Protocol for systematic review and meta-analysis: impact of statins as immune-modulatory agents on inflammatory markers in adults with chronic diseases

Abstract

IntroductionStatins, also known as 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors, are lipid-lowering agents that are central in preventing or reducing the complications of atherosclerotic cardiovascular disease. Because statins have anti-inflammatory properties, there is considerable interest in their therapeutic potential in other chronic inflammatory conditions. We aim to identify the statin with the greatest ability to reduce systemic inflammation, independent of the underlying disease entity.Methods and analysisWe aim to conduct a comprehensive search of published and peer-reviewed randomised controlled clinical trials, with at least one intervention arm of a Food & Drug Administration-licensed or European Medicines Agency-licensed statin and a minimum treatment duration of 12 weeks. Our objective is to investigate the effect of statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin) on lipid profile, particularly, cholesterol low-density lipoprotein and inflammation markers such as high-sensitive C reactive protein (hsCRP), CRP, tumour necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8, soluble cluster of differentiation 14 (sCD14) or sCD16 in adults, published in the last 20 years (between January 1999 and December 2019). We aim to identify the most potent statin to reduce systemic inflammation and optimal dosing. The following databases will be searched: Medline, Scopus, Web of Science and Cochrane Library of Systematic Reviews. The risk of bias of included studies will be assessed by Cochrane Risk of Bias Tool and Quality Assessment Tool for Quantitative Studies. The quality of studies will be assessed, to show uncertainty, by the Jadad Score. If sufficient evidence is identified, a meta-analysis will be conducted with risk ratios or ORs with 95% CIs in addition to mean differences.Ethics and disseminationEthics approval is not required as no primary data will be collected. Results will be presented at conferences and published in a peer-reviewed journal.PROSPERO registration numberCRD42020169919

Lipophilic vs. hydrophilic statins and psychiatric hospitalizations and emergency room visits in US Veterans with schizophrenia and bipolar disorder

“…With the emergence of case-control, longitudinal, and especially randomized controlled studies and their meta-analyses, the opposite picture emerged, i.e., that statins as a group are cognitively, affectively, and behaviorally safe and that they show beneficial effects in the treatment of mood disorders, schizophrenia, and cognitive disorders. These positive effects appear to be based on statins’ pleiotropic effects including multiple immune regulatory actions and antioxidant properties [ 17 , 18 ], as well as endothelial stabilizing [ 19 ] and neuroprotective effects [ 20 , 21 ]. Statins reduce NADPH oxidase and superoxide generation, inhibit the negative regulation of nitric oxide, increase free radical scavenging, decrease inflammatory cell transmigration from blood to tissue, inhibit the NLRP3 inflammasome, and reduce metalloproteinase expression [ 22 – 27 ].…”