Scanning the Genome for Coronary Risk

Anthony Rosenzweig, M.D.
Coronary artery disease remains an enormous clinical problem, affecting more than 15 million people in the United States alone, where it is the most common cause of death (accounting for one in three deaths).1 The prevalence of coronary heart disease is increasing at a particularly alarming rate in developing nations, which are ill equipped to shoulder the associated economic burden.2,3 The clinical need this represents underscores the importance of understanding the causes of coronary disease and identifying persons at risk.
Much progress has been made toward these goals. We now recognize many clinical risk factors — such as hyperlipidemia and diabetes — and realize that they can induce an inflammatory cascade marked by endothelial dysfunction, leukocyte recruitment, and proliferation of smooth-muscle cells, ultimately culminating in plaque formation.4 The addition of thrombosis, plaque rupture, or hemorrhage can lead to plaque instability and acute coronary syndromes. This suggests that risk factors could, in theory, affect primarily plaque formation or stability and in turn, measures of plaque burden (such as coronary calcification) or clinical events (such as myocardial infarction), respectively. However, most factors identified to date have qualitatively similar effects on both aspects of atherosclerosis