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 Papagianni; Holger 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

doi:10.1177/2047487314560664

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

Neurology

Research output: Contribution to journal › Review 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 language	English (US)
Pages (from-to)	194-205
Number of pages	12
Journal	European Journal of Preventive Cardiology
Volume	23
Issue number	2
DOIs	https://doi.org/10.1177/2047487314560664
State	Published - 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

Inflammatory markers and extent and progression of early atherosclerosis : Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. / 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; Franco, Oscar H.; Iglseder, Bernhard; Johnsen, Stein H.; Kavousi, Maryam; Lind, Lars; Liu, Jing; Mathiesen, Ellisiv B.; Norata, Giuseppe D.; Olsen, Michael H.; Papagianni, Aikaterini; Poppert, Holger; Price, Jackie F.; Sacco, Ralph L.; Yanez, David N.; Zhao, Dong; Schminke, Ulf; Bülbül, Alpaslan; Polak, Joseph F.; Sitzer, Matthias; Hofman, Albert; Grigore, Liliana; Dörr, Marcus; Su, Ta Chen; Ducimetière, Pierre; Xie, Wuxiang; Ronkainen, Kimmo; Kiechl, Stefan; Rundek, Tatjana; Robertson, Christine; Fagerberg, Björn; Bokemark, Lena; Steinmetz, Helmuth; Ikram, M. Arfan; Völzke, Henry; Lin, Hung Ju; Plichart, Matthieu; Tuomainen, Tomi Pekka; Desvarieux, Moise; McLachlan, Stela; Schmidt, Caroline; Kauhanen, Jussi; Willeit, Johann; Lorenz, Matthias W.; Sander, Dirk.

In: European Journal of Preventive Cardiology, Vol. 23, No. 2, 01.01.2016, p. 194-205.

Research output: Contribution to journal › Review article

Willeit, P, Thompson, SG, Agewall, S, Bergström, G, Bickel, H, Catapano, AL, Chien, KL, De Groot, E, Empana, JP, Etgen, T, Franco, OH, Iglseder, B, Johnsen, SH, Kavousi, M, Lind, L, Liu, J, Mathiesen, EB, Norata, GD, Olsen, MH, Papagianni, A, Poppert, H, Price, JF, Sacco, RL, Yanez, DN, Zhao, D, Schminke, U, Bülbül, A, Polak, JF, Sitzer, M, Hofman, A, Grigore, L, Dörr, M, Su, TC, Ducimetière, P, Xie, W, Ronkainen, K, Kiechl, S, Rundek, T, Robertson, C, Fagerberg, B, Bokemark, L, Steinmetz, H, Ikram, MA, Völzke, H, Lin, HJ, Plichart, M, Tuomainen, TP, Desvarieux, M, McLachlan, S, Schmidt, C, Kauhanen, J, Willeit, J, Lorenz, MW & 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, vol. 23, no. 2, pp. 194-205. https://doi.org/10.1177/2047487314560664

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 ; Franco, Oscar H. ; Iglseder, Bernhard ; Johnsen, Stein H. ; Kavousi, Maryam ; Lind, Lars ; Liu, Jing ; Mathiesen, Ellisiv B. ; Norata, Giuseppe D. ; Olsen, Michael H. ; Papagianni, Aikaterini ; Poppert, Holger ; Price, Jackie F. ; Sacco, Ralph L. ; Yanez, David N. ; Zhao, Dong ; Schminke, Ulf ; Bülbül, Alpaslan ; Polak, Joseph F. ; Sitzer, Matthias ; Hofman, Albert ; Grigore, Liliana ; Dörr, Marcus ; Su, Ta Chen ; Ducimetière, Pierre ; Xie, Wuxiang ; Ronkainen, Kimmo ; Kiechl, Stefan ; Rundek, Tatjana ; Robertson, Christine ; Fagerberg, Björn ; Bokemark, Lena ; Steinmetz, Helmuth ; Ikram, M. Arfan ; Völzke, Henry ; Lin, Hung Ju ; Plichart, Matthieu ; Tuomainen, Tomi Pekka ; Desvarieux, Moise ; McLachlan, Stela ; Schmidt, Caroline ; Kauhanen, Jussi ; Willeit, Johann ; Lorenz, Matthias W. ; Sander, Dirk. / Inflammatory markers and extent and progression of early atherosclerosis : Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. In: European Journal of Preventive Cardiology. 2016 ; Vol. 23, No. 2. pp. 194-205.

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

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.",

keywords = "Inflammation, atherosclerosis, meta-analysis",

author = "Peter Willeit and Thompson, {Simon G.} and Stefan Agewall and G{\"o}ran Bergstr{\"o}m and Horst Bickel and Catapano, {Alberico L.} and Chien, {Kuo Liong} and {De Groot}, Eric and Empana, {Jean Philippe} and Thorleif Etgen and Franco, {Oscar H.} and Bernhard Iglseder and Johnsen, {Stein H.} and Maryam Kavousi and Lars Lind and Jing Liu and Mathiesen, {Ellisiv B.} and Norata, {Giuseppe D.} and Olsen, {Michael H.} and Aikaterini Papagianni and Holger Poppert and Price, {Jackie F.} and Sacco, {Ralph L.} and Yanez, {David N.} and Dong Zhao and Ulf Schminke and Alpaslan B{\"u}lb{\"u}l and Polak, {Joseph F.} and Matthias Sitzer and Albert Hofman and Liliana Grigore and Marcus D{\"o}rr and Su, {Ta Chen} and Pierre Ducimeti{\`e}re and Wuxiang Xie and Kimmo Ronkainen and Stefan Kiechl and Tatjana Rundek and Christine Robertson and Bj{\"o}rn Fagerberg and Lena Bokemark and Helmuth Steinmetz and Ikram, {M. Arfan} and Henry V{\"o}lzke and Lin, {Hung Ju} and Matthieu Plichart and Tuomainen, {Tomi Pekka} and Moise Desvarieux and Stela McLachlan and Caroline Schmidt and Jussi Kauhanen and Johann Willeit and Lorenz, {Matthias W.} and Dirk Sander",

year = "2016",

month = jan,

day = "1",

doi = "10.1177/2047487314560664",

language = "English (US)",

volume = "23",

pages = "194--205",

journal = "European Journal of Preventive Cardiology",

issn = "2047-4873",

publisher = "SAGE Publications Ltd",

number = "2",

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TY - JOUR

T1 - Inflammatory markers and extent and progression of early atherosclerosis

T2 - Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration

AU - Willeit, Peter

AU - Thompson, Simon G.

AU - Agewall, Stefan

AU - Bergström, Göran

AU - Bickel, Horst

AU - Catapano, Alberico L.

AU - Chien, Kuo Liong

AU - De Groot, Eric

AU - Empana, Jean Philippe

AU - Etgen, Thorleif

AU - Franco, Oscar H.

AU - Iglseder, Bernhard

AU - Johnsen, Stein H.

AU - Kavousi, Maryam

AU - Lind, Lars

AU - Liu, Jing

AU - Mathiesen, Ellisiv B.

AU - Norata, Giuseppe D.

AU - Olsen, Michael H.

AU - Papagianni, Aikaterini

AU - Poppert, Holger

AU - Price, Jackie F.

AU - Sacco, Ralph L.

AU - Yanez, David N.

AU - Zhao, Dong

AU - Schminke, Ulf

AU - Bülbül, Alpaslan

AU - Polak, Joseph F.

AU - Sitzer, Matthias

AU - Hofman, Albert

AU - Grigore, Liliana

AU - Dörr, Marcus

AU - Su, Ta Chen

AU - Ducimetière, Pierre

AU - Xie, Wuxiang

AU - Ronkainen, Kimmo

AU - Kiechl, Stefan

AU - Rundek, Tatjana

AU - Robertson, Christine

AU - Fagerberg, Björn

AU - Bokemark, Lena

AU - Steinmetz, Helmuth

AU - Ikram, M. Arfan

AU - Völzke, Henry

AU - Lin, Hung Ju

AU - Plichart, Matthieu

AU - Tuomainen, Tomi Pekka

AU - Desvarieux, Moise

AU - McLachlan, Stela

AU - Schmidt, Caroline

AU - Kauhanen, Jussi

AU - Willeit, Johann

AU - Lorenz, Matthias W.

AU - Sander, Dirk

PY - 2016/1/1

Y1 - 2016/1/1

N2 - 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.

AB - 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.

KW - Inflammation

KW - atherosclerosis

KW - meta-analysis

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