Abstract
Background: Experimental studies indicate that two archetype chemokines circulating in the blood, IL-8 and GRO-α, are critical for atherogenesis. However, their association with measures of subclinical atherosclerosis has not been investigated. Hypothesis: Here we test the hypothesis that circulating IL8 and GRO-α protein are associated with the carotid artery intima media thickness (c-IMT) in a large European multicenter study: the c-IMT and c-IMT Progression as Predictors of Vascular Events in a High Risk European Population ( IMPROVE ) study . Methods: IMPROVE study participants (n=3,703), recruited in 5 European Countries (Sweden, Finland, the Netherlands, France and Italy), had at least three cardiovascular (CV) risk factors but not prevalent CV diseases. C-IMT measures (mm) (c-IMT mean , c-IMT max and c-IMT mean-max ) were recorded at baseline. Each measurement represent the average of 8 (4 left and 4 right) carotid segments. IL8 and GRO-α were measured in plasma from 3,452 participants (women, n=1,784; men, n=1,668) using the Olink ProSeek CVD array I and expressed in arbitrary units. We evaluated the association, expressed as beta coefficient (β) and 95% confidence intervals (CI), between chemokines and c-IMT using median regression. Models were adjusted by sex, age, body mass index, hypertension, diabetes, current smokers, hypercholesterolemia and latitude. Results: Higher levels of IL8 and GRO-α were observed in participants from Northern Europe as compared to those from Southern Europe [IL8: 50 (41-62) vs 36 (28-49) and GRO-α 108 (70-176) vs 42(22-95)]. At multivariable analysis only in men, levels of IL8 were positively associated with c-IMT measures: c-IMT mean [1.0 x 10 -4 (6.5 x 10 -5 -1.4 x 10 -4 ), p<0.01], c-IMT max [(6.5 x 10 -4 ,(4.8 x 10 -4 -8.2 x 10 -4 ), p<0.01] and c-IMT mean-max [1.7 x 10 -4 , (1.3 x 10 -4 -2.2 x 10 -4 ), p<0.01]. No corresponding association was observed for GRO-α and c-IMT measurements. Conclusions: The chemokine IL8, but not GRO-α, was associated with baseline c-IMT in men at high risk of CV events. Furthermore, our results suggest the presence of a European north-to-south gradient in chemokine levels. New studies are warranted to disentangle potential differences between IL8 and CV risk across sexes.
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