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

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

© 2014 European Society of 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-arte...

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Main Authors: Willeit, P., Thompson, S., Agewall, S., Bergström, G., Bickel, H., Catapano, A., Chien, K., De Groot, E., Empana, J., Etgen, T., Franco, O., Iglseder, B., Johnsen, S., Kavousi, M., Lind, L., Liu, J., Mathiesen, E., Norata, Giuseppe, Olsen, M., Papagianni, A., Poppert, H., Price, J., Sacco, R., Yanez, D., Zhao, D., Schminke, U., Bülbül, A., Polak, J., Sitzer, M., Hofman, A., Grigore, L., Dörr, M., Su, T., Ducimetière, P., Xie, W., Ronkainen, K., Kiechl, S., Rundek, T., Robertson, C., Fagerberg, B., Bokemark, L., Steinmetz, H., Ikram, M., Völzke, H., Lin, H., Plichart, M., Tuomainen, T., Desvarieux, M., McLachlan, S., Schmidt, C., Kauhanen, J., Willeit, J., Lorenz, M., Sander, D.
Format: Journal Article
Published: Sage Publications 2016
Online Access:http://hdl.handle.net/20.500.11937/55715
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Summary:© 2014 European Society of 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 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.

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