IMT or TPA?

IMT only valuable for people below age 45 

Carotid IMT measurements are of uncontested value to measure coronary risk. However, it remains still unclear, where and how to measure IMT exactly. Based on data from the Framingham cohort, measurements of IMT within the internal and common carotid artery would be best 1, others found that measurements of the common carotid IMT only would be sufficient 2. Further confusion may arise from a study that looked at different angels in the Meteor study:  the intraclass correlation based on duplicate baseline examinations ranged from 0.81 to 0.95 mm. Carotid IMT progression rates in the placebo group ranged from 0.0046 to 0.0177 mm/year, with SE ranging from 0.00134 to 0.00337. Treatment effects ranged from 0.0141 to 0.0388 mm/year. The protocols with highest reproducibility, highest carotid IMT progression/precision ratio and highest treatment effect/precision ratio were those measuring both near and far wall for at least two angles 3. From a clinical point of view, the assessment of coronary risk based on sub millimeter amounts of IMT and changes of IMT over time in conjunction with a method that still looks for the best way to perform the IMT measurements remain problematic at the individual level, proven by the metaanalysis in the PROG-IMT Study. As found in the Meteor study, it appears more feasible to measure plaque 4. Further, IMT measurements are influenced by many non imaging factors. As reported by Schmidt-Trucksäss, IMT changes from diastole to peak systole by -19% or -0.06 mm in a sample of 541 patients with 486’000 single images 5. Further, IMT is influenced by blood pressure, room temperature, noise and brightness of light in the examination room, non-empty bladder and meal taken less than 2 hours before the examination 5. Because TPA is far less sensitive to all these factors at the individual level, TPA measurements are anticipated to be much more reliable and reproducible.

While IMT predicted that Niacin is a better medication than Ezetimibe in the ARBITER trial, outcome studies have shown exactly the opposite: the Niacin study HPS2-THRIVE failed to show beneficial effects, the IMPROVE-IT study with Ezetimibe showed beneficial effects. In contrast, using TPA in an observational study, it was found that TPA regressed with Ezetimibe. Such observations about IMT render it’s use even more problematic.

A longterm TPA follow-up study from the Tromso cohort revealed that in subjects without plaque annual risk is 7/1000, which is about the risk to experience a myocardial infarction using nuclear scans (refer to TPALongtermTromso2014.pdf). IMT further reduced risk to 4/1000 per year, if IMT was found to be below 0.71 mm. Therefore, in subjects without plaque, IMT offers a small further risk stratificitaion from low risk to very low risk.

A new prognostic study puts IMT into perspective. It is useful in younger patients (< 45 years of age).

Summary

Because IMT measures intimal thickening, plaques or both, there has emerged a lot of confusion about the value of measuring IMT. TPA and other measures of total carotid plaque burden are  clearly defined methods that measure atherosclerosis only, thus avoiding the confounding due to thickening of the intima. IMT measurements are technically very demanding and influenced by many factors. Therefore, IMT is not suited to assess cardiovascular risk in subjects with carotid plaques, however, in younger patients below age 45 thickened IMT has an indepedent prognostic value. 

Further Citations:

1. Polak JF, Pencina MJ, Pencina KM, et al. Carotid-wall intima-media thickness and cardiovascular events. New Engl J Med. 2011;365:213-21.

2. Nambi V, Chambless L, He M, et al. Common carotid artery intima-media thickness is as good as carotid intima-media thickness of all carotid artery segments in improving prediction of coronary heart disease risk in the Atherosclerosis Risk in Communities (ARIC) study. European Heart Journal. 2011:ehr192-.

3. Dogan S, Plantinga Y, Crouse JR, et al. Algorithms to measure carotid intima-media thickness in trials: a comparison of reproducibility, rate of progression and treatment effect. Journal of Hypertension. 2011.

4. Peters SAE, Dogan S, Meijer R, et al. The Use of Plaque Score Measurements to Assess Changes in Atherosclerotic Plaque Burden Induced by Lipid-Lowering Therapy Over Time: The METEOR Study. Journal of Atherosclerosis and Thrombosis. 2011;18:784-795.

5. Schmidt A, Haller C. Intima-Media Thickness: Integration into Clinical Practice. Atherosclerosis. 2007;195(Abstract):e203-e209. Available at: http://spo.escardio.org/eslides/view.aspx?eevtid=40&fp=1937.