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Objective: Age and inflammation are risk factors for cardiovascular disease but the impact of inflammation on cardiovascular risk across the lifespan is not understood. We investigated whether an inflammatory burden is modulated by age in healthy subjects., Methods: Caucasian and African-American families were recruited from the general population (age range: 6-74 years, n = 267). Systemic inflammation was assessed by C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, haptoglobin and α-acid glycoprotein, and vascular inflammation was assessed by pentraxin-3 (PTX-3), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM). To collectively assess systemic or vascular factors across the age spectrum, a composite z-score for each marker category was calculated., Results: There was a contrasting pattern in systemic versus vascular inflammatory burden over age with an increase in systemic but a decrease in vascular markers in both ethnic groups. The results remained unchanged after adjustments for the covariates and covariance. When looking at individual markers to examine which markers are most contributing factors to the composite scores, CRP and SAA were significantly and positively associated with age, while PTX-3 and sVCAM were significantly and negatively associated with age in both ethnic groups., Conclusions: The composite z-score for systemic inflammation increased with age, while the composite z-score for vascular inflammation declined with age, irrespective of ethnicity. The findings illustrate a regulatory relationship between age and inflammation, and suggest that a perceived elevation of vascular markers among the very young may be an indication of physiological changes rather than reflecting a disease process., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

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., (Published by Elsevier Ireland Ltd.)

Objective: Levels of acute phase reactants are affected by age. The extent to which 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 (1) systemic (C-reactive protein, fibrinogen, and serum amyloid-A) and (2) vascular (lipoprotein-associated phospholipase A(2) and pentraxin-3) inflammation., Methods and Results: We determined lipoprotein-associated phospholipase A(2) mass and activity, C-reactive protein, fibrinogen, serum amyloid-A, and pentraxin-3 levels and other cardiovascular disease risk factors in 336 whites and 224 African Americans. Levels of systemic inflammatory markers increased significantly with age in both ethnic groups (P<0.05 for all), whereas 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 whites and African Americans, respectively)., Conclusions: We report an increase in the systemic but not vascular inflammatory burden with age. Levels of both categories of inflammatory markers with age were similar across ethnicity after adjustment for confounders. Our results underscore the importance of age in evaluating inflammatory markers to assess cardiovascular risk.

The separate roles of inflammation and insulin resistance (IR) in the pathogenesis of cardiovascular disease (CVD) are well recognized. We investigated whether presence of inflammation would modify coronary artery disease (CAD) risk prediction in subjects with or without IR. Insulin, glucose, CRP and fibrinogen levels were determined in 317 Caucasians and 222 African Americans undergoing diagnostic coronary angiography. Extent of CAD was defined by a composite score (0-75). The overall prevalence of IR (HOMA-IR>or=3.0) in Caucasians and African Americans was 32.5% and 22.9%, respectively (P<0.05). The degree of CAD (composite score) was higher in subjects with IR (20.7 vs. 14.5, P=0.014 and 20.1 vs. 13.1, P=0.031 for Caucasians and African Americans, respectively), and in a multiple regression model IR was an independent predictor for CAD in both groups. In both ethnic groups, subjects with a combination of IR and high CRP (>or=3mg/l) had significantly higher composite score compared to those with no IR and low CRP (<3mg/l) (21.2 vs. 13.9, P<0.05 and 20.9 vs. 10.2, P<0.05 for Caucasians and African Americans, respectively). Similarly, the composite score was significantly higher in subjects with IR and high fibrinogen (>or=340 mg/dl) compared to those with no IR and low fibrinogen. In conclusion, elevated levels of inflammatory markers were positively associated with IR. Further, a combination of IR and inflammation resulted in a higher degree of CAD in both Caucasians and African Americans. The results suggest that inflammation may potentiate the cardiovascular risk factor role of IR.

Background: A role of inflammation for cardiovascular disease (CVD) is established. Lipoprotein(a) [Lp(a)] is an independent CVD risk factor where plasma levels are determined by the apolipoprotein(a) [apo(a)] gene, which contains inflammatory response elements., Design: We investigated the effect of inflammation on allele-specific apo(a) levels in African-Americans and Caucasians. We determined Lp(a) levels, apo(a) sizes, allele-specific apo(a) levels, fibrinogen and C-reactive protein (CRP) levels in 167 African-Americans and 259 Caucasians., Results: Lp(a) levels were increased among African-Americans with higher vs. lower levels of CRP [<3 vs. > or =3 mg/liter (143 vs. 108 nmol/liter), P = 0.009] or fibrinogen (<340 vs. > or =340 mg/liter, P = 0.002). We next analyzed allele-specific apo(a) levels for different apo(a) sizes. No differences in allele-specific apo(a) levels across CRP or fibrinogen groups were seen among African-Americans or Caucasians for small apo(a) sizes (<22 kringle 4 repeats). Allele-specific apo(a) levels for medium apo(a) sizes (22-30 kringle 4 repeats) were significantly higher among African-Americans, with high levels of CRP or fibrinogen compared with those with low levels (88 vs. 67 nmol/liter, P = 0.014, and 91 vs. 59 nmol/liter, P < 0.0001, respectively). No difference was found for Caucasians., Conclusions: Increased levels of CRP or fibrinogen are associated with higher allele-specific medium-sized apo(a) levels in African-Americans but not in Caucasians. These findings indicate that proinflammatory conditions result in a selective increase in medium-sized apo(a) levels in African-Americans and suggest that inflammation-associated events may contribute to the interethnic difference in Lp(a) levels between African-Americans and Caucasians.