The placebo-controlled effect of percutaneous coronary intervention on exercise induced changes in anti- malondialdehyde-LDL antibody levels in stable coronary artery disease: a substudy of the ORBITA Trial
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Author(s)
Type
Journal Article
Abstract
Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significant
component of oxidized LDL. The effects of exercise on levels of MDA-LDL and antiMDA-LDL antibodies are not well understood. Furthermore, it is not known whether
these can be modified in patients with coronary artery disease by percutaneous
coronary intervention (PCI).
Methods: The Objective Randomised Blinded Investigation with optimal medical
Therapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multicentre randomised trial of PCI versus placebo procedure for angina relief. Serum
samples were available at four time-points: pre-randomisation pre- (P1) and post- (P2)
exercise and post-randomisation (six-weeks following the PCI or placebo procedure),
pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developed
assays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies.
Results: 196 of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severe
single vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial had
blood available for analysis. With exercise at pre-randomisation (P2 - P1) there was
no significant change in adjusted MDA-LDL (-0.001, 95% CI -0.004 to 0.001; p=0.287);
however, IgG and IgM anti-MDA-LDL significantly declined (-0.022, 95% CI -0.029 to
-0.014, p<0.0001; -0.016, 95% CI -0.024 to -0.008, p=0.0002, respectively). PCI did
not have a significant impact on either the pre-exercise values (P3 controlling for P1)
of MDA-LDL (p=0.102), IgG (p=0.444) or IgM anti-MDA-LDL(p=0.909). Nor did PCI
impact the exercise induced changes in these markers (P4 controlling for P1, P2, and
P3) for MDA-LDL (p=0.605), IgG (p=0.725) or IgM anti-MDA-LDL (p=0.171). Prerandomisation ischaemia on stress echo did not impact these interactions.
Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies in
patients with severe single vessel coronary disease, possibly indicating an induction
in homoeostatic clearance via the innate immune system. However, PCI did not
ameliorate this effect.
component of oxidized LDL. The effects of exercise on levels of MDA-LDL and antiMDA-LDL antibodies are not well understood. Furthermore, it is not known whether
these can be modified in patients with coronary artery disease by percutaneous
coronary intervention (PCI).
Methods: The Objective Randomised Blinded Investigation with optimal medical
Therapy of Angioplasty in stable angina (ORBITA) trial was the first blinded, multicentre randomised trial of PCI versus placebo procedure for angina relief. Serum
samples were available at four time-points: pre-randomisation pre- (P1) and post- (P2)
exercise and post-randomisation (six-weeks following the PCI or placebo procedure),
pre- (P3) and post- (P4) exercise. ELISAs were performed using laboratory-developed
assays for MDA-LDL (adjusted for Apolipoprotein B) and anti-MDA-LDL antibodies.
Results: 196 of the 200 patients (age 66.1 [SD 8.99] years, 28% female) with severe
single vessel coronary artery disease suitable for PCI enrolled in the ORBITA trial had
blood available for analysis. With exercise at pre-randomisation (P2 - P1) there was
no significant change in adjusted MDA-LDL (-0.001, 95% CI -0.004 to 0.001; p=0.287);
however, IgG and IgM anti-MDA-LDL significantly declined (-0.022, 95% CI -0.029 to
-0.014, p<0.0001; -0.016, 95% CI -0.024 to -0.008, p=0.0002, respectively). PCI did
not have a significant impact on either the pre-exercise values (P3 controlling for P1)
of MDA-LDL (p=0.102), IgG (p=0.444) or IgM anti-MDA-LDL(p=0.909). Nor did PCI
impact the exercise induced changes in these markers (P4 controlling for P1, P2, and
P3) for MDA-LDL (p=0.605), IgG (p=0.725) or IgM anti-MDA-LDL (p=0.171). Prerandomisation ischaemia on stress echo did not impact these interactions.
Conclusions: Exercise results in an acute reduction in anti-oxLDL antibodies in
patients with severe single vessel coronary disease, possibly indicating an induction
in homoeostatic clearance via the innate immune system. However, PCI did not
ameliorate this effect.
Date Issued
2021-10-11
Date Acceptance
2021-09-16
Citation
Frontiers in Cardiovascular Medicine, 2021, 8
ISSN
2297-055X
Publisher
Frontiers Media
Journal / Book Title
Frontiers in Cardiovascular Medicine
Volume
8
Copyright Statement
© 2021 Hartley, Shun-Shin, Caga-Anan, Rajkumar, Nowbar, Foley, Francis, Haskard, Khamis and Al-Lamee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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Sponsor
Wellcome Trust
British Heart Foundation
Wellcome Trust
Imperial College Healthcare NHS Trust- BRC Funding
Grant Number
FS/17/16/32560
203928/Z/16/Z
RDB02
Publication Status
Published
Article Number
ARTN 757030