The effect of hydroxychloroquine on cholesterol metabolism in statin treated patients after myocardial infarction

IF 1.4 Q3 PERIPHERAL VASCULAR DISEASE Atherosclerosis plus Pub Date : 2023-09-01 DOI:10.1016/j.athplu.2023.06.003
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
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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.

Trial Registration ClinicalTrials.gov Identifier: NCT02648464.

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羟氯喹对心肌梗死后他汀类药物治疗患者胆固醇代谢的影响
背景和目的评价羟氯喹(HCQ)对大剂量他汀类药物治疗心肌梗死患者血清和脂蛋白脂质以及血清胆固醇合成和吸收生物标志物的影响。方法将59例心肌梗死患者(n=59)随机分为两组,一组每日服用羟氯喹300mg(n=31),另一组服用安慰剂(n=28),疗程6个月,随访1年。结果他汀类药物降低了总胆固醇(羟氯喹组为−26±22%,安慰剂组为−28±19%,P=0.0931)、低密度脂蛋白胆固醇(分别为−38±26%和−44±23%,P=0.0299)和胆固醇合成生物标志物酶原缩醇、连丝甾醇,以及从基线到一年的睾酮比率(例如,血清睾酮比率分别为−17±45%和−15±41%,两者均P<;0.001,组间P=0.623)。作为补偿,胆固醇吸收在干预过程中增加(例如,血清胆固醇比分别为125±90%和113±72%,两组之间的P<0.001,P=0.488)。羟氯喹不会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,即结蛋白胆固醇比率从6个月增加到1年(与安慰剂相比,1年时P=0.007)。结论羟氯喹与大剂量他汀类药物联合使用,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的合成,此后,它会暂时干扰胆固醇的合成途径,最明显的表现是阻止羊毛甾醇比例的增加。试验注册ClinicalTrials.gov标识符:NCT02648464。
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来源期刊
Atherosclerosis plus
Atherosclerosis plus Cardiology and Cardiovascular Medicine
CiteScore
2.60
自引率
0.00%
发文量
0
审稿时长
66 days
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