Inflammatory markers and extent and progression of early atherosclerosis: Meta analysis of individual participant data from 20 prospective studies of the PROG IMT collaboration
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 collaboration 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 0.74 mm (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: 0.0082 mm for high sensitivity C reactive protein (p 0.001) 0.0072 mm for fibrinogen (p 0.001) and 0.0025 mm 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 assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.
European journal of preventive cardiology