Age as a Modulator of Inflammatory Cardiovascular Risk Factors

Abstract

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.

Diverging trajectory patterns of systemic versus vascular inflammation over age in healthy Caucasians and African-Americans

“…To collectively assess the trend patterns of the relationship between age and inflammatory markers, we constructed a composite z-score for each marker category (systemic or vascular inflammation) based on respective five and three different markers. This approach allows a comparison of individual inflammatory markers within each category at the same scale and provides a standardized way to assess the relative contribution of individual markers to the association with age 19 . Coefficient estimates for mixed-effects regression models associating age, ethnicity/race, and age-race interaction with the composite z-scores of systemic and vascular inflammation with and without adjustments for covariates are shown in Table 2.…”

“…PTX-3 concentration was assessed by ELISA using a commercially available kit (Enzo Life Sciences. Inc., Plymouth Meeting, PA) 19, 24 . Analyses were run according to the manufacturers’ specifications in duplicate samples with two different quality controls, which were within the recommended precision for each test.…”

“…Multiple testing was corrected by the Tukey’s Honestly Significant Difference (HSD) procedure to maintain the family-wise Type I error rate at 0.05. To construct a composite score of multiple markers, we first calculated a z-score for each inflammatory marker [z = (x - x − )/SD, where x is an individual marker value, x − is the mean marker value, and SD is the standard deviation of marker values] as previously described 19 . Using the individual z-scores, we next calculated a composite z-score for systemic inflammation [i.e., z-score (systemic) = Average (z-CRP, z-fibrinogen, z-SAA, z-HPTG, z-AGP)], and for vascular inflammation [z-score (vascular) = Average (z-PTX-3, z-sICAM-1, z-sVCAM-1].…”

“…Furthermore, there are ethnic differences in inflammatory biomarker levels in adults, potentially related to demographic or lifestyle-related factors 18 . Previously, we have shown heterogeneity in the relationship of systemic versus vascular inflammatory markers with age among middle-aged Caucasian and African-American adults undergoing coronary angiography 19 .…”

Vascular Inflammation in Metabolically Abnormal but Normal-Weight and Metabolically Healthy Obese Individuals Analyzed With 18F-Fluorodeoxyglucose Positron Emission Tomography

“…16 In our study, although serum LDL cholesterol levels showed no significant differences among body size phenotypes, vascular inflammation, represented as maximum TBR, in the MHO group was significantly greater than that of the MHNW group, even after adjusting for age, which is an important modulator of inflammatory CV risk factor. 17 Furthermore, many previous studies have shown that an increased hsCRP level is associated with an increased risk of CV events even after adjustment for traditional risk factors and hsCRP has been found in atherosclerotic plaques. 18 Vascular inflammation precedes the traditional risk factors.…”