Effect of statins on the plasma/serum levels of inflammatory markers in patients with cardiovascular disease; a systematic review and meta-analysis of randomized clinical trials

Abbasifard, Mitra; Kandelouei, Tahmineh; Aslani, Saeed; Razi, Bahman; Imani, Danyal; Fasihi, Mahdieh; Cicero, Arrigo F G; Sahebkar, Amirhossein

doi:10.1007/s10787-022-00926-y

Cited by 9 publications

(8 citation statements)

References 62 publications

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“…Compared with other lipid-lowering agents, simvastatin might be superior in reducing the risk of major adverse cardiovascular events in hypertriglyceridemic patients ( 88 ). Consistent with our findings, Mitra et al supported the notion that lipophilic statins (such as simvastatin) at high-intensity dosage could significantly decrease inflammatory factor TNF-α ( 89 ). In contrast, Neda et al tested the orientation of ligands (statins) and phosphorylcholine (the standard ligand of CRP) at the CRP active site using Molecular Operating Environment software ( 18 ).…”

Section: Discussionsupporting

confidence: 92%

“…In terms of dosage, according to the 2013 ACC/AHA Guideline ( 90 ), 40 mg/day is the maximum recommended dose of simvastatin because of the risk of rhabdomyolysis at higher doses, although it is classified as moderate-intensity statin therapy. Similar to our results, a higher intensity dosage is more likely to have better anti-inflammatory effects ( 89 ). In addition, high-dose statins (e.g., simvastatin 40 mg/day and atorvastatin 80 mg/day) are associated with the most significant benefits of secondary prevention in patients with ischemic stroke or transient ischemic attack ( 91 ).…”

Section: Discussionsupporting

confidence: 90%

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The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis

Zhang

Wang

Tian

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveThe objective of this study was to measure the efficacy of various types and dosages of statins on C-reactive protein (CRP) levels in patients with dyslipidemia or coronary heart disease.MethodsRandomized controlled trials were searched from PubMed, Embase, Cochrane Library, OpenGray, and ClinicalTrials.gov. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for data extraction and synthesis. The pairwise meta-analysis compared statins and controls using a random-effects model, and a network meta-analysis compared the types and dosages of statins using the Bayesian random-effects model. The PROSPERO registration number is CRD42021242067.ResultsThe study included 37 randomized controlled trials with 17,410 participants and 20 interventions. According to the pairwise meta-analysis, statins significantly decreased CRP levels compared to controls (weighted mean difference [WMD] = −0.97, 95% confidence interval [CI] [−1.31, −0.64], P < 0.0001). In the network meta-analysis, simvastatin 40 mg/day appeared to be the best strategy for lowering CRP (Rank P = 0.18, WMD = −4.07, 95% CI = [−6.52, −1.77]). The same was true for the high-sensitivity CRP, non-acute coronary syndrome (ACS), <12 months duration, and clear measurement subgroups. In the CRP subgroup (rank P = 0.79, WMD = −1.23, 95% CI = [−2.48, −0.08]) and ≥12-month duration subgroup (Rank P = 0.40, WMD = −2.13, 95% CI = [−4.24, −0.13]), atorvastatin 80 mg/day was most likely to be the best. There were no significant differences in the dyslipidemia and ACS subgroups (P > 0.05). Node-splitting analysis showed no significant inconsistency (P > 0.05), except for the coronary heart disease subgroup.ConclusionStatins reduced serum CRP levels in patients with dyslipidemia or coronary heart disease. Simvastatin 40 mg/day might be the most effective therapy, and atorvastatin 80 mg/day showed the best long-term effect. This study provides a reference for choosing statin therapy based on LDL-C and CRP levels.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis

Zhang

Wang

Tian

et al. 2022

Front. Cardiovasc. Med.

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“…It attaches to its receptors (ACE2) and stimulates inflammatory responses by producing and secreting cytokines and inflammatory cytokines such as IL-6. 14 According to PCT, the current study reported that patients with severe and non-severe group had a significantly higher means of PCT (p=0.001). By LSD, the mean of PCT was significantly higher in severe group and in nonsevere group (p= 0.001).…”

Section: Discussionmentioning

confidence: 48%

The role of C-reactive protein, procalcitonin, interleukin-6 and neutrophil / lymphocyte ratio as a laboratory biomarker in COVID-19

Al-Bayaa

2024

EJI

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Biomarkers such as Interleukin-6 (IL-6), Procalcitonin (PCT), C-reactive protein (CRP) and Neutrophil-Lymphocyte Ratio (NLR) have a role in the pathogenesis of severe coronavirus disease 2019 (COVID-19). The aim of this study was to explore the differences between serum levels of such biomarkers in severe and non-severe COVID-19 cases and compare them with normal people and to evaluate the sociodemographic variables and chronic diseases effect on the severity of COVID-19. The study included 160 subjects, divided into two groups, a case group of 80 patients, and a control group of 80 normal persons. The case group was divided into two subgroups: 40 severe COVID-19 patients and 40 patients with non-severe disease. Blood IL-6 was assessed by an enzyme-linked immunosorbent assay (ELISA), PCT by an immunoassay, CRP by an immunoturbidimetric assay and NLR from CBC. The levels of IL-6, PCT, CRP, and NLR were significantly higher in the case group than in control group (p= 0.001, for all). However, there was no difference between these biomarkers level in the non-severe COVID-19 subgroup and the control group (p>0.05 for all). The proportion of severe COVID-19 was significantly higher in patients aged >50 years, and in patients with chronic diseases (p=0.046 and p=0.001, respectively). We also found a strong correlation between such biomarkers and old age, and chronic diseases with the disease severity. There was a significant difference in the level of the three biomarkers (IL-6, PCT, CRP, and NLR) between patients’ subgroups and the control group. In conclusion, since the levels of these biomarkers are correlated with the severity of the COVID-19 disease, and there was a difference in the levels between the groups with severe and non-severe symptoms, we suggest a role of these biomarkers in predicting the severity COVID-19 disease and its poor prognosis.

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“…It was demonstrated in a systematic review that statin use did not affect serum concentrations of various inflammatory mediators including TNF-α, IL-6, sICAM and sVCAM ( He et al, 2023 ). At the same time, another meta-analysis of randomized clinical trials aimed to determine the effect of statins on serum levels of TNF-α, MCP-1, VCAM1 and IL-6 in patients with cardiovascular diseases showed that statins have a beneficial effect on reducing the serum levels of TNF-α ( Abbasifard et al, 2022 ). This highlights the complexity and diversity of the effects of statins on inflammatory processes in the body, and requires further research to fully understand their effects on inflammatory mediators.…”

Section: Discussionmentioning

confidence: 99%

The association of TNF-alpha secretion and mtDNA copy number in CD14+ monocytes of patients with obesity and CHD

Tolstik,

Kirichenko,

Markin

et al. 2024

Front. Mol. Biosci.

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IntroductionMitochondrial dysfunction may be one of the causes of inflammatory activation of monocytes and macrophages, which leads to excessive secretion of inflammatory mediators and the development of chronic inflammation.AimsThe study was aimed to evaluate the secretion of inflammatory cytokine tumor necrosis factor-α (TNF-α) in the primary culture of monocytes, and to analyze its relationship with the number of mitochondrial DNA (mtDNA) copies in the blood of patients with coronary heart disease (CHD) and obesity.Materials and methods108 patients with obesity and concomitant CHD and a control group of 25 participants were included in the study. CD14+ monocytes were isolated by a standard method in a ficoll-urographin gradient, followed by separation using magnetic particles. The number of mtDNA copies was estimated using qPCR.ResultsIt was demonstrated that the number of mtDNA copies was significantly increased in groups of patients with CHD and obesity + CHD in comparison with control group. mtDNA copy number positively correlated with basal and LPS-stimulated TNF-α secretion, the most significant correlation was found in the group of patients with CHD and obesity.ConclusionThus, the change in mtDNA copy number in CD14+ monocytes which indicates the presence of mitochondrial dysfunction, confirm the direct involvement of mitochondria in the violation of the inflammatory response of monocytes revealed in this study as an increased secretion of inflammatory cytokine TNF-α.

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Effect of statins on the plasma/serum levels of inflammatory markers in patients with cardiovascular disease; a systematic review and meta-analysis of randomized clinical trials

Cited by 9 publications

References 62 publications

The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis

The effect of various types and doses of statins on C-reactive protein levels in patients with dyslipidemia or coronary heart disease: A systematic review and network meta-analysis

The role of C-reactive protein, procalcitonin, interleukin-6 and neutrophil / lymphocyte ratio as a laboratory biomarker in COVID-19

The association of TNF-alpha secretion and mtDNA copy number in CD14+ monocytes of patients with obesity and CHD

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