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.
Inflammatory markers and extent and progression of early atherosclerosis : meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration / P. Willeit, S.G. Thompson, S. Agewall, G. Bergström, H. Bickel, A.L. Catapano, K. Chien, E. de Groot, J. Empana, T. Etgen, O.H. Franco, B. Iglseder, S.H. Johnsen, M. Kavousi, L. Lind, J. Liu, E.B. Mathiesen, G.D. Norata, M.H. Olsen, A. Papagianni, H. Poppert, J.F. Price, R.L. Sacco, D.N. Yanez, D. Zhao, U. Schminke, A. Bülbül, J.F. Polak, M. Sitzer, A. Hofman, L. Grigore, M. Dörr, T. Su, P. Ducimetière, W. Xie, K. Ronkainen, S. Kiechl, T. Rundek, C. Robertson, B. Fagerberg, L. Bokemark, H. Steinmetz, M.A. Ikram, H. Völzke, H. Lin, M. Plichart, T. Tuomainen, M. Desvarieux, S. Mclachlan, C. Schmidt, J. Kauhanen, J. Willeit, M.W. Lorenz, D. Sander. - In: EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY. - ISSN 2047-4873. - 23:2(2016 Nov 21), pp. 194-205. [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
A.L. Catapano;G.D. Norata;
2016
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.
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