@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: 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.",
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",
}