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Meta-Analysis
. 2012 Jun 2;379(9831):2053-62.
doi: 10.1016/S0140-6736(12)60441-3. Epub 2012 Apr 27.

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

Matthias W Lorenz  1 , Joseph F Polak, Maryam Kavousi, Ellisiv B Mathiesen, Henry Völzke, Tomi-Pekka Tuomainen, Dirk Sander, Matthieu Plichart, Alberico L Catapano, Christine M Robertson, Stefan Kiechl, Tatjana Rundek, Moïse Desvarieux, Lars Lind, Caroline Schmid, Pronabesh DasMahapatra, Lu Gao, Kathrin Ziegelbauer, Michiel L Bots, Simon G Thompson; PROG-IMT Study Group
Collaborators, Affiliations
Meta-Analysis

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

Matthias W Lorenz et al. Lancet. .

Erratum in

  • Lancet. 2012 Aug 4;380(9840):474

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 7·0 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 0·97 (95% CI 0·94-1·00) when adjusted for age, sex, and mean common carotid artery intima-media thickness, and 0·98 (0·95-1·01) 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 1·16, 95% CI 1·10-1·22, 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=-0·06 and r=-0·02).

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.

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Conflict of interest statement

Conflicts of interest

Michiel Bots has received grants from AstraZeneca, Dutch Heart Foundation, Organon, Pfizer, Servier, the Netherlands Organisation for Health Research and Development, and TNO-Zeist, and consultancy fees from AstraZeneca, Boeringher, Organon, Pfizer, Servier, Schering-Plough, and Unilever. He runs the Vascular Imaging Center in Utrecht, a core laboratory for cIMT measurements in national and international observational and intervention studies. All other authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1. Hazard ratios (HRs) per one SD increase in mean common carotid intima-media thickness progression for four endpoints
HRs are for risk of myocardial infarction (A), stroke (B), the combined endpoint (C), and death (D). HRs adjusted for vascular risk factors (model 4, see text). Weights are from random effects analysis. AIR=Atherosclerosis and Insulin Resistance study. ARIC=Atherosclerosis Risk in Communities Study. CAPS=Carotid Atherosclerosis Progression Study. CHS=Cardiovascular Health Study. EAS=Edinburgh Artery Study. INVADE=Interventionsprojekt zerebrovaskuläre Erkrankungen und Demenz im Landkreis Ebersberg. KIHD=Kuopio Ischaemic Heart Disease Study. PLIC=Progression of Lesions in the Intima of the Carotid. SHIP=Study of Health in Pomerania. Rotterdam=Rotterdam Study. Tromsø=Tromsø Study.
Figure 2
Figure 2. Hazard ratios (HRs) per one SD increase in mean common carotid intima-media thickness for four endpoints
HRs are for risk of myocardial infarction (A), stroke (B), the combined endpoint (C), and death (D). HRs adjusted for vascular risk factors (model 4, see text). Weights are from random effects analysis. AIR=Atherosclerosis and Insulin Resistance study. ARIC=Atherosclerosis Risk in Communities Study. CAPS=Carotid Atherosclerosis Progression Study. CHS=Cardiovascular Health Study. EAS=Edinburgh Artery Study. INVADE=Interventionsprojekt zerebrovaskuläre Erkrankungen und Demenz im Landkreis Ebersberg. KIHD=Kuopio Ischaemic Heart Disease Study. PLIC=Progression of Lesions in the Intima of the Carotid. SHIP=Study of Health in Pomerania. Rotterdam=Rotterdam Study. Tromsø=Tromsø Study.
Figure 3
Figure 3. Overall hazard ratio (HR) of the combined endpoint by quintile
Data shown for mean common carotid artery intima-media thickness progression (A) and mean common carotid artery intima-media thickness (B), relative to the lowest quintile. Bars are 95% CIs. HRs are adjusted for vascular risk factors (model 4, see text). Included studies: Atherosclerosis and Insulin Resistance study, Atherosclerosis Risk in Communities Study, Carotid Atherosclerosis Progression Study, Cardiovascular Health Study cohorts 1 and 2, Edinburgh Artery Study, Interventionsprojekt zerebrovaskuläre Erkrankungen und Demenz im Landkreis Ebersberg, Kuopio Ischaemic Heart Disease Study, Nothern Manhattan Study/The Oral Infections and Vascular Disease Epidemiology Study, Progression of Lesions in the Intima of the Carotid, Rotterdam Study, and Tromsø Study.
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