Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration

Peter Willeit, Simon G Thompson, Stefan Agewall, Göran Bergström, Horst Bickel, Alberico L Catapano, Kuo-Liong Chien, Eric de Groot, Jean-Philippe Empana, Thorleif Etgen, Oscar H Franco, Bernhard Iglseder (+42 others)
2014 European Journal of Preventive Cardiology  
Background-Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. Methods-Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT
more » ... involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. Results-Mean baseline CCA-IMT amounted to 0.74mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072mm for fibrinogen (p < 0.001); and 0.0025mm for leucocyte count (p = 0.033). 'Inflammatory load', defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest 'inflammatory load' had a greater CCA-IMT progression (p = 0.015). Conclusion-Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its Reprints and permissions: sagepub.co.uk/journalsPermissions.nav
doi:10.1177/2047487314560664 pmid:25416041 pmcid:PMC4544641 fatcat:y45orgn2bfgw5ny2rdy5c3xrw4