Reduction In C-reactive Protein Concentrations Research Articles

Effect of intermittent fasting on circulating inflammatory markers in obesity: A review of human trials.

Obesity is associated with low-grade inflammation. Weight loss, by means of dietary restriction, has been shown to reduce systemic inflammation. Intermittent fasting has recently gained popularity as a weight loss diet, but its effects on inflammatory markers in individuals with obesity have yet to be summarized. Accordingly, this review examined how the two main forms of intermittent fasting, i.e., time restricted eating (TRE) and alternate day fasting (ADF), impact body weight and key circulating inflammatory markers (i.e., C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6)), in adults with obesity. Results from this review reveal that TRE with various eating window durations (4-10 h per day) has no effect on circulating levels of CRP, TNF-alpha or IL-6, with 1-5% weight loss. As for ADF, reductions in CRP concentrations were noted when >6% weight loss was achieved. However, ADF had no effect on TNF-alpha or IL-6 concentrations, with this degree of weight loss. Thus, intermittent fasting has little or no effect on key inflammatory markers, but more research is warranted to confirm these preliminary findings.

Anti-Inflammatory Therapy for Acute Coronary Syndromes: Is It Time for a Shift in the Treatment Paradigm?

Anti-Inflammatory Therapy for Acute Coronary Syndromes: Is It Time for a Shift in the Treatment Paradigm?

A Meta-Analysis of Randomized Controlled Trials of the Effects of Soy Intake on Inflammatory Markers in Postmenopausal Women

BackgroundElevated concentrations of serum inflammatory cytokines, specifically TNF-α and IL-6, as well as C-reactive protein (CRP), are commonly observed after menopause. ObjectivesBecause soy isoflavones may have some anti-inflammatory potential, the aim of the present systematic review and meta-analysis of randomized controlled trials (RCTs) was to explore whether soy intake affects serum markers of inflammation in postmenopausal women. MethodsPubMed, Web of Science, and the Cochrane Library were systematically searched up to August 2020. All RCTs that met the following criteria were included: 1) studies of the effects of soy intake on inflammatory markers; 2) any date of publication; 3) conducted on postmenopausal women; 4) with sufficient quantitative data for meta-analysis. Effect sizes were expressed as weighted mean differences (WMDs) and 95% CIs. A total of 24 RCTs assessing the effects of soy intake on serum concentrations of CRP, TNF-α, and IL-6 were included in the analysis. A random-effects model was used to determine the overall effect. ResultsSoy supplementation significantly reduced CRP by 0.11 mg/L in postmenopausal women (95% CI: −0.22, −0.004 mg/L; P = 0.0414), but did not affect IL-6 or TNF-α. Significant reductions in CRP concentration occurred when natural soy products were given (WMD: −0.23 mg/L; 95% CI: −0.29, −0.17 mg/L; P < 0.001). This is equivalent to a ∼9% reduction in CRP concentration from baseline. ConclusionsAlthough our meta-analysis found evidence that soy products significantly reduce CRP concentrations in postmenopausal women, the mechanisms by which soy foods and their constituents affect inflammatory biomarkers still need to be clarified.This systematic review was registered at www.crd.york.ac.uk/prospero/ as CRD42020179232.

Effects of coenzyme Q10 supplementation on plasma C-reactive protein concentrations: A systematic review and meta-analysis of randomized controlled trials

The aim of this systematic review and meta-analysis of prospective interventional studies was to investigate the effects of coenzyme Q10 (CQ10) on plasma C-reactive protein (CRP) levels. PubMed/Medline, Web of Science (WoS), Cochrane Database and Google Scholar databases were searched (up to December 2016) to identify prospective studies evaluating the impact of CQ10 supplementation on CRP. Random effects models meta-analysis was used for quantitative data synthesis. Sensitivity analysis used the leave-one-out method, and heterogeneity was quantitatively assessed using the I2 index. Systematic review PROSPERO database registration: CRD42016038155. From a total of 119 entries identified via searches, 7 studies were finally included to the analysis. The results of the meta-analysis indicated a non-significant reduction in CRP concentrations following supplementation with CQ10 with a weighted mean difference [WMD] of −0.25mg/l (95% confidence intervals [CI] −0.56 to 0.06, I2=42.0%). The WMD for the effects on interleukin 6 (IL6) was −0.72pg/dl, (95% CI −1.24 to −0.24, I2=51.8%). These findings were robust in sensitivity analyses. Random-effects meta-regression revealed that changes in plasma CRP levels were independent of the dosage of CQ10 (slope: −0.0005; 95% CI: −0.005, 0.004; p=0.832) while duration of supplementation was the dependent mediator (slope: slope: −0.111; 95% CI: −0.21, −0.004; p=0.042). In conclusion, CQ10 supplementation has a borderline favourable effect on CRP levels, and a significant effect on IL-6 level. This suggests that CQ10 supplementation likely attenuates subclinical inflammation.

Providing evidence to support the development of whole grain dietary recommendations in the United Kingdom.

Observational evidence suggests that increased whole grain (WG) intake reduces the risks of many non-communicable diseases, such as CVD, type 2 diabetes, obesity and certain cancers. More recently, studies have shown that WG intake lowers all-cause and cause-specific mortality. Much of the reported evidence on risk reduction is from US and Scandinavian populations, where there are tangible WG dietary recommendations. At present there is no quantity-specific WG dietary recommendation in the UK, instead we are advised to choose WG or higher fibre versions. Despite recognition of WG as an important component of a healthy diet, monitoring of WG intake in the UK has been poor, with the latest intake assessment from data collected in 2000-2001 for adults and in 1997 for children. To update this information we examined WG intake in the National Diet and Nutrition Survey rolling programme 2008-2011 after developing our database of WG food composition, a key resource in determining WG intake accurately. The results showed median WG intakes remain low in both adults and children and below that of countries with quantity-specific guidance. We also found a reduction in C-reactive protein concentrations and leucocyte counts with increased WG intake, although no association with other markers of cardio-metabolic health. The recent recommendations by the UK Scientific Advisory Committee on Nutrition to increase dietary fibre intake will require a greater emphasis on consuming more WG. Specific recommendations on WG intake in the UK are warranted as is the development of public health policy to promote consumption of these important foods.

Meta-Analysis Comparing Rosuvastatin and Atorvastatin in Reducing Concentration of C-Reactive Protein in Patients With Hyperlipidemia.

We conducted a meta-analysis of 13 randomized trials comparing the efficacy of rosuvastatin versus atorvastatin in reducing concentrations of C-reactive protein (CRP). We searched PubMed, Ovid, and Elsevier databases until June 2014. Search terms included C-reactive protein or CRP, rosuvastatin, atorvastatin, randomized, randomly, and randomization; 13 trials (3798 patients) were included. Funnel plots for CRP were inspected to assess publication bias. The pooled analysis demonstrated the benefit of rosuvastatin over atorvastatin therapy for all 13 trials (mean difference [MD] = -0.11, which is standardized mean with no unit although the raw data before pooling is mg/L, 95% confidence interval -0.15 to -0.07, P < .0001) with no evidence of significant publication bias (I(2) = 6.9%, P = .377). Subgroup analysis indicated a significant benefit of rosuvastatin over atorvastatin regarding the 1/1 dose ratio (MD = -0.14, 95% CI -0.21 to -0.06) and 1/2 dose ratio (MD= -0.11, 95% CI -0.16 to -0.05). Cumulative and influence analyses showed accuracy and stability for the estimation mentioned earlier. Our meta-analysis shows that rosuvastatin produces better reduction in CRP concentrations than atorvastatin at a dose ratio of 1/1 and 1/2 (rosuvastatin/atorvastatin), respectively.

Sleep restoration is associated with reduced plasma C-reactive protein and depression symptoms in military personnel with sleep disturbance after deployment

BackgroundDeployed military personnel are vulnerable to chronic sleep disturbance, which is highly comorbid with post-traumatic stress disorder (PTSD) and depression, as well as declines in health-related quality of life (HRQOL). Inflammation is associated with HRQOL declines and sleep-related comorbidities; however, the impact of sleep changes on comorbid symptoms and inflammation in this population is unknown. MethodsIn this observational study, we examined the relationship between reported sleep changes and concentrations of inflammatory biomarkers, interleukin 6 (IL-6), and C-reactive protein (CRP) in peripheral blood. The sample was dichotomized into two groups: (1) decrease in Pittsburgh Sleep Quality Index (PSQI; restorative sleep) and (2) no change or increase in PSQI (no change). Mixed between–within subjects analysis of variance tests were used to determine group differences on changes of inflammation and comorbid symptoms. ResultsIn our sample of 66 recently deployed military personnel with insomnia, 34 participants reported restorative sleep whereas 32 reported no sleep changes. The two groups did not differ in demographic or clinical characteristics, with the exception of PTSD diagnosis at baseline. The restorative sleep group had significant reductions in CRP concentrations and depression symptoms, as well as reduced fatigue and improvements in emotional well-being, social functioning, and physical functioning at follow-up. ConclusionsMilitary personnel who report sleep restoration after deployment have reduced CRP concentrations, decreased severity of depression, and improved HRQOL. These findings suggest that treatment for sleep disturbances may be associated with improvements in mental and physical health, thereby supporting continued study in this line of research.

Infliximab for intensification of primary therapy for Kawasaki disease: a phase 3 randomised, double-blind, placebo-controlled trial

Kawasaki disease, the most common cause of acquired heart disease in developed countries, is a self-limited vasculitis that is treated with high doses of intravenous immunoglobulin. Resistance to intravenous immunoglobulin in Kawasaki disease increases the risk of coronary artery aneurysms. We assessed whether the addition of infliximab to standard therapy (intravenous immunoglobulin and aspirin) in acute Kawasaki disease reduces the rate of treatment resistance. We undertook a phase 3, randomised, double-blind, placebo-controlled trial in two children's hospitals in the USA to assess the addition of infliximab (5 mg per kg) to standard therapy. Eligible participants were children aged 4 weeks-17 years who had a fever (temperature ≥38·0°C) for 3-10 days and met American Heart Association criteria for Kawasaki disease. Participants were randomly allocated in 1:1 ratio to two treatment groups: infliximab 5 mg/kg at 1 mg/mL intravenously over 2 h or placebo (normal saline 5 mL/kg, administered intravenously). Randomisation was based on a randomly permuted block design (block sizes 2 and 4), stratified by age, sex, and centre. Patients, treating physicians and staff, study team members, and echocardiographers were all masked to treament assignment. The primary outcome was the difference between the groups in treatment resistance defined as a temperature of 38·0°C or higher at 36 h to 7 days after completion of the infusion of intravenous immunoglobulin. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00760435. 196 patients were enrolled and randomised: 98 to the infliximab group and 98 to placebo. One patient in the placebo group was withdrawn from the study because of hypotension before receiving treatment. Treatment resistance rate did not differ significantly (11 [11·2%] for infliximab and 11 [11·3%] for placebo; p=0·81). Compared with the placebo group, participants given infliximab had fewer days of fever (median 1 day for infliximab vs 2 days for placebo; p<0·0001). At week 2, infliximab-treated patients had greater mean reductions in erythrocyte sedimentation rate (p=0·009) and a two-fold greater decrease in Z score of the left anterior descending artery (p=0·045) than did those in the placebo group, but this difference was not significant at week 5. Participants in the infliximab group had a greater mean reduction in C-reactive protein concentration (p=0·0003) and in absolute neutrophil count (p=0·024) at 24 h after treatment than did those given placebo, but by week 2 this difference was not significant. At week 5, none of the laboratory values differed significantly compared with baseline. No significant differences were recorded between the two groups at any timepoint in proximal right coronary artery Z scores, age-adjusted haemoglobin values, duration of hospital stay, or any other laboratory markers of inflammation measured. No reactions to intravenous immunoglobulin infusion occurred in patients treated with infliximab compared with 13 (13·4%) patients given placebo (p<0·0001). No serious adverse events were directly attributable to infliximab infusion. The addition of infliximab to primary treatment in acute Kawasaki disease did not reduce treatment resistance. However, it was safe and well tolerated and reduced fever duration, some markers of inflammation, left anterior descending coronary artery Z score, and intravenous immunoglobulin reaction rates. US Food and Drug Administration, Robert Wood Johnson Foundation, and Janssen Biotech.

Effect of atorvastatin on circulating hsCRP concentrations: A sub-study of the Achieve Cholesterol Targets Fast with Atorvastatin Stratified Titration (ACTFAST) study

Background Elevated C-reactive protein (CRP) concentration is a risk factor for cardiovascular events that may add prognostic information. Statin treatment is associated with significant reductions in CRP concentrations, which appear to be unrelated to the magnitude of LDL-cholesterol reduction. We investigated the effect of atorvastatin, across its dose range, on high sensitivity (hs)CRP in subjects at high cardiovascular risk. Methods ACTFAST was a 12 week, prospective, multicenter, open-label trial in which high-risk subjects were assigned a starting dose of atorvastatin (10, 20, 40 or 80 mg/d) based on LDL-C and status of statin use at screening (1345 statin-free [SF] and 772 previously statin-treated [ST]). Results At baseline, ST subjects had significantly lower hsCRP levels than SF subjects (ST group 2.31, 95% CI 2.15, 2.48 mg/L vs. SF group 3.16, 95% CI 2.98, 3.34 mg/L, p < 0.05). In the SF group, atorvastatin 10 to 80 mg significantly ( p < 0.01) reduced hsCRP levels in a dose dependent-manner. In ST group, additional hsCRP reductions were observed over the statin used at baseline, which were not dose-dependent. Atorvastatin significantly decreased hsCRP concentrations in subjects with or without diabetes or the metabolic syndrome. Conclusions Atorvastatin treatment at different doses, particularly 80 mg, significantly reduced hsCRP serum concentrations. This reduction was observed in both SF and ST groups and was independent of the presence of metabolic syndrome and/or diabetes. The beneficial effect of atorvastatin was evident at 6 weeks, supporting the practice of early introduction of higher doses of atorvastatin in high-risk patients.

Effects of Antidiabetic and Antihyperlipidemic Agents on C-Reactive Protein

Type 2 diabetes mellitus (DM) increases the risk of cardiovascular disease, a major cause of morbidity and mortality. Central to type 2 DM is insulin resistance, a proinflammatory, hypercoagulable state that predisposes patients to develop cardiovascular disease and that is associated with risk factors for atherosclerosis including dyslipidemia, hypertension, inflammation, and altered hemostasis. Atherosclerosis is recognized as a chronic inflammatory disease of the arteries. C-reactive protein (CRP) is an acute-phase response protein that is considered both a marker of inflammation and a predictor of cardiovascular events including myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death. Evidence indicates that CRP has a direct proatherogenic effect through up-regulation of angiotensin II type 1 receptors and through the stimulation of other proinflammatory factors. Patients with type 2 DM tend to have higher CRP concentrations than do those without it, suggesting an increased role of inflammation in the accelerated atherosclerosis seen in these patients. Reducing CRP concentrations through lifestyle changes or pharmacotherapeutics could have clinical benefit; long-term studies are needed to determine whether reductions in CRP concentrations translate into improved cardiovascular outcomes. Because glucose and lipid levels as well as CRP concentrations are often elevated in patients with type 2 DM, an agent that positively affects multiple cardiovascular risk factors would be most beneficial. This article reviews available data on antidiabetic and antihyperlipidemic agents that reduce CRP concentrations in addition to their primary effect of lowering glucose or lipid levels.

Characterization of the Anti-Diabetic and Antioxidant Effects of Rehmannia Glutinosa in Streptozotocin-Induced Diabetic Wistar Rats

This study investigated the effects of Rehmannia glutinosa individually as well as in combination with the oral hypoglycemic agent, metformin in streptozotocin (STZ)-induced diabetic Wistar rats. R. glutinosa ethanolic extract was prepared and the constituents were characterized using fractionation by column chromatography, followed by high performance liquid chromatography-mass spectrometry. STZ (65 mg/kg) was injected intraperitoneally to induce diabetes in Wistar rats. The diabetic rats were divided into the following groups (each n = 6) and received the respective treatments for 30 days: (1) metformin (500 mg/kg), (2) R. glutinosa (200 mg/kg), (3) metformin (500 mg/kg) and R. glutinosa (200 mg/kg) and (4) diabetic control (DC). A reduction in plasma glucose levels caused by the herb was not as significant as metformin compared to the diabetic control (p < 0.05). However, R. glutinosa-treated group showed reductions in plasma C-reactive protein (CRP) levels compared to the diabetic controls (p < 0.05) as well as metformin-treated group (p < 0.05). An enhanced reduction in CRP concentration was observed in the group receiving both herb and metformin compared to metformin-treated group (p < 0.05). Reduction in CRP levels suggests an anti-inflammatory activity of the herb.

Reduction of C-reactive protein by a single 80 mg of simvastatin in patients with unstable angina

BackgroundIncreased concentrations of C-reactive protein (CRP) became widely accepted as a risk factor of the higher incidence of coronary events, and rapid lowering CRP by administration of drugs may produce early benefit to the coronary endothelium in patients with coronary heart disease and reduce angina and coronary events after revascularization. Limited information has been available, however, with respect to evaluating a potential effect of a single high-dose simvastatin on CRP in patients with unstable angina (UA) within 48 h. We investigated whether a rapid CRP reduction can be achieved by a single 80 mg of simvastatin therapy in patients with UA given immediately on admission. MethodsForty-two patients with rest chest pain were randomly assigned to a single placebo or 80 mg of simvastatin given at the time of admission plus standard therapy. Blood samples were also drawn at the time of admission, and 48 h later for measuring serum CRP concentrations. ResultsWe found that 80 mg of simvastatin induced significant reductions in serum median CRP concentrations and in mean CRP concentrations 48 h later following administration of simvastatin (25.4% and 32.7%, p<0.001, respectively). ConclusionsA single high-dose simvastatin, given in the early time on admission, is an effective therapy for controlling inflammatory response in patients with UA, and the benefit to the vascular endothelium might occur quickly by reduction of CRP concentrations in this high-risk subgroup.

PROVE-IT proves that lower is better: A contrary view

Epidemiological studies have demonstrated that low density lipoprotein (LDL) cholesterol and C-reactive protein (CRP) are both independent risk factors for future cardiovascular events. Statin therapy, initially developed to modify blood lipid concentrations, has also been shown to have potentially important pleiotropic effects, including a reduction in CRP concentrations. Recent clinical trials have demonstrated conflicting results regarding the benefits associated with intensively lowering LDL cholesterol. An analysis of these results suggests that the different effects of specific statins on CRP concentrations may be an important determinant of the observed overall benefit associated with therapy. These studies together prove that while lowering LDL is beneficial, lowering LDL and CRP is better.

Inflammation is associated with increased energy expenditure in patients with chronic kidney disease

Inflammation, a clinical condition observed in patients with chronic kidney disease (CKD), may be related to increased resting energy expenditure (REE). The main objective was to investigate the relation between inflammation and REE in patients with CKD who are not undergoing dialysis. We also aimed to analyze whether a decrease in C-reactive protein (CRP) would result in a reduction in REE. This study enrolled 132 patients with CKD who were not undergoing dialysis, who had creatinine clearance from 5 to 65 mL.min(-1).1.73 m(-2), and who were 53.6 +/- 16 y old; 82 (62.1%) were men. Twenty-nine patients had clinical signs of infection. REE was measured by using indirect calorimetry, and inflammation was evaluated by using high-sensitivity CRP measurement. Patients were divided according to tertiles of CRP with the following intertertile ranges: first tertile, CRP < or = 0.14 mg/dL (n = 43); second tertile, CRP 0.15-0.59 mg/dL (n = 46); and third tertile, CRP > or = 0.60 mg/dL (n = 43). REE was measured before and after treatment in 10 patients who had inflammation or infection. After adjustment for age, sex, and lean body mass, the REE of the third (1395 kcal/d; P = 0.02) and second (1355 kcal/d; P = 0.04) tertiles was significantly higher than that of the first tertile (1286 kcal/d). In the multiple linear regression analysis (n = 132), the independent determinants of REE were lean body mass, CRP, and age (R2 = 0.55). After treatment of infection in a subgroup of 10 patients, it was observed that a significant reduction in CRP concentration was accompanied by a significant reduction of 174 +/- 165 kcal that accounted for 13% of the initial REE. This study showed that inflammation is associated with increased REE in patients with CKD.

Effects of Atorvastatin on Low-Density Lipoprotein Cholesterol Phenotype and C-Reactive Protein Levels in Patients Undergoing Long-Term Dialysis

To determine the effects of atorvastatin on low-density lipoprotein cholesterol (LDL) particle size and C-reactive protein (CRP) concentrations in patients undergoing long-term hemodialysis. Another objective was to compare the effects of atorvastatin on lipoprotein profiles as determined by direct versus indirect assessment of lipoprotein composition. Randomized, parallel-group substudy. Two university-affiliated outpatient hemodialysis centers. Nineteen patients with LDL levels above 100 mg/dl and with at least two cardiovascular risk factors. Patients were randomized in a 1:1 ratio to atorvastatin 10 mg/day or no treatment (control) for 20 weeks. We compared the differences between LDL particle size and CRP levels at baseline and 20 weeks in the atorvastatin versus control groups. Baseline demographic characteristics were similar between the two groups. Atorvastatin therapy was associated with no change in mean LDL particle size (p=0.23) and with a 90% decrease in mean CRP level (p=0.52). When evaluated by standard chemical analysis, atorvastatin therapy reduced total cholesterol levels by 29% (p=0.025) and resulted in nonsignificant reductions in LDL, high-density lipoprotein cholesterol, and triglyceride levels. Treatment with atorvastatin was not associated with significant changes in lipoprotein profile as determined by nuclear magnetic resonance (NMR) spectroscopy. Treatment with atorvastatin did not affect LDL particle size but was associated with a sizable, yet nonsignificant, reduction in CRP concentrations. The drug had variable effects on lipoprotein concentrations as determined by chemical and NMR analytical methods. A larger study is necessary to provide definitive information on the effects of atorvastatin on LDL phenotype and CRP in patients with kidney disease.

Highly effective reduction of C-reactive protein in patients with coronary heart disease by extracorporeal low density lipoprotein apheresis

An association between C-reactive protein (CRP) and coronary heart disease (CHD) has been shown. CRP is present in atherosclerotic lesions, and there is increasing evidence that it may contribute to inflammation. Reduction of CRP concentrations otherwise considered normal may thus be of therapeutic value. Heparin-induced extracorporeal low density lipoprotein precipitation (HELP) is an established apheresis procedure to treat CHD patients with hypercholesterolemia. CRP concentrations were determined pre- and post-apheresis in 13 hypercholesterolemic CHD patients, during a total of 31 treatment procedures as well as in the interval between two treatments in six-patients using a high-sensitivity CRP assay. In addition, the effect of the HELP precipitation buffer on serum CRP concentrations was investigated in vitro. HELP treatment reduced CRP concentrations on average by 65%. The presence of CRP in the LDL precipitate of a patient was also confirmed by Western-blot analysis. In vitro experiments with serum samples revealed that CRP was partly co-precipitated with LDL. Greater fluctuation was observed in the post-apheresis concentrations of CRP compared with LDL. These results show that CRP can be very effectively lowered in CHD patients through the HELP system. This may further explain the stabilization and reduction of atherosclerotic plaques in hypercholesterolemic patients previously demonstrated with this treatment procedure.

Crohn's disease associated with spondyloarthropathy: effect of TNF-α blockade with infliximab on articular symptoms

Four patients with Crohn's disease and spondyloarthropathy were treated with infliximab for treatment-resistant gut inflammation. A substantial improvement in gastrointestinal signs and symptoms was noted, which was accompanied by a rapid reduction in C-reactive protein concentrations. Moreover, all four patients had a significant improvement of axial manifestations and/or peripheral arthritis, related to their spondyloarthropathy. This fast and substantial improvement of the articular manifestations of Crohn's disease after infliximab treatment warrants further investigation of the therapeutic potential of TNF-alpha blockade in other subtypes of spondyloarthropathies.

A pilot study of megestrol acetate and ibuprofen in the treatment of cachexia in gastrointestinal cancer patients.

Advanced gastrointestinal cancer patients with weight loss and an acute-phase response (n = 15) were given megestrol acetate (480 mg day(-1)) and ibuprofen (1200 mg day(-1)) for 6 weeks. Overall, there was an increase in body weight (P = 0.01) and a reduction in C-reactive protein concentrations (P = 0.02), with no change in total body water (P = 0.24) over this period. This regimen may be an effective non-toxic treatment for cancer cachexia and is worthy of further study.