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 | |
State | Published - Jan 1 2016 |
Keywords
- Inflammation
- atherosclerosis
- meta-analysis
ASJC Scopus subject areas
- Epidemiology
- Cardiology and Cardiovascular Medicine
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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
}
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 -