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.

Dorian O Haskard,Darrel P Francis,Christopher Rajkumar,Rasha K Al-Lamee,Matthew Shun-Shin,Ramzi Y Khamis,Mikhail Caga-Anan,Adam Hartley,Alexandra N Nowbar,Michael Foley

doi:10.3389/fcvm.2021.757030

Abstract

Aim: Malondialdehyde-modified low-density lipoprotein (MDA-LDL) forms a significant component of oxidised LDL. The effects of exercise on levels of MDA-LDL and anti-MDA-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, multi-centre randomised trial of PCI vs. placebo procedure for angina relief. Serum samples were available at four time-points: pre-randomisation pre- (P1) and post- (P2) exercise and post-randomisation (6-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: One hundred ninety-six 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). Pre-randomisation 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.

Highlights

Oxidised low-density lipoprotein is found both within atherosclerotic plaques and the plasma of patients with cardiovascular disease (CVD)
percutaneous coronary intervention (PCI), when compared to placebo, did not have a significant impact on pre-exercise (P3 controlling for P1) adjusted MDALDL, IgG or IgM anti-MDA-low-density lipoprotein (LDL) (p = 0.102, p = 0.444, p = 0.909 respectively)
There was no significant change in adjusted modification of LDL (MDA-LDL)

Summary

Introduction

Oxidised low-density lipoprotein (oxLDL) is found both within atherosclerotic plaques and the plasma of patients with cardiovascular disease (CVD). Oxidation specific epitopes (OSEs) on oxLDL can act as “danger associated molecular patterns,” whereby they undergo recognition by members of the innate immune system such as C-reactive protein, complement proteins and both “natural” and “adaptive” antibodies [3]. This provides an important homeostatic mechanism for oxLDL clearance [4]. The association of IgG anti-oxLDL antibodies with CVD is less clear [6]

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