RT Journal Article
SR Electronic
T1 ApoCIII-Lp(a) complexes in conjunction with Lp(a)-OxPL predict rapid progression of aortic stenosis
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 738
OP 745
DO 10.1136/heartjnl-2019-315840
VO 106
IS 10
A1 Romain Capoulade
A1 Michael Torzewski
A1 Manuel Mayr
A1 Kwan-Leung Chan
A1 Patrick Mathieu
A1 Yohan Bossé
A1 Jean G Dumesnil
A1 James Tam
A1 Koon K Teo
A1 Sean A. Burnap
A1 Jens Schmid
A1 Nora Gobel
A1 Ulrich F W Franke
A1 Amber Sanchez
A1 Joseph L Witztum
A1 Xiaohong Yang
A1 Calvin Yeang
A1 Benoit Arsenault
A1 Jean-Pierre Després
A1 Philippe Pibarot
A1 Sotirios Tsimikas
YR 2020
UL http://heart.bmj.com/content/106/10/738.abstract
AB 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 (Vpeak), 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 Vpeak (all p<0.05). After multivariable adjustment, patients in the top tertile of both apoCIII-Lp(a) and Lp(a) had significantly higher annualised Vpeak (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.Trial registration NCT00800800.