Lotta Ulander , Piia Simonen , Heli Tolppanen , Otto Hartman , Tuomas T. Rissanen , Kari K. Eklund , Marita Kalaoja , Mika Kurkela , Mikko Neuvonen , Mikko Niemi , Janne T. Backman , Helena Gylling , Juha Sinisalo , on behalf of the OXI pilot trial
{"title":"The effect of hydroxychloroquine on cholesterol metabolism in statin treated patients after myocardial infarction","authors":"Lotta Ulander , Piia Simonen , Heli Tolppanen , Otto Hartman , Tuomas T. Rissanen , Kari K. Eklund , Marita Kalaoja , Mika Kurkela , Mikko Neuvonen , Mikko Niemi , Janne T. Backman , Helena Gylling , Juha Sinisalo , on behalf of the OXI pilot trial","doi":"10.1016/j.athplu.2023.06.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background and aims</h3><p>To evaluate the effect of hydroxychloroquine (HCQ) on serum and lipoprotein lipids and serum biomarkers of cholesterol synthesis and absorption in myocardial infarction patients with a high-dose statin.</p></div><div><h3>Methods</h3><p>Myocardial infarction patients (n = 59) with a constant statin dose were randomized to receive hydroxychloroquine 300 mg (n = 31) or placebo (n = 28) daily for six months and followed up for one year.</p></div><div><h3>Results</h3><p>Statin reduced total-c (−26 ± 22% in hydroxychloroquine and −28 ± 19% in placebo group, P = 0.931), LDL-c (−38 ± 26% vs. −44 ± 23%, respectively, P = 0.299), and cholesterol synthesis biomarkers zymostenol, desmosterol, and lathosterol ratios from baseline to one year (e.g., serum lathosterol ratio −17 ± 45% vs. −15 ± 41%, respectively, P < 0.001 for both, P = 0.623 between groups). Compensatorily, cholesterol absorption increased during the intervention (e.g., serum campesterol ratio 125 ± 90% vs. 113 ± 72%, respectively, P < 0.001 for both, P = 0.488 between groups). Hydroxychloroquine did not affect cholesterol concentrations or cholesterol absorption. It prevented the statin-induced increase in cholesterol precursor, desmosterol ratio, from six months to one year in the hydroxychloroquine group (P = 0.007 at one year compared to placebo).</p></div><div><h3>Conclusions</h3><p>Combined with a high-dose statin, hydroxychloroquine had no additional effect on serum cholesterol concentration or cholesterol absorption. However, the findings suggest that hydroxychloroquine interferes with lanosterol synthesis, and thereafter, it temporarily interferes with the cholesterol synthesis pathway, best seen in halting the increase of the desmosterol ratio.</p><p>Trial Registration ClinicalTrials.gov Identifier: NCT02648464.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"53 ","pages":"Pages 26-32"},"PeriodicalIF":1.4000,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10336266/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Atherosclerosis plus","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2667089523000123","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
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Abstract
Background and aims
To evaluate the effect of hydroxychloroquine (HCQ) on serum and lipoprotein lipids and serum biomarkers of cholesterol synthesis and absorption in myocardial infarction patients with a high-dose statin.
Methods
Myocardial infarction patients (n = 59) with a constant statin dose were randomized to receive hydroxychloroquine 300 mg (n = 31) or placebo (n = 28) daily for six months and followed up for one year.
Results
Statin reduced total-c (−26 ± 22% in hydroxychloroquine and −28 ± 19% in placebo group, P = 0.931), LDL-c (−38 ± 26% vs. −44 ± 23%, respectively, P = 0.299), and cholesterol synthesis biomarkers zymostenol, desmosterol, and lathosterol ratios from baseline to one year (e.g., serum lathosterol ratio −17 ± 45% vs. −15 ± 41%, respectively, P < 0.001 for both, P = 0.623 between groups). Compensatorily, cholesterol absorption increased during the intervention (e.g., serum campesterol ratio 125 ± 90% vs. 113 ± 72%, respectively, P < 0.001 for both, P = 0.488 between groups). Hydroxychloroquine did not affect cholesterol concentrations or cholesterol absorption. It prevented the statin-induced increase in cholesterol precursor, desmosterol ratio, from six months to one year in the hydroxychloroquine group (P = 0.007 at one year compared to placebo).
Conclusions
Combined with a high-dose statin, hydroxychloroquine had no additional effect on serum cholesterol concentration or cholesterol absorption. However, the findings suggest that hydroxychloroquine interferes with lanosterol synthesis, and thereafter, it temporarily interferes with the cholesterol synthesis pathway, best seen in halting the increase of the desmosterol ratio.