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

ObjectiveApolipoprotein 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.MethodsApoE genotypes, systemic (C-reactive protein [CRP], fibrinogen, serum amyloid-A [SAA]) and vascular inflammatory markers (Lipoprotein-associated phospholipase A2 [Lp-PLA2] and pentraxin-3 [PTX-3]) were assessed in 324 Caucasians and 208 African Americans, undergoing coronary angiography.ResultsFor both ethnic groups, Lp-PLA2 index, an integrated measure of Lp-PLA2 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-PLA2 index in both ethnic groups (P = 0.027 and P = 0.010, respectively).ConclusionThe presence of the apo E4 isoform was associated with a higher level of Lp-PLA2 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.

► Studied the relationship between apoE genetic variation and inflammation. ► Assessed markers of systemic and vascular inflammation. ► Lp-PLA2 index increased significantly across apoE isoform groups. ► Apo E4 carriers in the top CVD score tertile had higher Lp-PLA2 index. ► Genetic variation at the apoE locus may impact CVD risk via vascular inflammation.