Reduction In hs-CRP Research Articles

Effect of Phytosterols on Serum Levels of C-Reactive Protein: A Time- and Dose-Response Meta-analysis of Randomized Controlled Trial.

Phytosterols are recognized for their cholesterol-reducing effects and are commonly used as dietary supplements or added to foods due to their potential cardiovascular benefits. However, evidence regarding the impact of phytosterol supplementation on inflammatory markers remains inconclusive. This systematic review and meta-analysis aim to evaluate the effect of phytosterols in reducing levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP). A systematic literature search of the primary databases was conducted up to May 2024 to identify eligible studies. The measurement of effect sizes was determined using WMD (weighted mean difference) and 95% CI. For the meta-analysis, 14 publications (19 study arms) for hs-CRP and 10 publications (16 study arms) for CRP were included. The pooled analysis showed that the administration of phytosterol did not significantly reduce CRP compared to control with WMD= -0.04mg/l (95% CI: -0.28 to 0.20, P = 0.74). However, phytosterol supplementation significantly decreased the hs-CRP level compared to the control group with WMD of -0.25mg/l (95% CI: -0.42 to -0.07, P = 0.006). The WMD for hs-CRP reduction was - 0.36mg/l (95% CI: -0.53 to -0.18, P < 0.001) for supplementation with a phytosterol dose ≥ 2000mg/day compared to the control group. Phytosterol supplementation may be effective in reducing hs-CRP levels.

IMPACT OF ANTIHYPERTENSIVE DRUGS ON C REACTIVE PROTEIN (HS-CRP) AND NEUTROPHIL LYMPHOCYTE RATIO (NLR)

Many studies showed the association between inflammation and Hypertension. Inflammatory markers may highlight the state of inflammation in hypertensive patients. This study aimed to investigate impact of antihypertensive drugs on high sensitive C-reactive protein (hsCRP) and neutrophil lymphocyte ratio (NLR). A comparative cross sectional study was conducted on 86 hypertensive patients attending cardiology outpatient clinic in Al-Gamhuoria Modern General Hospital, Aden, in the period from October to December 2023. Participants were divided into three groups: patients treated with mono-therapy from inhibitors of renin angiotensin aldosterone system (RAASI), patients treated with mono-therapy antihypertensive not acting on RAAS (NRAASI) and patients treed with combination of them (drug combination). Data on Age, Sex, BP level, BMI, duration of hypertension (HTN), family history of HTN, and medications used were collected. Blood samples for measuring HsCRP, neutrophils, lymphocytes were drawn. Descriptive statics and chi-square tests were used for data analysis. Almost equivalent distribution for males and females between groups, with a large proportion of the patients within each group laid in the age group 35-55 years. The median values of hypertension duration were 36, 48, and 54 months for RAASIs, NRAASIs and drug combination group, respectively. The target BP was obtained by 46.9% 45.5% and 50% of patients treated with RAASIs, NRAASIs and drug combination respectively. There was a statistically significant difference between SBP and DBP in patients with controlled BP and those with uncontrolled SBP levels and treated by different drug regimens (P=0.000 for each Bp level). There were significant differences between values of hs-CRP of patients with controlled (P=0.000) or uncontrolled (P=0.046) BP and treated with different modalities. The median differences in NLR between the groups were statistically significant; including groups of all patients P=.032, of patients having controlled BP P=0.014 as well as uncontrolled BP P=0.038. Comparing the uncontrolled of BP of the three groups we found the highest prevalence (9.3%)of patients with uncontrolled BP and had the lower level hsCRP (≤3mg /l) was in RAASIs group, while those with higher prevalence (11.6%) of uncontrolled BP and higher level of hs-CRP ( &gt;3mg/l) was in drug combination group. In conclusion, hypertensive patients treated with RAASI, NRAASI and drug combination and reached BP target showed significant reduction in hsCRP and NLR. Patients with uncontrolled BP treated with RAASIs revealed slightly lower hs-CRP than other groups. Careful selection of antihypertensive drugs may affect risks of CVD. This study recommends further prospective studies exploring the anti-inflammatory effect of antihypertensive drugs to ameliorate possible risks of cardiovascular disease.

Bempedoic acid – new agent in hiperlipidemia treatment – literature review

Hyperlipidemia is becoming more and more severe condition among modern society. High-fat diet, sedentary lifestyle, lack of physical activity are the common factors leading to overweight, obesity and problems with serum lipid control. Dyslipidemia is one of the most important agents contributing to cardiovascular diseases snd therefore lower quality of life, disability and preamature death. This forces to constatnt searching for lipid-lowering drugs, that can be successfully use in the patients suffering from poor lipid control. Bempedoic acid (ETC-1020) is one of the newest, first in the class medicine, firstly approved to use in the USA on 21st February 2020 in monotheraphy, and then on 26th February in combination with ezetimibe. It is a small synthetic prodrug molecule that is activated by acyl-CoA synthetase in the liver. Bempedoic acid inhibits competitively adenosine triphosphate citrate lyase (ACL) and as a result it stops the further production of cholesterol and fatty acids. Research shows the ability of ETC-1020 to decline of LDL-C cholesterol up to 24%. It is also responsible for total cholesterol, non-HDL-C, ApoB and hs-CRP reduction. Bempedoic acid is characterized by good pharmacokinetics and pharmacodynamics. ECT-1020 has also a good drug-to-drug interaction profile. Many clinical trials have reported efficacy and safety of use with minimal side effects. Because of its target point is located in the liver and kidney, it can be successfully use in patients with statin intolerance due to bypassing decline of muscle cholesterol biosyntheisis, that is the main cause of musculosketelar adverse effects.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure.

Sodium-dependent glucose transporter 2 inhibitors (SGLT2i) have shown efficacy in reducing heart failure (HF) burden in a very heterogeneous groups of patients, raising doubts about some contemporary assumptions of their mechanism of action. We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy. Two groups of patients were included in the study: the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control. To evaluate the outcomes regarding natriuretic peptide, oxidative stress, inflammation, blood pressure, heart rate, cardiac function, and body weight. The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain (GLS), N-terminal pro-brain natriuretic peptide, myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and systolic and diastolic blood pressure. To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up, a rise in stroke volume index, body mass index (BMI) decrease, and lack of heart rate increase, linear regression analysis was performed. There was a greater reduction of MPO, hsCRP, GLS, and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up. Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI, while the predictor of stroke volume index increase was SGLT2i therapy itself. SGLT2i affect body composition, reduce cardiac load, improve diastolic/systolic function, and attenuate the sympathetic response. Glycemic control contributes to the improvement of heart function, blood pressure control, oxidative stress, and reduction in inflammation.

Inflammatory markers and noncoding-RNAs responses to low and high compressions of HIIT with or without berberine supplementation in middle-aged men with prediabetes.

This study compared the capacity of two different models of HIIT [high-(HC) and low-(LC) compression], with or without the use of berberine (BBR), on NOD-like receptor pyrin domain-containing protein-3 (NLRP3), H19, interleukin (IL)-1β, high-sensitivity C-reactive protein (hs-CRP), and insulin resistance markers. Fifty-four middle-aged men with overweight or obesity and prediabetes [fasting blood glucose (FBG) 110-180 mg/dL] were randomly and equally assigned to the HC, LC, HC + BBR, LC + BBR, BBR, and non-exercising control (CON) groups. The HC (2:1 work-to-rest) and LC (1:1 work-to-rest) home-based training programs included 2-4 sets of 8 exercises at 80%-95% HRmax, twice a week for 8 weeks. Participants in the berberine groups received approximately 1000 mg daily. All exercise interventions led to a significant reduction in hs-CRP, IL-1β, insulin, FBG, and insulin resistance index (HOMA-IR) versus CON. Notably, there was a significant reduction in FBG and HOMA-IR with the BBR group compared to the baseline. Both NLRP3 and H19 experienced a significant drop only with LC in comparison to the baseline. While both exercise protocols were beneficial overall, LC uniquely exhibited more anti-inflammatory effects, as indicated by reductions in H19 and NLRP3. However, the addition of berberine to the exercise programs did not demonstrate additional benefits.

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 &gt;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.

Role of Growth Hormone Therapy in Metabolic-Dysfunction-Associated Steatotic Liver Disease: A Systematic Review and Meta-Analysis.

Multiple observation studies and meta-analysis have linked growth hormone (GH) deficiency with metabolic-dysfunction-associated steatotic liver disease (MASLD). No meta-analysis has analysed the efficacy and safety of GH therapy on different aspects of MASLD. We undertook this meta-analysis to address this gap in knowledge. Electronic databases were searched for RCTs involving patients with MASLD receiving GH therapy. Primary outcome was to evaluate changes in radiologic measures of MASLD (magnetic resonance spectroscopy (MRS) and ultrasonography) and liver enzymes. Secondary outcomes were to evaluate alterations in body composition parameters [dual-energy X-ray absorptiometry (DXA)], lipids, glycaemia and side effects. From initially searched 1047 articles, data from three RCTs (120 patients) which fulfilled all criteria were analysed. After 6 months of GH therapy in MASLD, the per cent reduction in intrahepatic lipid (MRS) was significantly higher with GH as compared to placebo [MD -5.85% (95%CI:-11.41- -0.30); P = 0.04; I2 = 63%]. Visceral adipose tissue (VAT) area reduction (DXA) was significantly higher with GH [MD-9.94 cm2 (95%CI:-19.04- -0.84); P = 0.03; I2 = 0%]. Serum insulin-like growth factor-1 (IGF-1) was significantly raised in MASLD patients receiving GH as compared to placebo [MD +166.86 ng/ml (95%CI: 79.19-254.53); P < 0.0.001; I2 = 90%]. High-sensitivity C-reactive protein (hsCRP) was significantly lower in patients receiving GH [MD -0.89 mg/L (95%CI:-1.40--0.38); P = 0.0.0006; I2 = 0%]. Patients receiving GH had similar changes in triglycerides [MD-1.06 mg/L (95%CI:-20.45-18.34); P = 0.91; I2 = 15%] and fasting glucose [MD -0.56 mg/L (95%CI:-4.67-3.55); P = 0.79; I2 = 39%]. Gamma-glutamyl transpeptidase was significantly lower in patients receiving GH [MD -7.86 U/L (95%CI:-12.46--3.27); P = 0.0008; I2 = 0%]. No increase in new-onset hypothyroidism was noted [OR 5.49 (95%CI: 0.25-121.18); P = 0.28]. Short-term 6-month GH therapy in MASLD is associated with a significant reduction in intrahepatic lipid content, visceral adiposity, GGT and hsCRP without any increased occurrence of dysglycaemia or hypothyroidism.

Associations between food groups and biomarkers of inflammation: Are some foods groups more protective than others?

The consumption of healthy foods such as whole grains, vegetables, fruits, nuts, legumes, dairy, and fish is associated with decreased risk of cardiovascular disease (CVD). CVD is an inflammatory disease caused by atherosclerosis. Inflammation is measured clinically using hsCRP, however hsCRP is not specific to CVD. Novel pro-inflammatory markers, such as platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2), have garnered attention due to their specific roles in endothelial dysfunction and CVD risk. During the COVID 19 outbreak research highlighted a potential interaction between PAF and Lp-PLA2 and the SARS COVID 19 virus(1-3) and related adenovirus-vector and mRNA vaccines.4 This cross-sectional study investigated the association between PAF, Lp-PLA2, hsCRP, and intake of healthy food groups including fruit, cruciferous and other vegetables, grains, meat and poultry, fish and seafood, nuts and legumes, and dairy in 100 adults (49 ± 13 years, 31% male) with variable CVD risk. Data were collected across four groups during May and July 2021 (Groups 1 and 2 - CVD risk factors) and January and April 2022 (Groups 3 and 4 - no CVD risk factors). Fasting PAF, Lp-PLA2 and hsCRP and usual dietary intake (food frequency questionnaire) were measured. Food intake was converted into serves and classified into food groups. Correlations and multiple regressions were performed. Contrary to expectations, mean PAF was lower for groups 1 and 2 (n = 46, mean PAF 3.31 ± 1.66 ng/mL) compared to groups 3 and 4 (n = 54, mean PAF 19.82 ± 12.95 ng/mL) p &lt; 0.001 with a large effect size (eta squared 0.665). Cruciferous vegetables were associated with lower levels of PAF (β = -.27, CI [−0.41, −0.14], p &lt; .001) with a one serve increase in cruciferous vegetables per day associated with an 24% reduction in PAF. Nuts and legumes were associated with lower levels of hsCRP (β = -.51, CI [−0.81, −0.22], p&lt;.001) with an increase of one serve per day associated with a 40% reduction in hsCRP. There were small inverse associations between cheese and both PAF (β = -.15, CI [−0.27, −0.03], p = .017) and Lp-PLA2 (β = -.26, CI [−0.47, −0.04], p = .024), however these were not significant at the Bonferroni-adjusted P&lt;.005 level. In conclusion, cruciferous vegetables and nut and legume consumption were associated with lower levels of inflammation. The lack of associations between PAF and Lp-PLA2 and other healthy foods may be due to confounding by COVID-19 infection and vaccination programs which prevents any firm conclusion on the relationship between PAF, Lp-PLA2 and food groups. Future research should aim to examine the relationship with these novel markers and healthy food groups in a non-pandemic setting.

Evaluation of the effect of a dietary supplementation with a red yeast rice and fish oil-containing nutraceutical on lipid pattern, high sensitivity C-reactive protein, and endothelial function in moderately hypercholesterolaemic subjects: a double-blind, placebo-controlled, randomized clinical trial.

Red yeast rice and omega-3 polyunsaturated fatty acids (PUFAs) are dietary supplements with well-known lipid-lowering, anti-inflammatory, and vascular health improving effects. However, they have rarely been tested in combination. The aim of our study was to test the short-term effect of a combined nutraceutical including red yeast rice and PUFAs on plasma lipids, jigh-sensitive C-reactive protein (hsCRP), and endothelial function in healthy subjects. We carried out a double-blind, randomized, placebo-controlled clinical trial with parallel groups testing the effect of 8 weeks of supplementation with softgels containing red yeast rice (2.8 mg monacolins) and PUFAs (588 mg of fish oil, standardized in PUFAs: 350 EPA, 45 mg DHA) versus placebo. A full lipid panel, hsCRP, and endothelial reactivity were measured at the baseline and after 8 weeks of treatment. The tested combined nutraceutical was very well tolerated, and after 8 weeks of supplementation it was associated with a 17.3 ±3.4% reduction of lipid-density lipoprotein-cholesterol (LDL-C), a 12.1 ±2.2% reduction of total cholesterol (TC), a 22.3 ±4.3% reduction of apoB, and a -14.9 ±1.8% reduction of hsCRP, as well as a significant improvement of pulse volume change by 5.0 ±0.9%. The tested combined dietary supplement containing red yeast rice and PUFAs was very well tolerated and significantly improved LDL-C, TC, apoB, hsCRP and endothelial function in healthy subjects with suboptimal LDL-cholesterolaemia.

The dose-response effect of aerobic exercise on inflammation in colon cancer survivors.

Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1:1:1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor necrosis factor-alpha receptor 2 (sTNFαR2). Mixed models for repeated measures were used to test the hypothesis that exercise was associated with dose-response reductions in inflammation; exploratory analyses examined treatment effects by cancer stage. In the overall population, aerobic exercise was not associated with dose-response reductions in hs-CRP, IL6, or sTNFαR2. Cancer stage modified the association between randomized group and hs-CRP (P=0.022) and IL6 (P<0.001) but not sTNFαR2 (P=0.39). In stage I-II disease, compared to control, exercise was not associated with inflammation outcomes. In stage III disease, compared to control, low-dose exercise reduced hs-CRP: -35.4% (95% CI: -70.1, -0.7) and IL6: -29.6% (95% CI: -58.4, -0.8) but not sTNFαR2: 2.7% (95% CI: sTNFαR2: -15.7, 21.1); high-dose exercise was not associated with inflammation outcomes in stage III disease. This exploratory analysis offers preliminary data to support the hypothesis that inflammation may mediate the association between physical activity and disease-free survival in colon cancer. clinicaltrials.gov, identifier NCT02250053.

The cross-sectional relationship between vitamin C and high-sensitivity C-reactive protein levels: insights from NHANES database.

Ascorbic acid or vitamin C has antioxidant and anti-inflammatory properties that may impact markers of inflammation like C-reactive protein (CRP). However, studies specifically on vitamin C and high-sensitivity CRP (hs-CRP) have been scarce. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey 2017-2018 dataset including 5,380 U.S. adults aged ≥20 years. Multiple regression models examined the relationship between plasma vitamin C and serum hs-CRP while adjusting for potential confounders. Stratified analyses and curve fitting assessed effect modification and nonlinearity. An inverse association was found between plasma vitamin C and serum hs-CRP overall (β = -0.025, 95% CI: -0.033 to -0.017, p < 0.00001) and in subgroups except for the "other Hispanic" subgroup in model II (β = -0.009, 95% CI: (-0.040, 0.023), p = 0.5885). The relationship was nonlinear, with the greatest hs-CRP reduction observed up to a plasma vitamin C level of 53.1 μmol/L. The results showed a non-linear negative correlation between vitamin C levels and hs-CRP in adults. These results suggest vitamin C intake may reduce inflammation and cardiovascular risk, but only up to 53.1 μmol/L plasma vitamin C.

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.

The association between dietary quality scores with C-reactive protein and novel biomarkers of inflammation platelet-activating factor and lipoprotein-associated phospholipase A2: a cross-sectional study

Healthy dietary patterns are associated with lower inflammation and cardiovascular disease (CVD) risk and adherence can be measured using diet quality scores. Inflammation is traditionally measured with C-reactive protein (hsCRP), however there is interest in novel pro-inflammatory markers platelet-activating factor (PAF) and lipoprotein-associated phospholipase A2 (Lp-PLA2) that are specifically involved in endothelial dysfunction and inflammation. This cross-sectional study investigated the association between PAF, Lp-PLA2, hsCRP, and six diet scores. One hundred adults (49 ± 13 years, 31% male) with variable CVD risk were recruited. Fasting PAF, Lp-PLA2 and hsCRP and usual dietary intake were measured. Adherence to Dietary Approaches to Stop Hypertension (DASH), Dairy-adjusted DASH, Vegetarian Lifestyle Index, Healthy Eating Index for Australians (HEIFA), Mediterranean Diet Adherence Screener (MEDAS) and PREDIMED-Plus (erMedDiet) scores were calculated. Correlations and multiple regressions were performed. hsCRP, but not PAF, independently correlated with several diet scores. Lp-PLA2 independently correlated with Vegetarian Lifestyle Index only in unadjusted models. A one-point increase in adherence to the DASH Index, the Dairy-adjusted DASH Index and the Vegetarian Lifestyle Index was associated with a 30%, 30%, and 33% reduction in hsCRP levels, respectively. Smaller effects were seen with the other diet scores with a one-point increase in adherence resulting in a 19%, 22% and 16% reduction in hsCRP with HEIFA, MEDAS, erMedDiet scores, respectively. The lack of stronger associations between the novel markers of inflammation and diet scores may be due to confounding by COVID-19 infection and vaccination programs, which prevents any firm conclusion on the relationship between PAF, Lp-PLA2 and healthy dietary patterns. Future research should aim to examine the relationship with these novel markers and healthy dietary patterns in a non-pandemic setting.

Evaluation of the efficacy and safety of bempedoic acid in women and men: Pooled analyses from phase 3 trials

Background and aimsSex-specific differences in the response to lipid-lowering therapies have been reported. Here, we assessed the effect of bempedoic acid in women and men using pooled, patient-level data from four phase 3 clinical trials of bempedoic acid. MethodsPatients were grouped into two pools: 1) atherosclerotic cardiovascular disease (ASCVD) and/or heterozygous familial hypercholesterolemia (HeFH) “on statins” and 2) “low-dose or no statin”. Percent changes from baseline to at least week 12 in low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (non–HDL-C), total cholesterol (TC), apolipoprotein B (Apo B), and high-sensitivity C-reactive protein (hsCRP), as well as safety, were analyzed by statin pool and sex. ResultsOverall, 3623 patients were included (bempedoic acid, 2425; placebo, 1198). Significant reductions in lipid parameters and hsCRP were observed with bempedoic acid vs. placebo in both sexes in the ASCVD and/or HeFH on statins (n = 3009) and the low-dose or no statin (n = 614) pools (p ≤ 0.002). Compared with men, women had significantly greater placebo-corrected reductions in LDL-C (−21.2% vs. −17.4%; p = 0.044), non–HDL-C (−17.3% vs. −12.1%; p = 0.003), TC (−13.8% vs. −10.5%; p = 0.012), and Apo B (−16.0% vs. −11.3%; p = 0.004) in the ASCVD and/or HeFH on statins pool. Women had similar reductions to men in lipid parameters in the low-dose or no statin pool and hsCRP in both pools. The safety of bempedoic acid was comparable between sexes. ConclusionsIn this pooled analysis, women experienced significant improvements in levels of LDL-C and other lipid parameters with bempedoic acid.

Effect of dietary supplementation with Diuripres® on blood pressure, vascular health, and metabolic parameters in individuals with high-normal blood pressure or stage I hypertension: The CONDOR randomized clinical study.

Our aim was to evaluate if a nutritional intervention with a dietary supplement (Diuripres®) containing magnesium, standardized extract of orthosiphon, hawthorn, and hibiscus could positively affect blood pressure (BP), vascular health, and metabolic parameters in 60 individuals with high-normal BP or stage I hypertension. Participants followed a low-fat low-sodium Mediterranean diet for 4 weeks before being randomly allocated to 8-week treatment with two pills each day of either Diuripres® or placebo. Diuripres® significantly decreased systolic BP compared to placebo after 4 weeks (3.1 ± 0.8 mmHg; p < 0.05) and more consistently after 8 weeks (3.4 ± 0.9 mmHg; p < 0.05). At 8-week follow-up, after correction for multiple testing, dietary supplementation with Diuripres® was associated with significant improvements in diastolic BP (-3.1 ± 0.6 mmHg; p < 0.05), aortic BP (-4.3 ± 0.4 mmHg; p < 0.05), and high-sensitivity C-reactive protein (hs-CRP; 0.04 ± 0.01 mg/dL; p < 0.05) in comparison with baseline. The reductions in diastolic BP (--3.8 ± 0.7 mmHg; p < 0.05), aortic BP (-5.2 ± 1.0 mmHg; p < 0.05), and hs-CRP (-0.03 ± 0.01 mg/dL; p < 0.05) were also significant compared to placebo. Therefore, our study shows that dietary supplementation with Diuripres® may be useful in individuals with high-normal BP or stage I hypertension.

Impaired Gonadotropin-Lowering Effects of Metformin in Postmenopausal Women with Autoimmune Thyroiditis: A Pilot Study.

Metformin has been found to reduce elevated gonadotropin levels. Hashimoto's thyroiditis is the most common thyroid disorder in iodine-sufficient areas, and it often develops in postmenopausal women. The aim of this study was to investigate whether autoimmune thyroiditis determines the impact of metformin on gonadotrope secretory function. Two matched groups of postmenopausal women were studied: 35 with euthyroid Hashimoto's thyroiditis (group A) and 35 without thyroid disorders (group B). Throughout the study, all participants received oral metformin (2.55-3 g daily). Plasma glucose, insulin, gonadotropins, estradiol, progesterone, thyrotropin, free thyroid hormones, prolactin, adrenocorticotropic hormone, insulin-like growth factor-1, hsCRP, thyroid peroxidase, and thyroglobulin antibody titers were measured at the beginning of the study and six months later. At entry, both groups differed in thyroid peroxidase antibody titers, thyroglobulin antibody titers, and hsCRP levels. In group A, baseline antibody titers correlated positively with hsCRP and negatively with insulin sensitivity. Although metformin improved glucose homeostasis and reduced hsCRP levels in both study groups, these effects were more pronounced in group B than in group A. Only in group B did metformin decrease FSH levels and tend to reduce LH levels. Thyroid antibody titers and the levels of the remaining hormones did not change throughout the study. The impact of metformin on gonadotropin levels correlated with their baseline values and the degree of improvement in insulin sensitivity, as well as with the baseline and treatment-induced reduction in hsCRP. Moreover, the impact on gonadotropins and insulin sensitivity in group A depended on baseline antibody titers. The obtained results indicate that coexisting autoimmune thyroiditis impairs the gonadotropin-lowering effects of metformin in postmenopausal women.

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

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

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

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

Meta-analysis of the effect of colchicine on C-reactive protein in patients with acute and chronic coronary syndromes.

The anti-inflammatory drug colchicine has recently shown benefits in the prevention of major adverse cardiovascular events (MACE) in patients with the acute coronary syndrome (ACS) and chronic coronary syndromes (CCS). This meta-analysis focuses on understanding Colchicine's effects on the high-sensitivity C-reactive protein (hs-CRP) to provide mechanistic insight to explain its clinical event reduction. A computerized search of MEDLINE was conducted to retrieve journal articles with studies performed on humans from 1 January 2005 to 1 January 2022, using keywords: 'Colchicine AND Coronary', 'Colchicine AND CRP', and 'Colchicine AND Coronary Artery Disease'. Studies were included if they measured hs-CRP changes from baseline, and colchicine or placebo were given to patients with ACS or CCS. Thirteen studies with a biomarker subgroup population of 1636 patients were included in the hs-CRP meta-analysis. Of those 13 studies, 8 studies with a total population of 6016 reported clinical events defined as myocardial infarction (MI), stroke, cardiovascular death, periprocedural MI, repeat angina after PCI and repeat revascularization. Multivariate analysis revealed a weak negative correlation of -0.1056 ( P = 0.805) between change in CRP and clinical events. Overall, colchicine treatment resulted in a greater reduction in hs-CRP levels compared with placebo (Mean Difference: -1.59; 95% Confidence Interval, -2.40 to -0.79, P = 0.0001) and clinical events (Odds Ratio: 0.78; 95% Confidence Interval 0.64 to 0.95, P = 0.01). Colchicine therapy is associated with a reduction in hs-CRP and clinical events in patients with ACS and CCS. This finding supports colchicine's anti-inflammatory efficacy via CRP reduction to explain its clinical benefit.