Carotid intima-media thickness and markers of inflammation, endothelial damage and hemostasis

Background. Different soluble molecules involved in inflammation, endothelial damage, or hemostasis are recognized as potential cardiovascular risk markers. Studies to assess the role of these markers in the atherosclerotic process by evaluating their relationship to carotid intima-media thickness (C-IMT) tend to provide contrasting results. Purpose. To perform a review of studies addressing the association between C-IMT and soluble markers and to investigate whether the observed inconsistencies could be explained by the characteristics of the patients included in different studies, for example prevalence of atherosclerotic disease (atherosclerotic burden), gender, age, or occurrence of specific vascular risk factors (VRFs). Data sources. PubMed and Embase (January 1990 to March 2006). Study selection. Articles in English reporting original cross-sectional studies. Data extraction. Two authors independently extracted data on study design, population, sample size, ultrasonic methodology, and statistical approach. Data synthesis. Despite the marked heterogeneity of results presented in the literature, meta-analysis established that studies showing positive associations between C-IMT and plasma levels of C-reactive protein (CRP) or fibrinogen are in the majority. Funnel plot analyses suggested the absence of an important publication bias. Data on the relationships between C-IMT and other soluble markers are by contrast scanty, contradictory, or unconfirmed by multivariate (as opposed to univariate) analyses, and the freedom from publication bias here cannot be vouched for. The degree of atherosclerotic burden in the population studied does not account for the heterogeneity of findings reported. Gender, noninsulin-dependent diabetes mellitus (NIDDM) and hypercholesterolemia influence the association between C-IMT and CRP. Blood pressure and hypercholesterolemia influence the association between C-IMT and fibrinogen. For all the other soluble markers considered, the number of groups was too small for this kind of statistical considerations. Limitations. Heterogeneity in ultrasound methodologies and in statistical approach limited comparability between studies. For most soluble markers, publication bias of positive results cannot be excluded. Conclusions. Only CRP and fibrinogen seem to be unequivocally related to C-IMT. For all the other soluble markers considered, no clear-cut conclusions can be drawn.