LAUSR

Introduction Lipoprotein apheresis (LA), an extra-corporeal lipid lowering technique is a promising new therapeutic technique for the treatment of coronary artery disease. Patients with high levels of Lipoprotein(a) but normal cholesterol levels are challenging to treat, and therefore this technique offers a novel therapeutic avenue. Levels of oxLDL are well known to correlate with both the degree of atherosclerosis in patients, as well as their risk of cardiovascular events. Antibodies against oxLDL are recognised to form immune complexes and are implicated in the clearance of oxLDL. Methods We tested the effect of LA on levels of oxLDL as well and anti-oxLDL antibody levels as a sub-study of a randomised controlled trial in 20 patients with refractory angina, raised Lp(a)>500 mg/L and LDL cholesterol<4 mmol/L (average baseline level was 2.16 mmol/L) with three months of blinded weekly LA or sham, followed by crossover. Enzyme-linked immunosorbent assays (ELISA) were used to measure levels of MDA-LDL (oxLDL), as well as IgG and IgM anti oxLDL antibody levels at baseline as well as after 3 month periods of active and sham treatment. Results Baseline oxLDL levels were correlated with both baseline LDL (r=0.69, p=0.001) and Lp(a) levels (r=0.63; p=0.03). OxLDL was reduced by 30% after apheresis. There was a mean drop of −0.11 units (U) (95% CI −0.13,–0.09) from 0.37±0.06 to 0.26±0.04. During sham oxLDL levels did not change significantly with a mean change of −0.01 (95% CI −0.04, 0.02) from 0.35±0.07 to 0.34±0.07 (p<0.0001 between treatment arms). IgG and IgM anti-oxLDL levels were both reduced by 22% after apheresis; IgG from 0.61±0.21 to 0.47±0.20; p=0.0036 (optical density units, [ODU]); whilst IgM was reduced by a median value of 0.15 ODU from 0.66±0.43 to 0.54±0.36; p=0.012. IgG and IgM anti-oxLDL levels were not affected by the sham procedure. Conclusions LA significantly reduced oxLDL levels as well as anti-oxLDL antibody levels in patients with raised Lp(a). Whilst the mechanism could be due to the direct binding of all the studied proteins to the charged dextran column of the apheresis apparatus, it is more likely that the reduction of anti-oxLDL antibodies is the result of IgG- and IgM-oxLDL immune complex depletion via lipoprotein extraction by the column. We have previously reported a therapeutic benefit of LA on this patient population. Given the pathogenic role of oxidised LDL in coronary artery disease, it is plausible that these demonstrable reductions in oxLDL and their associated antibodies (or immune complexes) may represent one of the mechanisms by which LA leads to clinical benefits in patients with refractory angina and raised Lp(a).