Changes In hs-CRP 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.

Effect of central dialysis fluid delivery system on markers of inflammation in hemodialysis patients

BackgroundThe utilization of ultrapure dialysate has been shown to decrease dialysate contamination and mitigate inflammatory responses. The central dialysate delivery system (CDDS) has the potential to attain a level of purity similar to ultrapure dialysate. Nevertheless, there is limited research examining the impact of CDDS on inflammation in comparison to single-patient dialysis fluid delivery system(SPDDS). This study aims to investigate the effects of CDDS utilizing ultrapure dialysate on ameliorating the microinflammatory state in hemodialysis patients.MethodA retrospective cohort clinical study enrolled a total of 125 hemodialysis patients, with 58 patients from the CDDS unit and 67 patients from the SPDDS unit. Each participant was monitored for a period of 6 months, and the repeated measurement data was analyzed using a generalized linear mixed models (GLMM).ResultsThe average age of the studty cohort was 56.22 ± 12.64 years. The GLMM analysis showed a significant time*group interaction effect on hs-CRP changes over the follow-up period (β = -1.966, FTime* CDDS group = 13.389, P < 0.001). A linear mixed model analysis with random slope showed that a different slope was observed between CDDS group and SPDDS group (βCDDS =—0.793; βSPDDS = 0.791), indicating a decreased hs-CRP levels in CDDS group, while increased in the SPDDS group over the follow-up period. However, no significant time*group interaction effect were observed on albumin and β2-microglobulin levels during follow-up period(β2-microglobulin: β = -0.658, FTime* CDDS group = 1.228, P = 0.269; albumin: β = 0.012, FTime* CDDS group = 1.429, P = 0.233).ConclusionUsing ultrapure dialysate in the CDDS is associated with an improvement in hs-CRP levels compared to standard dialysate, which might confer long-term clinical advantages.

Prediction of in-hospital mortality in patients with myocardial infarction and type 2 diabetes: the role of cellular indices of systemic inflammation

Aim. To assess the value of cellular indices of systemic inflammation in the prognosis of in-hospital mortality in patients with ST-segment elevation myocardial infarction (MI) in combination with type 2 diabetes (T2D).Material and methods. The retrospective case-control study included 125 patients with myocardial infarction and T2D, 25 of whom died during the index hospitalization. The cellular composition of the blood and the level of high-sensitivity C-reactive protein (hsCRP) were determined on the first and third days of hospitalization. In the groups of deceased and surviving patients, cellular indices of systemic inflammation were calculated and compared (neutrophil-lymphocyte ratio (NLR), neutrophil-monocyte ratio (NMR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR), systemic inflammation index (SII), systemic inflammation response index (SIRI)) and average hsCRP levels). The prognostic role of the studied parameters was assessed using univariate and multivariate logistic regression.Results. Deceased patients, compared with survived ones, had higher Killip class, body mass index, number of stents implanted, higher hsCRP levels, and lower left ventricular ejection fraction. Inhospital mortality was associated with hsCRP (odds ratio of 1,03 with 95% confidence interval of 1,003-1,05, p=0,029), NLR (2,56 [1,73-9,78], p&lt;0,001), NMR (1,16 [1,001-1,35], p=0,04), MLR (23,7 [3,1-182,6], p=0,002), SII (1,001 [1,0-1,001], p=0,028), SIRI (1,29 [1,09-1,52], p=0,003) 48 hours after admission, as well as with the degree of hsCRP change (1,03 [1,003-1,05], p=0,025), NLR (1,58 [1,21-2,06], p=0,001), SII (1,001 [1,0-1,001], p=0,028) during the first three days. Adjusted multivariate regression analysis identified a set of independent predictors with greatest accuracy in assessing the death probability: NLR, SII and SIRI 48 hours after admission, the degree of hsCRP change, body mass index and the num ber of implanted stents.Conclusion. The work demonstrated the significance of cellular indices of systemic inflammation (NLR, SII and SIRI) in assessing the prognosis of in-hospital mortality in patients with MI combined with T2D.

Trajectory of C-Reactive Protein and Incident Heart Failure in Black Adults: The Jackson Heart Study.

Increased hsCRP (high-sensitivity C-reactive protein), a marker of inflammation, is associated with incident cardiovascular events. We aim to determine whether the baseline or trajectory of hsCRP levels over time predicts incident heart failure (HF) hospitalization. JHS (Jackson Heart Study) participants' (n=3920 Black adults) hsCRP levels were measured over 3 visits (from 2000 to 2013). We assessed the association of hsCRP at baseline (visit 1) with incident HF hospitalization using Cox proportional hazards models. Furthermore, we assessed the association of the trajectory of hsCRP over repeated measurements (visits 1-3) with incident HF using joint models. Hazard ratios are reflective of an increase in hsCRP by 1 SD on a log2 scale. We also assessed the association of change in hsCRP between visit 1 and visit 3 with Cox proportional hazards models by grouping patients by low (<2 mg/L) and high (≥2 mg/L) hsCRP levels. The 4 groups were low-to-low (referent), low-to-high, high-to-low, and high-to-high. Mean baseline age of participants was 54±13 years, and 63.8% were women. Over a median follow-up of 12 years, 308 (7.9%) participants were hospitalized with incident HF. Baseline hsCRP was not associated with incident HF (adjusted hazard ratio, 1.08 [95% CI, 0.96-1.22]). However, increasing hsCRP levels over repeated measures were associated with a higher risk of incident HF overall (adjusted hazard ratio, 1.22 [95% CI, 1.03-1.44]) and HF with preserved ejection fraction (adjusted hazard ratio, 1.30 [95% CI, 1.02-1.65]) but not HF with reduced ejection fraction (P>0.05). Furthermore, changes in hsCRP from low-to-high and high-to-low levels were associated with incident HF (P<0.05). While baseline hsCRP was not associated with incident HF, an increasing trajectory of hsCRP over time was associated with increased risk for incident HF (particularly HF with preserved ejection fraction). Temporal change in hsCRP may be an important marker of risk for incident HF with preserved ejection fraction in Black adults.

Association between inflammatory markers, body composition and frailty in home-dwelling elderly: an 8-year follow-up study

Frailty has been linked to inflammation and changes in body composition, but the findings are inconsistent. To explore this, we used the Frailty Index (FI) definition to (1) investigate the association between levels of inflammatory markers (baseline) and change in FI score after 8 years of follow-up and (2) investigate the longitudinal associations between inflammatory markers, body composition, and frailty. Home-dwelling elderly (≥ 70 years) were invited to participate in the study and re-invited to a follow-up visit 8 years later. This study includes a total of 133 participants. The inflammatory markers included were high-sensitive C-reactive protein (hs-CRP), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), and glycoprotein acetyls (Gp-acetyls). We used the body composition markers fat mass, fat-free mass, and waist circumference. The FI score consisted of 38 variables. Additional clinical assessments such as blood pressure and body mass index (BMI), as well as information about daily medications, were collected at both visits. Linear regression model and Spearman’s rank correlation were used to investigate associations. We showed that the FI score increased after 8 years, and participants with higher hs-CRP levels at baseline had the largest change in the FI score. Changes in fat mass were significantly correlated with changes in hs-CRP and IL-6, and changes in waist circumference were significantly correlated with changes in TNF-α. The use of drugs increased during the 8 years of follow-up, which may have attenuated the associations between inflammation and frailty. However, elevated concentrations of hs-CRP in the elderly may be associated with an increased risk of frailty in subsequent years.

Efficacy of AI-Guided (GenAISTM) Dietary Supplement Prescriptions versus Traditional Methods for Lowering LDL Cholesterol: A Randomized Parallel-Group Pilot Study.

Emerging evidence suggests that personalized dietary supplement regimens can significantly influence lipid metabolism and cardiovascular risk. The efficacy of AI-guided dietary supplement prescriptions, compared with standard physician-guided prescriptions, remains underexplored. In a randomized, parallel-group pilot study, 70 patients aged 40-75 years with LDL-C levels between 70 and 190 mg/dL were enrolled. Participants were randomized to receive either AI-guided dietary supplement prescriptions or standard physician-guided prescriptions for 90 days. The primary endpoint was the percent change in LDL-C levels. Secondary endpoints included changes in total cholesterol, HDL-C, triglycerides, and hsCRP. Supplement adherence and side effects were monitored. Sixty-seven participants completed the study. The AI-guided group experienced a 25.3% reduction in LDL-C levels (95% CI: -28.7% to -21.9%), significantly greater than the 15.2% reduction in the physician-guided group (95% CI: -18.5% to -11.9%; p < 0.01). Total cholesterol decreased by 15.4% (95% CI: -19.1% to -11.7%) in the AI-guided group compared with 8.1% (95% CI: -11.5% to -4.7%) in the physician-guided group (p < 0.05). Triglycerides were reduced by 22.1% (95% CI: -27.2% to -17.0%) in the AI-guided group versus 12.3% (95% CI: -16.7% to -7.9%) in the physician-guided group (p < 0.01). HDL-C and hsCRP changes were not significantly different between groups. The AI-guided group received a broader variety of supplements, including plant sterols, omega-3 fatty acids, red yeast rice, coenzyme Q10, niacin, and fiber supplements. Side effects were minimal and comparable between groups. AI-guided dietary supplement prescriptions significantly reduce LDL-C and triglycerides more effectively than standard physician-guided prescriptions, highlighting the potential for AI-driven personalization in managing hypercholesterolemia.

The relationship between levels of tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in the serum of elderly and acute myocardial infarction.

This study aimed to explore the relationship between the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hypersensitive C-reactive protein (hs-CRP) and the prognosis of acute myocardial infarction (AMI) patients after percutaneous coronary intervention (PCI) treatment. A total of 118 early-onset AMI patients who successfully received PCI (in the PCI group, blood samples were collected before PCI, 12, 24, 48 h after PCI, and 90 d follow-up period) and 52 AMI patients who received only cardioangiography (CAG) (in the CAG group, blood samples were collected before CAG, 12, 24, 48 h after CAG, and 90 d follow-up period). The serum levels of IL-6, hs-CRP and TNF-α were detected, and the incidence of major adverse cardiac events (MACE) in the PCI group during follow-up was observed. The basic levels of IL-6, hs-CRP, and TNF-α between the PCI group and the CAG group were not statistically different (P>0.05); there was no statistically significant difference in changes of serum IL-6, hs-CRP, and TNF-α in the CAG group before and after CAG (P>0.05); IL-6, hs-CRP, and TNF-α in the PCI group were significantly higher than those before treatment (P<0.01); in the PCI group, the levels of IL-6, hs-CRP and TNF-α between the MACE group and the MACE-free group were statistically different (P<0.05). Serum IL-6, hs-CRP and TNF-α levels in AMI patients after PCI significantly increased in the short term, and PCI may induce an inflammatory response; the high levels of inflammatory cytokines, IL-6, hs-CRP, and TNF-α, in peripheral blood may have an important reference value for MACE and short-term prognosis in early-onset AMI patients after PCI.

Blood Profiles of Community-Dwelling People with Sarcopenia: Analysis Based on the China Health and Retirement Longitudinal Study

Introduction: Routine blood factors can be economical and easily accessible candidates for sarcopenia screening and monitoring. The associations between sarcopenia and routine blood factors remain unclear. This study aimed to examine sarcopenia and blood factor associations based on a nation-wide cohort in China. Methods: A total of 1,307 participants and 17 routine blood indices were selected from two waves (year 2011 and year 2015) of the China Health and Retirement Longitudinal Study (CHARLS). The diagnosis of sarcopenia was based on the criteria proposed by the Asian Working Group for Sarcopenia (AWGS 2019). Generalized mixed-effects models were performed for association analyses. A logistic regression (LR) model was conducted to examine the predictive power of identifying significant blood factors for sarcopenia. Results: A higher sarcopenia risk was cross-sectionally associated with elevated blood concentrations of high-sensitivity C-reactive protein (hsCRP) (OR = 1.030, 95% CI [1.007, 1.053]), glycated hemoglobin (HbA1c) (OR = 1.407, 95% CI [1.126, 1.758]) and blood urea nitrogen (BUN) (OR = 1.044, 95% CI [1.002, 1.089]), and a decreased level of glucose (OR = 0.988, 95% CI [0.979, 0.997]). A higher baseline hsCRP value (OR = 1.034, 95% CI [1.029, 1.039]) and a greater over time change in hsCRP within 4 years (OR = 1.034, 95% CI [1.029, 1.039]) were associated with a higher sarcopenia risk. A higher BUN baseline value was related to a decreased sarcopenia risk over time (OR = 0.981, 95% CI [0.976, 0.986]), while a greater over time changes in BUN (OR = 1.034, 95% CI [1.029, 1.040]) and a smaller over time change in glucose (OR = 0.992, 95% CI [0.984, 0.999]) within 4 years were also related to a higher sarcopenia risk. LR based on significant blood factors (i.e., hsCRP, HbA1c, BUN, and glucose), and sarcopenia status in year 2015 yielded an area under the curve of 0.859 (95% CI: 0.836–0.882). Conclusion: Routine blood factors involved in inflammation, protein metabolism, and glucose metabolism are significantly associated with sarcopenia. In clinical practice, plasma hsCRP, BUN, blood sugar levels, sex, age, marital status, height, and weight might be helpful for sarcopenia evaluation and monitoring.

COVID-19 with high-sensitivity CRP associated with worse dynamic clinical parameters and outcomes.

This study aimed to evaluate the relationship between high-sensitivity C-reactive protein (hsCRP) in hospitalized COVID-19 patients and their clinical outcomes, including trajectory of hsCRP changes during hospitalization. Patients with positive COVID-19 tests between 2021 and 2023 were admitted to two hospitals. Among 184 adult patients, approximately half (47.3%) had elevated hsCRP levels upon admission, which defined as exceeding the laboratory-specific upper limit of test (> 5.0 mg/L). Clinical outcomes included critical illness, acute kidney injury, thrombotic events, intensive care unit (ICU) requirement, and death during hospitalization. Elevated hsCRP levels had a higher risk of ICU requirement than those with normal, 39.1% versus 16.5%; adjusted odds ratio (aOR), 2.3 [95% CI, 1.05-5.01]; p = 0.036. Patients with extremely high (≥2 times) hsCRP levels had aOR, 2.65 [95% CI, 1.09-6.45]; p < 0.001. On the fifth day hospitalization, patients with high hsCRP levels associated with acute kidney injury (aOR, 4.13 [95% CI, 1.30-13.08]; p = 0.016), ICU requirement (aOR, 2.67 [95%CI, 1.02-6.99]; p = 0.044), or death (aOR, 4.24 [95% CI, 1.38-12.99]; p = 0.011). The likelihood of worse clinical outcomes increased as hsCRP levels rose; patients with elevated hsCRP had lower overall survival rate than those with normal (p = 0.02). The subset of high hsCRP patients with high viral load also had a shorter half-life compared to those with normal hsCRP level (p = 0.003). Elevated hsCRP levels were found to be a significant predictor of ICU requirement, acute kidney injury, or death within 5 days after hospitalization in COVID-19 patients. This emphasized the importance of providing more intensive care management to patients with elevated hsCRP.

Effect of pentoxifylline on endothelial dysfunction, oxidative stress and inflammatory markers in STEMI patients.

Aim: ST-elevation myocardial infarction (STEMI) patients suffer higher mortality and adverse outcomes linked to endothelial dysfunction (ED). Methods: 43 patients were randomized to pentoxifylline (PTX) 400mg thrice daily (n=22) or placebo (n=21). Soluble vascular cell adhesion molecule-1, malondialdehyde, interleukin-1 (IL-1), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-α (TNF-α)were assessed at baseline and 2months. Results: After 2months, no significant difference was observed in markers' levels between the 2 groups. However, a within-group comparison revealed a statistically significant change in hs-CRP in the PTX group (10.057 (9.779-10.331) versus 9.721 (6.102-10.191)), p=0.032. Conclusion: PTX for 2months in STEMI patients was safe and well-tolerated but had no significant detectable effect on ED, oxidative stress or inflammatory markers. Clinical Trial Registration: NCT04367935 (ClinicalTrials.gov).

Coagulation and inflammatory response after intramuscular or intradermal mRNA-1273 SARS-CoV-2 vaccine: secondary analysis of a randomized trial

BackgroundFractional-dosed intradermal (i.d.) vaccination produces antibody concentrations above the proposed proxy for protection against severe disease as compared with intramuscular (i.m.) vaccination and may be associated with a decreased prothrombotic effect. ObjectivesTo assess changes in coagulation following standard dosed i.m. or fractional-dosed i.d. (one-fifth of i.m.) mRNA-1273 SARS-CoV-2 vaccine and to determine the association between the inflammatory response and coagulation. MethodsThis study was embedded in a randomized controlled trial assessing the immunogenicity of an i.d. fractional-dosed mRNA-1273 vaccine. Healthy participants, aged 18 to 30 years, were randomized (2:1) to receive either 2 doses of i.d. or i.m. vaccine. Blood was drawn prior to first and second vaccination doses and 1 and 2 weeks after the second dose. The outcomes were changes in coagulation parameters (primary endpoint peak height of the thrombin generation curve) and inflammation (high-sensitivity C-reactive protein [hs-CRP]). ResultsOne hundred twenty-three participants were included (81 i.d.; 42 i.m.). Peak height increased after vaccination (i.m., 28.8 nmol; 95% CI, 6.3-63.8; i.d., 17.3 nmol; 95% CI, 12.5-47.2) and recovered back to baseline within 2 weeks. I.m. vaccination showed a higher inflammatory response compared with i.d. vaccination (extra increase hs-CRP, 0.92 mg/L; 95% CI, 0.2-1.7). Change in endogenous thrombin potential was associated with change in hs-CRP (beta, 28.0; 95% CI, 7.6-48.3). ConclusionA transient increase in coagulability after mRNA-1273 SARS-CoV-2 vaccination occurred, which was associated with the inflammatory response. While i.d. administration showed antibody concentrations above the proposed proxy for protection against severe disease, it was associated with less systemic inflammation. Hence, i.d. vaccination may be safer.

Adherence to the MIND diet and the odds of mild cognitive impairment in generally healthy older adults: The 3-year DO-HEALTH study

BackgroundThe Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet may slow cognitive decline in older adults. A potential mechanism could be possible anti-inflammatory properties of the MIND-diet. ObjectiveTo examine whether adherence to the MIND diet at baseline is associated with the odds of mild cognitive impairment (MCI) and changes in biomarkers of inflammation (High-sensitivity C-reactive Protein(hsCRP), interleukin-6(IL-6)) over three years in adults ≥70 years. MethodsAdherence to the MIND diet was assessed by food frequency questionnaire (FFQ) at baseline and after three years. Presence of MCI based on the Montreal Cognitive Assessment (MoCA) was defined as <26 (MCI26), or <24 (MCI24). We performed a minimally adjusted model controlling for sex, prior fall, linear spline at age 85, time, treatment and study site. The fully adjusted model also adjusted for education, BMI, physical activity, depression score, daily energy intake, and comorbidity score. To assess the change in inflammatory markers from baseline, we used linear-mixed-effect models adjusted for the same variables plus the respective baseline concentrations. Sensitivity analyses accounting for practice effects of repeated cognitive tests using the reliable change index for both MoCA cut-offs were done. ResultsWe included 2028 of 2157 DO-HEALTH participants (60.5% women; mean age 74.88 years) with complete data. Adherence to the MIND diet at baseline was not associated with cognitive decline over three years, neither at MoCA < 26 (OR (95%CI) = 0.99 (0.94–1.04)) nor at MoCA < 24 (OR (95%CI) = 1.03 (0.96–1.1)). Applying the reliable change index to the two cut-offs confirmed the findings. Further, the MIND diet adherence was not associated with the change in MoCA score from baseline in DO-HEALTH. For inflammatory biomarkers MIND-diet baseline adherence was not associated with changes in hsCRP or IL-6. ConclusionAdherence to the MIND-diet was neither associated with the odds of MCI, nor with hsCRP or IL-6 at baseline. Moreover, change in MIND-diet over three years was not associated with changes in hsCRP or IL-6.

Effects of weight loss through dietary intervention on pain characteristics, functional mobility, and inflammation in adults with elevated adiposity.

The relationship between adiposity and pain is complex. Excess weight increases the risk for chronic musculoskeletal pain (CMP), driven by increased biomechanical load and low-grade systemic inflammation. Pain limits physical function, impacting energy balance contributing to weight gain. The primary aims of this study were to profile pain characteristics in participants with overweight or obesity and determine if weight loss through dietary-induced energy restriction, and presence of CMP, or magnitude of weight loss, was associated with changes in adiposity, pain, functional mobility, and inflammation. This was a secondary analysis of data from adults (25-65 years) with overweight or obesity (BMI 27.5-34.9 kg/m2) enrolled in a 3-month, 30% energy-restricted dietary intervention to induce weight loss (January 2019-March 2021). Anthropometric measures (weight, waist circumference and fat mass), pain prevalence, pain severity (McGill Pain Questionnaire, MPQ), pain intensity (Visual Analog Scale, VAS), functional mobility (timed up and go, TUG) and inflammation (high sensitivity C-Reactive Protein, hsCRP) were assessed at baseline and 3-months. One hundred and ten participants completed the intervention and had weight and pain assessed at both baseline and 3-months. Participants lost 7.0 ± 0.3 kg, representing 7.9% ± 3.7% of body mass. At 3-months, functional mobility improved (TUG -0.2 ± 0.1 s, 95% CI -0.3, -0.1), but there was no change in hsCRP. Compared to baseline, fewer participants reported CMP at 3-months (n = 56, 51% to n = 27, 25%, p < 0.001) and presence of multisite pain decreased from 22.7% to 10.9% (p < 0.001). Improvements in anthropometric measures and functional mobility did not differ between those presenting with or without CMP at baseline. Improvements in pain were not related to the magnitude of weight loss. Weight loss was effective in reducing pain prevalence and improving functional mobility, emphasizing the importance of considering weight-loss as a key component of pain management. identifier, ACTRN12618001861246.

Long-term green-Mediterranean diet may favor fasting morning cortisol stress hormone; the DIRECT-PLUS clinical trial.

Fasting morning cortisol (FMC) stress hormone levels, are suggested to reflect increased cardiometabolic risk. Acute response to weight loss diet could elevate FMC. Richer Polyphenols and lower carbohydrates diets could favor FMC levels. We aimed to explore the effect of long-term high polyphenol Mediterranean diet (green-MED) on FMC and its relation to metabolic health. We randomized 294 participants into one of three dietary interventions for 18-months: healthy dietary guidelines (HDG), Mediterranean (MED) diet, and Green-MED diet. Both MED diets were similarly hypocaloric and lower in carbohydrates and included walnuts (28 g/day). The high-polyphenols/low-meat Green-MED group further included green tea (3-4 cups/day) and a Wolffia-globosa Mankai plant 1-cup green shakeFMC was obtained between 07:00-07:30AM at baseline, six, and eighteen-months. Participants (age=51.1years, 88% men) had a mean BMI of 31.3kg/m2, FMC=304.07nmol\L, and glycated-hemoglobin-A1c (HbA1c)=5.5%; 11% had type 2 diabetes and 38% were prediabetes. Baseline FMC was higher among men (308.6 ± 90.05nmol\L) than women (269.6± 83.9nmol\L;p=0.02). Higher baseline FMC was directly associated with age, dysglycemia, MRI-assessed visceral adiposity, fasting plasma glucose (FPG), high-sensitivity C-reactive-protein (hsCRP), testosterone, Progesterone and TSH levels (p ≤ 0.05 for all). The 18-month retention was 89%. After 6 months, there were no significant changes in FMC among all intervention groups. However, after 18-months, both MED groups significantly reduced FMC (MED=-1.6%[-21.45 nmol/L]; Green-MED=-1.8%[-26.67 nmol/L]; p<0.05 vs. baseline), as opposed to HDG dieters (+4%[-12 nmol/L], p=0.28 vs. baseline), whereas Green-MED diet FMC change was significant as compared to HDG diet group (p=0.048 multivariable models). Overall, 18-month decrease in FMC levels was associated with favorable changes in FPG, HbA1c, hsCRP, TSH, testosterone and MRI-assessed hepatosteatosis, and with unfavorable changes of HDLc (p<0.05 for all, weight loss adjusted, multivariable models). Long-term adherence to MED diets, and mainly green-MED/high polyphenols diet, may lower FMC, stress hormone, levels,. Lifestyle-induced FMC decrease may have potential benefits related to cardiometabolic health, irrespective of weight loss. ClinicalTrials.gov, identifier NCT03020186.

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.

Abstract 16779: Tirzepatide Reduces High-Sensitivity C-reactive Protein in Patients With Type 2 Diabetes and High Cardiovascular Risk: A Post Hoc Analysis of the SURPASS-4 Trial

Background: People with type 2 diabetes (T2D) who have elevated levels of high-sensitivity C-reactive protein (hsCRP) face a greater risk of myocardial infarction and coronary death. Early data for tirzepatide (TZP), a GIP/GLP-1 receptor agonist, suggest a hsCRP lowering effect. Here, we compare the effect of TZP and insulin glargine (iGlar) on hsCRP in patients with T2D and established or high risk for cardiovascular (CV) disease. Methods: hsCRP concentration was quantified by immunoassay (Roche, Indianapolis, IN) with lower limits of detection at concentrations of 0.15 mg/L. Plasma was collected from 1995 fasted participants at baseline (329, 328, 338, and 1000 on 5, 10, 15 mg TZP and on iGlar, respectively) and 52 weeks in SURPASS-4. The % changes of hsCRP from baseline were estimated by mixed model with repeated measures. The shifts in hsCRP risk categories (hsCRP &gt;3 mg/L or 1-3 mg/L versus &lt;1 mg/L) from baseline to 52 weeks are reported. The linear relationship between % change from baseline of hsCRP and change in body mass index (BMI) was analyzed using Pearson correlation coefficient. Results: Baseline hsCRP (mean ± SD, 5.6 ± 12.5 mg/L) was elevated in this study population. Among the participants, 48%, 36%, and 16% were in the &gt;3, 1-3 and &lt;1 mg/L hsCRP categories, respectively. Participants in the elevated hsCRP categories had higher body weight and BMI at baseline. After 52 weeks of treatment, the 5, 10, 15 mg TZP and iGlar groups resulted in -38.0%, -44.2%, -47.8%, and 0.6% changes in the concentration of hsCRP, respectively. More TZP-treated patients improved their hsCRP categories when compared with iGlar-treated participants (Table). The reduction in hsCRP in the pooled TZP groups correlated with the reduction of BMI (r=0.07, p=0.049). Conclusions: Tirzepatide treatment significantly lowers hsCRP in patients with T2D and increased CV risk versus baseline and iGlar. Substantially more participants shift to a lower hsCRP category when compared with insulin glargine.

Adjunctive canakinumab reduces peripheral inflammation markers and improves positive symptoms in people with schizophrenia and inflammation: A randomized control trial

BackgroundClinical trials of anti-inflammatories in schizophrenia do not show clear and replicable benefits, possibly because patients were not recruited based on elevated inflammation status. Interleukin 1-beta (IL-1β) mRNA and protein levels are increased in serum, plasma, cerebrospinal fluid, and brain of some chronically ill patients with schizophrenia, first episode psychosis, and clinical high-risk individuals. Canakinumab, an approved anti-IL-1β monoclonal antibody, interferes with the bioactivity of IL-1β and interrupts downstream signaling. However, the extent to which canakinumab reduces peripheral inflammation markers, such as, high sensitivity C-reactive protein (hsCRP) and symptom severity in schizophrenia patients with inflammation is unknown. Trial designWe conducted a randomized, placebo-controlled, double-blind, parallel groups, 8-week trial of canakinumab in chronically ill patients with schizophrenia who had elevated peripheral inflammation. MethodsTwenty-seven patients with schizophrenia or schizoaffective disorder and elevated peripheral inflammation markers (IL-1β, IL-6, hsCRP and/or neutrophil to lymphocyte ratio: NLR) were randomized to a one-time, subcutaneous injection of canakinumab (150 mg) or placebo (normal saline) as an adjunctive antipsychotic treatment. Peripheral blood hsCRP, NLR, IL-1β, IL-6, IL-8 levels were measured at baseline (pre injection) and at 1-, 4- and 8-weeks post injection. Symptom severity was assessed at baseline and 4- and 8-weeks post injection. ResultsCanakinumab significantly reduced peripheral hsCRP over time, F(3, 75) = 5.16, p = 0.003. Significant hsCRP reductions relative to baseline were detected only in the canakinumab group at weeks 1, 4 and 8 (p’s = 0.0003, 0.000002, and 0.004, respectively). There were no significant hsCRP changes in the placebo group. Positive symptom severity scores were significantly reduced at week 8 (p = 0.02) in the canakinumab group and week 4 (p = 0.02) in the placebo group. The change in CRP between week 8 and baseline (b = 1.9, p = 0.0002) and between week 4 and baseline (b = 6.0, p = 0.001) were highly significant predictors of week 8 change in PANSS Positive Symptom severity scores. There were no significant changes in negative symptoms, general psychopathology or cognition in either group. Canakinumab was well tolerated and only 7 % discontinued. ConclusionsCanakinumab quickly reduces peripheral hsCRP serum levels in patients with schizophrenia and inflammation; after 8 weeks of canakinumab treatment, the reductions in hsCRP are related to reduced positive symptom severity. Future studies should consider increased doses or longer-term treatment to confirm the potential benefits of adjunctive canakinumab in schizophrenia.Australian and New Zealand Clinical Trials Registry number: ACTRN12615000635561.

C-reactive protein: perioperative changes and prognostic significance in assessing the risk of atrial fibrillation in patients after coronary bypass surgery

Aim. To study the level of high-sensitivity C-reactive protein (hsCRP) before coronary artery bypass surgery (CABG) and on days 7-10, as well as to assess the association of perioperative changes in hsCRP with the risk of postoperative atrial fibrillation (POAF).Material and methods. The study included 80 patients (71 (88,75%) men) who underwent an elective CABG in Cardiac Surgery Department of Sklifosovsky Research Institute of Emergency Medicine. The first episode of POAF was considered an episode of arrhythmia, registered by electrocardiography (ECG), Holter monitoring (HM) or bedside cardiac monitor in the intensive care unit. Depending on the development of atrial fibrillation in the postoperative period, patients were divided into 2 following groups: patients with POAF (n=20), patients without POAF (n=60). The serum level of hsCRP was studied twice: before surgery and 7-10 after CABG in patients of both groups.Results. Both groups did not differ significantly in the initial concentration of hsCRP (p=0,802). In the postoperative period, patients in both groups showed a significant increase in hsCRP compared with the initial concentration — up to 39,1 [19,6; 64,0] mg/l in the POAF group (p&lt;0,001) and up to 29,3 [19,7; 45,6] mg/l in the group without POAF (p=0,001), but the difference between the groups was not significant (p=0,338). Serum hsCRP concentration at 7-10 days after CABG in patients of both groups was significantly higher than the baseline (p&lt;0,001). However, no association between POAF risk and hsCRP concentration was found (p&gt;0,05).Conclusion. In patients after CABG, on days 7-10, there is a significantly higher level of hsCRP compared with the initial concentration. There were no significant differences in the level of hsCRP between patients with and without POAF. The POAF of is not associated with an initially elevated level of hsCRP and hsCRP level on days 7-10 after CABG.

Effects of Tocotrienol-Rich Fraction Supplementation in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There are a large number of studies that have reported benefits of tocotrienol-rich fraction (TRF) in various populations with different health status. To date, no systematic reviews have examined randomized controlled trials (RCTs) on the effect of TRF supplementations specifically in patients with type 2 diabetes mellitus (T2DM). This systematic review and meta-analysis aim to examine the changes in HbA1c (glycated hemoglobin), blood pressure, and serum Hs-CRP (C-reactive protein high sensitivity) levels at post-TRF supplementation. Online databases including PubMed, Scopus, OVID Medline, and Cochrane Central Register of Controlled Trials were searched from inception until March 2023 for RCTs supplementing TRF in patients with T2DM. A total of 10 studies were included in the meta-analysis to estimate the pooled effect size. The Cochrane Risk-of-Bias (RoB) Assessment Tool was utilized to evaluate the RoB in individual studies. The meta-analysis revealed that TRF supplementation at a dosage of 250-400 mg significantly decreased HbA1c (-0.23, 95% CI: -0.44, -0.02, P < 0.05, n = 754), particularly where the intervention duration is less than 6 mo (-0.47%, 95% CI: -0.90, -0.05, P < 0.05, n = 126) and where duration of diabetes is less than 10 y (-0.37, 95% CI: -0.68, -0.07, P < 0.05, n = 83). There was no significant reduction in systolic and diastolic blood pressure and serum Hs-CRP (P > 0.05). The present meta-analysis demonstrated that supplementing with TRF in patients with T2DM decreased HbA1c but does not decrease systolic and diastolic blood pressure and serum Hs-CRP.

Effects of febuxostat on markers of endothelial dysfunction and renal progression in patients with chronic kidney disease

Hyperuricemia relates to chronic kidney disease (CKD) progression and impaired endothelial function. Febuxostat is potent and effective for decreasing serum uric acid levels. Information for the effect of febuxostat treatment on markers of endothelial dysfunction and renal injury among patients with CKD remains limited. A total of 84 patients with CKD stages III-IV with asymptomatic hyperuricemia were randomly assigned to either the febuxostat (40 mg/day, N = 42) or the matching control (N = 42) group for 8 weeks. Serum asymmetric dimethylarginine (ADMA), estimated glomerular filtration rate (eGFR), urine albumin, high sensitivity C-reactive protein (hs-CRP), ankle brachial index (ABI) and serum uric acid were measured at baseline and at the end of study. Febuxostat administration significantly reduced the serum uric acid concentration among patients with CKD when compared with control [− 3.40 (95% CI − 4.19 to − 2.62) vs. − 0.35 (95% CI − 0.76 to 0.06) mg/dL; P < 0.001, respectively). No significant difference in the changes in serum ADMA, hs-CRP, eGFR and albuminuria was identified between the two groups. Subgroup analysis among patients with decreased serum uric acid after febuxostat, the estimated GFR change between the febuxostat and the control group showed significant difference at 8 weeks (2.01 (95% CI 0.31 to 3.7) vs. 0.04 (95% CI − 1.52 to 1.61) mL/min/1.73 m2; P = 0.030, respectively). Adverse events specific to febuxostat were not observed. Febuxostat effectively reduced serum uric acid in the CKD population without improving endothelial dysfunction. It was able to preserve renal function in the subgroup of patients with CKD and lower serum uric acid level after treatment.Trial registration: Thai Clinical Trials, TCTR20210224005: 24/022021 http://www.thaiclinicaltrials.org/show/TCTR20210224005.