Ulander Lotta, Simonen Piia, Tolppanen Heli, Hartman Otto, Rissanen Tuomas T, Eklund Kari K, Kalaoja Marita, Kurkela Mika, Neuvonen Mikko, Niemi Mikko, Backman Janne T, Gylling Helena, Sinisalo Juha
Heart and Lung Center, Cardiology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Heart Center, North Karelia Central Hospital, Joensuu, Finland.
Atheroscler Plus. 2023 Jun 26;53:26-32. doi: 10.1016/j.athplu.2023.06.003. eCollection 2023 Sep.
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.
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.
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).
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.Trial Registration ClinicalTrials.gov Identifier: NCT02648464.
评估羟氯喹（HCQ）对高剂量他汀类药物治疗的心肌梗死患者血清及脂蛋白脂质以及胆固醇合成与吸收的血清生物标志物的影响。
将59例服用恒定剂量他汀类药物的心肌梗死患者随机分为两组，一组每日服用300毫克羟氯喹（31例），另一组每日服用安慰剂（28例），为期6个月，并随访1年。
他汀类药物降低了总胆固醇（羟氯喹组降低26±22%，安慰剂组降低28±19%，P = 0.931）、低密度脂蛋白胆固醇（分别为-38±26%和-44±23%，P = 0.299），以及从基线到1年的胆固醇合成生物标志物羊毛甾烯醇、麦角甾醇和羊毛甾醇比率（例如，血清羊毛甾醇比率分别为-17±45%和-15±41%，两者P均<0.001，组间P = 0.623）。作为补偿，干预期间胆固醇吸收增加（例如，血清菜油甾醇比率分别为125±90%和113±72%，两者P均<0.001，组间P = 0.488）。羟氯喹不影响胆固醇浓度或胆固醇吸收。在羟氯喹组中，它阻止了他汀类药物诱导的胆固醇前体麦角甾醇比率从6个月到1年的增加（与安慰剂相比，1年时P = 0.007）。
与高剂量他汀类药物联合使用时，羟氯喹对血清胆固醇浓度或胆固醇吸收没有额外影响。然而，研究结果表明羟氯喹会干扰羊毛甾醇合成，进而暂时干扰胆固醇合成途径，最明显的表现是阻止麦角甾醇比率的增加。试验注册ClinicalTrials.gov标识符：NCT02648464。
