Changes In hsCRP Levels Research Articles

Dynamic changes in hs-CRP and risk of all-cause mortality among middle-aged and elderly adults: findings from a nationwide prospective cohort and mendelian randomization

IntroductionThe general population experiences mortality rates that are related to high levels of high-sensitivity C-reactive protein (hs-CRP). We aim to assess the linkage of longitudinal trajectories in hs-CRP levels with all-cause mortality in Chinese participants.MethodsWe utilized data from the China Health and Retirement Longitudinal Study (CHARLS). The exposures were dynamic changes in the hs-CRP and cumulative hs-CRP from 2012 to 2015, and the outcome was all-cause mortality. All participants were categorized into four trajectories according to hs-CRP levels. Multivariable logistic regression analysis, adjusted for potential confounders, was employed to evaluate the relationship of different trajectories of hs-CRP with mortality risk. A two-sample Mendelian randomization (TSMR) method and SHapley Additive exPlanations (SHAP) for identifying determinants of mortality risk were also employed.ResultsThe study included 5,445 participants with 233 deaths observed, yielding a mortality proportion of 4.28%. Compared to individuals maintaining low, stable levels of hs-CRP (Class 1), individuals with sustained elevated levels of hs-CRP (Class 4), those experiencing a progressive rise in hs-CRP levels (Class 2), or those transitioning from elevated to reduced hs-CRP levels (Class 3) all faced a significantly heighted death risk, with adjusted Odds Ratios (ORs) ranging from 2.34 to 2.47 across models. Moreover, a non-linear relationship was found between them. Further TSMR analysis also supported these findings. SHAP showed that hs-CRP was the fifth most important determinant of mortality risk.ConclusionsOur study shows all-cause mortality increases with dynamic changes in hs-CRP levels among middle-aged and elderly adults in China, and cumulative hs-CRP shows an L-shaped relationship with all-cause mortality.

Pleiotropic effect of teneligliptin versus glimepiride add-on therapy on hs-CRP and cardiorenal parameters in Indian type 2 diabetes patients: An open-labeled randomized controlled trial

Abstract Objective: The objective of the study was to estimate the pleiotropic effect of teneligliptin on high-sensitivity C-reactive protein (hs-CRP) levels and some cardiorenal parameters in comparison to glimepiride, both as add-on therapy to metformin. Methodology: This 12-week open-label, parallel-group, randomized controlled trial was conducted among Indian people with type 2 diabetes mellitus and on metformin monotherapy with poor glycemic control (glycated hemoglobin >7% or 53 mmol/mol). The endpoints were mean change in hs-CRP levels, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine, blood urea, estimated glomerular filtration rate (eGFR), and change in cardiovascular (CV) risk categories from baseline to end of 12 weeks. Results: Seventy participants were randomized (1:1) to receive either teneligliptin 20 mg once daily (n = 35) or glimepiride 1 mg twice daily (BD) (n = 35) as an add-on to metformin 500 mg BD. The mean age of the participants was 50.65 and 50.7 years in arms 1 and 2, respectively. At 12-weeks end, teneligliptin add-on caused a statistically significant reduction in hs-CRP compared to glimepiride in both per-protocol (PP) and intention-to-treat (ITT) sets. No significant difference was observed for changes in SBP and DBP, creatinine, urea, eGFR levels, and CV risk category in both PP and ITT sets. Conclusion: Teneligliptin add-on resulted in favorable effects on hs-CRP levels and comparable effects on cardiorenal parameters compared to glimepiride add-on therapy at 12-weeks end. This trial has been prospectively registered in CTRI (Clinical Trials Registry of India). Registration number: CTRI/2021/08/035342.

Prospective association of comorbid hypertension and depressive symptoms with C-reactive protein in older adults

BackgroundHypertension and depressive symptoms often occur together in the older population, and each has been separately linked to elevated C-reactive protein (CRP). This study investigated the prospective association between comorbid hypertension and depressive symptoms and high-sensitivity CRP (hs-CRP) in a Chinese older population. MethodsThis study used data from 4978 participants aged 50 and above, who took part in two waves (2011 and 2015) of the China Health and Retirement Longitudinal Study (CHARLS). Hypertension, depressive symptoms and hs-CRP were measured. Logistic regressions adjusted for confounding variables were used to examine the association between the baseline comorbidity of hypertension and depressive symptoms and the change in hs-CRP levels. ResultsHypertension and depressive symptoms did not show independent associations with an elevated level of hs-CRP. Participants with comorbid hypertension and depressive symptoms were more likely to develop a higher level of hs-CRP at follow-up (OR = 1.39, 95 % CI: 1.12–1.74) even after adjusting for covariates. Sex- and age-stratified analyses indicated that the association between the comorbidity and higher levels of hs-CRP were prone to be observed in women (OR = 1.55, 95 % CI: 1.16–2.08) and older adults (OR = 1.74, 95 % CI: 1.20–2.52). ConclusionsComorbid hypertension and depressive symptoms is related to a higher risk of elevated hs-CRP levels. This association appears to be more pronounced among women and older adults compared to their counterparts. LimitationDepression was self-reported by participants, which might be considered less unreliable than clinical diagnoses.

Abstract 11735: The Effect of Different NLRP3 Inflammasome Inhibitors on High-Sensitivity C-reactive Protein in Patients After Percutaneous Coronary Intervention

Background: Colchicine treatment inhibits the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome assembly and reduces atherothrombotic cardiovascular events in coronary artery disease (CAD). However, the effects of other inhibitors targeting NLRP3 inflammasome needs further verification in CAD. Aims: This study aimed to investigate whether inhibitors targeting NLRP3 inflammasome besides colchicine are effective in patients after percutaneous coronary interventions (PCI). Methods: The study included 132 patients aged 18-80 years who completed the planned PCI and were treated with aggressive secondary prevention strategies for four weeks. The subjects were randomly assigned to one of the following treatment groups for four weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in hsCRP levels at the end of four weeks. Results: In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male and 28 (25.69%) were female. The percentage changes in hsCRP after four weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups respectively. Compared with the control group, the colchicine group showed significantly greater reduction in hsCRP levels (P=0.022). The tranilast and oridonin groups did not show obvious changes. In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin,myeloperoxidase, myeloblastin), platelet aggregation (glycoprotein VI) and endothelial damage (galectin-3) were reduced with colchicine therapy. Conclusions: Colchicine could reduce hsCRP in patients after PCI, which is likely to act on neutrophils. Colchicine may still be the important choice for anti-inflammatory treatment of CAD.

Effect of GH Deficiency Caused by Nonfunctioning Pituitary Masses on Serum C-reactive Protein Levels.

GH supplementation for GH deficiency (GHD) has been reported to decrease high-sensitivity C-reactive protein (hs-CRP), an inflammatory marker; however, the association between GHD and hs-CRP remains unclear. We aimed to clarify the impact of impaired GH secretion due to pituitary masses on hs-CRP levels. We retrospectively examined the association between GH secretion, assessed using GH-releasing peptide-2, and serum hs-CRP levels before and a year after the pituitary surgery in patients with nonfunctioning pituitary neuroendocrine tumor or Rathke cleft cyst. Among 171 patients, 55 (32%) presented with severe GHD (peak GH response to GH-releasing peptide-2 < 9 ng/mL). Serum hs-CRP levels were significantly higher in patients with severe GHD than in those without (P < .001) and significantly correlated with the peak GH (r = -0.50, P < .001). Multiple regression analyses showed that the peak GH significantly and negatively predicted hs-CRP levels (β = -0.345; 95% CI, -0.533 to -0.158) and the lowest quartile of the peak GH (<5.04 ng/mL) were significantly associated with increase in hs-CRP levels (exp [β] = 1.840; 95% CI, 1.209 to 2.801), after controlling for other anterior hormones and metabolic parameters. Postoperative change in the peak GH (N = 60) significantly predicted change in hs-CRP levels (β = -0.391; 95% CI, -0.675 to -0.108), independent of alterations in other anterior hormones and metabolic parameters. The inverse association between GH secretion and hs-CRP levels highlights the protective role of GH in the increase in hs-CRP.

Efficacy and safety of interleukin-6 inhibition with ziltivekimab in patients at high risk of atherosclerotic events in Japan (RESCUE-2): A randomized, double-blind, placebo-controlled, phase 2 trial

BackgroundDespite optimal treatment, a residual inflammatory risk often remains in patients with atherosclerotic cardiovascular disease. In a US-based phase 2 trial, ziltivekimab, a fully human monoclonal antibody targeting the interleukin-6 ligand, significantly reduced biomarkers of inflammation compared with placebo in patients at high atherosclerotic risk. Here, we report the efficacy and safety of ziltivekimab in Japanese patients. MethodsRESCUE-2 was a randomized, double-blind, 12-week, phase 2 trial. Participants aged ≥20 years with stage 3–5 non-dialysis-dependent chronic kidney disease and high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L were randomized to receive placebo (n = 13) or subcutaneous ziltivekimab 15 mg (n = 11) or 30 mg (n = 12) at Weeks 0, 4, and 8. The primary endpoint was percentage change in hsCRP levels from baseline to end of treatment (EOT; mean of Week 10 and Week 12 values). ResultsAt EOT, median hsCRP levels were reduced by 96.2 % in the 15 mg group (p < 0.0001 versus placebo), by 93.4 % in the 30 mg group (p = 0.002 versus placebo), and by 27.0 % in the placebo group. Serum amyloid A and fibrinogen levels were also reduced significantly. Ziltivekimab was well tolerated and did not affect total cholesterol to high-density lipoprotein cholesterol ratios. There was a small, but statistically significant increase in triglyceride levels with ziltivekimab 15 mg and 30 mg compared with placebo. ConclusionsThe efficacy and safety results support the development of ziltivekimab for secondary prevention and the treatment of patients at high atherosclerotic risk.ClinicalTrials.gov identifier, NCT04626505.

Non-fasting changes of Hs-CRP level in Chinese patients with coronary heart disease after a daily meal

High-sensitivity C-reactive protein (hs-CRP) is a key inflammatory factor in atherosclerotic cardiovascular diseases. In Chinese patients with coronary heart disease (CHD), the changes in hs-CRP levels after a daily meal and the effect of statins on those were never explored. A total of 300 inpatients with CHD were included in this study. Hs-CRP levels were measured in the fasting and non-fasting states at 2 h and 4 h after a daily breakfast. All inpatients were divided into two groups according to fasting hs-CRP ≤ 3 mg/L or not. Group with fasting hs-CRP ≤ 3 mg/L had a significantly higher percentage of patients with statins using ≥ 1 month (m) before admission than that with fasting hs-CRP > 3 mg/L (51.4% vs. 23.9%, P < 0.05). Hs-CRP levels increased significantly in the non-fasting state in two groups (P < 0.05). About 32% of patients with non-fasting hs-CRP > 3 mg/L came from those with fasting hs-CRP ≤ 3 mg/L. In conclusion, hs-CRP levels increased significantly in CHD patients after a daily meal. It suggested that the non-fasting hs-CRP level could be a better parameter to evaluate the inflammation state of CHD patients rather than fasting hs-CRP level.

Effects of interleukin-6 inhibition with ziltivekimab in patients at high risk of atherosclerotic events in Japan: results from the phase 2 RESCUE-2 trial

Abstract Introduction In the US phase 2 RESCUE trial, ziltivekimab, a fully human monoclonal antibody against the ligand of the pro-inflammatory cytokine interleukin-6, was shown to reduce biomarkers of inflammation in patients with chronic kidney disease (CKD) and elevated levels of high-sensitivity C-reactive protein (hsCRP), a marker of inflammation and cardiac risk.1 Here, we present outcomes from the phase 2 RESCUE-2 trial of ziltivekimab in a patient population from Japan. Purpose To evaluate the efficacy and safety of ziltivekimab 15 mg and 30 mg compared with placebo in Japanese patients with non-dialysis-dependent CKD (NDD-CKD). Methods We conducted a randomized, double-blind, placebo-controlled trial in 36 patients aged ≥20 years with stage 3–5 NDD-CKD and hsCRP ≥2 mg/L. Patients were randomly assigned to receive subcutaneous ziltivekimab 15 mg (n=11) or 30 mg (n=12), or placebo (n=13) at weeks 0, 4 and 8. The primary endpoint was percentage change in hsCRP levels from baseline to end of treatment (EOT) (average of week 10 and week 12 values); secondary endpoints included percentage change from baseline to EOT in levels of fibrinogen, serum amyloid A (SAA), N-terminal pro B-type natriuretic peptide (NT-proBNP) and lipids. Analysis of endpoints was performed using Wilcoxon two-sample test; differences between treatment groups were calculated using the Hodges–Lehmann estimator. Results Baseline characteristics are shown in the Table. At EOT, median hsCRP levels were reduced by 96% and 93% in the ziltivekimab 15 mg and 30 mg groups, respectively, compared with 27% for placebo (both p&amp;lt;0.001 vs placebo). At both doses, ziltivekimab provided rapid and sustained suppression of hsCRP over the 12-week treatment period (Figure). Statistically significant reductions in levels of the inflammatory markers SAA (15 mg: 71%; 30 mg: 58%; placebo: 30%; both p&amp;lt;0.01 vs placebo) and fibrinogen (38%; 34%; 2%; both p&amp;lt;0.0001 vs placebo) were also observed. Ziltivekimab was well tolerated, did not result in persistent neutropenia or thrombocytopenia, and had minimal effect on liver enzyme levels. There was a non-significant increase in low-density lipoprotein levels and a neutral effect on high-density lipoprotein levels. There was a limited, but statistically significant (p&amp;lt;0.05 vs placebo) increase in triglycerides, whereby levels increased in some patients and decreased in others. Conclusion Ziltivekimab effectively reduced inflammatory biomarkers associated with atherosclerosis in patients from Japan with CKD and residual inflammatory risk as measured by hsCRP. A significant reduction of more than 90% in hsCRP levels for both doses of ziltivekimab was demonstrated, with a safety profile similar to placebo. Overall, the results of the RESCUE-2 trial in Japan are consistent with the efficacy and safety results of the US-based RESCUE trial. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was funded by Novo Nordisk A/S. Medical writing support was provided by Johanna Scheinost PhD, PharmaGenesis Oxford Central, Oxford, UK, with funding from Novo Nordisk A/S.

The impact of a comprehensive pharmaceutical care intervention in addition to cardiac rehabilitation program on outcomes of post-acute coronary syndrome patients: A pilot study

ObjectiveTo test the efficacy of Comprehensive pharmaceutical care intervention added to cardiac rehabilitation program(CR programs) in improving echocardiographic parameters, nutritional status and High sensitivity C-Reactive Protein(hs-CRP), in post-acute coronary syndrome patients. MethodsA prospective; randomized, controlled study. 40 post-acute coronary syndrome patients, participating in CR program, were randomly allocated to either the control group(n = 20) or the intervention group(n = 20). Pharmaceutical care intervention included face-to-face education about the disease, healthy lifestyle, medication adherence, drug related problems management and goal setting. hs-CRP and cardiac parameters were measured at baseline and after 3 months. ResultsAfter three months,the intervention group showed a significant decrease in left ventricular end systolic volume (p = 0.0026) and left ventricular end diastolic volume (p = 0.0009) compared to the control group. Also, intervention group showed a significant increase in nutritional status (p = 0.037) and the patients' knowledge about the disease and drugs (p = 0.0001). However, there was no significant change in hscrp level between groups. ConclusionOur findings indicate that Comprehensive pharmaceutical care intervention added to CR programs significantly improved cardiac parameters and nutritional status. This is best explained by increasing adherence to cardiovascular medications and to healthier lifestyle and optimizing medication knowledge and doses. Practice implicationsImplementing Comprehensive pharmaceutical care intervention added to CR programs could improve the cardiac function and nutritional status of post-acute coronary syndrome patients.

High-sensitivity C-reactive protein as prognostic and predictive marker in metastatic non-small cell lung carcinoma : A prospective single center study.

e21101 Background: Systemic inflammation has been linked to incidence, progression, and poor outcomes in various cancers including non-small cell lung carcinoma (NSCLC). High-sensitivity CRP (hs-CRP) assays, generally used to assess cardiovascular risk, have rarely been evaluated in lung cancer studies. This study aimed to evaluate if baseline and on-treatment measurements of serum hs-CRP could provide prognostic and predictive information for patients with metastatic NSCLC treated with chemotherapy. Methods: In this single institutional prospective study 85 patients with metastatic NSCLC without targetable alterations who were treated with chemotherapy were included between 1st January 2020 and 31st December 2020, with a minimum follow-up duration of 6 months. Patients with coronary artery disease, active infections, autoimmune conditions, and chronic liver disease were excluded. Measurements of hs-CRP for all patients were done at baseline and every 12 weeks while on treatment. Patients were grouped by changes in hs-CRP levels compared to baseline levels as reduction (≥ 20% decline), and non-reduction (&lt; 20% decline) to assess association with radiologic response and progression- free survival (PFS). Results: Pre-treatment hs-CRP values were elevated for the majority (92.9% patients with ≥ 1 mg/L, 70.6% with ≥ 3 mg/L, and 42.3% with ≥ 10 mg/dL). No significant association was detected between the pre-treatment hs-CRP value and the number of metastatic sites (P = 0.4), histology (P = 0.3), or smoking status (P = 0.7). At a median follow-up of 13.7 months, the median PFS was 7.8 months (95% confidence interval [CI] 5.3 - 10.3). Patients with hs-CRP ≥10 mg/L had shorter PFS than those with hs-CRP &lt; 10 mg/L (Median PFS 7.5 months [95% CI 4.9 - 10] vs. 8.4 months [95% CI 0.1 - 17.4]; hazard ratio [HR] 1.8, 95% CI 1-3.4, P = 0.04). hs-CRP reduction (≥20% decline) after 12 weeks of treatment initiation predicted radiological response (P &lt; 0.001). Median PFS was 14.7 months (95% CI 7.4 – 22.1) in patients who demonstrated hs-CRP reduction (≥20% decline) at 12 weeks compared to 3.1 months (95% CI 2.3 – 3.9) in patients who did not (HR 0.17, 95% CI 0.08 - 0.33, P &lt; 0.001). Conclusions: Elevated hs-CRP at baseline was found to be a poor prognostic factor, while hs-CRP reduction by 20% or more on treatment predicted radiologic response and longer PFS in metastatic NSCLC patients treated with chemotherapy. Our findings of potential predictive and prognostic value of hs-CRP in metastatic NSCLC warrant validation in larger prospective studies.

Dietary Intake and Elevated C-Reactive Protein Levels in US Military Veterans.

Elevated inflammatory markers, such as high sensitivity C-reactive protein (hs-CRP), have been associated with the pathogenesis of cardiovascular disease (CVD)-related diseases. However, limited studies have evaluated the potential association between dietary consumption and hs-CRP levels in a large, nationally representative sample, and fewer have investigated their role in ethnic and racial minority military populations. The goal of this study is to explore the relationship between dietary intake, health behaviors, and hs-CRP in individuals with prior military status and whether these associations differ by race/ethnicity. A complex, multistage, probability sample design was used from the National Health and Nutrition Examination (NHANES) 2015–2018 waves. Our results indicate that previously deployed military service members had a higher prevalence of clinically elevated hs-CRP levels than civilians. Differences in hs-CRP among deployed veterans and civilians remained even after multivariable adjustment. Individuals classified as overweight and obese demonstrated clinically elevated hs-CRP levels compared with those with a normal body mass index (BMI). Dietary factors did not attenuate the association between changes in hs-CRP levels and veteran status. These findings suggest the need for further investigation into how military-specific stressors contribute to unfavorable health outcomes for the military population.

Effect of Anagliptin versus Sitagliptin on Inflammatory Markers: Sub-Analysis from the REASON Trial.

PurposeExperimental evidence has suggested that dipeptidyl peptidase-4 (DPP-4) inhibitors have an anti-inflammatory effect as well as a glucose-lowering effect, but this has yet to be confirmed in diabetic patients. Therefore, we examined the anti-inflammatory effects of two kinds of DPP-4 inhibitors in patients who participated in the randomized evaluation of anagliptin (ANA) vs sitagliptin (SITA) on low-density lipoprotein cholesterol in diabetes (REASON) Trial, which compared low-density lipoprotein-cholesterol lowering effects between (ANA) and SITA in patients with type 2 diabetes, dyslipidemia, and atherosclerotic vascular lesions.Patients and MethodsThe studied patients consisted of 177 patients who received ANA 200 mg per day and 176 patients who received SITA 50 mg per day for 52 weeks. We measured high-sensitivity C-reactive protein (hs-CRP), white blood cells (WBC), and interleukin-6 (IL-6) before and after treatment for 52 weeks, and the changes in inflammatory markers were measured as the differences between baseline and 52 weeks. Furthermore, we checked the relationship between the change in hs-CRP and several clinical factors such as the baseline hs-CRP level, use of a moderate-intensity statin, presence of coronary artery disease (CAD) and taking a previous DDP-4 inhibitor.ResultsThe levels of the inflammatory markers hs-CRP, WBC, and IL-6 were determined to have not significantly changed from baseline to the final follow-up in each arm; furthermore, the changes in these markers were not significantly different between the two groups. The change in hs-CRP level was not affected by the baseline hs-CRP level, use of a moderate-intensity statin, presence of coronary artery disease, and absence of prior DPP-4 inhibitor use.ConclusionIn this sub-analysis from the REASON Trial, taking a DPP-4 inhibitor, either ANA or SITA, for 52 weeks did not affect the levels of inflammatory markers.

Nocturnal Continuous Positive Airway Pressure (nCPAP) Decreases High-Sensitivity C-Reactive Protein (hs-CRP) in Obstructive Sleep Apnea-Hypopnea Syndrome.

Background Systemic and airway inflammation has recently been linked to obstructive sleep apnea-hypopnea syndrome (OSAHS) and is considered to be a probable risk factor for OSAHS-induced cardiovascular damage. High-sensitivity C-reactive protein (hs-CRP), as an inflammatory mediator, may be useful for the prediction of the risk of cardiovascular disease (CVD) and assessment of nocturnal continuous positive airway pressure (nCPAP) therapy effect in OSAHS patients. Methods A prospective, controlled, cross-sectional study was conducted on 64 consecutive adult subjects with suspected sleep-disordered breathing (SDB). Results OSAHS was confirmed in 43 patients (24 normotensive and 19 hypertensive patients) and ruled out in 21 normotensive subjects (controls). The median plasma level of hs-CRP did not differ significantly between OSAHS patients and controls. It showed an unmarked rise with the severity of OSAHS (p = 0.20) and was not correlated with AHI (p = 0.067; r = 0.28). After adjusting for cervical perimeter (CP), waist-to-hip ratio (WHR), and blood sugar level, hs-CRP level of 1 mg/dL or greater was significantly more often observed in OSAHS patients compared with controls (p = 0.032; OR = 5.60) and was also significantly associated with AHI (p = 0.021). A significant decrease in the median plasma hs-CRP level was observed in CPAP compliant patients (p = 0.006). Of those, only normotensive patients showed a significant decrease in plasma hs-CRP level. In hypertensive ones, however, the hs-CRP level dropped but not significantly. Using a linear regression model, the change in hs-CRP level (Δhs-CRP) following a 6-month-nCPAP therapy was found to positively correlate with the baseline hs-CRP level for both hypertensive (p = 0.02; r = 0.68), and even more normotensive OSAHS patients (p < 0.0001; r = 0.89). Conclusion nCPAP therapy may have a cardiovascular protective effect in OSAHS patients. hs-CRP level would be useful as a valuable predictor of success in OSAHS treatment monitoring.

Association Between Long-term Functional Outcome and Change in hs-CRP Level in Patients With Acute Ischemic Stroke.

Elevated high-sensitivity C-reactive protein (hs-CRP) has been suggested as a risk factor for ischemic stroke. However, the predictive value of hs-CRP for long-term outcomes is poorly defined. Therefore, we conducted this study to evaluate whether change in hs-CRP level plays a role in the prognostic value of long-term functional disability. We studied 263 patients with acute ischemic stroke and 104 healthy controls (67.5±11.26 and 68.17±11.21 y, respectively). hs-CRP was measured on admission and on the seventh day of hospitalization. The patients were classified into 2 groups on the basis of difference in hs-CRP level from admission to the seventh day of hospitalization (group 1, hs-CRP on admission>the seventh hospital day; group 2, hs-CRP on admission<the seventh hospital day). The correlation between change in hs-CRP level and functional disability using the modified Rankin Scale score (mRS) at 1, 3, 6, and 12 months after stroke onset was analyzed. We observed significant differences between initial hs-CRP level in all patients (0.96±2.82 mg/dL) and healthy controls (0.34±0.71 mg/dL, P=0.029). Significant differences in mRS at the 4 different timepoints was not observed between 2 groups (P=0.453, 0.225, 0.229, and 0.396, respectively). The Spearman rank-order correlation coefficients showed that change in hs-CRP level increasingly differed over time and was statistically correlated with mRS (coefficient/P: at 1 mo, 0.139/0.024; at 3 mo, 0.149/0.015; at 6 mo, 0.147/<0.001; and at 12 mo, 0.134/0.03). However, the results were very low correlation coefficients, despite their statistical significance. This study did not clearly show an association between increase in hs-CRP level over time and long-term functional disability.

P1375ORAL VITAMIN C EFFECT ON HEPCIDIN LEVEL IN HAEMODIALYSIS PATIENTS WITH FUNCTIONAL IRON DEFICIENCY ANAEMIA

Abstract Background and Aims Hepcidin is a key regulatory peptide in iron homeostasis, inhibiting iron absorption by binding to ferroportin. Inflammatory mediated increase in hepcidin levels and reduced clearance in hemodialysis (HD) patients lead to functional iron deficiency ( FID) and Erythropoiesis-stimulating agent (ESA) resistance. Ascorbic acid (Vitamin C) may be used as adjuvant therapy in FID anemia through its anti-inflammatory and anti-oxidant nature, but there was limited studies investigating the direct relation between vitamin C and hepcidin level in HD patients. We Aimed to test the reducing therapeutic effect of oral vitamin C supplement on hepcidin level among hemodialysis patients with functional iron deficiency anaemia. Method This study is an open label randomized controlled clinical trial that was conducted in hemodialysis units of Ain Shams University hospitals, 48 prevalent HD patients with mean age of 46.48 ± 15.57 years were included ,Group 1 (study group) :31 patients [13(41.9%) males &amp; 18(58.1%) females] who received the conventional treatment of erythropoietin stimulating agents together with oral supplementation of vitamin C 500 mg every other day dose for 3 months. Group 2 (control group): included 17 patients [8(47.1%) males and 9 (52.9%) females] who received only the conventional therapy of erythropoietin stimulating agents according to their Hb levels. The patients enrolled in the study were patients on regular conventional HD for more than 6 months with functional iron deficiency anemia, defined as: hemoglobin level &amp;lt;11 gm/dl, ferritin level &amp;gt;200 ng/ml and TSAT &amp;gt;20 %. Patients with history of non-renal causes of anemia including malignancy, end-stage liver disease, or chronic hypoxia, patients with evidence of active or occult bleeding, patients who received blood transfusion within the last 4 months, history of recent hospitalization or infection requiring antibiotics within the last 4 weeks and patients with evidenced iron deficiency anemia were all excluded from the study .Laboratory parameters including serum hepcidin level, highly sensitive CRP (hsCRP) titer, CBC, kidney function tests and iron indices were measured at baseline and after 3 months . Results Oral vitamin C supplementation in Group 1(study group) resulted in statistically significant reduction in Hepcidin levels in the study group [mean 2506.45± 1320.53 pg/ml to 1748.39 ±1432.28 pg/ml ](P=0.03), and highly significant reduction in hsCRP level [mean 8603.23 ±2547.77 ng/ml to 5611.29 ±2829.27 ng/ml](P=0.001) after 3months of treatment. On comparing the two groups regarding changes in Hepcidin levels during follow up, illustrates that vitamin C together with time resulted in significant reduction of hepcidin levels in the study group (P&amp;lt;0.05) by repeated measure ANOVA test (Figure 1). Comparison between the two groups regarding change in hsCRP levels during follow up showed there was a highly significant change in the mean hsCRP over time, and the mean hsCRP differed significantly between the two groups (Figure 2). A significant reduction in serum iron and ferritin levels was observed in study group after treatment vitamin C but the change of the mean of S. ferritin level didn’t differ significantly in comparison to control group . Decreased EPO requirements and elevation of hemoglobin level were observed in the study group but without a statistical significance compared to the control group, this might be attributed to the short period of vit C supplementation. There was a highly significant correlation between serum hepcidin and hsCRP (r=0.46, P&amp;lt;0.01) . Conclusion : Oral Vitamin C may be promising therapy in decreasing serum hepcidin and hsCRP in prevalent hemodialysis patients with functional iron deficiency anemia.

Teneligliptin as an add on Therapy to Oral Anti diabetic agents in type 2 Diabetes Mellitus

A study was conducted on a novel dipeptidyl peptidase-4 inhibitor, Teneligliptin when given as an add on therapy with oral anti diabetic agents in patients with type 2 diabetes mellitus. Previously diagnosed subjects with type 2 diabetes (T2DM) were assigned 20 mg/day teneligliptin along with other anti-diabetic drugs. At 3 months, levels of glycemic parameters like HbA1C, fasting blood glucose levels, Post Prandial levels as well as non-glycemic parameters like lipid profile (Total cholesterol, LDL, HDL, Triglycerides), hsCRP level, serum creatinine, Blood urea, BMI were compared with those at baseline. Teneligliptin as an add on therapy led to significant reduction in glycemic parameters like HbA1c (1.6±0.97mg/dl), fasting blood glucose (45.86±62.85), and post prandial levels (72.73±47.97) from the baseline values (p <0.000). Significant co relation was observed between change in HbA1c level and baseline HbA1C levels. Significant reduction in the total cholesterol levels were observed (p < 0.000) but other lipid profile parameters like HDL, LDL, and triglycerides were not shown to be statistically significant after treatment. No change in hsCRP level and BMI was observed. Addition of teneligliptin to oral anti diabetic agents led to a significant improvement in glycemic control in subjects with type 2 diabetes mellitus without causing any weight change.

Association Between Inflammatory Biomarker C-Reactive Protein and Radiotherapy-Induced Early Adverse Skin Reactions in a Multiracial/Ethnic Breast Cancer Population.

Purpose This study examined an inflammatory biomarker, high-sensitivity C-reactive protein (hsCRP), in radiotherapy (RT)-induced early adverse skin reactions or toxicities in breast cancer. Patients and Methods Between 2011 and 2013, 1,000 patients with breast cancer who underwent RT were evaluated prospectively for skin toxicities through the National Cancer Institute-funded Wake Forest University Community Clinical Oncology Program Research Base. Pre- and post-RT plasma hsCRP levels and Oncology Nursing Society skin toxicity criteria (0 to 6) were used to assess RT-induced skin toxicities. Multivariable logistic regression analyses were applied to ascertain the associations between hsCRP and RT-induced skin toxicities after adjusting for potential confounders. Results The study comprised 623 white, 280 African American, 64 Asian/Pacific Islander, and 33 other race patients; 24% of the patients were Hispanic, and 47% were obese. Approximately 42% and 15% of patients developed RT-induced grade 3+ and 4+ skin toxicities, respectively. The hsCRP levels differed significantly by race and body mass index but not by ethnicity. In multivariable analysis, grade 4+ skin toxicity was significantly associated with obesity (odds ratio [OR], 2.17; 95% CI, 1.41 to 3.34], post-RT hsCRP ≥ 4.11 mg/L (OR, 1.61; 95% CI, 1.07 to 2.44), and both factors combined (OR, 3.65; 95% CI, 2.18 to 6.14). Above-median post-RT hsCRP (OR, 1.93; 95% CI, 1.03 to 3.63), and change in hsCRP (OR, 2.80; 95% CI, 1.42 to 5.54) were significantly associated with grade 4+ skin toxicity in nonobese patients. Conclusion This large prospective study is the first to our knowledge of hsCRP as an inflammatory biomarker in RT-induced skin toxicities in breast cancer. We demonstrate that nonobese patients with elevated RT-related change in hsCRP levels have a significantly increased risk of grade 4+ skin toxicity. The outcomes may help to predict RT responses and guide decision making.

The effects of different therapeutic modalities on cardiovascular risk factors in women with polycystıc ovary syndrome: A randomızed controlled study

ObjectiveThis study was designed to evaluate the effects of 3 mg drospirenone/30 μg ethinyl estradiol (OC) alone or combined with 1700 mg metformin on metabolic risk factors. Materials and methodsIn this randomized, prospective, controlled study, 87 non-obese (18–30 BMI) women of reproductive age (18–39) with polycystic ovary syndrome (PCOS) were assigned to control (n = 17), OC (n = 21), combination (n = 20) and metformin (n = 29) therapy groups. ResultsAdiponectin levels changed −28.27%, −20.37% and 35.78% after OC, combination and metformin therapies, respectively. High sensitive C-reactive protein levels (hsCRP) changed with OC, combination and metformin therapies by 102.32%, 3.2% and −7.14%, respectively. Plasminogen activator inhibitor-1 levels decreased 41.34% in the metformin group. Apolipoprotein-B levels changed in a manner similar to changes in hsCRP levels. The homeostatic model insulin resistance index changed significantly between the groups following treatment (p = 0.001). ConclusionSix cycles of treatments with OC alone may cause metabolic variables to deteriorate in non-obese women with PCOS. The addition of metformin to OC may ameliorate some aspects of this effect.

Comparison of hs-CRP level between low calorie high protein to standard protein diet in obese individuals with weight cycling - a randomised trial

Background: Obesity is associated with various health problems. Low-grade inflammation is a condition found in obese people and contributes to the development of various diseases. The objective of this study was to compare the effects of calorie restriction diet with high-protein (HP) or standard protein (SP) to inflammation marker (hs-CRP) in obese individuals with weight cycling. Methods: 61 healthy obese men and women (25 – 49 years old) with a history of weight cycling were recruited and were randomly assigned to one of the intervention groups, HP or SP groups. Both groups were suggested to reduce their daily caloric intake by 1000 kcal with regular physical activity for 56 days. Subjects in HP group were given a daily protein intake of 22-30% from total daily caloric intake, while SP group were prescribed 12-20%. Dietary consultation was conducted through daily reminder by phone and weekly counseling. The measurement of hs-CRP level was performed prior to and at the end of the intervention. Results: 54 subjects completed the program, yet due to several reasons only 32 of them were measured for hsCRP before and after completing the program, 15 from HP group and 17 from SP group. After completing the 56-day diet program, SP group experienced reduction of hs-CRP by -0.446 + 4.239, while HP underwent increase by 0.135 + 2.389. The mean difference of change in hs-CRP level between the two groups were not statistically significant (P=0.094). Conclusion: Low calorie diet with either HP or SP for 8 weeks significantly reduced body weight (P&lt;0.001) and BMI (P&lt;0.001) in healthy obese subjects but the difference of change in the hs-CRP level between them were not significant. The protein composition of a low calorie diet may not affect the inflammatory state of obese individuals with weight cycling. Trial registration number: NCT03374150

Hepatic, Renal, Hematologic, and Inflammatory Markers in HIV-Infected Children on Long-term Suppressive Antiretroviral Therapy.

Data on long-term toxicity of antiretroviral therapy (ART) in HIV-infected children are sparse. PENPACT-1 was an open-label trial in which HIV-infected children were assigned randomly to receive protease inhibitor (PI)- or nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based ART. We examined changes in clinical, immunologic, and inflammatory markers from baseline to year 4 in the subset of children in the PENPACT-1 study who experienced viral suppression between week 24 and year 4 of ART. Liver enzyme, creatinine, and cholesterol levels and hematologic parameters were assessed during the trial. Cystatin C, high-sensitivity C-reactive protein (hs-CRP), interleukin 6 (IL-6), d-dimer, and soluble CD14 (sCD14) were assayed from cryopreserved specimens. Ninety-nine children (52 on PI-based and 47 on NNRTI-based ART) met inclusion criteria. The median age at initiation of ART was 6.5 years (interquartile range [IQR], 3.7-13.4 years), and 22% were aged <3 years at ART initiation; 56% of the PI-treated children received lopinavir/ritonavir, and 70% of NNRTI-treated children received efavirenz initially. We found no evidence of significant clinical toxicity in either group; growth, liver, kidney, and hematologic parameters either remained unchanged or improved between baseline and year 4. Total cholesterol levels increased modestly, but no difference between the groups was found. IL-6 and hs-CRP levels decreased more after 4 years in the NNRTI-based ART group. The median change in IL-6 level was -0.35 pg/ml in the PI-based ART group and -1.0 in the NNRTI-based ART group (P = .05), and the median change in hs-CRP level was 0.25 µg/ml in the PI-based ART group and -0.95 µg/ml in the NNRTI-based ART group (P = .005). These results support the safety of prolonged ART use in HIV-infected children and suggest that suppressive NNRTI-based regimens can be associated with lower levels of systemic inflammation.