A schematic simplification of the challenge related to the risk assessment and diagnosis of atherothrombosisAtherosclerosis is a diffuse systemic disease that is characterised by the local build-up of lipid-rich plaques within the walls of large arteries. The atherothrombotic processes are multi-genetic, being influenced also by dietary and environmental components, and are apparent as early as the second decade in life with an increased incidence in the elderly. Atherothrombosis involves inflammatory processes with an array of metabolic, molecular and cellular manifestations in tissues, e.g., those depicted within the arterial wall. A varying degree of these intimal processes are reflected by the biochemistry of body fluids, such as plasma or serum. The biological heterogeneity as well as the slow development and progression of pathological conditions make the borderline between ‘health’ and ‘disease’ indistinct. One option to approach the problem is 1H NMR metabonomics of serum equipped with a chemometric classifier, e.g., a self-organising map. On the left a hypothetical SOM is shown together with four partially overlapping clusters that are thought to represent the metabolic changes in the arterial intima. While definite classification as ‘healthy’ and ‘diseased’ may not be available by nature, the metabonomics approach with a holistic look at the multi-dimensional metabolic changes may prove useful in the assessment and follow up of an individual ‘health path’ (represented by the light cyan line within the SOM) alongside the interplay between metabolic pathways and their consequences.

A potential scheme utilising MR methodologies in the risk assessment of atherothrombotic events. At risk assessment point I the molecular constituents of serum, including lipoprotein subclasses, could be assessed by in vitro 1H NMR metabonomics for non-symptomatic individuals. If high long-term risk for atherothrombotic events is indicated, non-invasive in vivo MR imaging could follow for the potential detection of plaque (risk assessment point IIa) and subsequent compositional evaluation of the vulnerability of the detected plaque(s) for rupture or erosion (IIb). Depending on the outcome from the plaque detection and assessment by MRI the individual could accordingly be directed for further actions. If vulnerable plaque at point IIb would be detected, considerations for aggressive drug therapy or invasive therapies such as angiographic stenting or bypass surgery would be needed. In the case of an individual with an experienced acute coronary syndrome (ACS) (III) in vitro 1H NMR metabonomics could be used to complement the clinical protocols when evaluating the risk for recurrent cardiovascular events and the proper individual treatment options. For some symptomatic patients in vivo MRI might also be feasible at point III for direct assessment of plaque composition and vulnerability. The recent MR findings and developments awaken confidence that this kind of scheme might be operational in the near future saving both human suffering and societal health costs.