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, Stein H. Johnsen, Maryam Kavousi, Lars Lind, Jing Liu, Ellisiv B. Mathiesen, Giuseppe D. Norata, Michael H. Olsen, Aikaterini PapagianniHolger Poppert, Jackie F. Price, Ralph L. Sacco, David N. Yanez, Dong Zhao, Ulf Schminke, Alpaslan Bülbül, Joseph F. Polak, Matthias Sitzer, Albert Hofman, Liliana Grigore, Marcus Dörr, Ta Chen Su, Pierre Ducimetière, Wuxiang Xie, Kimmo Ronkainen, Stefan Kiechl, Tatjana Rundek, Christine Robertson, Björn Fagerberg, Lena Bokemark, Helmuth Steinmetz, M. Arfan Ikram, Henry Völzke, Hung Ju Lin, Matthieu Plichart, Tomi Pekka Tuomainen, Moise Desvarieux, Stela McLachlan, Caroline Schmidt, Jussi Kauhanen, Johann Willeit, Matthias W. Lorenz, Dirk Sander

Research output: Contribution to journalReview article

39 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)194-205
Number of pages12
JournalEuropean Journal of Preventive Cardiology
Volume23
Issue number2
DOIs
StatePublished - Jan 1 2016

Keywords

  • Inflammation
  • atherosclerosis
  • meta-analysis

ASJC Scopus subject areas

  • Epidemiology
  • Cardiology and Cardiovascular Medicine

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    Willeit, P., Thompson, S. G., Agewall, S., Bergström, G., Bickel, H., Catapano, A. L., Chien, K. L., De Groot, E., Empana, J. P., Etgen, T., Franco, O. H., Iglseder, B., Johnsen, S. H., Kavousi, M., Lind, L., Liu, J., Mathiesen, E. B., Norata, G. D., Olsen, M. H., ... Sander, D. (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), 194-205. https://doi.org/10.1177/2047487314560664