@article {1382, title = {Carotid intima-media thickness progression to predict cardiovascular events in the general population (the PROG-IMT collaborative project): a meta-analysis of individual participant data.}, journal = {Lancet}, volume = {379}, year = {2012}, month = {2012 Jun 02}, pages = {2053-62}, abstract = {

BACKGROUND: Carotid intima-media thickness (cIMT) is related to the risk of cardiovascular events in the general population. An association between changes in cIMT and cardiovascular risk is frequently assumed but has rarely been reported. Our aim was to test this association.

METHODS: We identified general population studies that assessed cIMT at least twice and followed up participants for myocardial infarction, stroke, or death. The study teams collaborated in an individual participant data meta-analysis. Excluding individuals with previous myocardial infarction or stroke, we assessed the association between cIMT progression and the risk of cardiovascular events (myocardial infarction, stroke, vascular death, or a combination of these) for each study with Cox regression. The log hazard ratios (HRs) per SD difference were pooled by random effects meta-analysis.

FINDINGS: Of 21 eligible studies, 16 with 36,984 participants were included. During a mean follow-up of 7{\textperiodcentered}0 years, 1519 myocardial infarctions, 1339 strokes, and 2028 combined endpoints (myocardial infarction, stroke, vascular death) occurred. Yearly cIMT progression was derived from two ultrasound visits 2-7 years (median 4 years) apart. For mean common carotid artery intima-media thickness progression, the overall HR of the combined endpoint was 0{\textperiodcentered}97 (95\% CI 0{\textperiodcentered}94-1{\textperiodcentered}00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0{\textperiodcentered}98 (0{\textperiodcentered}95-1{\textperiodcentered}01) when also adjusted for vascular risk factors. Although we detected no associations with cIMT progression in sensitivity analyses, the mean cIMT of the two ultrasound scans was positively and robustly associated with cardiovascular risk (HR for the combined endpoint 1{\textperiodcentered}16, 95\% CI 1{\textperiodcentered}10-1{\textperiodcentered}22, adjusted for age, sex, mean common carotid artery intima-media thickness progression, and vascular risk factors). In three studies including 3439 participants who had four ultrasound scans, cIMT progression did not correlate between occassions (reproducibility correlations between r=-0{\textperiodcentered}06 and r=-0{\textperiodcentered}02).

INTERPRETATION: The association between cIMT progression assessed from two ultrasound scans and cardiovascular risk in the general population remains unproven. No conclusion can be derived for the use of cIMT progression as a surrogate in clinical trials.

FUNDING: Deutsche Forschungsgemeinschaft.

}, keywords = {Cardiovascular Diseases, Carotid Intima-Media Thickness, Disease Progression, Follow-Up Studies, Humans, Myocardial Infarction, Prognosis, Risk Assessment, Stroke}, issn = {1474-547X}, doi = {10.1016/S0140-6736(12)60441-3}, author = {Lorenz, Matthias W and Polak, Joseph F and Kavousi, Maryam and Mathiesen, Ellisiv B and V{\"o}lzke, Henry and Tuomainen, Tomi-Pekka and Sander, Dirk and Plichart, Matthieu and Catapano, Alberico L and Robertson, Christine M and Kiechl, Stefan and Rundek, Tatjana and Desvarieux, Mo{\"\i}se and Lind, Lars and Schmid, Caroline and DasMahapatra, Pronabesh and Gao, Lu and Ziegelbauer, Kathrin and Bots, Michiel L and Thompson, Simon G} } @article {6612, 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.}, journal = {Eur J Prev Cardiol}, volume = {23}, year = {2016}, month = {2016 Jan}, pages = {194-205}, 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). {\textquoteright}Inflammatory load{\textquoteright}, 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 {\textquoteright}inflammatory load{\textquoteright} 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 {\textquoteright}inflammatory load{\textquoteright} suggest important combined effects of the three inflammatory markers on early atherosclerosis.

}, issn = {2047-4881}, doi = {10.1177/2047487314560664}, author = {Willeit, Peter and Thompson, Simon G and Agewall, Stefan and Bergstr{\"o}m, G{\"o}ran and Bickel, Horst and Catapano, Alberico L and Chien, Kuo-Liong and de Groot, Eric and Empana, Jean-Philippe and Etgen, Thorleif and Franco, Oscar H and Iglseder, Bernhard and Johnsen, Stein H and Kavousi, Maryam and Lind, Lars and Liu, Jing and Mathiesen, Ellisiv B and Norata, Giuseppe D and Olsen, Michael H and Papagianni, Aikaterini and Poppert, Holger and Price, Jackie F and Sacco, Ralph L and Yanez, David N and Zhao, Dong and Schminke, Ulf and B{\"u}lb{\"u}l, Alpaslan and Polak, Joseph F and Sitzer, Matthias and Hofman, Albert and Grigore, Liliana and D{\"o}rr, Marcus and Su, Ta-Chen and Ducimetiere, Pierre and Xie, Wuxiang and Ronkainen, Kimmo and Kiechl, Stefan and Rundek, Tatjana and Robertson, Christine and Fagerberg, Bj{\"o}rn and Bokemark, Lena and Steinmetz, Helmuth and Ikram, M Arfan and V{\"o}lzke, Henry and Lin, Hung-Ju and Plichart, Matthieu and Tuomainen, Tomi-Pekka and Desvarieux, Mo{\"\i}se and McLachlan, Stela and Schmidt, Caroline and Kauhanen, Jussi and Willeit, Johann and Lorenz, Matthias W and Sander, Dirk} } @article {7846, title = {Predictive value for cardiovascular events of common carotid intima media thickness and its rate of change in individuals at high cardiovascular risk - Results from the PROG-IMT collaboration.}, journal = {PLoS One}, volume = {13}, year = {2018}, month = {2018}, pages = {e0191172}, abstract = {

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.

METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95\% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C.

CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

}, keywords = {Aged, Cardiovascular Diseases, Carotid Intima-Media Thickness, Female, Humans, Intersectoral Collaboration, Male, Middle Aged, Prognosis, Risk Factors}, issn = {1932-6203}, doi = {10.1371/journal.pone.0191172}, author = {Lorenz, Matthias W and Gao, Lu and Ziegelbauer, Kathrin and Norata, Giuseppe Danilo and Empana, Jean Philippe and Schmidtmann, Irene and Lin, Hung-Ju and McLachlan, Stela and Bokemark, Lena and Ronkainen, Kimmo and Amato, Mauro and Schminke, Ulf and Srinivasan, Sathanur R and Lind, Lars and Okazaki, Shuhei and Stehouwer, Coen D A and Willeit, Peter and Polak, Joseph F and Steinmetz, Helmuth and Sander, Dirk and Poppert, Holger and Desvarieux, Mo{\"\i}se and Ikram, M Arfan and Johnsen, Stein Harald and Staub, Daniel and Sirtori, Cesare R and Iglseder, Bernhard and Beloqui, Oscar and Engstr{\"o}m, Gunnar and Friera, Alfonso and Rozza, Francesco and Xie, Wuxiang and Parraga, Grace and Grigore, Liliana and Plichart, Matthieu and Blankenberg, Stefan and Su, Ta-Chen and Schmidt, Caroline and Tuomainen, Tomi-Pekka and Veglia, Fabrizio and V{\"o}lzke, Henry and Nijpels, Giel and Willeit, Johann and Sacco, Ralph L and Franco, Oscar H and Uthoff, Heiko and Hedblad, Bo and Suarez, Carmen and Izzo, Raffaele and Zhao, Dong and Wannarong, Thapat and Catapano, Alberico and Ducimetiere, Pierre and Espinola-Klein, Christine and Chien, Kuo-Liong and Price, Jackie F and Bergstr{\"o}m, G{\"o}ran and Kauhanen, Jussi and Tremoli, Elena and D{\"o}rr, Marcus and Berenson, Gerald and Kitagawa, Kazuo and Dekker, Jacqueline M and Kiechl, Stefan and Sitzer, Matthias and Bickel, Horst and Rundek, Tatjana and Hofman, Albert and Mathiesen, Ellisiv B and Castelnuovo, Samuela and Landecho, Manuel F and Rosvall, Maria and Gabriel, Rafael and de Luca, Nicola and Liu, Jing and Baldassarre, Damiano and Kavousi, Maryam and de Groot, Eric and Bots, Michiel L and Yanez, David N and Thompson, Simon G} }