{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T14:03:41Z","timestamp":1788185021241,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T00:00:00Z","timestamp":1630886400000},"content-version":"vor","delay-in-days":248,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:p><jats:italic>Background<\/jats:italic>. Elevated plasma low\u2010density lipoprotein cholesterol (LDL\u2010C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL\u2010C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high\u2010intensity statins or a combination of high\u2010intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL\u2010C lowering independent pleiotropic effects. Oxidative modification of LDL (ox\u2010LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. <jats:italic>Objective<\/jats:italic>. The aim of this systematic review and meta\u2010analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox\u2010LDL. <jats:italic>Methods<\/jats:italic>. PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta\u2010analysis was evaluated according to the Cochrane instructions. Meta\u2010analysis was performed using Comprehensive Meta\u2010Analysis (CMA) V2 software. Evaluation of funnel plot, Begg\u2019s rank correlation, and Egger\u2019s weighted regression tests were used to assess the presence of publication bias. <jats:italic>Results<\/jats:italic>. Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta\u2010analysis. A total of 1874 patients are included in this meta\u2010analysis. This meta\u2010analysis suggests that high\u2010intensity statin treatment is associated with a significant decrease in circulating concentrations of ox\u2010LDL when compared with low\u2010to\u2010moderate treatment (SMD: \u20100.675, 95% CI: \u20100.994, \u20100.357, <jats:italic>p<\/jats:italic> &lt; 0.001; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>: 55.93%). There was no difference concerning ox\u2010LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: \u20100.129, 95% CI: \u20100.330, \u20100.071, <jats:italic>p<\/jats:italic> = 0.206; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>: 45.3%), but there was a significant reduction in circulating concentrations of ox\u2010LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: \u20100.220, 95% CI: \u20100.369, \u20100.071, <jats:italic>p<\/jats:italic> = 0.004; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>: 0%). <jats:italic>Conclusion<\/jats:italic>. High\u2010dose statin or combination of statins with ezetmibe reduces plasma ox\u2010LDL in comparison low\u2010to\u2010moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox\u2010LDL plasma concentrations.<\/jats:p>","DOI":"10.1155\/2021\/9661752","type":"journal-article","created":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T16:43:09Z","timestamp":1630946589000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low\u2010Density Lipoprotein Levels: A Systematic Review and Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1155","volume":"2021","author":[{"given":"Tannaz","family":"Jamialahmadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Baratzadeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u017deljko","family":"Reiner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis E.","family":"Simental-Mend\u00eda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suowen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey V.","family":"Susekov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul D.","family":"Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8656-1444","authenticated-orcid":false,"given":"Amirhossein","family":"Sahebkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,6]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehr158"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-012-0313-7"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2013.80"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2016.01.018"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2015.08.003"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep09902"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1160\/TH14-11-0937"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1160\/th15-08-0620"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.08.014"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12654"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz455"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.7326\/M19-0365"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-88416-z"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2021.03.007"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.acvd.2020.06.003"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2019.03.014"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2004.00299.x"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21228745"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.08.037"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.2174\/1381612820666141013134447"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.1995.tb06652.x"},{"key":"e_1_2_9_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000033829.14012.18"},{"key":"e_1_2_9_23_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000014762.06201.06"},{"key":"e_1_2_9_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehz962"},{"key":"e_1_2_9_25_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0123088"},{"key":"e_1_2_9_26_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11596-018-1892-3"},{"key":"e_1_2_9_27_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0142430"},{"key":"e_1_2_9_28_2","volume-title":"Handbook for Systematic Reviews of Interventions. 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