Plasma Levels Of hs-CRP Research Articles

Plasma high-sensitivity C-reactive protein measured prior to transplant is related to prediabetes in first-year kidney transplant recipients: A single-center cross-sectional study in Vietnam

AimTo determine the rate of prediabetes among and the pre-transplant plasma high-sensitivity C-reactive protein (hs-CRP) value predictive of prediabetes in patients during their first year post-living donor kidney transplant. MethodsA total of 538 patients underwent living donor kidney transplantation between January 2018 and December 2020, 413 of whom met the inclusion criteria for this study. All patients underwent oral glucose tolerance tests (OGTTs) with 75 g glucose/200 mL solution, starting 3 months post-transplant and repeating the test every 3 months for the first year. Clinical and paraclinical indicators and plasma hs-CRP concentrations were quantified the day prior to the transplant. Prediabetes was diagnosed according to the American Diabetes Association 2018 criteria as a 2-h OGTT result between 140 mg/dL (7.8 mmol/L) and 199 mg/dL (11.0 mmol/L). ResultsThe rate of prediabetes among the study subjects was 38.3 % (158/413). Body mass index (BMI) and pre-transplant plasma triglycerides, high-density lipoprotein cholesterol (HDLC), and hs-CRP levels were related factors predictive of prediabetes in patients within the first year post-kidney transplant based on multivariate logistic regression and receiver operative characteristic curve models. Hs-CRP was the factor with the best predictive value (area under the curve = 0.89; p < 0.001). ConclusionsPre-transplant plasma hs-CRP levels were a good predictor of prediabetes in the first year post-living donor kidney transplant.

Elevated Plasma High Sensitive C-Reactive Protein and Triglyceride/High-Density Lipoprotein Cholesterol Ratio are Risks Factors of Diabetes Progression in Prediabetes Patients After Kidney Transplant: A 3-Year Single-Center Study in Vietnam.

Determination the rate of developing post-transplant diabetes mellitus (PTDM) in prediabetic patients and the relationship with plasma hs-CRP levels and TG/HDL-C ratio in patients after kidney transplantation from living donors followed for 3 years. A total of 206 post-transplant patients diagnosed with prediabetes by oral glucose tolerance test (OGTT) were included in the study. At the time of diagnosis of prediabetes, all patients were clinically examined, paraclinical tests were performed, plasma hs-CRP was quantified, and the TG/HDL-C ratio was determined. Patients are individualized and given a reasonable diet and exercise regimen. Patients had their fasting blood glucose measured monthly or had an OGTT every 3 months. Patients meeting the criteria for diagnosis of PTDM according to the American Diabetes Association (ADA)-2018 were collected during 3 years of follow-up. The study group had an average age of 39.46 ± 10.26 years old, including 74.8% males and 25.2% females. The rate of patients who had a development of PTDM from prediabetes was 29.6% (61/206 patients). BMI, plasma TG, HDL-C, hs-CRP, and TG/HDL-C ratio at the time of prediabetes diagnosis were factors related to the progression of PTDM, in which hs-CRP and TG/HDL-C ratio were good predictors (with AUC = 0.85 and 0.874, respectively; p < 0.001). After 3 years of follow-up, nearly one-third of prediabetic patients developed PTDM post-living donor kidney transplantation. BMI, plasma TG, HDL-C, hs-CRP, and the TG/HDL-C ratio were linked to DM progression, with hs-CRP and TG/HDL-C being the strongest predictors.

Interleukin-6 positively correlates with cardiovascular disease predictor algorithms and biomarker in rheumatoid arthritis patients.

Chronic inflammation is believed as the main culprit of the link between cardiovascular disease (CVD) and rheumatoid arthritis (RA). Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a key role in RA pathophysiology and also correlates with joint destruction and disease activity. This study evaluates the association between IL-6 plasma level and cardiac biomarker NT-proBNP, HS-CRP, CVD predictor algorithms, Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), as well as with CXCL9 and its receptor, CXCR3 in RA patients compared to the controls. Sixty RA patients (30 early and 30 late) and 30 healthy persons were included in this study. IL-6 and NT-proBNP plasma levels were measured by the ELISA. Also, HS-CRP plasma levels were quantified using the immunoturbidimetric assay. The CVD risk was assessed by the FRS and SCORE. IL-6 plasma levels were significantly higher in the early and late RA patients compared to the controls (p < 0.001). There was a positive correlation between IL-6 with DAS-28 (p = 0.007, r = 0.346), BPS (p = 0.002, r = 0.396), BPD (p = 0.046, r = 0.259), SCORE (p < 0.001, r = 0.472), and FRS (p < 0.001, r = 0.553), and a negative association with HDL (p = 0.037, r = -0.270), in the patients. Also, IL-6 plasma level positively correlated with HS-CRP (p = 0.021, r = 0.297) and NT-proBNP (p = 0.045, r = 0.260) in the patients. Furthermore, a positive association was found between IL-6 plasma levels and CXCL9 (p = 0.002, r = 0.386), and CXCR3 (p = 0.018, r = 0.304) in the patients. Given the interesting association between IL-6 with various variables of CVD, IL-6 may be considered a biomarker for assessing the risk for future cardiovascular events in RA patients.

Does physical activity and inflammation mediate the job stress-headache relationship? A sequential mediation analysis in the ELSA-Brasil study

BackgroundEvidence indicates that physical activity reduces stress and promote a myriad of health-enhancing effects through anti-inflammatory mechanisms. However, it is unknown whether these mechanisms interfere in the association between psychosocial job stress and headache disorders. ObjectiveTo test whether physical activity and its interplay with the systemic inflammation biomarkers high-sensitivity C-reactive protein (hs-CRP) and acute phase glycoproteins (GlycA) would mediate the associations between job stress and headache disorders. MethodsWe cross-sectionally evaluated the baseline data from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) regarding job stress (higher demand and lower control and support subscales), migraine and tension-type headache (ICHD-2 criteria), self-reported leisure-time physical activity, and plasma hs-CRP and GlycA levels. Conditional process analyses with a sequential mediation approach were employed to compute path coefficients and 95 % confidence intervals (CI) around the indirect effects of physical activity and biomarkers on the job stress-headache relationship. Separate models were adjusted for sex, age, and depression and anxiety. Further adjustments added BMI smoking status, and socioeconomic factors. ResultsIn total, 7,644 people were included in the study. The 1-year prevalence of migraine and tension-type headache were 13.1 % and 49.4 %, respectively. In models adjusted for sex, age, anxiety, and depression, the association between job stress (lower job control) and migraine was mediated by physical activity [effect = −0.039 (95 %CI: −0.074, −0.010)] but not hs-CRP or GlycA. TTH was associated with higher job control and lower job demand, which was mediated by the inverse associations between physical activity and GlycA [Job Control: effect = 0.0005 (95 %CI: 0.0001, 0.0010); Job Demand: effect = 0.0003 (95 %CI: 0.0001, 0.0007]. Only the mediating effect of physical activity in the job stress-migraine link remained after further adjustments including socioeconomic factors, BMI, smoking, and the exclusion of major chronic diseases. ConclusionIn the ELSA-Brasil study, physical activity reversed the link between job stress and migraine independently of systemic inflammation, while the LTPA-mediated downregulation of GlycA was associated with lower job stress-related TTH.

Cardiorespiratory Fitness Decreases High-Sensitivity C-Reactive Protein and Improves Parameters of Metabolic Syndrome.

To evaluate the relationship between cardiorespiratory fitness (CRF), expressed as maximal oxygen uptake (ml.kg-1.min-1), metabolic syndrome (MetS), and high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation. The relationship between CRF, MetS, and hs-CRP was examined in a cohort of 173 men and women. CRF was evaluated using a Bruce protocol treadmill test and measured as estimated maximal oxygen uptake (VO2 max). Participants' physical activity status was self-reported. Plasma hs-CRP levels were measured using a standardized immunoassay, and the diagnostic criteria for MetS were based on guidelines established by the International Diabetes Federation (IDF). An inverse association was observed between hs-CRP levels and estimated VO2 max (p<0.01). Additionally, hs-CRP increased linearly with the number of MetS criteria present (p<0.01), while the estimated VO2 max decreased as the number of MetS criteria increased (p<0.01). Moreover, higher estimated VO2 max correlated with increased self-reported physical activity levels (p<0.01). Notably, participants engaging in two to three hours of exercise per week had hs-CRP levels ≤2.5 mg/L (p=0.018), considered a low-to-moderate risk range. Higher CRF, reflected by an estimated VO2 max, ≥45 ml/kg/min, is associated with lower hs-CRP levels and fewer MetS criteria. Additionally, regular physical activity, corresponding to higher VO2 max, appears to reduce systemic inflammation and ameliorate MetS risk factors. These findings support the mechanisms by which improved CRF and exercise may lower the risk of cardiovascular diseases (CVD) and type 2 diabetes (T2DM).

FIBROSIS AS AN ADDITIONAL RISK FACTOR FOR STROKE DEVELOPMENT IN HYPERTENSIVE PATIENTS WITH ATRIAL FIBRILLATION (RETROSPECTIVE STUDY)

Objective: Atrial fibrillation (AF) is a common issue that is increasingly prevalent, particularly in hypertensive patients and leads to severe complications, notably stroke. Several prothrombotic factors are elevated in AF, contributing to an increased risk of stroke. Tissue factor (TF) is the main initiator of the blood coagulation cascade, also involved in inflammation and fibrogenesis. Atrial fibrosis plays a central role in creating the substrate for AF, with the Transforming Growth Factor (TGF-B1) identified as a key cytokine involved in the pathogenesis of atrial fibrosis. The aim of this study is to investigate the relationship between atrial fibrosis and the risk of developing transient ischemic attack (TIA) or stroke in hypertensive patients with AF (retrospective study). Design and method: We observed 445 hypertensive patients with nonvalvular AF over three years (2017-2019). Clinical examination included a study of complaints, physical, laboratory, and instrumental examination, along with additional biochemical blood tests, such as TF, hsCRP, IL-6, and TGF-B1. Blood tests were determined using the ELISA method. Treatment regimens for all patients included standard therapy (anticoagulants, antiarrhythmic, and symptomatic medication). Studies were conducted based on open-label protocols, using the universal statistical packages SPSS 13.0. Results: The obtained results have shown that among the 445 hypertensive patients with AF within three years, TIA or stroke was detected in 128 patients (28.8%). We found that in these patients, the level of TF is statistically elevated compared to other patients with AF (1350±65 vs. 850±33 pg/ml). Hypertensive patients undergoing TIA or stroke exhibited a significant increase in levels of inflammatory and fibrosis markers compared with other hypertensive patients with AF. Significant differences between hsCRP levels were observed (8.6±1.4 vs. 4.2±1.6, p=0.002); IL-6 levels (6.4±0.8 vs. 3.6±1.2 pg/ml, p=0.043); and TGF-B1 levels (1240±75 vs. 900±43 pg/ml, p=0.02). Moreover, plasma levels of hs-CRP were higher among AF patients at high risk of stroke (3 or more) according to CHA2DS2-VASc (p=0.002). Conclusions: We have demonstrated that fibrosis and inflammation markers, along with coagulation cascade markers, are additional prognostic criteria contributing to the development of TIA or stroke in hypertensive patients with AF.

Abstract 5212: Prognostic biomarkers for breast cancer: Metabolic and inflammatory pathways

Abstract Objective: To assess the prognostic significance of molecular biomarkers, particularly metabolic and Inflammatory pathways using samples from a prospective study of breast cancer patients undergoing adjuvant radiotherapy (RT). Methods: We used ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) for measuring urine metabolites. Following normalization to osmolality, log transformation, and imputation of missing values, we used Welch’s two-sample t-test to identify biochemicals that differed significantly by progression status. We measured pre- and post-RT plasma high-sensitivity C-reactive protein (hsCRP) levels. Progression-free survival (PFS) was calculated from the date of diagnosis to the date of disease progression or last follow-up. Univariable and multivariable Cox proportional hazards regression models assessed the associations between hsCRP and PFS. Results: In 120 breast cancer patients, carbohydrate metabolism, branch-chain amino acid (BCAA) metabolism, phosphatidylcholine metabolism, arginine metabolism, oxidative stress-related metabolites, androgenic steroids, and nucleotide metabolism had the most notable differences in patients with progression versus progression-free cases. In 488 breast cancer patients, RT significantly increased plasma hsCRP levels, and post-RT hsCRP levels were significantly higher in deceased vs. alive patients (p=0.031). In multivariable models, hsCRP had a prognostic value for all-stage and stage 0-II patients. Conclusions: In our study of breast cancer patients receiving adjuvant RT, multiple metabolite biomarkers and post-RT plasma CRP levels were associated with a worse prognosis. BCAAs and fatty acids regulate cell metabolism by affecting mitochondrial function and inflammation signals. Thus, our findings suggest a potential role of metabolic and inflammatory pathways in breast cancer prognosis. These molecules may have potential utility as prognostic biomarkers for breast cancer patients undergoing adjuvant RT and targets for intervention. Keywords: breast cancer, metabolomics, inflammation, prognosis Citation Format: Alexandra N. McMahon, Cristiane Takita, Jean L. Wright, Isildinha M. Reis, Eunkyung Lee, George Yang, Jennifer J. Hu. Prognostic biomarkers for breast cancer: Metabolic and inflammatory pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5212.

Association of Hepatic Steatosis and Fibrosis Indices With Insulin Sensitivity and Inflammation in the POP-ABC Study.

The cardiometabolic significance of subclinical liver fat in otherwise healthy individuals is unclear. This work aimed to evaluate the association of hepatic steatosis/fibrosis with cardiometabolic risk markers and incident prediabetes among healthy adults. This is a post hoc analysis of data from the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The participants underwent assessments, including clinical examination, oral glucose tolerance test, insulin sensitivity, insulin secretion, plasma high-sensitivity C-reactive protein (hsCRP), and adiponectin levels, with the primary outcome of incident prediabetes during 5-year follow-up. Liver steatosis and fibrosis were assessed using the hepatic steatosis index (HSI) and the Fibrosis-4 (Fib-4) index, and participants were stratified by baseline quartiles (Q) of each index. Among 343 (193 African American, 150 European American) participants (mean age 44.2 ± 10.6 years, body mass index 30.2 ± 7.28, fasting glucose 91.8 ± 6.80 mg/dL, and 2-hour glucose 125 ± 26.5 mg/dL), the mean baseline HSI was 39.7 ± 8.21 and Fib-4 index was 0.80 ± 0.41. Baseline HSI correlated with insulin sensitivity (r = -0.44; P < .0001), hsCRP (r = 0.37; P < .0001), and adiponectin (r = -0.24; P < .0001), as did Fib-4 index: insulin sensitivity (r = 0.14; P = .046), hsCRP (r = -0.17; P = .0021), adiponectin (r = -0.22; P < .0001). During 5 years of follow-up, prediabetes occurred in 16.2%, 21.6%, 31.5%, and 30.6% among participants in Q1 to Q4 of baseline HSI, respectively (log-rank P = .02). The prediabetes hazard ratio was 1.138 (95% CI, 1.027-1.261) for baseline HSI. Among initially normoglycemic individuals, hepatic steatosis predicted progression to prediabetes, probably via mechanisms that involve insulin resistance and inflammation.

Biochemical changes in overweight and obese patients after taking 5 mg of Tadalafil for two weeks

Background: obesity enhances a chronic inflammation and oxidative stress and damages the vascular endothelium. Tadalafil restores signaling of NO signaling and may decrease circulating oxidative stress and markers of inflammation, and improves parameters of metabolism through a number of mechanisms. The aim of this study to show what the effects of the administration of tadalafil (TAD) on inflammation, and oxidative stress markers in obese male patients. Methods: 32 male subjects with BMI more than 23 and age range 30-50 years old underwent with TAD 5mg for 14 days .Plasma level of MDA , GsH ,IL-6 and Hs-CRP before the taking of drugs and after 14 days of treatment . Results: Treatment with TAD caused a non-significant reduction in MDA group (0.093±0.027 versus 0.082± 0.032, P- value is 0.196), a non-significant increase in plasma GsH (0.1074±0.007 versus 0.109±0.009 , p-value is 0.538), a non-significant of reduction in plasma level of plasma Hs-CRP and IL-6 (4.377± 0.702 versus 4.272± 0.693, p-value is 0.599) and (24.668± 6.001 versus 23.56± 2.587 ,p-value is 0.401)respectively . Conclusion: We have concluded that TAD therapy has non –significant effect on anti-inflammatory and anti-oxidant activity if used in short term but this effect may be significant if used for long term or use large dose

Evaluation of the efficacy of hydro-alcoholic extract of Evolvulus alsinoides L. for the treatment of primary hypertension – A randomized controlled trial

Ethnopharmacological relevanceEvolvulus alsinoides L. (Sankhaholi) has been traditionally used in Unani (Greco-Arabic) medicine to treat diverse cardiovascular disorders. Notably, preclinical and clinical investigations have substantiated its remarkable potential as an antihypertensive agent. Aim of the studyThe aim of this study was to compare the efficacy of hydroalcoholic extract of Evolvulus alsinoides L. and ramipril in treating hypertension using a higher dose of the test drug within the recommended limit. Materials and methodsIn this open-label randomized controlled trial, 57 participants (29 in the test group, 28 in the control group) completed the 42-day study. The test group received 630 mg of dried hydro-alcoholic extract of Evolvulus alsinoides L. in capsule form orally once daily, while the control group received 5 mg of Ramipril orally once daily. Participants in both groups were advised to adhere to the Dietary Approaches to Stop Hypertension (DASH) eating plan in terms of diet and lifestyle adjustments recommended by JNC-8. The primary outcome measures were changes in systolic and diastolic blood pressure as well as changes in plasma levels of hsCRP and IL6. Secondary outcome measures included changes in symptoms such as palpitations, giddiness, headaches, fatigue and shortness of breath. Headaches, palpitations, and giddiness were assessed using a customized Visual Analog Scale (VAS) graded as “none,” “mild,” “moderate,” and “severe”. Fatigue was assessed on a binary scale as either absent or present, and dyspnea was assessed using the modified Medical Research Council (mMRC) scale for breathlessness. Both primary and secondary outcomes were assessed at baseline and each follow-up visit (2nd week, 4th week, and 6th week) until the completion of the trial. ResultsAt the end of the trial, the mean differences for the primary outcomes were as follows:SBP:−1.8895%CI:−4.82,1.05,p=0.203,d=0.33, DBP: −2.8395%CI:−4.67,−0.10,p=0.003,d=0.8, hsCRP: −1.4095%CI:−2.80,−0.003,p=0.49,d=0.53, and IL6: −88.6795%CI:−148.90,−28.43,p=0.005,d=0.78. No statistically significant differences were observed between the two groups for any of the secondary outcomes. ConclusionsBased on the preliminary results, it can be inferred that the hydro-alcoholic extract of Evolvulus alsinoides L. exhibits significant antihypertensive potential, comparable to that of ramipril. Furthermore, it appears that Evolvulus alsinoides L. may be more effective than ramipril in reducing the biochemical markers of inflammation associated with primary hypertension. However, additional research is required to validate these findings.

Investigations of leukocyte and inflammatory markers in pregnancies complicated by preeclampsia

ObjectivesPreeclampsia is a frequent and potentially fatal pregnancy complication. It can be challenging to make a timely diagnosis. Identifying clinically useful biochemical markers would be a remedying tool to support the diagnosis of preeclampsia. The aim was to investigate differential cell counts and acute phase reactants as diagnostic markers of preeclamptic third-trimester pregnancies and in relation to pregnancy term, gravidity and the severity of hypertension. MethodsBased on a cohort of 421 pregnant women, we included 174 participants (case n = 84, control n = 90) during the third trimester. Peripheral blood was sampled to measure differential white blood cell counts and acute phase reactants on the day of inclusion. ResultsThe neutrophil-to-lymphocyte ratio and plasma haptoglobin levels were significantly increased in healthy pregnancies compared with preeclamptic pregnancies. Plasma ferritin levels and albumin levels were respectively increased and decreased in cases of preeclampsia compared with controls. Albumin was specific among multigravida. Plasma transferrin and high-sensitivity C-reactive protein (hs-CRP) levels were significantly decreased and increased, respectively, in cases with preterm preeclampsia compared with term preeclampsia. ConclusionPlasma ferritin and albumin levels reflected higher inflammation in cases with preeclampsia compared with healthy pregnancies; the same did plasma transferrin and hs-CRP levels in preterm versus term preeclampsia. When considering the normal ranges plasma albumin and hs-CRP levels identified preeclamptic from healthy third-trimester pregnancies and preterm from term preeclampsia cases, respectively, with near-acceptable diagnostic performances. Further validation of the diagnostic value will require larger sample-sized studies with paired plasma and serum samples.

Serum Magnesium Levels in Patients with Chronic Kidney Disease: Is There a Relationship with Inflammation Status?

Magnesium (Mg2+) is a fundamental mineral that maintains cellular function, and low levels may be linked to inflammation in patients with chronic kidney disease (CKD). This cross-sectional study evaluated the correlation between serum Mg2+ levels and the inflammatory status in patients undergoing dialysis. Two hundred patients with CKD [150 undergoing hemodialysis (HD), 50 (18) years; BMI 24 (4.8) kg/m²; and 50 patients on peritoneal dialysis (PD), 54 (17.7) years; BMI, 27.5 (7.3) kg/m²] were included. Serum Mg2+ levels were evaluated using a colourimetric test and commercial kit. Inflammatory markers were assessed by ELISA and multiplex bead-based assay. Lipid peroxidation was evaluated using thiobarbituric acid-reactive substances. The median serum Mg2+ levels were 2.3 (0.5) mg/dL, and 21% of patients presented Mg2+ deficiency (< 2.07mg/dL or 0.85 mmol/L). We found no difference in Mg2+ serum levels between the two groups. A significant negative correlation was observed between serum Mg2+ levels and plasma hs-CRP (r =-0.17, p = 0.01), IL-8 (r =-0.35, p = 0.01), and MCP-1 (r =-0.31, p = 0.03) levels. Mg2+ serum levels were negatively correlated with inflammatory status in patients with CKD on dialysis.

Uric acid plasma levels are associated with C-reactive protein concentrations and the extent of coronary artery lesions in patients with acute coronary syndromes.

Many studies have pointed out that inflammation plays a pivotal role in pathophysiology of acute coronary syndromes (ACS) because several inflammatory molecules impair the endothelial functions in the coronary circulation and promote atherothrombotic events. Recently, many clinical/experimental evidences indicate that elevated plasma levels of uric acid (UA) might be considered a risk factor for developing ACS. It has been reported that elevated UA doses impair physiologic functions of endothelial cells, shifting them toward a pro atherothrombotic phenotype. In the present manuscript, we investigated the relationship between UA plasma levels, inflammatory burden, and extension of coronary atherosclerotic disease in patients with ACS. Patients with a clinical presentation of ACS (ST-elevated and non-ST-elevated myocardial infarction) admitted to the Vanvitelli Catheterization Laboratory at Monaldi Hospital in 2019, before the COVID-19 pandemia, were retrospectively analyzed. Biochemical profile, type of ACS presentation, as well as extension of coronary atherosclerosis were assessed. A total of 132 ACS patients were included in the analysis, and grouped into 3 tertiles according to the UA values (UA < 4.72mg/dl, UA between 4.72 and 6.15mg/dl, and UA > 6.15mg/dl). Patients with UA plasma levels ≥ 6.15mg/dL showed higher levels of C-reactive protein (mean of 5.1mg/dL) as compared to patients with lower UA plasma levels. Moreover, the former group of patients showed higher levels of cardiac troponin and CPK, and presented more often with multivessel disease and complex coronary stenosis (type C of Ellis classification). Even though monocentric and with limited sample size, the present study shows that plasma levels of UA and hs-CRP are elevated in ACS patients and are associated with a more severe coronary disease, suggesting a potential role of UA in the pathophysiology of acute coronary events.

1491-P: ER Stress Drives the VEGF Expression in Monocytic Cells by Mechanisms Involving CHOP/ROS/HIF-1alpha/NRF2 and NF-kappaB/p38 MAPK Pathways

Obesity is marked by metabolic inflammation and by metabolic impairment caused by increased endotoxin, free fatty acids, and vascular endothelial growth factor (VEGF) levels; and involves the endoplasmic reticulum (ER) stress as well. However, it remains unclear whether the ER stress can induce/amplify VEGF expression in metabolically-stressed monocytic cells; and if so, by which mechanism(s). To test this, metabolic stress was induced in THP-1 monocytic cells by treating cells separately with lipopolysaccharide (LPS), palmitic acid (PA), and oleic acid (OA), in presence/absence of ER stressor thapsigargin (TG). Gene expression of VEGF/ER stress markers was assessed by qRT-PCR, protein expression by ELISA, ROS by DCFH-DA assay, phosphorylation of HIF-1α, NF-κB, ERK1/2, and p38 MAPK by immunoblotting, and the insulin response in stressed cells by glucose-uptake assay. Regarding clinical analyses, adipose VEGF gene and protein expression was detected using qRT-PCR and IHC, respectively, while plasma hs-CRP, TNF-α, MDA, and OX-LDL levels were measured by ELISA. The experimental data show that a cooperative interaction between the metabolic and ER stresses led to the expression of VEGF, ROS, CHOP, ATF6, SOD2, and NRF2 (P˂0.05), as well as stimulated the CHOP and NRF2 promoter activities in reporter cells (P˂0.05). However, the glucose uptake was not impaired. The VEGF expression was dependent on phosphorylation of HIF-1α, NF-κB, and p38 MAPK; and the inhibitors of NF-κB/MAPK pathways as well as antioxidants or ROS scavengers suppressed the VEGF production. Further, individuals with obesity showed increased VEGF expression which associated positively with plasma levels of hs-CRP, TNF-α, MDA, and OX-LDL (P≤0.05). Overall, our findings support a cooperativity model in which the ER and metabolic stresses interact to augment VEGF expression in monocytic cells via the mechanisms involving CHOP/ROS/HIF-1α/NRF2 and NF-κB/p38 MAPK pathways. Disclosure S.A.K.Sindhu: None. F.Alzaid: None. F.Almulla: None. R.Ahmad: None. N.Akhter: None. A.Wilson: None. H.Arefanian: None. A.Al madhoun: None. R.S.Thomas: None. S.P.Kochumon: None. F.Alrashed: None. F.Bahman: None. Funding Kuwait Foundation for the Advancement of Sciences (RA2015-027, RA2010-003, RAHM-2019-022)

Sympathoinhibitory electroacupuncture (EA) interacts positively with anti-inflammatory EA alleviating blood pressure in hypertensive rats.

Elevated sympathetic activity and chronic inflammation are known contributory factors observed in hypertension. We have observed that sympathoinhibitory electroacupuncture (SI-EA) at acupoints ST36-37 alleviates sympathetic activity and hypertension. Additionally, EA at acupoints SP6-7 exerts anti-inflammatory (AI-EA) effects. However, it is not known whether simultaneous stimulation of this combination of acupoints attenuates or enhances individual effects. A 2 × 2 factorial design was used to test the hypothesis that combining SI-EA and AI-EA (cEA) leads to greater reduction of hypertension by decreasing sympathetic activity and inflammation in hypertensive rats than either set of acupoints alone. Dahl salt-sensitive hypertensive (DSSH) rats were treated with four EA regimens including cEA, SI-EA, AI-EA, and sham-EA twice weekly for five weeks. A group of normotensive (NTN) rats served as control. Systolic and diastolic BP (SBP and DBP) and heart rate (HR) were measured non-invasively by tail-cuff. Plasma norepinephrine (NE), high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) concentrations were determined with ELISA at the completion of treatments. DSSH rats on high salt diet progressively developed moderate hypertension within five weeks. DSSH rats treated with sham-EA showed continuous increase in SBP and DBP and elevations in plasma NE, hs-CRP, and IL-6 levels relative to NTN control. Both SI-EA and cEA decreased SBP and DBP, and had corresponding changes in biomarkers (NE, hs-CRP, and IL-6) compared with sham-EA. AI-EA prevented SBP and DBP elevation and decreased IL-6 and hs-CRP relative to sham-EA. Importantly in DSSH rats that received repetitive cEA treatment, SI-EA interacted positively with AI-EA leading to greater reduction of SBP, DBP, NE, hs-CRP, and IL-6 than SI-EA or AI-EA alone. These data suggest that by targeting both elevated sympathetic activity and chronic inflammation, cEA regimen results in a greater reduction of BP effects in treating hypertension compared to using individual SI-EA or AI-EA alone.

Self-compassion, but not compassion toward others, is associated with better physical health: A cross-sectional study.

Compassion is a modifiable construct that is associated with better physical health outcomes but, to our knowledge, has seldom been studied in people with schizophrenia (PwS) despite its applicability to counteract widespread depression in this community that might prevent positive health behaviors. We hypothesized that, compared to non-psychiatric comparison subjects (NCs), PwS would have lower compassion toward self (CTS), lower compassion toward others (CTO), and a positive association between compassion and health outcomes, such as physical wellbeing, comorbidities, and plasma hs-CRP. This cross-sectional study examined differences in physical health, CTS, and CTO in 189 PwS and 166 NCs. We used general linear models to analyze the relationship between compassion and health. As hypothesized, PwS had lower levels of CTS and CTO, worse physical well-being, more comorbidities, and higher levels of plasma hs-CRP than NCs. In the combined sample, higher CTS was significantly associated with better physical well-being and fewer comorbidities, while higher CTO was significantly associated with more comorbidities. In PwS alone, higher CTS was significantly associated with better physical well-being and lower levels of hs-CRP. CTS seemed to have a larger positive association with physical health than CTO, with depression acting as a potential mediator for CTS. Exploring effects of CTS interventions on physical health and health behaviors could be a promising next step.

Cardiometabolic Risk Factors in Atorvastatin-Treated Women with Euthyroid Autoimmune Thyroiditis

Introduction: Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to reduce thyroid antibody titers. The aim of this study was to investigate plasma markers of cardiometabolic risk in statin-treated women with thyroid autoimmunity. Methods: We compared two matched groups of euthyroid women with hypercholesterolemia receiving atorvastatin treatment: subjects with autoimmune (Hashimoto’s) thyroiditis (group A, n = 29) and subjects without thyroid pathology (group B, n = 29). Plasma lipids, glucose homeostasis markers, as well as circulating levels of uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and 25-hydroxyvitamin D were measured before atorvastatin treatment and 6 months later. Results: At entry, both groups differed in antibody titers, insulin sensitivity, and plasma levels of uric acid, hsCRP, fibrinogen, homocysteine, and 25-hydroxyvitamin D. Atorvastatin-induced reduction in hsCRP and homocysteine, but not in total cholesterol and LDL-cholesterol, was more pronounced in group B than in group A. Only in group B, the drug decreased uric acid and fibrinogen and increased 25-hydroxyvitamin D. In group A, atorvastatin reduced insulin responsiveness. Conclusion: The obtained results indicate that euthyroid women with Hashimoto’s thyroiditis may benefit to a lesser degree from atorvastatin treatment than other populations of women with hypercholesterolemia.

PS-BPC12-7: ANTI-INFLAMMATORY AND PRO-INFLAMMATORY BIOMARKERS IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND HYPERTENSION

Introduction: Non-alcoholic fatty liver disease (NAFLD) affects up to 50% of patients with hypertension (HT). Research data indicate a decrease in the activity of anti-inflammatory biomarkers with a simultaneous increase in the levels of pro-inflammatory agents. Objective: To assess the changes in anti-inflammatory systems (using kallistatin, IL-10) and pro-inflammatory activity (using IL-1β; and high-sensitivity CRP (hsCRP)) in patients with NAFLD under the influence of concomitant HT. Design and method: 63 patients with NASH and HT and 52 patients with isolated NASH were examined. Plasma kallistatin, IL-10, IL-1β; and hsCRP levels were evaluate using ELISA. The results were statistically processed using standard methods. Results: Kallistatin levels in patients with NAFLD and HT were on average 65.03 ng/ml (95% CI 61.38; 68.68), which was significantly lower than in the group with isolated NAFLD (83.42 ng/ml (95% CI 81.89; 84.94), p &lt; 0.001) and control results (111.70 ng/ml (95% CI 106.14; 113.22), p &lt; 0.001). The level of anti-inflammatory IL-10 in the group of NAFLD and HT also reached minimal values (12.69 pg/ml (95% CI 11.93; 12.95) against 14.34 pg/ml (95% CI 13.27; 14,34) in the group with isolated NAFLD (p &lt; 0.001) and 16.19 pg/ml (95% CI 15.15; 17.74) in the control group (p &lt; 0.001)). The opposite results were observed in the study of IL-1β; content, which was increased in the group with NAFLD and HT (17.55 pg/ml (95% CI 17.06; 19.73) versus 15.72 pg/ml (95% CI 15,25; 17.44) in the group with isolated NAFLD (p &lt; 0.001) and 8.26 (95% CI 7.79; 8.46) in the control group (p &lt; 0.001)). In addition, patients with NAFLD and HT had an increase in CRP (7.90 mg/l (95% CI 7.96; 8.75) versus 6.55 mg/l (95% CI 6.47; 7.57) in the group with isolated NAFLD (p &lt; 0.001) and 2.07 mg/l (95% CI 1.83; 2.85 mg/l) in the control group (p &lt; 0.001)). It has been shown that with the progression of HT in patients with NAFLD, the level of kallistatin significantly decreases (p &lt; 0.001, p = 0.011 for the HT stage and BP grade) and IL-10 (p &lt; 0.001) with a simultaneous increase in IL-1β; (p &lt; 0.001) and CRP levels (p &lt; 0.001). Conclusions: Thus, patients with NAFLD and HT are likely to experience changes in biomarker status toward a pro-inflammatory profile and deepening of these deviations with the progression of concomitant hypertension.

High hs-CRP levels after an attempted suicide: A matched case-control study

• Plasma levels of hs-CRP are higher in subjects who had recently attempted suicide compared to age- and sex-matched healthy subjects. • The lack of correlations between hs-CRP levels measured shortly after the attempted suicide vs. depression severity and other psychological symptoms suggests that inflammation may be specifically related to suicidal behavior. We found significantly higher levels of hs-CRP in 27 subjects who had recently attempted suicide compared to 27 age- and sex-matched healthy subjects. Moreover, the levels of hs-CRP in suicide attempters were not related to background or psychopathological characteristics, nor to the methods of suicide attempt. Our matched case-control study confirms previous observations of high levels of the inflammation marker hs-CRP in patients who have attempted suicide, irrespective of their underlying type and levels of psychopathology.

Biomarkers in Determining the Risk of Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease and Hypertension

IntroductionNon-alcoholic steatohepatitis (NASH) affects up to 50% of patients with arterial hypertension (HT). Laboratory biomarkers are believed to help in liver fibrosis (LF) risk determination in patients with NASH and HT. PurposeTo assess the kallistatin, IL-10, IL-1β and high-sensitivity CRP (hsCRP) significance in LF risk evaluation in patients with NASH and HT. Methods. 63 patients with NASH and HT and 52 patients with isolated NASH were examined. Plasma kallistatin, IL-10, IL-1β and hsCRP levels were evaluate using ELISA. The results were statistically processed with the ROC analysis, the area under ROC curve (AUC), sensitivity (SE) and specificity (SP) were determined. ResultsKallistatin showed excellent diagnostic characteristics for LF development and progression risk determination in patients with NASH and HT (AUC=0.975, p=0.003, SE=95%, SP=100%; AUC=0.881, p<0.001; SE=95%, SP=76.9%) and isolated NASH (AUC=0.867, p<0.001); SE=76.5%, SP=81.0%; AUC=0.889, p<0.001, SE=92.3%, SP=81.3%). Interleukins showed good diagnostic characteristics for LF development risk in both groups (IL-10: AUC=0.769, p=0.012, SE=70%, SP=64.1%; AUC=0.710, p=0.009, SE=94.4%, SP=69.2%, IL 1β: AUC=0.752, p=0.02, SE=71.8%, SP=75.0%, AUC=0.788, p=0.007, SE= 84.6%, SP=66.7%), hsCRP showed diagnostical potential only in NASH and HT patients (AUC=0.849, p<0.001, SE=71.8%; SP=75.0%). Simultaneous evaluation of all biomarkers showed excellent and very good diagnostic characteristics for LF development and progression risk determination in NASH and HT patients (AUC=1.000, SE=100%, SP=100%, p=0.002; AUC=0.874, SE=82.1%, SP=85.0%, p<0.001) and isolated NASH group (AUC=0.874, SE=94.1%, SP=71.4%, p<0.001; AUC=0.889, SE=84.6%, SP=94.4%, p<0.001). ConclusionsThis allows us to offer kallistatin, IL-10, IL-1β, and hsCRP combination for LF identification in patients with NASH and HT.