Objective
Levels of acute phase reactants are impacted by age. To what extent cardiovascular risk associated with aging is due to an increase in the inflammatory burden is not known. We assessed the relationship with age of inflammatory markers, representing a) systemic (C-reactive protein [CRP], fibrinogen and serum amyloid-A [SAA]) and b) vascular (lipoprotein-associated phospholipase A2 [Lp-PLA2] and pentraxin-3 [PTX-3]) inflammation.
Methods and Results
We determined Lp-PLA2 mass and activity, CRP, fibrinogen, SAA, and PTX-3 levels and other CVD risk factors in 336 Caucasians and 224 African Americans. Levels of systemic inflammatory markers increased significantly with age in both ethnic groups (P<0.05 for all), while trend patterns of vascular inflammatory markers did not change significantly with age for either group. In multivariate regression models adjusting for confounding variables, age remained independently associated with a composite z-score for systemic, but not vascular inflammation (β=0.250, P<0.001 and (β=0.276, P<0.001, for Caucasians and African Americans respectively).
Conclusions
We report an increase in the systemic, but not vascular, inflammatory burden over age. Levels of both categories of inflammatory markers over age were similar across ethnicity after adjustment for confounders. Our results underscore the importance of age in evaluating inflammatory markers to assess cardiovascular risk.
We are of the opinion that increased Lp-PLA2 levels may partially contribute to endothelial dysfunction by the progression of inflammation. In addition, increased complex formation with Vn is likely to bring about the increase of PAI-1 activity in patients with preeclampsia. Moreover, increased t-PA and decreased Vn levels may also be the consequences of compensatory mechanisms against disease progression.
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 A2 [Lp-PLA2] and pentraxin-3 [PTX-3]) were assessed in 324 Caucasians and 208 African Americans, undergoing coronary angiography.
Results
For 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).
Conclusion
The 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.
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