TPA vs IMT
Measurement of carotid IMT is widely regarded as a way to quantify preclinical atherosclerosis; however there are important problems with this assumption.
Carotid IMT measurements are of 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). Further confusion may arise from a study that looked at different angles 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 (2). 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. As found in the Meteor study, it appears more feasible to measure plaque (3). 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 (4). 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 (4). 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.
There are two main ways to measure IMT: in the far wall of the distal common carotid at a site deliberately chosen to avoid plaque (the Mannheim consensus) (5), or at various sites in the carotid including the bulb, and including plaque thickness in the measurement. Failure to distinguish these two approaches, in studies reporting the use of "IMT", has caused a great deal of confusion1. In the Tromsø study, the only large study in which both IMT and plaque were measured, IMT in the distal common did not predict myocardial infarction by the time of the 6-year followup visit (6), whereas IMT in the bulb (including plaque thickness in cases with plaque did predict coronary risk, and carotid total plaque area was still more strongly predictive. In the report of the followup for 10 years (7), IMT did not predict stroke, but TPA strongly predicted stroke risk.
The figure on the right shows an example of two study participants with similar IMT; however the one with the slightly lower IMT had twice the plaque area (8). This illustrates the problem of measuring IMT to assess burden of atherosclerosis.
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. 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.
3. 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.
4. 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
5. Touboul PJ, Hennerici MG, Meairs S et al. Mannheim intima-media thickness consensus. Cerebrovasc Dis 2004;18(4):346-349.
6. Johnsen SH, Mathiesen EB, Joakimsen O et al. Carotid atherosclerosis is a stronger predictor of myocardial infarction in women than in men: a 6-year follow-up study of 6226 persons: the Tromso Study. Stroke 2007;38(11):2873-2880.
7. Mathiesen EB, Johnsen SH, Wilsgaard T, Bonaa KH, Lochen ML, Njolstad I. Carotid Plaque Area and Intima-Media Thickness in Prediction of First-Ever Ischemic Stroke: A 10-Year Follow-Up of 6584 Men and Women: The Tromso Study. Stroke 2011;42(4):972-978.
8. Al Shali,K, House, AA, Hanley, AJ, Khan, HM, Harris, SB, Mamakeesick, M, Zinman, B, Fenster, A, Spence, JD, and Hegele, RA. Differences between carotid wall morphological phenotypes measured by ultrasound in one, two and three dimensions. Atherosclerosis 2005; 178:319-325.