Clinical Research
Cardiovascular Risk
Measurements of Carotid Intima-Media Thickness and of Interadventitia Common Carotid Diameter Improve Prediction of Cardiovascular Events: Results of the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) Study

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Objectives

The goal of this study was to compare the performance of several measures of carotid intima-media thickness (C-IMT) as predictors of cardiovascular events (CVEs), and to investigate whether they add to the predictive accuracy of Framingham risk factors (FRFs).

Background

Various markers of subclinical atherosclerosis have been identified as predictors of CVEs, but the most powerful variable is still under debate.

Methods

A cohort study was carried out in 5 European countries. A total of 3,703 subjects (median age 64.4 years; 48% men) were followed-up for a median of 36.2 months, and 215 suffered a first CVE (incidence: 19.9/1,000 person-years).

Results

All measures of C-IMT and the interadventitia common carotid artery diameter (ICCAD) were associated with the risk of CVEs, after adjustment for FRFs and therapies (all p < 0.005). The average of 8 maximal IMT measurements (IMTmean-max), alone or combined with ICCAD, classified events and non-events better than the common carotid mean IMT (net reclassification improvement [NRI]: +11.6% and +19.9%, respectively; both p < 0.01). Compared with classification based on FRFs alone, the NRI resulting from the combination of FRFs+ICCAD+IMTmean-max was +12.1% (p < 0.01). The presence of at least 1 plaque (maximum IMT >1.5 mm) performed significantly worse than composite IMTs that incorporated plaques (p < 0.001). Adjusted Kaplan-Meier curves showed that individuals with a FRS = 22.6% (cohort average), and both IMTmean-max and ICCAD above the median, had a 6.5% risk to develop a CVE over 3 years versus a 3.4% risk for those with the same FRS, and both IMTmean-max and ICCAD below the median.

Conclusions

A risk stratification strategy based on C-IMT and ICCAD as an adjunct to FRFs is a rational approach to prevention of cardiovascular disease.

Key Words

cardiovascular disease
carotid artery intima-media thickness
carotid diameter
reclassification analyses
risk prediction

Abbreviations and Acronyms

CI
confidence interval
C-IMT
carotid artery intima-media thickness
CVE
cardiovascular event
FRF
Framingham risk factor
FRS
Framingham risk score
HR
hazard ratio
ICCAD
interadventitia common carotid artery diameter
IDI
integrated discrimination improvement
IMT
intima-media thickness
NRI
net reclassification improvement
ROC
receiver-operating characteristic
VRF
vascular risk factor

Cited by (0)

This work was supported by the European Commission (number: QLG1-CT-2002-00896), the Swedish Heart-Lung Foundation, the Swedish Research Council (projects 8691 and 0593), the Foundation for Strategic Research, the Stockholm County Council (project 562183), the Academy of Finland (grant #110413), and the British Heart Foundation (RG2008/008). None of the aforementioned funding organizations or sponsors has had a specific role in design or conduct of the study; collection, management, analysis, or interpretation of the data; or preparation, review, or approval of the manuscript. Dr. Giral has received payment from AstraZeneca, Pfizer, and Merck Sharp and Dohme for the development of educational presentations. Dr. Tremoli is a consultant to F. Hoffmann-LaRoche, Ltd. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.