional interventions high in antioxidant/anti-inflammatory properties (anthocyanin-rich foods, such as blueberries/elderberries) may decrease risk of memory loss and cognitive decline, evidence for such effects in mild cognitive impairment (MCI) is limited. This study examined preliminary effects of American elderberry (Sambucus nigra subsp. canadensis) juice on cognition and inflammatory markers in patients with MCI. In a randomized, double-blind, placebo-controlled trial, patients with MCI (n = 24, Mage = 76.33 ± 6.95) received American elderberry (n = 11) or placebo (n = 13) juice (5 mL orally 3 times a day) for 6 months. At baseline, 3 months, and 6 months, patients completed tasks measuring global cognition, verbal memory, language, visuospatial cognitive flexibility/problem solving, and memory. A subsample (n = 12, 7 elderberry/5 placebo) provided blood samples to measure serum inflammatory markers. Multilevel models examined effects of the condition (elderberry/placebo), time (baseline/3 months/6 months), and condition by time interactions on cognition/inflammation outcomes. Attrition rates for elderberry (18%) and placebo (15%) conditions were fairly low. The dosage compliance (elderberry-97%; placebo-97%) and completion of cognitive (elderberry-88%; placebo-87%) and blood-based (elderberry-100%; placebo-100%) assessments was high. Elderberry (not placebo) trended (p = 0.09) towards faster visuospatial problem solving performance from baseline to 6 months. For the elderberry condition, there were significant or significantly trending decreases over time across several markers of low-grade peripheral inflammation, including vasorin, prenylcysteine oxidase 1, and complement Factor D. Only one inflammatory marker showed an increase over time (alpha-2-macroglobin). In contrast, for the placebo, several inflammatory marker levels increased across time (L-lactate dehydrogenase B chain, complement Factor D), with one showing deceased levels over time (L-lactate dehydrogenase A chain). Daily elderberry juice consumption in patients with MCI is feasible and well tolerated and may provide some benefit to visuospatial cognitive flexibility. Preliminary findings suggest elderberry juice may reduce low-grade inflammation compared to a placebo-control. These promising findings support the need for larger, more definitive prospective studies with longer follow-ups to better understand mechanisms of action and the clinical utility of elderberries for potentially mitigating cognitive decline.

Role of inflammatory signaling pathways involving the CD40–CD40L–TRAF cascade in diabetes and hypertension—insights from animal and human studies

CD40L–CD40–TRAF signaling plays a role in atherosclerosis progression and affects the pathogenesis of coronary heart disease (CHD). We tested the hypothesis that CD40L–CD40–TRAF signaling is a potential therapeutic target in hyperlipidemia, diabetes, and hypertension. In mouse models of hyperlipidemia plus diabetes (db/db mice) or hypertension (1 mg/kg/d angiotensin-II for 7 days), TRAF6 inhibitor treatment (2.5 mg/kg/d for 7 or 14 days) normalized markers of oxidative stress and inflammation. As diabetes and hypertension are important comorbidities aggravating CHD, we explored whether the CD40L–CD40–TRAF signaling cascade and their associated inflammatory pathways are expressed in CHD patients suffering from comorbidities. Therefore, we analyzed vascular bypass material (aorta or internal mammary artery) and plasma from patients with CHD with diabetes and/or hypertension. Our Olink targeted plasma proteomic analysis using the IMMUNO-ONCOLOGY panel revealed a pattern of step-wise increase for 13/92 markers of low-grade inflammation with significant changes. CD40L or CD40 significantly correlated with 38 or 56 other inflammatory targets. In addition, specific gene clusters that correlate with the comorbidities were identified in isolated aortic mRNA of CHD patients through RNA-sequencing. These signaling clusters comprised CD40L–CD40–TRAF, immune system, hemostasis, muscle contraction, metabolism of lipids, developmental biology, and apoptosis. Finally, immunological analysis revealed key markers correlated with comorbidities in CHD patients, such as CD40L, NOX2, CD68, and 3-nitrotyrosine. These data indicate that comorbidities increase inflammatory pathways in CHD, and targeting these pathways will be beneficial in reducing cardiovascular events in CHD patients with comorbidities.

The value of neck adipose tissue as a predictor for metabolic risk in health and type 2 diabetes

Upper-body adiposity is adversely associated with metabolic health whereas the opposite is observed for the lower-body. The neck is a unique upper-body fat depot in adult humans, housing thermogenic brown adipose tissue (BAT), which is increasingly recognised to influence whole-body metabolic health. Loss of BAT, concurrent with replacement by white adipose tissue (WAT), may contribute to metabolic disease, and specific accumulation of neck fat is seen in certain conditions accompanied by adverse metabolic consequences. Yet, few studies have investigated the relationships between neck fat mass (NFM) and cardiometabolic risk, and the influence of sex and metabolic status. Typically, neck circumference (NC) is used as a proxy for neck fat, without considering other determinants of NC, including variability in neck lean mass. In this study we develop and validate novel methods to quantify NFM using dual x-ray absorptiometry (DEXA) imaging, and subsequently investigate the associations of NFM with metabolic biomarkers across approximately 7000 subjects from the Oxford BioBank. NFM correlated with systemic insulin resistance (Homeostatic Model Assessment for Insulin Resistance; HOMA-IR), low-grade inflammation (plasma high-sensitivity C-Reactive Protein; hsCRP), and metabolic markers of adipose tissue function (plasma triglycerides and non-esterified fatty acids; NEFA). NFM was higher in men than women, higher in type 2 diabetes mellitus compared with non-diabetes, after adjustment for total body fat, and also associated with overall cardiovascular disease risk (calculated QRISK3 score). This study describes the development of methods for accurate determination of NFM at scale and suggests a specific relationship between NFM and adverse metabolic health.

Salivary α-amylase activity is associated with cardiometabolic and inflammatory biomarkers in overweight/obese, non-diabetic Qatari women.

Obesity, prevalent in approximately 80% of Qatar's adult population, increases the risk of complications like type 2 diabetes and cardiovascular diseases. Predictive biomarkers are crucial for preventive strategies. Salivary α-amylase activity (sAAa) inversely correlates with obesity and insulin resistance in adults and children. However, the connection between sAAa and cardiometabolic risk factors or chronic low-grade inflammation markers remains unclear. This study explores the association between serum sAAa and adiposity markers related to cardiovascular diseases, as well as markers indicative of chronic low-grade inflammation. Serum samples and clinical data of 1500 adult, non-diabetic, Overweight/Obese participants were obtained from Qatar Biobank (QBB). We quantified sAAa and C reactive protein (CRP) levels with an autoanalyzer. Cytokines, adipokines, and adiponectin of a subset of 228 samples were quantified using a bead-based multiplex assay. The associations between the sAAa and the adiposity indices and low-grade inflammatory protein CRP and multiple cytokines were assessed using Pearson's correlation and adjusted linear regression. The mean age of the participants was 36 ± 10 years for both sexes of which 76.6% are women. Our analysis revealed a significant linear association between sAAa and adiposity-associated biomarkers, including body mass index β -0.032 [95% CI -0.049 to -0.05], waist circumference β -0.05 [95% CI -0.09 to -0.02], hip circumference β -0.052 [95% CI -0.087 to -0.017], and HDL β 0.002 [95% CI 0.001 to 0.004], albeit only in women. Additionally, sAAa demonstrated a significant positive association with adiponectin β 0.007 [95% CI 0.001 to 0.01]while concurrently displaying significant negative associations with CRP β -0.02 [95% CI -0.044 to -0.0001], TNF-α β -0.105 [95% CI -0.207 to -0.004], IL-6 β [95% CI -0.39 -0.75 to -0.04], and ghrelin β -5.95 [95% CI -11.71 to -0.20], specifically within the female population. Our findings delineate significant associations between sAAa and markers indicative of cardiovascular disease risk and inflammation among overweight/obese adult Qatari females. Subsequent investigations are warranted to elucidate the nuances of these gender-specific associations comprehensively.

EXPRESS: Effectiveness of HMG-CoA reductase inhibitors on inflammation and metabolic markers in the US-Mexico border Hispanic population.

HMG-CoA reductase inhibitors (statins) are commonly used for dyslipidemia management to reduce the risk of cardiovascular disease (CVD). High-sensitivity C-reactive protein (hs-CRP) is an emerging systematic low-grade inflammatory marker associated with atherosclerotic CVD development. Despite racial/ethnic disparities in the use and response of statins and the anti-inflammatory effects of statins, the effectiveness of statins on inflammation and metabolic markers is unknown among Hispanics. We performed a retrospective cohort study using 150 adult patients scheduled for an annual physical exam at a family medicine clinic between January 1, 2021, and December 31, 2021. Effect size with a 95% confidence interval (CI) was estimated using adjusted regression analyses. Among 150 patients, 52 (34.67%) received statins. Patients who received statins had significantly reduced median hs-CRP (1.9 vs. 3.2, p=0.007), mean low-density lipoprotein (LDL-C) (101.18 vs. 124.6, p<0.001), and total cholesterol (172.6 vs. 194.5, p<0.001) concentrations compared to those who did not receive statins. In the propensity-scores matched analysis, lower concentrations of log-transformed hs-CRP (regression coefficient [RC], -0.48; 95%CI: -0.89, -0.07), LDL-C (RC, -19.57; 95%CI: -33.04, -6.1), and total cholesterol (RC, -23.47; 95%CI: -38.96, -7.98) were associated with statin use. In addition, hepatic steatosis (adjusted relative risk [aRR]=0.25; 95%CI: 0.08, 0.78, p= 0.017) was significantly lower among patients with the use of statins. Our study suggests that HMG-CoA reductase inhibitors may help reduce inflammation among Hispanic patients with dyslipidemia and hypertension. These findings have useful implications for preventing risk and disparities associated with cardiovascular and other inflammatory-induced diseases among the fastest-growing US Hispanic minorities.

Multifunctional dietary interventions, low-grade inflammation and cardiometabolic profile: a scoping review.

Growing evidence highlights the significant impact of diet to modify low-grade inflammation closely linked to cardiometabolic profile. Multifunctionnal diets, combining several compounds have been shown to beneficially impact metabolic parameters. This study synthesizes the knowledge on the impact of RCTs combining dietary multifunctional compounds on low-grade inflammation in humans. We investigate whether the effects of dietary multifunctional interventions on inflammatory markers were parallel to alterations of cardiometabolic parameters. We considered both the integrated dietary interventions (ID, i.e. global diets such as Mediterranean, Nordic…) and the dietary interventions based on selected bioactive mix (BM) compounds, in healthy individuals and those at cardiometabolic risk. Out of 221 screened publications, we selected 27 studies: 11 for BM (polyphenols and/or omega-3 fatty acids and/or antioxidants and/or dietary fiber) and 16 for ID (Mediterranean, paleo, Nordic, Dietary Approaches to Stop Hypertension (DASH) diet…). ID studies reflected significant improvements in inflammatory markers (CRP, IL-6, IL-10, IL-1b), concomitantly with beneficial changes in metabolic parameters. In BM studies, pronounced effects on low-grade inflammatory markers were observed, while improvements in metabolic parameters were not consistent. Both types of studies suggested a favorable impact on oxidative stress, a factor closely linked to the inflammatory profile. Our findings showed that multifunctional RCT diets have differential role in managing low-grade inflammation and cardiometabolic health, with a large heterogeneity in explored inflammatory markers. Further research is imperative to elucidate the link between low-grade inflammation and other cardiometabolic risk factors, such as intestinal inflammation or postprandial inflammatory dynamics, aiming to attain a comprehensive understanding of the mechanisms involved in these processes. These future investigations not only have the potential to deepen our insights into the connections among these elements but also pave the way for significant advancements in the prevention and management of conditions related to the cardiovascular and metabolic systems.

Low-grade inflammation and serotonin 4 receptor binding in the healthy and the depressed brain

Inflammatory status affects healthy brain function and also low-grade inflammation putatively contributes to the pathophysiology of Major Depressive Disorder (MDD). This psychoneuro-immunological interplay is complex, bidirectional, and not fully understood. Also, it is not clear to what extent depressive states induce inflammation and/or if increased inflammation leads to depressive symptoms by affecting brain biology including serotonin signaling. The serotonin 4 receptor (5-HT4R) is an interesting new antidepressant target; direct stimulation has antidepressant-like, and pro-cognitive effects, and may also index serotonin tone at least in the adult healthy brain.Here, we investigate whether a peripheral marker of low-grade inflammation (hsCRP) is associated with 5-HT4R brain binding in both a healthy and in an unmedicated MDD group. 5-HT4R PET imaging data and hsCRP measures from 112 healthy and 79 unmedicated MDD individuals were available from the Cimbi database. We evaluated the associations between hsCRP level and 5-HT4R binding in three regions of interest (neocortex, hippocampus, and neostriatum) using multiple linear regression models adjusted for relevant covariates.We did not observe a statistically significant association between hsCRP and 5-HT4R binding. This applied to both the healthy and the MDD group.Our findings do not support a coupling between low-grade inflammation and brain 5-HT4R availability, which suggests that the serotonergic system is not sensitive to low-grade inflammation captured by hsCRP, neither in healthy nor in depressed states. Future studies are needed to test if the brain serotonin system is coupled to other inflammatory markers, for instance in conditions with high-grade and/or prolonged immunoactivation.

Difference of thrombocyte profile between obesity and central obesity in women

Background: Obesity considered as a low-grade inflammation. Increased body fat has known to trigger inflammation. Platelet profile is a number of platelet-related parameters that can predict inflammation consisting of: platelet count (PLT), Platelet Larger Cell Ratio (P-LCR), Mean Platelet Volume (MPV). Differences in platelet profiles (PLT, P-LCR, MPV) in women with and without central obesity have only been investigated in a few studies.Objective: To prove differences in platelet profiles in women with and without central obesity.Materials and Methods: A cross-sectional observational study was conducted on 88 women with and without central obesity in RSND during July-September 2021. Data included age, abdominal circumference, hip circumference, PLT, P-LCR, and MPV. PLT, P-LCR, and MPV were measured using Sysmex XS-500i instrument. Statistical analysis was using Mann-Whitney test.Results: Mean of women PLT with and without central obesity were 338.72±71.09x103/uL and 309.09±44.36x103/uL. Difference platelet levels in women with and without central obesity was p=0.022. Median MPV of women with and without central obesity were 10.5 (8.5-11.8)fL and 9.7 (8.5-11.6)fL. Difference MPV values in women with and without central obesity was p=0.000. Median P-LCR of women with and without central obesity were 28.2 (12.3-44.3)% and 21.5 (15.2-37.1)%, respectively. Difference P-LCR value in women with and without central obesity was p=0.002.Conclusion: Platelet profiles (PLT, MPV, P-LCR) can be used as a marker of chronic low-grade inflammation in women with central obesity.Keywords : central obesity; MPV; PLT; P-LCR