C-reactive protein: a target for therapy to reduce inflammation

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 26, 2023

C-reactive protein (CRP) is well-recognized as a sensitive biomarker of inflammation. Association elevations in plasma/serum CRP level with disease state has received considerable attention, even though not specific indicator single state. Circulating levels have been monitored varying degree success to gauge severity or predict progression and outcome. Elevations implicated useful marker identify patients at risk for cardiovascular certain cancers, guide therapy context-dependent manner. Since strong associations do establish causality, the pathogenic role often over-interpreted. functions an important modulator host defense against bacterial infection, tissue injury autoimmunity. exists conformationally distinct forms, which exhibit functional properties help explaining diverse, contradictory effects attributed CRP. In particular, dissociation native pentameric into its subunits, monomeric CRP, unmasks “hidden” pro-inflammatory activities Here, we review recent advances targeting strategies, therapeutic lowering circulating development antagonists, conformation change inhibitor particular. We will also discuss their potential mitigating deleterious actions under various pathologies, including cardiovascular, pulmonary autoimmune diseases cancer.

Language: Английский

---

Effect of lipid-lowering therapies on C-reactive protein levels: a comprehensive meta-analysis of randomized controlled trials

Cardiovascular Research, Journal Year: 2024, Volume and Issue: 120(4), P. 333 - 344

Published: Feb. 19, 2024

Abstract Chronic low-degree inflammation is a hallmark of atherosclerotic cardiovascular (CV) disease. To assess the effect lipid-lowering therapies on C-reactive protein (CRP), biomarker inflammation, we conducted meta-analysis according to PRISMA guidelines. Databases were searched from inception July 2023. Inclusion criteria were: (i) randomized controlled trials (RCTs) in human, Phase II, III, or IV; (ii) English language; (iii) comparing drugs vs. placebo; (iv) reporting effects CRP levels; (v) with intervention duration more than 3 weeks; (vi) and sample size (for both control group) over 100 subjects. The between-group (treatment-placebo) absolute mean differences 95% confidence intervals calculated for each drug class separately. A total 171 668 subjects 53 RCTs included. levels (mg/L) significantly decreased by statins [−0.65 (−0.87 −0.43), bempedoic acid; −0.43 (−0.67 −0.20), ezetimibe; −0.28 (−0.48 −0.08)], omega-3 fatty acids [omega3FAs, −0.27 (−0.52 −0.01)]. was reduced −0.40 (−1.17 0.38) fibrates, although not statistically significant. slight increase concentration observed proprotein convertase subtilisin/kexin type 9 inhibitors [0.11 (0.07–0.14)] cholesteryl-ester transfer [0.10 (0.00–0.21)], latter being Meta-regression analysis did show significant correlation between changes LDL cholesterol (LDL-C) triglycerides. Statins, acid, ezetimibe, omega3FAs reduce serum concentration, independently LDL-C reductions. impact this anti-inflammatory terms CV prevention needs further investigation.

Language: Английский

---

The pan-PPAR agonist lanifibranor improves cardiometabolic health in patients with metabolic dysfunction-associated steatohepatitis

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 10, 2024

Abstract Lanifibranor, a pan-PPAR agonist, improves liver histology in patients with metabolic dysfunction-associated steatohepatitis (MASH), who have poor cardiometabolic health (CMH) and cardiovascular events as major mortality cause. NATIVE trial secondary exploratory outcomes (ClinicalTrials.gov NCT03008070) were analyzed for the effect of lanifibranor on IR, lipid glucose metabolism, systemic inflammation, blood pressure (BP), hepatic steatosis (imaging histological grading) all original analysis. With lanifibranor, triglycerides, HDL-C, apolipoproteins, insulin, HOMA-IR, HbA1c, fasting (FG), hs-CRP, ferritin, diastolic BP improved significantly, independent diabetes status: most prediabetes returned to normal FG levels. Significant adiponectin increases correlated CMH marker improvement; had an average weight gain 2.5 kg, 49% gaining ≥2.5% weight. Therapeutic benefits similar regardless change. Here, we show that effects MASH are accompanied improvement, indicative potential clinical benefits.

Language: Английский

---

Coffee or tea: Anti-inflammatory properties in the context of atherosclerotic cardiovascular disease prevention

Pharmacological Research, Journal Year: 2022, Volume and Issue: 187, P. 106596 - 106596

Published: Dec. 5, 2022

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of premature death worldwide. Inflammation and its biomarkers, like C-reactive protein (CRP), among risk factors, such as hypertension, lipid disorders, diabetes, may be also responsible for residual (CVD) risk. Modern lipid-lowering treatment with statins, ezetimibe, PCSK9 inhibitors, or bempedoic acid does not fully protect against inflammation. The recommendations International Lipid Expert Panel (ILEP) indicate selected nutraceuticals anti-inflammatory properties. Diet have a significant impact on Especially interesting in context inflammation consumption coffee tea. These drinks many observational studies significantly reduced mortality. question whether effects these contribute to observed clinical effects. Thus, this narrative review, we primarily discuss properties consuming tea coffee. Based comprehensive analysis their meta-analyses, inconsistent results were obtained, which makes it impossible conclusively state how clinically potential black green are. A number confounding factors can inconsistency available results. Consumption appears increase adiponectin concentrations, decrease reactive oxygen species, low density lipoprotein (LDL) cholesterol concentrations (effect tea, etc.). Despite still uncertain effect coffee, recommend part healthy diet.

Language: Английский

---

Role of High-Sensitivity C-reactive Protein (Hs-CRP) in Non-communicable Diseases: A Review

Cureus, Journal Year: 2022, Volume and Issue: unknown

Published: Oct. 12, 2022

Non-communicable diseases like cardiovascular diseases, cerebrovascular diabetes mellitus, and cancer are very common causes of death worldwide. Therefore, the need to search for novel, affordable, easily accessible biomarkers risk factors non-communicable continues, which can predict future having these with greater accuracy precision. In this context, among available biomarkers, high-sensitivity C-reactive protein (Hs-CRP) is considered be best-suited marker. Various drug intervention trials demonstrated positive results in reducing Hs-CRP individuals raised levels. Numerous pharmacological non-pharmacologic interventions form lifestyle modifications, exercise, cessation smoking being investigated study their effect on serum (CRP) This review article discusses role its isoforms pathogenesis various disease conditions, affecting concentration, prognostic value, comparison other factors. Further, clinical significance chronic inflammatory degenerative nervous system including recent advances management has also been discussed.

Language: Английский

---

Anti-Inflammatory Effects of Lipid-Lowering Drugs and Supplements—A Narrative Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(6), P. 1517 - 1517

Published: March 21, 2023

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Since establishment “lipid hypothesis”, according to which, cholesterol level is directly correlated risk CVD, many different lipid-lowering agents have been introduced in clinical practice. A majority these drugs, addition their properties, may also exhibit some anti-inflammatory and immunomodulatory activities. This hypothesis was based on observation that a decrease lipid levels occurs along with inflammation. Insufficient reduction inflammation during treatment drugs could be one explanations for failure recurrent CVD events. Thus, aim this narrative review evaluate properties currently available medications including statins, ezetimibe, bile acid sequestrants (BAS), proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, fibrates, omega-3 fatty acids, niacin, as well dietary supplements novel used modern times.

Language: Английский

---

Long-Term Efficacy and Tolerability of PCSK9 Targeted Therapy: A Review of the Literature

Drugs, Journal Year: 2024, Volume and Issue: 84(2), P. 165 - 178

Published: Jan. 25, 2024

Increased plasma levels of low-density lipoprotein cholesterol (LDL-C) are causally associated with atherosclerotic cardiovascular disease (ASCVD), and statins that lower LDL-C have been the cornerstone ASCVD prevention for decades. However, guideline-recommended targets not achieved in about 60% statin users. Proprotein convertase subtilisin/kexin type 9 (PCSK9)-targeted therapy effectively lowers has shown to reduce risk. A growing body scientific clinical evidence shows PCSK9-targeted offers an excellent safety tolerability profile a low incidence side effects short term. In this review, we present discuss current pertaining long-term efficacy therapy.

Language: Английский

---

Association between stroke and systemic inflammation response index (SIRI): a National Health and Nutrition Examination Survey (NHANES) Study 2015–2020

BMJ Neurology Open, Journal Year: 2025, Volume and Issue: 7(1), P. e000718 - e000718

Published: March 1, 2025

The present study aimed to compare the relationship between history of stroke and four different inflammatory indices, including high-sensitivity C reactive protein (hsCRP), burden index (IBI), neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response (SIRI). In this cross-sectional study, data from National Health Nutrition Examination Survey 2015 2020 were used, yielding a sample 25 531 participants. Individuals younger than 20, pregnant women, patients with cancer missing cases excluded. Baseline characteristics markers mentioned above analysed. Logistic regression models assessed association indices stroke. Of 7828 eligible cases, 271 (3.4%) had Stroke was more prevalent among older subjects, smokers, diabetes, hypertension dyslipidaemia, those less physically active. All elevated considerably in survivors, according crude analysis. After adjusting for covariates, hsCRP (p=0.519, 95% CI: 0.961 1.083), NLR (p=0.125, 0.947 1.565) IBI (p=0.157, 0.991 1.060) did not reveal any significant difference survivors control subjects. SIRI only significantly associated (p=0.005, 1.154 2.274). This revealed that hsCRP, IBI, SIRI, is one independently Our findings, conjunction pre-existing evidence observational experimental studies, highlight role monocytes as component chronic inflammation, which may induce vascular thrombotic events,

Language: Английский

---

Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials

Cardiovascular Diabetology, Journal Year: 2022, Volume and Issue: 21(1)

Published: Sept. 2, 2022

Abstract Background Exploratory analysis to determine the effect of semaglutide versus comparators on high-sensitivity C-reactive protein (hsCRP) in subjects with type 2 diabetes. Methods Trials once-weekly subcutaneous (SUSTAIN 3) and once-daily oral (PIONEER 1, 2, 5) hsCRP data were analyzed. Subjects diabetes (N = 2482) received (n 1328) or (placebo, n 339; exenatide extended-release, 405; empagliflozin, 410). ratio baseline at end-of-treatment was analyzed overall, by clinical cutoff (< 1.0, ≥ 1.0 ≤ 3.0, > 3.0 mg/L), tertile, estimated glomerular filtration rate PIONEER 5 (a trial which conducted a population chronic kidney disease [CKD]). Mediation analyses assessed change glycated hemoglobin (HbA 1c ) and/or body weight (BW) reductions. Results Geometric mean similar across trials (range 2.7–3.0 mg/L). Semaglutide reduced levels cutoffs tertiles from all (estimated treatment ratios [ETRs] comparators: 0.70–0.76; p < 0.01) except placebo (ETR [95% CI]: 0.83 [0.67–1.03]; 0.05). The partially mediated (20.6–61.8%) HbA BW. Conclusions ratios-to-baseline (not significant CKD). This via reductions BW potentially direct semaglutide. appears have an anti-inflammatory effect, is being further investigated ongoing trials. Trial registrations: ClinicalTrials.gov identifiers: NCT01885208 (first registered June 2013), NCT02906930 September 2016), NCT02863328 August NCT02827708 July 2016).

Language: Английский

---

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review

Nutrients, Journal Year: 2023, Volume and Issue: 15(10), P. 2288 - 2288

Published: May 12, 2023

Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic disease (ASCVD). Red yeast rice (RYR) nutraceutical widely used as lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin K, which structurally identical to lovastatin targets the same enzyme biosynthesis. supplementation reduces LDL-C by approximately 15–34% versus placebo, with similar effect low-dose, first-generation statins in subjects mild-to-moderate dyslipidemia. has also demonstrated beneficial reductions up 45% placebo ASCVD events secondary prevention studies. at dose that provides about 3 mg/d K well tolerated, an adverse event profile low-dose statins. therefore treatment option people hypercholesterolemia who ineligible statin therapy, those unable implement lifestyle modifications, eligible therapy but unwilling take pharmacologic therapy.

Language: Английский

---