Introduction to surrogate markers.

The clinical complications of atherosclerosis and atherothrombotic disease represent the major causes of morbidity and mortality in the United States and worldwide. The disorders that shorten life expectancy include myocardial infarction and ischemia, heart failure, stroke, renal failure, peripheral vascular disease, sudden death, and dementia, in all of which atherothrombotic disease is the most common cause. Efforts to delay or prevent these morbid events have been the focus of all clinical trials aimed at documenting the efficacy of therapeutic interventions. Furthermore, these events have served as the definition of disease used to establish population risk and risk factors. The underlying disease that eventuates in these morbid events begins in the arterial wall and progresses through well-known mechanisms that include endothelial dysfunction, inflammation, plaque formation, plaque rupture, and thrombosis. Risk factors are markers that are statistically related to the risk of morbid events, presumably because they identify or contribute to one or more of the vascular processes that lead to these events, but they do not necessarily identify the disease itself. New insights and expanding technology now make it possible to identify …