Abstract 11896: The ASCOT Anti-oxidised LDL Antibodies Substudy, IgG Anti-malondialdehyde-ldl Antibodies are Independent Predictors of Protection From Cardiovascular Events in a Substudy of the Anglo-scandinavian Cardiac Outcomes Trial

Abstract

Background: Atherosclerosis is a chronic inflammatory disease involving humoral and cell-mediated immunity. We aimed to determine if antibodies to modified or ‘oxidised’ LDL predicted incident cardiovascular disease (CVD) in hypertension.

Methods: We studied a non-diabetic subgroup (age 63±7 yr; 92% male) of the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Classical risk factors plus CRP and IgG and IgM antibodies against malondialdehyde-modified LDL (MDA-LDL) and phosphorylcholine (PC) were measured at baseline and after one year on atorvastatin (10 mg daily; n=100) or placebo (n=100). Carotid intima-media thickness (CIMT) was measured at one year. The primary endpoint was major adverse CVD events (MACE) over a median follow-up of 5 years. Survival analysis was performed and data presented as hazard ratios (HR [95% CI]).

Results: Higher levels of IgG anti MDA-LDL antibodies were associated with a significantly reduced risk of MACE (Log rank test for trend = 0.03; HR = 0.33 [0.13, 0.85]; p = 0.02 in an unadjusted Cox model).This was not attenuated by further adjustment for Framingham CVD score + baseline CRP (adjusted HR = 0.35 [0.13, 0.96]; p=0.04). In a tertile-based Kaplan-Meier survival estimate, the MACE rate in the highest tertile of the study cohort for IgG anti MDA-LDL levels was 16% that in the lowest tertile. Antibody levels to MDA-LDL and PC did not correlate with LDL or CIMT. There was a weak correlation between baseline IgG anti MDA-LDL antibodies and baseline CRP (r=0.16 p<0.05). Antibodies to MDA-LDL and PC were unaffected by atorvastatin despite a 1.53 [1.42,1.63]] mmol/litre reduction in LDL in the atorvastatin limb (p<0.001 by paired t-test). CRP was significantly reduced in the atorvastatin treated group at 1 year (p<0.001).

Conclusions: High IgG anti MDA-LDL antibody levels are strongly associated with significant protection from MACE, independent of classical risk factors, and CRP. Furthermore levels are stable despite one year of atorvastatin and lowered LDL, suggesting the characteristics of a robust biomarker. Mechanisms by which these antibodies are associated with CVD protection require further study.