ApoCIII-Lp(a) complexes in conjunction with Lp(a)-OxPL predict rapid progression of aortic stenosis

被引：38

作者：

Capoulade, Romain ^{[1
,2
]}

Torzewski, Michael ^{[3
]}

Mayr, Manuel ^{[4
]}

Chan, Kwan-Leung ^{[5
]}

Mathieu, Patrick ^{[1
]}

Bosse, Yohan ^{[1
]}

Dumesnil, Jean G. ^{[1
]}

Tam, James ^{[6
]}

Teo, Koon K. ^{[7
]}

Burnap, Sean A. ^{[4
]}

Schmid, Jens ^{[3
]}

Gobel, Nora ^{[3
]}

Franke, Ulrich F. W. ^{[3
]}

Sanchez, Amber ^{[8
]}

Witztum, Joseph L. ^{[9
]}

Yang, Xiaohong ^{[10
]}

Yeang, Calvin ^{[10
]}

Arsenault, Benoit ^{[1
]}

Despres, Jean-Pierre ^{[1
]}

Pibarot, Philippe ^{[1
]}

Tsimikas, Sotirios ^{[10
]}

机构：

[1] Ctr Rech Inst Univ Cardiol & Pneumol Quebec, Quebec Heart & Lung Inst, Quebec City, PQ, Canada

[2] Univ Nantes, Inst Thorax, INSERM, CNRS,CHU Nantes, F-44000 Nantes, France

[3] Robert Bosch Krankenhaus, Dept Cardiovasc Surg, Stuttgart, Baden Wurttembe, Germany

[4] Kings Coll London, Kings British Heart Fdn Ctr, London, England

[5] Univ Ottawa, Dept Med, Heart Inst, Ottawa, ON, Canada

[6] St Boniface Hosp Res, Dept Internal Med, Winnipeg, MB, Canada

[7] McMaster Univ, Dept Med, Hamilton, ON, Canada

[8] Univ Calif San Diego, Dept Nephrol, La Jolla, CA 92093 USA

[9] Univ Calif San Diego, Dept Endocrinol & Metab, La Jolla, CA 92093 USA

[10] Univ Calif San Diego, Dept Cardiol, La Jolla, CA 92093 USA

来源：

HEART | 2020年 / 106卷 / 10期

基金：

加拿大健康研究院;

关键词：

echocardiography; aortic stenosis; lipoproteins and hyperlipidaemia; cardiac surgery; OF-FUNCTION MUTATIONS; APOLIPOPROTEIN C-III; OXIDIZED PHOSPHOLIPIDS; TARGETING APOLIPOPROTEIN(A); CARDIOVASCULAR EVENTS; DOUBLE-BLIND; LIPOPROTEIN(A); RISK; METAANALYSIS; INHIBITION;

D O I：

10.1136/heartjnl-2019-315840

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective This study assessed whether apolipoprotein CIII-lipoprotein(a) complexes (ApoCIII-Lp(a)) associate with progression of calcific aortic valve stenosis (AS). Methods Immunostaining for ApoC-III was performed in explanted aortic valve leaflets in 68 patients with leaflet pathological grades of 1-4. Assays measuring circulating levels of ApoCIII-Lp(a) complexes were measured in 218 patients with mild-moderate AS from the AS Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. The progression rate of AS, measured as annualised changes in peak aortic jet velocity (V-peak), and combined rates of aortic valve replacement (AVR) and cardiac death were determined. For further confirmation of the assay data, a proteomic analysis of purified Lp(a) was performed to confirm the presence of apoC-III on Lp(a). Results Immunohistochemically detected ApoC-III was prominent in all grades of leaflet lesion severity. Significant interactions were present between ApoCIII-Lp(a) and Lp(a), oxidised phospholipids on apolipoprotein B-100 (OxPL-apoB) or on apolipoprotein (a) (OxPL-apo(a)) with annualised V-peak (all p<0.05). After multivariable adjustment, patients in the top tertile of both apoCIII-Lp(a) and Lp(a) had significantly higher annualised V-peak (p<0.001) and risk of AVR/cardiac death (p=0.03). Similar results were noted with OxPL-apoB and OxPL-apo(a). There was no association between autotaxin (ATX) on ApoB and ATX on Lp(a) with faster progression of AS. Proteomic analysis of purified Lp(a) showed that apoC-III was prominently present on Lp(a). Conclusion ApoC-III is present on Lp(a) and in aortic valve leaflets. Elevated levels of ApoCIII-Lp(a) complexes in conjunction with Lp(a), OxPL-apoB or OxPL-apo(a) identify patients with pre-existing mild-moderate AS who display rapid progression of AS and higher rates of AVR/cardiac death.

引用

页码：738 / 745

页数：8

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