Surrogate markers for atherosclerotic disease

Novel treatment modalities for cardiovascular prevention are emerging rapidly. Since it is virtually impossible to evaluate all these new compounds in long-term trials using clinical end points, there is an urgent need for validated surrogate markers of atherosclerosis to save both time and costs. Over the last decade, the use of imaging markers has been widely introduced into drug-development strategies. Here we will discuss the most commonly used techniques.

Whereas both testing of endothelial function, assessed as flow-mediated dilation, and assessment of carotid intima-media thickness have been shown to predict future cardiovascular events, predominantly intima-media thickness has been used successfully as a surrogate marker in intervention studies. More recently, standardization of intravascular ultrasound has also enabled reproducible assessment of coronary atheroma volume. Multidetector computed tomography and electron-beam computed tomography have proven useful in providing quantitative information on plaque burden and coronary calcium content, respectively. Although cardiovascular magnetic resonance (CMR) is improving continuously, additional technical improvements will be mandatory before this technique can be implemented in multicenter clinical studies.

The imaging modalities reviewed here all provide specific information on either functionality or morphology of the vasculature. The value of carotid intima-media thickness for cardiovascular risk prediction has been studied most extensively. Whereas assessment of plaque burden using intravascular ultrasound appears to be the most direct way to quantify coronary changes, its predictive value for future cardiovascular events remains to be established. Awaiting further technical improvements, CMR is expected to provide the most valuable information for the evaluation of atherosclerosis in the near future.