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

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Date

2016-01

Authors

Willeit, Peter
Thompson, Simon G
Agewall, Stefan
Bergström, Göran
Bickel, Horst
Catapano, Alberico L
Chien, Kuo-Liong
de Groot, Eric
Empana, Jean-Philippe
Etgen, Thorleif

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Abstract

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.

Type

Journal article

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Subjects

PROG-IMT study group, Humans, Disease Progression, Inflammation, C-Reactive Protein, Fibrinogen, Leukocyte Count, Atherosclerosis, Carotid Intima-Media Thickness, Biomarkers

Citation

Published Version (Please cite this version)

10.1177/2047487314560664

Publication Info

Willeit, Peter, Simon G Thompson, Stefan Agewall, Göran Bergström, Horst Bickel, Alberico L Catapano, Kuo-Liong Chien, Eric de Groot, et al. (2016). Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. European journal of preventive cardiology, 23(2). pp. 194–205. 10.1177/2047487314560664 Retrieved from https://hdl.handle.net/10161/31169.

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