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Published on: October 12, 2017
Oxidised LDL and Anti-Oxidised LDL Antibodies Are Reduced by Lipoprotein Apheresis in a Randomised Controlled Trial
Tina Z Khan1,2, Adam Hartley3, Dorian Haskard3
1National Heart and Lung Institute, Imperial College London, Guy Scadding Building, Cale Street, London SW3 6LY, UK.
Insights
Lipoprotein apheresis (LA) significantly reduces oxidized LDL (oxLDL) and anti-oxLDL antibodies in patients with refractory angina and high lipoprotein(a) (Lp(a)). This suggests LA may offer cardiovascular benefits by targeting these markers.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Clinical Trials
Background:
- Elevated lipoprotein(a) (Lp(a)) is a significant risk factor for cardiovascular disease, particularly in refractory angina.
- Oxidized LDL (oxLDL) levels correlate with atherosclerotic burden and cardiovascular events.
- Anti-oxLDL antibodies are involved in oxLDL clearance, and Lipoprotein apheresis (LA) reduces Lp(a) and cardiovascular events.
Purpose of the Study:
- To investigate the effect of Lipoprotein apheresis (LA) on oxidized LDL (oxLDL) and anti-oxLDL antibody levels.
- To assess these effects in patients with refractory angina and elevated Lp(a).
Main Methods:
- A randomized controlled crossover trial involving 20 patients with refractory angina and Lp(a) > 500 mg/L.
- Patients received three months of blinded weekly LA or sham therapy, followed by crossover.
- Enzyme-linked immunosorbent assays (ELISA) quantified oxLDL and IgG/IgM anti-oxLDL antibody levels at baseline and post-treatment.
Main Results:
- Lipoprotein apheresis (LA) resulted in a 30% reduction in oxLDL levels (p < 0.0001 vs. sham).
- LA also led to a 22% reduction in IgG and IgM anti-oxLDL antibodies (p = 0.0036 and p = 0.012, respectively, vs. sham).
- Sham therapy showed no significant changes in oxLDL or anti-oxLDL levels.
Conclusions:
- Lipoprotein apheresis (LA) significantly lowers oxLDL and anti-oxLDL antibodies in patients with refractory angina and elevated Lp(a).
- These reductions represent potential mechanisms underlying the symptomatic and prognostic benefits of LA in this patient group.
- LA may be a valuable therapeutic strategy for managing cardiovascular risk in patients with high Lp(a) and refractory angina.
Abstract:
Aims: An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation between oxidised LDL (oxLDL) levels and atherosclerotic burden as well as rates of cardiovascular events. Antibodies against oxLDL (anti-oxLDL) are involved in the removal of oxLDL. Lipoprotein apheresis (LA), which removes lipoproteins using extra-corporeal processes, is an established means of reducing Lp(a), and thereby reduces cardiovascular events. The aim of this study was to investigate the effect of LA on oxLDL and anti-oxLDL levels amongst those with refractory angina in the context of raised Lp(a). Methods: We performed a sub-study within a randomised controlled crossover trial involving 20 patients with refractory angina and raised Lp(a) > 500 mg/L, comparing the effect of three months of blinded weekly LA or sham, followed by crossover to the opposite study arm. We utilized enzyme-linked immunosorbent assays (ELISA) to quantify oxLDL and IgG/ IgM anti-oxLDL antibody levels at baseline and following three months of active LA or sham sessions. Results: Following three months of LA, there was a 30% reduction in oxLDL from 0.37 ± 0.06 to 0.26 ± 0.04 with a mean drop of -0.11 units (U) (95% CI -0.13, -0.09) compared to no significant change with sham therapy (p < 0.0001 between treatment arms). LA also led to a 22% reduction in levels of IgG and IgM anti-oxLDL, again with no significant change demonstrated during sham (p = 0.0036 and p = 0.012, respectively, between treatment arms). Conclusion: Amongst patients with refractory angina in the context of elevated Lp(a), LA significantly lowers levels of oxLDL and anti-oxLDL antibodies, representing potential mechanisms by which LA yields symptomatic and prognostic benefits in this patient cohort.
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