Apo E4 and lipoprotein-associated phospholipase A2 synergistically increase cardiovascular risk

Abstract

Objective: Apolipoprotein E (apoE) has been implicated as conveying increased risk for coronary artery disease (CAD). Previous studies suggest a role of apoE as a modulator of immune response and inflammatory properties. We hypothesized that the presence of apo E4 is associated with an increased inflammatory burden in subjects with CAD as compared to subjects without CAD.

Methods: ApoE genotypes, systemic (C-reactive protein [CRP], fibrinogen, serum amyloid-A [SAA]) and vascular inflammatory markers (Lipoprotein-associated phospholipase A(2) [Lp-PLA(2)] and pentraxin-3 [PTX-3]) were assessed in 324 Caucasians and 208 African Americans, undergoing coronary angiography.

Results: For both ethnic groups, Lp-PLA(2) index, an integrated measure of Lp-PLA(2) mass and activity, increased significantly and stepwise across apoE isoforms (P = 0.009 and P = 0.026 for African Americans and Caucasians respectively). No differences were found for other inflammatory markers tested (CRP, fibrinogen, SAA and PTX-3). For the top cardiovascular score tertile, apo E4 carriers had a significantly higher level of Lp-PLA(2) index in both ethnic groups (P = 0.027 and P = 0.010, respectively).

Conclusion: The presence of the apo E4 isoform was associated with a higher level of Lp-PLA(2) index, a marker of vascular inflammation. Our results suggest that genetic variation at the apoE locus may impact cardiovascular disease risk through enhanced vascular inflammation.

Figure 1

Relative mean differences (delta) in the Lp-PLA₂ index between apo E4 and apo E2 carriers across Caucasians and African Americans. Comparison between unadjusted and adjusted for LDL cholesterol, HDL cholesterol and Lp(a) levels.

Figure 2

Lp-PLA₂ index levels among apoE genotypes across composite score tertiles in Caucasians and African Americans. * P < 0.05 across apoE genotypes and across composite score tertiles within each ethnic group.