Reduction In C-reactive Protein Research Articles

Effect of Pemafibrate on Cerebrovascular Atherosclerosis in Patients with Stroke and Hypertriglyceridemia.

The Pemafibrate for Prevention of Atherosclerotic Diseases in Stroke (PPAR Stroke) study aimed to assess the effects of pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, on the progression of cerebrovascular atherosclerosis in patients with stroke and hypertriglyceridemia. Ninety-nine patients (mean age, 65.6 years; male, 74.7%) with hypertriglyceridemia and a history of stroke or transient ischemic attack of non-cardioembolic origin were included in this prospective single-arm study. Hypertriglyceridemia was defined as a fasting serum triglyceride (TG) level ≥ 150 mg/dL. All patients were treated with pemafibrate (0.2 mg or 0.1 mg/day) for 2 years. The primary outcome was change in carotid intima-media thickness (IMT) from baseline at 2 years, as assessed using carotid ultrasonography. The secondary outcomes were changes in blood biomarker levels and progression of intracranial artery stenosis on magnetic resonance angiography. The mean TG level significantly decreased from 269 mg/dL at baseline to 139 mg/dL at 2 years (P＜0.001) and high-density lipoprotein cholesterol level increased from 49 to 54 mg/dL (P＜0.001), whereas low-density lipoprotein cholesterol level remained unchanged. Significant reductions in high-sensitivity C-reactive protein and interleukin-6 levels were also observed (P=0.003 and P=0.002, respectively). With regard to mean IMT in the internal carotid arteries, the difference was significant for the left side (1.59 mm at baseline vs. 1.52 mm at 2 years; P=0.009) and borderline significant for the right side (1.32 mm at baseline vs. 1.28 mm at 2 years; P=0.053). Among the 48 stenotic lesions in the intracranial arteries, regression and progression was observed in 9 (18.8%) and 4 (8.3%) cases, respectively. Pemafibrate was observed to have TG-lowering and anti-inflammatory effects and could attenuate atherosclerosis progression in the intra- and extracranial arteries of patients with stroke and hypertriglyceridemia.

High-dose Intravenous N-Acetylcysteine in Mechanically Ventilated Patients with COVID-19 Pneumonia: A Propensity-Score Matched Cohort Study.

Current therapies for severe COVID-19, such as steroids and immunomodulators are associated with various side effects. N-acetylcysteine (NAC) has emerged as a potential adjunctive therapy with minimal side effects for patients with cytokine storm due to COVID-19. However, evidence supporting high-dose intravenous NAC in severe COVID-19 pneumonia requiring mechanical ventilation is limited. We conducted a retrospective analysis of consecutive patients aged ≥ 18 who were admitted for acute respiratory failure (PaO2/FiO2 ratio <300) with SARS-CoV-2 infection to the Intensive Care Unit (ICU) of Queen Elizabeth Hospital from fifth July 2020 to 31st October 2022. Inclusion was limited to patients who required mechanical ventilation. High-dose NAC refers to a dosage of 10 g per day. The primary outcome was all-cause mortality within 28 days. Propensity-score matched analysis using logistic regression was performed. Among the 136 patients analyzed, 42 (40.3%) patients received NAC. The unmatched NAC patients displayed a higher day-28 mortality (12 (28.6%) versus 4 (6.5%), p = 0.005) and fewer ventilator-free days (18.5 (0-23.0) versus 22.0 (18.3-24.0), p = 0.015). No significant differences were observed in ICU and hospital length of stays among survivors. In patients who were not treated with tocilizumab, those receiving NAC exhibited a trend toward a quicker reduction in C-reactive protein compared to those who did not receive NAC.After propensity score matching which included 64 patients with 33 (51.6%) receiving NAC, no significant differences were found in 28-day mortality, ventilator-free days, or ICU and hospital length of stay. After adjusting for potential confounders, logistic regression of the propensity score-matched population did not demonstrate that the use of NAC independently affected 28-day mortality. In patients with COVID-19 pneumonia requiring mechanical ventilation and receiving standard COVID-19 treatment, the addition of high-dose NAC did not lead to improved clinical outcomes.

Abstract 4131381: Comparison of Dietary Macronutrient Interventions for Weight and Cardiovascular Risk Factor Reduction: A Systematic Review and Network Meta-analysis of Randomized Controlled Trial

Background: Dietary interventions play a crucial role in weight management and reducing cardiovascular risk factors. Our study aims to compare the effectiveness of four dietary macronutrient interventions on weight loss and cardiovascular (CV) risk factor reduction through a systematic review and network meta-analysis. Methods: We conducted a comprehensive literature search on PubMed, Scopus, Embase, and Cochrane Library up till May 2024 to identify randomized controlled trials (RCTs) comparing four macronutrient dietary interventions including Mediterranean Diet (MD), Keto, Dietary Approaches to Stop Hypertension (DASH), and Intermittent Fasting (IF) with study period ≥ 6 months or 24 weeks. The primary outcomes of interest were weight loss, systolic blood pressure (SBP), Diastolic blood pressure (DBP), Body Mass Index (BMI), High density lipoprotein (HDL), Low density Lipoprotein (LDL), cholesterol levels and C-reactive protein (CRP) levels. Outcomes were reported as standard mean difference (SMD). Results: Our analysis identified 50 studies enrolling 5368 patients (MD=3554; DASH=838; Keto=206; IF=770). Regarding BP outcome, MD and DASH had significant reduction in SBP and DBP respectively (MD [SBP]: -0.76 mmHg vs DASH [DBP]: -1.92 mmHg) respectively. In contrast, IF showed a significant rise in SBP (0.87). MD participants also had significant weight loss (-1.06 kg) and a moderate decrease in BMI (-0.79) when compared with other diets. Furthermore, IF, keto, and MD showed moderate increase in HDL levels (0.61, 0.77 and 0.33) respectively. In contrast, DASH resulted in a moderate decline in HDL levels (-0.92). IF and MD resulted in modest decline in LDL levels (-0.45 and -0.42) respectively. In contrast, Keto demonstrated non-significant rise in LDL (0.35). DASH showed a significant decrease in triglycerides (-3.02). Lastly, MD demonstrated a significant reduction in CRP (-0.89). Conclusions: MD and DASH were superior to other dietary interventions in terms of weight loss and CV risk factors. Further research is required to tailor specific types of dietary interventions and assess their long-term efficacy on weight loss and CV risk reduction.

Azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a phase II randomised controlled trial

BackgroundAfrican children with severe malaria are at increased risk of non-typhoidal salmonellae co-infection. Broad-spectrum antibiotics are recommended by guidelines but the optimal class and dose have not been established. We investigated the optimal dose of oral dispersible azithromycin and whether simple clinical criteria and point-of-care biomarkers could target antibiotics to those at greatest risk of bacterial co-infection.MethodsWe conducted a phase I/II trial in Ugandan children with severe malaria comparing a 5-day course of azithromycin: 10, 15 and 20 mg/kg of azithromycin (prescribed by weight bands) spanning the dose-range effective for other salmonellae infection. We generated relevant pharmacokinetic (PK) data by sparse sampling during dosing intervals and investigated associations between azithromycin exposure and potential mechanisms (PK-pharmacodynamics) using change in C-reactive protein (CRP), a putative marker of sepsis, at 72 h (continuous) and microbiological cure (7-day) (binary), alone and as a composite with 7-day and 90-day survival. To assess whether clinical or biomarkers could identify those at risk of sepsis, a non-severe malaria control was concurrently enrolled.ResultsBetween January 2020 and January 2022, 105 cases were randomised azithromycin doses: 35 to 10 mg/kg, 35 to 15 mg/kg and 35 to 20 mg/kg. Fifty non-severe malaria controls were concurrently enrolled. CRP reduced in all arms by 72 h with a mean reduction of 65.8 mg/L (95% CI 57.1, 74.5) in the 10 mg/kg arm, 64.8 mg/L (95% CI 56.5, 73.1; p = 0.87) in the 20 mg/kg arm and a smaller reduction 51.2 mg/L (95% CI 42.9, 59.5; p = 0.02) in the 15 mg/kg arm. Microbiological cure alone outcome was not analysed as only one pathogen was found among cases. Three events contributed to the composite outcome of 7-day survival and microbiological cure, with no events in the 15 mg/kg arm. The odds ratio comparing 20 vs 10 mg/kg was 0.50 (95% CI 0.04, 5.79); p = 0.58. Due to the low number of pathogens identified, it was not possible to identify better methods for targeting antibiotics including both the cases and controls.ConclusionsWe found no evidence for an association between systemic azithromycin exposure and reduction in CRP. Further work is needed to better identify children at highest risk from bacterial co-infection.Trial registrationISRCTN49726849 (registered on 27th October 2017).

The Effect of Black Chokeberry (Aronia melanocarpa) on Human Inflammation Biomarkers and Antioxidant Enzymes: A Systematic Review of Randomized Controlled Trials.

Consuming antioxidant-rich foods has been associated with potential benefits in managing chronic diseases by reducing oxidative stress and inflammation. This systematic review aimed to evaluate the effects of Aronia melanocarpa (aronia berry or chokeberry) on human inflammation biomarkers and antioxidant enzymes. A systematic search was conducted across multiple databases, including PubMed, Scopus, Science Direct, and Web of Science, to identify relevant studies investigating the potential effects of aronia on human inflammation biomarkers and antioxidant enzymes between April 2022 and November 2023. The selection of studies followed the PRISMA guidelines, data screening was conducted by 4 independent reviewers, and data extraction and risk-of-bias assessments were performed by 2 independent reviewers using the Cochrane Risk of Bias 2 tool. A total of 1986 studies were screened, and 18 studies that met the inclusion criteria were included in a systematic review that investigated the anti-inflammatory effects of aronia on various health parameters. These studies primarily focused on the effects of aronia on cardiometabolic diseases, performance in sport, and other health parameters. This study examined the effects of Aronia intervention on human health outcomes using aronia juice, extract, or oven-dried powder for a period of 4 to 13 weeks. The primary health parameters considered were C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), interleukin-8 (IL-8), interleukin-10 (IL-10), interleukin-1ß (IL-1ß), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione peroxidase (GSH-Px). The results showed that aronia had a beneficial effect on several inflammatory cytokines, including reductions in CRP, TNF-α and IL-6 concentrations, as well as elevated IL-10 levels. Moreover, positive changes have been observed in antioxidant enzyme systems, including; elevated SOD, GSH-Px and CAT activity. The findings of the presented studies provide evidence that Aronia melanocarpa may have beneficial effects on inflammatory markers. PROSPERO registration No. CRD42022325633.

Modulation of Inflammatory Markers in Type 2 Diabetes Mellitus Through Gut Microbiome-Targeted Interventions: An umbrella review on meta-analyses

Background & AimsType 2 diabetes mellitus (T2DM) poses a significant global health challenge due to various lifestyle factors contributing to its prevalence and associated complications. Chronic low-grade inflammation, characterized by elevated levels of inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), plays a pivotal role in the pathogenesis of T2DM. Modulation of the gut microbiota through microbiome-targeted therapy (MTT), including probiotics, prebiotics, and synbiotics, has emerged as a potential strategy to mitigate inflammation and improve metabolic outcomes in T2DM. MethodsA systematic review and meta-analysis were conducted following PRISMA guidelines to evaluate the impact of MTT on inflammatory markers in patients with T2DM. Searches were performed in PubMed, Scopus, and Web of Science databases up to June 2024, with inclusion criteria limited to English-language meta-analyses of randomized controlled trials (RCTs) assessing the effects of probiotics, prebiotics, or synbiotics on inflammatory markers in T2DM patients. ResultsTen meta-analyses met the inclusion criteria, comprising studies investigating the effects of various MTT interventions on CRP, IL-6, and TNF-α levels in T2DM patients. Meta-analysis results indicated significant reductions in CRP (SMD: -0.070; 95% CI: -0.119 to -0.020) and TNF-α (SMD: -0.370; 95% CI: -0.554 to -0.186) levels following MTT, while IL-6 reductions (SMD: -0.070; 95% CI: -0.269 to 0.129) did not reach statistical significance. However, heterogeneity in study quality, intervention protocols, and participant demographics posed challenges in interpretation. ConclusionsWhile improvements in inflammatory markers with MTT have been observed, significant limitations—such as heterogeneity in study quality and variation in intervention protocols—highlight the need for further research to confirm its efficacy and clarify underlying mechanisms. Future studies should aim to address these limitations by exploring variations in dosage, supplement formulations, and bacterial strains, which are crucial for improving the reliability and broader applicability of MTT in the management of T2DM.

Impact of cardiovascular risk factors in cardiac (reverse) remodelling induced by pregnancy

Abstract Introduction Haemodynamic overload during pregnancy induces cardiac remodelling, characterised by cardiac hypertrophy and chamber enlargement, associated with deterioration of diastolic function, despite preservation of the systolic function. After delivery, the woman's heart undergoes reverse remodelling(RR), and myocardial function and structure normalise to their pre-gravid state. The impact of cardiovascular risk factors(CRF) in cardiac remodelling and RR, namely, on cardiac function and structure, is variable and remains to be clarified. Purpose To characterise cardiac remodelling and RR during pregnancy and postpartum, respectively, and to investigate CRF's impact in these processes. Methods This prospective cohort study included volunteer pregnant women (healthy [H group] or obese and/or hypertensive and/or with gestational diabetes [CRF group]) recruited in two tertiary centres between 2019 and 2022. Women were evaluated by transthoracic echocardiography at the 1st trimester [1T,10-15 weeks, baseline], 3rd trimester [3T,30-35 weeks, peak of cardiac remodelling] of pregnancy as well as at the 1st, 6th and 12th month after delivery (during RR). Blood samples were collected in each evaluation moment to quantify plasma troponin I (cTnI), procollagen I COOH-terminal propeptide (PICP), ST2/IL33-receptor, C-reactive protein (CRP) and relaxin-2 by ELISA. Generalised linear mixed-effects models were used to evaluate the extent of RR and its potential predictors. Results We included 130 pregnant women with a median age of 33 [30,36] years, 41.5% with at least one CRF. As shown in Table 1, pregnant women developed cardiac hypertrophy with significant atrial and ventricular enlargement from 1T to 3T in both groups. A significant rise in filling pressures was also documented. During postpartum, a significant regression of cardiac hypertrophy and dilation was verified in the two study groups, accompanied by a significant decrease of E/e’ as soon as 1 month after delivery. These cardiac anatomical and functional adaptations induced by pregnancy were accompanied by a significant reduction in plasma cTnI, PICP, ST2/IL33-receptor, CRP and relaxin-2 levels from 3T to 6-months after delivery. Compared to the healthy pregnant women, the CRF group showed higher relative wall thickness (RWT) for all time points of the follow-up period, with similar values of indexed cardiac mass and volumes. Pregnant women with CRF revealed higher E/e’, contrasting with lower ejection fraction and worse global longitudinal strain. Conclusion The significant cardiac reverse remodelling occurred as soon as 1 month after delivery, returning to basal values 6 months postpartum, supported by a significant reduction of levels of plasma biomarkers related to myocardial injury, repair, fibrosis, and inflammation. Pregnant women with CRF showed higher RWT, impaired relaxation and subclinical LV dysfunction when compared with healthy women at all time points of the study.

Effects of a diverse prebiotic fibre blend on inflammation, the gut microbiota and affective symptoms in metabolic syndrome: a pilot open-label randomised controlled trial.

Emerging evidence suggests that low-grade systemic inflammation plays a key role in altering brain activity, behaviour and affect. Modulation of the gut microbiota using prebiotic fibre offers a potential therapeutic tool to regulate inflammation, mediated via the production of short-chain fatty acids (SCFA). However, the impact of prebiotic consumption on affective symptoms and the possible contribution from inflammation, gut symptoms and the gut microbiome are currently underexamined. In this 12-week study, the effects of a diverse prebiotic blend on inflammation, gut microbiota profiles and affective symptoms in a population with metabolic syndrome (MetS) were examined. Sixty males and females with MetS meeting the criteria for MetS were randomised into a treatment group (n 40), receiving 10 g per day of a diverse prebiotic blend and healthy eating advice, and a control group (n 20), receiving healthy eating advice only. Our results showed a significant reduction in high sensitivity C-reactive protein (hs-CRP) in the treatment (-0·58 [-9·96 to-2·63]) compared with control (0·37 [-3·64 to-3·32]), alongside significant improvements in self-reported affective scores in the treatment compared with the control group. While there were no differences in relative abundance between groups at week 12, there was a significant increase from baseline to week 12 in fecal Bifidobacterium and Parabacteroides in the treatment group, both of which are recognised as SCFA producers. Multivariate regression analyses further revealed an association between gastrointestinal symptoms and hs-CRP with affective scores. Together, this study provides preliminary support for a diverse prebiotic blend for mood, stress and anxiety.

Hypercholesterolemia and inflammation-Cooperative cardiovascular risk factors.

Maintaining low concentrations of plasma low-density lipoprotein cholesterol (LDLc) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and delays the age at which mature atherosclerotic plaques develop. This substantially reduces the lifetime risk of atherosclerotic cardiovascular disease (ASCVD) events.In this context, plaque development and vulnerability result not only from lipid accumulation but also from inflammation. Changes in the composition of immune cells, including macrophages, dendritic cells, T cells, B cells, mast cells and neutrophils, along with altered cytokine and chemokine release, disrupt the equilibrium between inflammation and anti-inflammatory mechanisms at plaque sites. Considering that it is not a competition between LDLc and inflammation, but instead that they are partners in crime, the present narrative review aims to give an overview of the main inflammatory molecular pathways linked to raised LDLc concentrations and to describe the impact of lipid-lowering approaches on the inflammatory and lipid burden. Although remarkable changes in LDLc are driven by the most recent lipid lowering combinations, the relative reduction in plasma C-reactive protein appears to be independent of the magnitude of LDLc lowering. Identifying clinical biomarkers of inflammation (e.g. interleukin-6) and possible targets for therapy holds promise for monitoring and reducing the ASCVD burden in suitable patients.

High dose cotrimoxazole treatment in patients with severe COVID-19: A randomised controlled trial

Background: Cotrimoxazole for severe COVID-19 may have a better prognosis because of its antibacterial, immunomodulatory, and anti-inflammatory activities. We examined the efficacy of high-dose cotrimoxazole therapy in terms of duration of hospital stays and reduction in mortality in severe COVID-19 infections. Methods: From May to November 2021, we conducted a double blind randomised controlled trial with two parallel groups in the COVID units of Bangabandhu Sheikh Mujib Medical University and Anwar Khan Modern Medical College Hospital, Dhaka. One group received standard therapy in addition to an oral dose of 960 mg of cotrimoxazole twice daily for 7 days (intervention group), while the other group received standard treatment and a placebo (standard group). Pre-protocol analysis was done. Results: A total of 188 patients were enrolled, but 166 completed the study. Of them, 93 were in the intervention group and 73 were in standard group. The mean ages of the groups were similar (intervention, 56.2 and standard, 59.2 years) (P=0.10). The mortality at 28 days between groups was also similar (11.8% in the intervention group and 15.0% in the standard group) (P=0.56). The hospital stay was 13.7 days for the intervention group and 13.5 days for the standard group (P=0.86). However, the reduction in C-reactive protein was statistically significant in the intervention group, with a mean decline of 23.6 mg/L (95% confidence interval, 0.5–46.7 mg/L). Conclusion: High-dose cotrimoxazole did not benefit in shortening in-hospital stay or reducing mortality at day 28 in patients with severe COVID-19. However, the decline in the C-reactive protein level was significant, necessitating further research.

Impact of Omega-3 Fatty Acid Supplementation in Parenteral Nutrition on Inflammatory Markers and Clinical Outcomes in Critically Ill COVID-19 Patients: A Randomized Controlled Trial.

The heightened inflammatory response observed in COVID-19 patients suggests that omega-3 fatty acids (O3FA) may confer anti-inflammatory benefits. This randomized, double-blind, single-center clinical trial aimed to evaluate the effect of O3FA supplementation in parenteral nutrition (PN) on inflammatory markers in COVID-19 patients admitted to the intensive care unit (ICU). A total of 69 patients were randomized into three groups: one received standard lipid emulsion, and two received O3FA (Omegaven®) at doses of 0.1 g/kg/day and 0.2 g/kg/day, respectively, in addition to Smoflipid®. The primary outcomes measured were serum levels of C-reactive protein (CRP) and interleukin-6 (IL-6) on days 1, 5, and 10 of PN initiation. Secondary outcomes included additional inflammatory markers (TNF-α, IFN-γ, IL-1Ra, CXCL10), hepatic function, triglyceride levels, and clinical outcomes such as mortality and length of ICU and hospital stay. Results indicated a significant reduction in CRP, IL-6, and CXCL10 levels in the group receiving 0.1 g/kg/day O3FA compared to the control. Additionally, the higher O3FA dose was associated with a shorter ICU and hospital stay. These findings suggest that O3FA supplementation in PN may reduce inflammation and improve clinical outcomes in critically ill COVID-19 patients.

The Impact of Exercise on C-reactive Protein Levels in Hypertensive Patients: A Systematic Review.

Hypertension, defined as persistently elevated blood pressure, is a prevalent chronic condition and a significant global health issue, closely linked to cardiovascular complications, with inflammation being one of the underlying mechanisms. In hypertensive patients, C-reactive protein (CRP), an inflammatory marker, is often elevated and associated with increased cardiovascular risk. Alongside pharmacotherapy, exercise is recommended as a non-pharmacological approach to managing hypertension, with evidence suggesting that exercise can also reduce inflammation. This study examines the impact of exercise on CRP levels in hypertensive patients. Fourteen studies focusing on exercise interventions and physical fitness related to CRP in individuals with high blood pressure were identified through an extensive search of PubMed, PubMed Central, ScienceDirect, Cochrane Library, and Google Scholar. The findings indicated that most studies involving aerobic exercise consistently demonstrated reductions in CRP levels among hypertensive patients, with significant effects observed under supervised conditions, and additional benefits seen when combined with dietary control. Resistance training showed mixed results, with significant reductions in CRP observed primarily in longer-term interventions. Combined exercise training, incorporating both aerobic and resistance elements, effectively reduced CRP levels and improved cardiovascular health markers. Physical fitness assessments, such as a bicycle exercise test to exhaustion, revealed a relationship between physical fitness and decreased CRP levels. Therefore, regular, consistent aerobic and combined training, as well as prolonged resistance exercise, significantly reduce CRP levels in hypertensive patients, highlighting exercise's role as a non-pharmacological strategy for managing hypertension through the reduction of inflammation. Further research is essential to validate these findings and investigate the underlying mechanisms and differential effects of various exercise modalities.

A tailored machine learning approach for mortality prediction in severe COVID-19 treated with glucocorticoids.

<sec><title>BACKGROUND</title>The impact of severe COVID-19 pneumonia on healthcare systems highlighted the need for accurate predictions to improve patient outcomes. Despite the established efficacy of glucocorticoids (GCs), variable patient responses are observed, and the existing clinical scores are limited in predicting non-responders. We propose a machine learning (ML) based approach to predict mortality in COVID-19 pneumonia treated with GCs.</sec><sec><title>METHODS</title>This is an ML-driven retrospective analysis involving 825 patients. We leveraged XGBoost to select the most appropriate features from the initial 52, including clinical and laboratory data. Six different ML techniques were compared. Shapley additive explanation (SHAP) values were used to describe the influence of each feature on classification. Internal validation was performed.</sec><sec><title>RESULTS</title>Nine key predictors of death were identified: increasing C-reactive protein (CRP), decreasing arterial partial pressure of oxygen to fraction of inspired oxygen ratio (PaO₂/FiO₂), age, coronary artery disease, invasive mechanical ventilation, acute renal failure, chronic heart failure, PaO₂/FiO₂ earliest value, and body mass index. Random forest achieved the highest test area under the receiver operating characteristic curve at 0.938 (95% CI 0.903-0.969). SHAP values highlighted age and PaO₂/FiO₂ improvement as the most influential features; the latter showed a higher impact than CRP reduction over time.</sec><sec><title>CONCLUSION</title>The proposed ML algorithm effectively predicts the risk of hospital death in COVID-19 pneumonia patients undergoing GCs. This approach can be adapted to datasets measuring similar clinical variables.</sec>.

Inflammation in Obesity-Related HFpEF: The STEP-HFpEF Program

BackgroundInflammation is thought to be an important mechanism for the development and progression of obesity-related heart failure with preserved ejection fraction (HFpEF). In the STEP-HFpEF Program, once-weekly 2.4 mg semaglutide improved heart failure–related symptoms, physical limitations, and exercise function, reduced the levels of C-reactive protein (CRP), a biomarker of inflammation, and reduced body weight in participants with obesity-related HFpEF. However, neither the prevalence nor the clinical characteristics of patients who have various magnitudes of inflammation in the context of obesity-related HFpEF have been well described. Furthermore, whether the beneficial effects of semaglutide on the various HF efficacy endpoints in the STEP-HFpEF Program are modified by the baseline levels of inflammation has not been fully established. Finally, the relationship between weight reduction and changes in CRP across the STEP-HFpEF Program have not been fully defined. ObjectivesThis study sought to: 1) evaluate baseline characteristics and clinical features of patients with obesity-related HFpEF that have various levels of inflammation in the STEP-HFpEF Program; 2) determine if the effects of weekly semaglutide 2.4 mg vs placebo across all key outcomes are influenced by baseline levels of inflammation assessed by CRP levels; and 3) determine the relationship between change in CRP and weight loss in the STEP-HFpEF Program. MethodsThis was a secondary analysis of pooled data from 2 international, double-blind, placebo-controlled, randomized trials (STEP-HFpEF and STEP-HFpEF DM). The outcomes were change in the dual primary endpoints (health status [measured by the Kansas City Cardiomyopathy Questionnaire—Clinical Summary Score (KCCQ-CSS)] and body weight) from baseline to 52 weeks according to baseline CRP levels. Additional efficacy endpoints included change in 6-minute walk distance (6MWD), a hierarchical composite endpoint that included death, heart failure events, and differences in the change in the KCCQ-CSS and 6MWD, and levels of CRP in semaglutide- vs placebo-treated patients. Patients were stratified into 3 categories based on baseline CRP levels (<2, ≥2 to <10, and ≥10 mg/L). ResultsIn total, 1,145 patients were randomized, of which 71% of patients had evidence of inflammation (CRP ≥2 mg/L). At baseline, those with higher levels of inflammation were younger, were more likely to be female, and had higher body mass index, worse health status (KCCQ-CSS), and shorter 6MWD. Semaglutide vs placebo led to reductions in HF-related symptoms and physical limitations as well as body weight, and to improvements in 6MWD and the hierarchical composite endpoint that were consistent across baseline CRP categories (all P interaction nonsignificant). Semaglutide also reduced CRP to a greater extent than placebo regardless of baseline CRP levels (P interaction = 0.32). Change in CRP from baseline to 52 weeks was similar regardless of the magnitude of weight loss (P interaction = 0.91). ConclusionsInflammation is highly prevalent in obesity-related HFpEF. Semaglutide consistently improved HF-related symptoms, physical limitations, and exercise function, and reduced body weight across the categories of baseline CRP. Semaglutide also reduced inflammation, regardless of either baseline CRP or magnitude of weight loss during the trials. (Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity [STEP-HFpEF; NCT04788511]; Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes [STEP HFpEF DM; NCT04916470])

A systematic review and meta-analysis of randomized trials of substituting soymilk for cow’s milk and intermediate cardiometabolic outcomes: understanding the impact of dairy alternatives in the transition to plant-based diets on cardiometabolic health

BackgroundDietary guidelines recommend a shift to plant-based diets. Fortified soymilk, a prototypical plant protein food used in the transition to plant-based diets, usually contains added sugars to match the sweetness of cow’s milk and is classified as an ultra-processed food. Whether soymilk can replace minimally processed cow’s milk without the adverse cardiometabolic effects attributed to added sugars and ultra-processed foods remains unclear. We conducted a systematic review and meta-analysis of randomized controlled trials, to assess the effect of substituting soymilk for cow’s milk and its modification by added sugars (sweetened versus unsweetened) on intermediate cardiometabolic outcomes.MethodsMEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched (through June 2024) for randomized controlled trials of ≥ 3 weeks in adults. Outcomes included established markers of blood lipids, glycemic control, blood pressure, inflammation, adiposity, renal disease, uric acid, and non-alcoholic fatty liver disease. Two independent reviewers extracted data and assessed risk of bias. The certainty of evidence was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). A sub-study of lactose versus sucrose outside of a dairy-like matrix was conducted to explore the role of sweetened soymilk which followed the same methodology.ResultsEligibility criteria were met by 17 trials (n = 504 adults with a range of health statuses), assessing the effect of a median daily dose of 500 mL of soymilk (22 g soy protein and 17.2 g or 6.9 g/250 mL added sugars) in substitution for 500 mL of cow’s milk (24 g milk protein and 24 g or 12 g/250 mL total sugars as lactose) on 19 intermediate outcomes. The substitution of soymilk for cow’s milk resulted in moderate reductions in non-HDL-C (mean difference, − 0.26 mmol/L [95% confidence interval, − 0.43 to − 0.10]), systolic blood pressure (− 8.00 mmHg [− 14.89 to − 1.11]), and diastolic blood pressure (− 4.74 mmHg [− 9.17 to − 0.31]); small important reductions in LDL-C (− 0.19 mmol/L [− 0.29 to − 0.09]) and c-reactive protein (CRP) (− 0.82 mg/L [− 1.26 to − 0.37]); and trivial increases in HDL-C (0.05 mmol/L [0.00 to 0.09]). No other outcomes showed differences. There was no meaningful effect modification by added sugars across outcomes. The certainty of evidence was high for LDL-C and non-HDL-C; moderate for systolic blood pressure, diastolic blood pressure, CRP, and HDL-C; and generally moderate-to-low for all other outcomes. We could not conduct the sub-study of the effect of lactose versus added sugars, as no eligible trials could be identified.ConclusionsCurrent evidence provides a good indication that replacing cow’s milk with soymilk (including sweetened soymilk) does not adversely affect established cardiometabolic risk factors and may result in advantages for blood lipids, blood pressure, and inflammation in adults with a mix of health statuses. The classification of plant-based dairy alternatives such as soymilk as ultra-processed may be misleading as it relates to their cardiometabolic effects and may need to be reconsidered in the transition to plant-based diets.Trial registrationClinicalTrials.gov identifier, NCT05637866.

The systemic impact of non-surgical treatment of peri-implantitis with or without adjunctive systemic metronidazole: Secondary analysis of a randomized clinical trial.

The aim of this study was to evaluate the systemic effect of non-surgical peri-implantitis treatment (NSPIT) with or without the administration of systemic metronidazole. In this secondary analysis from a previously published clinical trial (NCT03564301), peri-implantitis patients were randomized into two groups: test, receiving NSPIT plus 500 mg of oral systemic metronidazole three times a day for 7 days (n = 10); and control group, receiving NSPIT plus placebo (n = 11). Serum samples were obtained at baseline, 3 and 6 months after therapy to determine levels of inflammatory biomarkers, lipid fractions and complete blood counts. Both treatment modalities produced improvements in clinical and radiographic parameters. After 6 months from NSPIT, a substantial reduction in C-reactive protein (6.9 mg/dL; 95% CI: 3.7 to 9.9, p < .001) and low-density lipoprotein cholesterol (21.8 mg/dL; 95% CI: -6.9 to 50.5, p = .013) as well as a modest increase in neutrophils counts (0.4 × 103/μL; 95% CI: -0.4 to 1.1, p = .010) was observed in the control group while the test group showed a significant reduction of TNF-α (110.1; 95% CI: 38.9 to 181.4, p = .004). NSPIT showed a short-term beneficial systemic effect regardless of adjunctive use of systemic metronidazole.

Dapagliflozin, inflammation and left ventricular remodelling in patients with type 2 diabetes and left ventricular hypertrophy

Background and AimsSodium-glucose co-transporter 2 (SGLT2) inhibitors have beneficial effects in heart failure (HF), including reverse remodelling, but the mechanisms by which these benefits are conferred are unclear. Inflammation is implicated in the pathophysiology of heart failure (HF) and there are some pre-clinical data suggesting that SGLT2 inhibitors may reduce inflammation. There is however a lack of clinical data. The aim of our study was to investigate whether improvements in cardiac remodelling caused by dapagliflozin in individuals with type 2 diabetes (T2D) and left ventricular hypertrophy (LVH) were associated with its effects on inflammation.MethodsWe measured C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and interleukin 10 (IL-10) and neutrophil-to-lymphocyte ratio (NLR) in plasma samples of 60 patients with T2D and left ventricular hypertrophy (LVH) but without symptomatic HF from the DAPA-LVH trial in which participants were randomised dapagliflozin 10 mg daily or placebo for 12 months and underwent cardiac magnetic resonance imaging (CMR) at baseline and end of treatment. The primary analysis was to investigate the effect of dapagliflozin on inflammation and to assess the relationships between changes in inflammatory markers and LV mass and global longitudinal strain (GLS) and whether the effect of dapagliflozin on LV mass and GLS was modulated by baseline levels of inflammation.ResultsFollowing 12 months of treatment dapagliflozin significantly reduced CRP compared to placebo (mean difference of -1.96; 95% CI -3.68 to -0.24, p = 0.026). There were no significant statistical changes in other inflammatory markers. There were modest correlations between improvements in GLS and reduced inflammation (NLR (r = 0.311), IL-1β (r = 0.246), TNF-α (r = 0.230)) at 12 months.ConclusionsDapagliflozin caused a significant reduction in CRP compared to placebo. There were correlations between reductions in inflammatory markers including IL-1β and improvements in global longitudinal strain (but not reduced LV mass). Reductions in systemic inflammation might play a contributory role in the cardiovascular benefits of dapagliflozin.Trial registrationClinicaltrials.gov NCT02956811 (06/11/2016).

Efficacy and safety of infliximab and adalimumab in inflammatory bowel disease patients

IntroductionInflammatory bowel disease (IBD), consists of two primary types: Ulcerative Colitis (UC) and Crohn’s Disease (CD). Infliximab (IFX) and Adalimumab (ADA) are frequently utilized in the management of moderate to severe cases of IBD.AimThis study aimed to assess the efficacy and safety of IFX and ADA in individuals diagnosed with moderate to severe IBD.MethodThis study is a prospective open-labeled randomized parallel study that included moderate to severe IBD patients treated with either IFX or ADA. A total of 56 patients participated, with 34 patients received IFX and 22 patients received ADA. Various measures, including Crohn’s Disease Activity Index (CDAI), Mayo Score/ Disease Activity Index (DAI), and C-reactive protein (CRP) levels, were taken at baseline and week 14 to assess the efficacy of the treatments. In addition, the levels of drugs and sTREM-1 were measured at 14 weeks. Patient safety was monitored throughout the study period.ResultsIn the group received IFX, there was a notable decrease in CDAI (P = 0.045), DAI (P = 0.026), and CRP (P = 0.023 for CD, and P = 0.021 for UC) levels. In addition, the group received ADA experienced a significant reduction in CDAI (P = 0.001), DAI (P = 0.032), and CRP (P < 0.018 for CD and P = 0.003 for UC) levels. Responders had higher drug concentrations than non-responders, notably IFX concentration was higher in responders with CD (P = 0.001) and UC (P < 0.001). ADA concentration was higher in UC (P <= 0.001) and all CD patients responded to the treatment. The same trend was observed for sTREM-1 levels in CD and UC patients (P = 0.042, and P = 0.015, respectively) in the IFX group. In UC patients treated with ADA, the level of sTREM-1 was significantly low (P = 0.002).ConclusionBoth IFX and ADA have a good safety profile and deliver a beneficial clinical and laboratory response in moderate-severe IBD patients.Clinical Trial RegistrationThis study is registered on ClinicalTrials.gov under the identifier NCT05291039. (You can access the study at https://clinicaltrials.gov/study/NCT05291039 (First Posted: March 22, 2022).

Lactoferrin efficacy in treating hyperferritinemia in patients suffering from pathologies unrelated to hereditary hemochromatosis.

Ferritin (Ftn), a globular protein, sequesters 4500 atoms of iron per molecule. Elevated serum Ftn levels (hyperferritinemia) is an indicator of iron homeostasis disorders. We present the results of an observational study involving 17 patients with hyperferritinemia unrelated to hereditary hemochromatosis (HH). All participants received treatment with 200mg of bovine lactoferrin (bLf) once (n=14) or twice (n=3) a day before meals. The patients, treated with 200mg/day of bLf, exhibited a significant increase in red blood cells (+10%, p<0.001), hemoglobin (+4%, p<0.001), and hematocrit (+15%, p=0.004), accompanied by a significant reduction in serum Ftn levels (-52%, p<0.001), C-reactive protein (CRP) (-85.0%, p<0.001), and D-dimers (-19%, p<0.001). Among the three patients treated with 400mg/day of bLf, two had effects similar to those of patients bLf-treated with 200mg/day and one experienced a strong reduction of Ftn, CRP, and erythrocyte sedimentation rate (from -97% to -75%). The decrease in serum Ftn levels due to bLf treatment was largely independent of gender (p=0.78), age (p=0.66), baseline symptoms (p=0.20), and concomitant acute (p=0.34) and chronic (p=0.53) infections. Although this observational pilot study yields positive effects in patients with hyperferritinemia unrelated to HH treated with bLf, a larger sample size is needed for conclusive results.

Is Curcumin Intake Really Effective for Chronic Inflammatory Metabolic Disease? A Review of Meta-Analyses of Randomized Controlled Trials.

This review aimed to examine the effects of curcumin on chronic inflammatory metabolic disease by extensively evaluating meta-analyses of randomized controlled trials (RCTs). We performed a literature search of meta-analyses of RCTs published in English in PubMed®/MEDLINE up to 31 July 2023. We identified 54 meta-analyses of curcumin RCTs for inflammation, antioxidant, glucose control, lipids, anthropometric parameters, blood pressure, endothelial function, depression, and cognitive function. A reduction in C-reactive protein (CRP) levels was observed in seven of ten meta-analyses of RCTs. In five of eight meta-analyses, curcumin intake significantly lowered interleukin 6 (IL-6) levels. In six of nine meta-analyses, curcumin intake significantly lowered tumor necrosis factor α (TNF-α) levels. In five of six meta-analyses, curcumin intake significantly lowered malondialdehyde (MDA) levels. In 14 of 15 meta-analyses, curcumin intake significantly reduced fasting blood glucose (FBG) levels. In 12 of 12 meta-analyses, curcumin intake significantly reduced homeostasis model assessment of insulin resistance (HOMA-IR). In seven of eight meta-analyses, curcumin intake significantly reduced glycated hemoglobin (HbA1c) levels. In eight of ten meta-analyses, curcumin intake significantly reduced insulin levels. In 14 of 19 meta-analyses, curcumin intake significantly reduced total cholesterol (TC) levels. Curcumin intake plays a protective effect on chronic inflammatory metabolic disease, possibly via improved levels of glucose homeostasis, MDA, TC, and inflammation (CRP, IL-6, TNF-α, and adiponectin). The safety and efficacy of curcumin as a natural product support the potential for the prevention and treatment of chronic inflammatory metabolic diseases.