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Eur J Prev Cardiol. 2016 Jan;23(2):194-205. doi: 10.1177/2047487314560664. Epub 2014 Nov 21.

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

Author information

1
The Department of Public Health and Primary Care, University of Cambridge, UK Department of Neurology, Medical University Innsbruck, Austria.
2
The Department of Public Health and Primary Care, University of Cambridge, UK.
3
Institute of Clinical Sciences, University of Oslo, and the Department of Cardiology, Oslo University Hospital Ullevål, Norway.
4
Wallenberg Laboratory for Cardiovascular Research, University of Gothenburg, Sweden.
5
Department of Psychiatry and Psychotherapy, University Hospital of the Technische Universität München, Germany.
6
Department of Pharmacological Sciences, University of Milan, and IRCSS Multimedica Sesto S Giovanni, Milan, Italy.
7
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
8
Academic Medical Centre, Cardiology and Thoracic Surgery, and Imagelabonline and Cardiovascular, Amsterdam, The Netherlands.
9
INSERM, U970, Université Paris Descartes, France.
10
Department of Neurology, Kliniken Südostbayern, Klinikum Traunstein, Germany.
11
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands.
12
Department of Geriatric Medicine, Paracelsus Medical University, and the Gemeinnützige Salzburger Landeskliniken Betriebsgesellschaft GmbH, Christian-Doppler-Klinik, Salzburg, Austria.
13
Department of Neurology and Neurophysiology, University Hospital of Northern Norway, and the Department of Clinical Medicine, University of Tromsø, Tromsø, Norway.
14
Department of Medicine, Uppsala University, Sweden.
15
Department of Epidemiology, Beijing Institute of Heart, Lung and Blood Vessel Diseases, PR China.
16
Department of Pharmacological Sciences, University of Milan, and the SISA Centre for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy.
17
Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases, Odense University Hospital, Denmark.
18
Department of Nephrology, Aristotle University of Thessaloniki, Hippokration General Hospital, Greece.
19
Department of Neurology, University Hospital of the Technische Universität München, Germany.
20
Centre for Population Health Sciences, University of Edinburgh, UK.
21
Department of Neurology, Miller School of Medicine, University of Miami, FL, USA.
22
Department of Biostatistics, University of Washington, Seattle, WA, USA.
23
Department of Neurology, Greifswald University Clinic, Germany.
24
Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany.
25
Tufts University School of Medicine, Tufts Medical Center, Boston, MA, USA.
26
Department of Neurology, University Hospital Frankfurt, Frankfurt am Main, Germany Department of Neurology, Klinikum Herford, Germany.
27
Department of Epidemiology, Erasmus Medical Centre, Rotterdam, the Netherlands Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
28
Department B for Internal Medicine, University Medicine Greifswald, and the German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Germany.
29
Department of Internal Medicine, National Taiwan University, Taipei, Taiwan.
30
University Paris Sud-XI, Kremlin-Bicêtre, France.
31
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
32
Department of Neurology, Medical University Innsbruck, Austria.
33
Institute for Community Medicine, SHIP/Clinical-Epidemiological Research, Greifswald, Germany.
34
Department of Internal Medicine, National Taiwan University, Taipei, Taiwan Health Management Centre, National Taiwan University Hospital, Taipei, Taiwan.
35
INSERM, U970, Université Paris Descartes, France Gerontology Department, Broca Hospital, Paris, France.
36
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA, and the École des Hautes Études en Santé Publique, and INSERM U738, Paris, France.
37
Department of Neurology, Benedictus Krankenhaus Tutzing and Feldafing, Tutzing, Germany and Technische Universität München, Germany D.Sander@mac.com.

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

PMID:
25416041
PMCID:
PMC4544641
DOI:
10.1177/2047487314560664
[Indexed for MEDLINE]
Free PMC Article

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