Review
Carotid intima-media thickness for cardiovascular risk assessment: Systematic review and meta-analysis

https://doi.org/10.1016/j.atherosclerosis.2013.01.025Get rights and content

Abstract

Objective

B-mode ultrasound measurement of the carotid intima-media thickness (CIMT) is a widely used marker for atherosclerosis and is associated with future cardiovascular events. This article provides a review and meta-analysis of the published evidence on the association of CIMT with future cardiovascular events and its additional value to traditional cardiovascular risk prediction models.

Methods

A systematic review and meta-analysis of the evidence on the association of CIMT with future cardiovascular events and the additional value of CIMT to traditional cardiovascular risk prediction models was conducted. The association of CIMT with future cardiovascular events and the additional value of CIMT were calculated using random effects analysis.

Results

The literature search yielded 1196 articles of which 15 articles provided sufficient data for the meta-analysis. A 1 SD increase in CIMT was predictive for myocardial infarction (HR 1.26, 95% CI 1.20–1.31) and for stroke (HR 1.31, 95% CI 1.26–1.36). A 0.1 mm increase in CIMT was predictive for myocardial infarction (HR 1.15, 95% CI 1.12–1.18) and for stroke (HR 1.17, 95% CI 1.15–1.21). The overall performance of risk prediction models did not significantly increase after addition of CIMT data. The areas under the curve increased from 0.726 to 0.729 (p = 0.8).

Conclusions

CIMT as measured by B-mode ultrasound is associated with future cardiovascular events. However, the addition of CIMT to traditional cardiovascular risk prediction models does not lead to a statistical significantly increase in performance of those models.

Introduction

Data from the European Society of Cardiology demonstrates that cardiovascular disease accounts for 38–42% of the mortality in Europe [1]. Atherosclerosis is the underlying cause of the majority of clinical cardiovascular events. This generalized inflammatory disease is characterized by an accumulation of lipids, inflammatory cells, and development of scar tissue covered by a fibrous cap build within the walls of large and medium-sized arteries [2].

Individuals with subclinical atherosclerosis should preferably be identified at an early stage, so that primary preventive measures can be initiated [3]. The development of atherosclerosis usually takes decades, and one of the first detectable stages of atherosclerosis is thickening of the arterial wall. Carotid ultrasound is a widely used imaging modality for the detection of subclinical atherosclerosis [4]. B-mode ultrasound measurement of carotid intima-media thickness (CIMT) is frequently used for non-invasive evaluation of subjects at risk of atherosclerosis. Still, the exact risk of cardiovascular events associated with an increased CIMT in general populations is not entirely clear. More importantly, the additional value of CIMT measurement on top of currently used risk prediction models is not entirely clear as well.

Therefore the goals of this review and meta-analysis were 1. to provide a short historical perspective on CIMT measurement using ultrasound, 2. to discuss current CIMT acquisition and measurement methods, 3. to assess the association of CIMT with future cardiovascular events using up-to-date data from cohort studies, 4. to determine the additional value of CIMT measurement in cardiovascular-risk prediction and 5. to provide recommendations for future studies on the role of CIMT for cardiovascular risk assessment.

Section snippets

Historical perspective on carotid intima-media thickness measurement

In 1986, Pignoli et al. reported the first in vitro results of a study investigating the arterial wall thickness with real-time B-mode ultrasound [5]. In that initial study, the distance between two parallel echogenic lines correlated well with the intima-media thickness (IMT) measured on pathologic examination. The authors concluded that B-mode ultrasound represented a useful tool for the measurement of IMT of human arteries in vivo. Subsequently, Persson et al. demonstrated in an in vivo

How to measure CIMT?

In 2008 the American Society of Echocardiography has published a consensus statement, which provides a protocol for CIMT measurement [14]. CIMT measurement should be obtained in both the left and right carotid artery. Images of the far wall should be made of the distal 1 cm of the common carotid artery in 3 angles. The CIMT is calculated in R-wave gated still frames. Mean CIMT is calculated as the mean of the left and the right measurements. Semi-automated CIMT measurement tools have proven to

Search strategy and data extraction

A systematic search of the literature published in the MEDLINE database was performed using PubMed on the 10th of January 2012 to find: 1. articles on the association of CIMT with future cardiovascular events and 2. articles on the additional value of CIMT to existing cardiovascular risk assessment tools. Search terms were ‘Carotid intima-media thickness’, ‘Prognosis’, ‘Outcome’, ‘Prediction’, and ‘Association’. The MOOSE guidelines for meta-analysis of observational studies were followed [19].

Results

From the 30 articles found in the literature search, 17 articles were excluded from the meta-analysis of the association of CIMT with future cardiovascular events because they did not report sufficient data [7], [20], [21], [24], [25], [26], [27], [28], [33], [34], [35], [38], [40], [41], [42], [45], [47]. An overview of the remaining articles is provided in Table 1. Eventually 7 articles reported an association of CIMT with future myocardial infarction [22], [29], [31], [32], [37], [39], [44].

Discussion

This systematic review and meta-analysis demonstrates a positive association between increasing CIMT and cardiovascular risk. With the overall estimates in this meta-analysis it has become clear that 1 SD increase of CCA–CIMT increases the risk for myocardial infarction by 26%. A 1 SD increase in CIMT increases the risk for stroke by 31%. The current meta-analysis differs from previously published reports because it provides the most recent follow-up results of multiple cohort studies [50].

Conclusion

Carotid intima-media thickness as measured by B-mode ultrasound is a predictor of future myocardial infarction and stroke. The addition of CIMT to cardiovascular risk prediction models based on traditional cardiovascular risk factors leads to a small increase in the performance of those models. Nevertheless this increment is not statistically significant. Thus, the addition of CIMT measurements to traditional cardiovascular risk prediction models has no clinical value so far.

Acknowledgment

The authors gratefully thank Professor Ellisiv B. Mathiesen, doctor David Couper and doctor Suzette E. Elias-Smale for providing additional data or helping to find additional data.

This research was supported by the Center for Translational Molecular Medicine and the Netherlands Heart Foundation (PARISk).

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