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 › peer-review

55 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

Access to Document

10.1177/2047487314560664

Cite this

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 › peer-review

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.

@article{33c7da5a3fb54a3e821855a48129f45b,

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",

note = "Funding Information: SA has received speaker{\textquoteright}s honoraria from Sanofi, Siemens, Pfizer, Boehringer-Ingelheim, Orion Pharma, and Astra Zeneza and is on the advisory board for Astra Zeneca. OHF works in ErasmusAGE, a centre for aging research across the life course funded by Nestl{\'e} Nutrition (Nestec Ltd), Metagenics Inc., and AXA. Nestl{\'e} Nutrition (Nestec Ltd.), Metagenics Inc. and AXA had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript. MHO received a Research Grant from Merck & Co., Inc., West Point, PA. None of the other authors report conflicts of interest. Acknowledgements Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (grant no. DFG Lo 1569/2-1 to the PROG-IMT project); the National Heart, Lung and Blood Institute, Bethesda, MD, USA in collaboration with the Atherosclerosis Risk In Communities (ARIC) investigators (the ARIC Study, for which a restricted access dataset was used) and contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC85084, N01HC35129, N01HC85085, N01HC45133, and grant no. HL080295, with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS) for the data of Cardiovascular Health Study (CHS); the Pustertaler Verein zur Praevention von Herz- und Hirngefaesserkrankungen, Gesundheitsbezirk Bruneck, and the Assessorat fuer Gesundheit (Province of Bolzano, Italy) (to the Bruneck study); the Stiftung Deutsche Schlaganfall-Hilfe (to the Carotid Atherosclerosis Progression Study); the National Institute on Aging (NIA; grant no. AG023629); the National Institute of Neurological Disorders and Stroke (grant no. R37 NS 029993 to the Northern Manhattan Study/The Oral Infections and Vascular Disease Epidemiology Study); the National Institute of Dental and Craniofacial Research, Bethesda, MD, USA (grant no. R01 DE 13094 to the Oral Infections, Carotid Atherosclerosis, and Stroke study; AOK Bayern (to the Interventionsprojekt zerebrovaskula ¨ re Erkrankungen und Demenz im Landkreis Ebersberg study); the Netherlands Foundation for Scientific Research (ZonMw, Vici 918-76-619 to the Rotterdam Study); the Federal Ministry of Education and Research (grant nos. BMBF 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania (to The Study of Health in Pomerania, part of the Community Medicine Research net of the University of Greifswald, Germany). The work was performed at: the Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany; the Department of Neurology, Benedictus Krankenhaus Tutzing and Feldafing, Tutzing, Germany; and the Technische Universita¨t Mu¨ nchen, Munich, Germany. The ARIC data was provided through the NHLBI data repository (BioLINCC). This article does not necessarily convey the opinions or views of the ARIC Study or the National Heart, Lung and Blood Institute. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. Etude sur le vieillissement arte´ riel was organized with an agreement between INSERM and Merck, Sharp, and Dohme-Chibret. A complete list of collaborators of the PROG-IMT project is shown in the online Supplementary Material. Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (grant no. DFG Lo 1569/2-1 to the PROG-IMT project); the National Heart, Lung and Blood Institute, Bethesda, MD, USA in collaboration with the Atherosclerosis Risk In Communities (ARIC) investigators (the ARIC Study, for which a restricted access dataset was used) and contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC85084, N01HC35129, N01HC85085, N01HC45133, and grant no. HL080295, with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS) for the data of Cardiovascular Health Study (CHS); the Pustertaler Verein zur Praevention von Herz- und Hirngefaesserkrankungen, Gesundheitsbezirk Bruneck, and the Assessorat fuer Gesundheit (Province of Bolzano, Italy) (to the Bruneck study); the Stiftung Deutsche Schlaganfall-Hilfe (to the Carotid Atherosclerosis Progression Study); the National Institute on Aging (NIA; grant no. AG023629); the National Institute of Neurological Disorders and Stroke (grant no. R37 NS 029993 to the Northern Manhattan Study/The Oral Infections and Vascular Disease Epidemiology Study); the National Institute of Dental and Craniofacial Research, Bethesda, MD, USA (grant no. R01 DE 13094 to the Oral Infections, Carotid Atherosclerosis, and Stroke study; AOK Bayern (to the Interventionsprojekt zerebrovaskul{\"a}re Erkrankungen und Demenz im Landkreis Ebersberg study); the Netherlands Foundation for Scientific Research (ZonMw, Vici 918-76-619 to the Rotterdam Study); the Federal Ministry of Education and Research (grant nos. BMBF 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania (to The Study of Health in Pomerania, part of the Community Medicine Research net of the University of Greifswald, Germany). Publisher Copyright: {\textcopyright} 2014 European Society of Cardiology.",

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",

}

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

N1 - Funding Information: SA has received speaker’s honoraria from Sanofi, Siemens, Pfizer, Boehringer-Ingelheim, Orion Pharma, and Astra Zeneza and is on the advisory board for Astra Zeneca. OHF works in ErasmusAGE, a centre for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd), Metagenics Inc., and AXA. Nestlé Nutrition (Nestec Ltd.), Metagenics Inc. and AXA had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review or approval of the manuscript. MHO received a Research Grant from Merck & Co., Inc., West Point, PA. None of the other authors report conflicts of interest. Acknowledgements Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (grant no. DFG Lo 1569/2-1 to the PROG-IMT project); the National Heart, Lung and Blood Institute, Bethesda, MD, USA in collaboration with the Atherosclerosis Risk In Communities (ARIC) investigators (the ARIC Study, for which a restricted access dataset was used) and contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC85084, N01HC35129, N01HC85085, N01HC45133, and grant no. HL080295, with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS) for the data of Cardiovascular Health Study (CHS); the Pustertaler Verein zur Praevention von Herz- und Hirngefaesserkrankungen, Gesundheitsbezirk Bruneck, and the Assessorat fuer Gesundheit (Province of Bolzano, Italy) (to the Bruneck study); the Stiftung Deutsche Schlaganfall-Hilfe (to the Carotid Atherosclerosis Progression Study); the National Institute on Aging (NIA; grant no. AG023629); the National Institute of Neurological Disorders and Stroke (grant no. R37 NS 029993 to the Northern Manhattan Study/The Oral Infections and Vascular Disease Epidemiology Study); the National Institute of Dental and Craniofacial Research, Bethesda, MD, USA (grant no. R01 DE 13094 to the Oral Infections, Carotid Atherosclerosis, and Stroke study; AOK Bayern (to the Interventionsprojekt zerebrovaskula ¨ re Erkrankungen und Demenz im Landkreis Ebersberg study); the Netherlands Foundation for Scientific Research (ZonMw, Vici 918-76-619 to the Rotterdam Study); the Federal Ministry of Education and Research (grant nos. BMBF 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania (to The Study of Health in Pomerania, part of the Community Medicine Research net of the University of Greifswald, Germany). The work was performed at: the Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany; the Department of Neurology, Benedictus Krankenhaus Tutzing and Feldafing, Tutzing, Germany; and the Technische Universita¨t Mu¨ nchen, Munich, Germany. The ARIC data was provided through the NHLBI data repository (BioLINCC). This article does not necessarily convey the opinions or views of the ARIC Study or the National Heart, Lung and Blood Institute. A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. Etude sur le vieillissement arte´ riel was organized with an agreement between INSERM and Merck, Sharp, and Dohme-Chibret. A complete list of collaborators of the PROG-IMT project is shown in the online Supplementary Material. Funding Information: This work was supported by the Deutsche Forschungsgemeinschaft (grant no. DFG Lo 1569/2-1 to the PROG-IMT project); the National Heart, Lung and Blood Institute, Bethesda, MD, USA in collaboration with the Atherosclerosis Risk In Communities (ARIC) investigators (the ARIC Study, for which a restricted access dataset was used) and contracts HHSN268201200036C, HHSN268200800007C, N01 HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, N01HC85084, N01HC35129, N01HC85085, N01HC45133, and grant no. HL080295, with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS) for the data of Cardiovascular Health Study (CHS); the Pustertaler Verein zur Praevention von Herz- und Hirngefaesserkrankungen, Gesundheitsbezirk Bruneck, and the Assessorat fuer Gesundheit (Province of Bolzano, Italy) (to the Bruneck study); the Stiftung Deutsche Schlaganfall-Hilfe (to the Carotid Atherosclerosis Progression Study); the National Institute on Aging (NIA; grant no. AG023629); the National Institute of Neurological Disorders and Stroke (grant no. R37 NS 029993 to the Northern Manhattan Study/The Oral Infections and Vascular Disease Epidemiology Study); the National Institute of Dental and Craniofacial Research, Bethesda, MD, USA (grant no. R01 DE 13094 to the Oral Infections, Carotid Atherosclerosis, and Stroke study; AOK Bayern (to the Interventionsprojekt zerebrovaskuläre Erkrankungen und Demenz im Landkreis Ebersberg study); the Netherlands Foundation for Scientific Research (ZonMw, Vici 918-76-619 to the Rotterdam Study); the Federal Ministry of Education and Research (grant nos. BMBF 01ZZ9603, 01ZZ0103 and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania (to The Study of Health in Pomerania, part of the Community Medicine Research net of the University of Greifswald, Germany). Publisher Copyright: © 2014 European Society of Cardiology.

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

UR - http://www.scopus.com/inward/record.url?scp=84953253796&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84953253796&partnerID=8YFLogxK

U2 - 10.1177/2047487314560664

DO - 10.1177/2047487314560664

M3 - Review article

C2 - 25416041

AN - SCOPUS:84953253796

VL - 23

SP - 194

EP - 205

JO - European Journal of Preventive Cardiology

JF - European Journal of Preventive Cardiology

SN - 2047-4873

IS - 2

ER -

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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