The effect of metabolic surgery on lipoprotein(A), oxidised phospholipids and biomarkers of lipoprotein oxidation

Background: Obesity results in increased oxidative stress which can be manifested by elevation in oxidised phospholipids (OxPL) and autoantibodies (AA) and immune complexes (IC) to oxidation-specific epitopes. Lp(a) is a major carrier of OxPL, and both Lp(a) and OxPL circulating on apoB-100 (OxPL-apoB) containing particles are independent predictors of cardiovascular disease. Lp(a) and OxPL-apoB levels are modestly correlated in cross-sectional studies. The impact of metabolic surgery on Lp(a), OxPL-apoB and AA and IC to oxidised LDL (OxLDL) is unclear. Aims: To determine the impact of metabolic surgery on levels of Lp(a), OxPL-apoB, and AA and IC to OxLDL. Methods: We conducted a prospective study of 59 patients with severe obesity undergoing metabolic surgery and 16 controls receiving medical weight management. Lp(a), OxPL-apoB, IgG and IgM AA to malondialdehyde-modified LDL (MDA-LDL), apoB IC, and markers of inflammation and glycaemia were measured at baseline, 6months and 12months after surgery. Results: Weight reduction was significant following surgery but only marginal following medical management [percentage change (%Δ) in BMI -31.0±8.7% vs -2.8±4.2%, P<0.001]. Lp(a) levels increased after surgery (P=0.002) and the %Δ correlated with %Δfasting glucose (ρ=-0.262, P=0.050), %Δinsulin (ρ=-0.285, P=0.036) and %ΔHOMA-IR (ρ=-0.290, P=0.034). In contrast, there were decreases in OxPL-apoB (P=0.001) and OxPL-apoB to Lp(a) ratio (P<0.001). Significant declines were also noted in IgG and IgM MDA-LDL and IgG and IgM apoB IC (all P<0.001). OxLDL levels (Mercodia assay), however, were unchanged. Lp(a), OxPL-apoB, IgG and IgM MDA-LDL and IgG and IgM apoB IC did not change significantly following medical weight management. Discussion: Bariatric surgery results in improvement in oxidative stress as evidenced by reductions in levels of OxPL and AA and IC to OxLDL. Lp(a) is increased in association with improvement in markers of glycaemia. The divergent changes in Lp(a) and OxPL-apoB suggests different pathophysiological relationships of the metabolism of Lp(a) and the generation and transport of OxPL following metabolic surgery.