Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment.


AIMS:Subjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a). METHODS AND RESULTS:In this multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median [interquartile range (IQR)]: age 60.0 [54.0-67.0] years, Lp(a) 200.0 [155.5-301.5] nmol/L [80.0 (62.5-121.0) mg/dL]; mean [standard deviation (SD)] LDL-C 3.7 [1.0] mmol/L [144.0 (39.7) mg/dL]; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420 mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% [95% confidence interval (CI) 65.8-55.5] and Lp(a) by 13.9% (95% CI 19.3-8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L [60.1 (28.1) mg/dL], and the median (IQR) Lp(a) level was 188.0 (140.0-268.0) nmol/L [75.2 (56.0-107.2) mg/dL]. Arterial wall inflammation [most diseased segment target-to-background ratio (MDS TBR)] in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (-8.3%) vs. placebo (-5.3%) [treatment difference -3.0% (95% CI -7.4% to 1.4%); P = 0.18]. CONCLUSION:Evolocumab treatment in patients with median baseline Lp(a) 200.0 nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.


Eur Heart J


European heart journal


Stiekema LCA,Stroes ESG,Verweij SL,Kassahun H,Chen L,Wasserman SM,Sabatine MS,Mani V,Fayad ZA




Has Abstract


2019-09-01 00:00:00














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    pub_type: 杂志文章


    authors: Lancellotti P,Suter TM,López-Fernández T,Galderisi M,Lyon AR,Van der Meer P,Cohen Solal A,Zamorano JL,Jerusalem G,Moonen M,Aboyans V,Bax JJ,Asteggiano R

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    pub_type: 杂志文章


    authors: Baur LH,Schipperheyn JJ,Cats VM,van der Wall EE,Baan J,van Dijk AD,Bruschke AV

    更新日期:1992-11-01 00:00:00

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    更新日期:1998-06-01 00:00:00

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    authors: Ge J,Haude M,Görge G,Liu F,Erbel R

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    更新日期:1992-04-01 00:00:00

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    更新日期:1988-01-01 00:00:00

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    journal_title:European heart journal

    pub_type: 杂志文章


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    pub_type: 临床试验,杂志文章,随机对照试验


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    journal_title:European heart journal

    pub_type: 杂志文章,评审


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    pub_type: 杂志文章


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    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Lejeune PO,Delooz HH

    更新日期:1987-03-01 00:00:00

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    journal_title:European heart journal

    pub_type: 杂志文章


    authors: Raman SV,Phatak K,Hoyle JC,Pennell ML,McCarthy B,Tran T,Prior TW,Olesik JW,Lutton A,Rankin C,Kissel JT,Al-Dahhak R

    更新日期:2011-03-01 00:00:00