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

Pubmed ID: 25416041

Pubmed Central ID: PMC4544641

Journal: European journal of preventive cardiology

Publication Date: Jan. 1, 2016

MeSH Terms: Humans, Disease Progression, Atherosclerosis, Carotid Intima-Media Thickness, Fibrinogen, Leukocyte Count, C-Reactive Protein, Inflammation, Biomarkers

Grants: HL080295, HHSN268200800007C, HHSN268201200036C, N01 HC035129, N01 HC045133, N01 HC085084, N01 HC085085, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, R01 AG023629, R01 DE013094, R01 HL080295, R37 NS 029993, R37 NS029993, U01 HL080295, R56 AG023629, RG/08/014/24067, AG023629, N01 HC55222, N01HC35129, N01HC45133, N01HC85084, N01HC85085, MR/L003120/1

Authors: Franco OH, Lorenz MW, Polak JF, Kavousi M, Mathiesen EB, Völzke H, Tuomainen TP, Sander D, Plichart M, Catapano AL, Kiechl S, Rundek T, Desvarieux M, Lind L, Thompson SG, Sacco RL, Hofman A, Johnsen SH, Agewall S, Sitzer M, Steinmetz H, Dörr M, Schminke U, Poppert H, Bickel H, Kauhanen J, Ronkainen K, Empana JP, Norata GD, Grigore L, Willeit J, Bokemark L, Fagerberg B, Liu J, Zhao D, Chien KL, Ikram MA, Price JF, Robertson C, Willeit P, Bergström G, de Groot E, Etgen T, Iglseder B, Olsen MH, Papagianni A, Yanez DN, Bülbül A, Su TC, Ducimetière P, Xie W, Lin HJ, McLachlan S, Schmidt C

Cite As: 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, PROG-IMT study group. Inflammatory markers and extent and progression of early atherosclerosis: Meta-analysis of individual-participant-data from 20 prospective studies of the PROG-IMT collaboration. Eur J Prev Cardiol 2016 Jan;23(2):194-205. Epub 2014 Nov 21.

Studies:

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.