Is Coronary Atherosclerosis One Disease or Many?

Abstract

Age-adjusted mortality from coronary artery disease (CAD) has decreased substantially in recent decades, in large part, related to a combination of lifestyle modifications, pharmacological therapies, and revascularization strategies. But do we need a new approach? The All of Us Research Program (a cohort study within the Precision Medicine Initiative) will begin enrollment of ≥1million participants in 2017. This landmark resource will enable investigation into the substantial interindividual variation in physiology, risk of disease, and response to therapy. Perhaps CAD patients, currently lumped together in the guidelines and minds of clinicians, actually have one of many disease subtypes. Each such subtype might lead to CAD via a distinct driving pathway and thus benefit from distinct therapeutic approaches. The ability to transform disease taxonomy in this fashion is an often-cited expectation of precision medicine.1 Alternatively, the manifestation of CAD might reflect a quantitative blend of causal risk pathways in each individual (Figure). Precision medicine might enable identification of new risk pathways, each with broad relevance to the CAD population. Figure. Coronary atherosclerosis: one disease or many? One potential paradigm for precision medicine is that additional phenotyping might lead to the identification of a distinct driver (depicted by various colors in this schematic) in each individual. Alternatively, the manifestation of coronary artery disease in each individual may relate to a quantitative blend of such causal factors. Although not mutually exclusive, this dichotomy may help to frame expectations for the All of Us Research Program and other similar precision medicine biobanks. Human genetics studies of CAD provide an opportunity to explore the 2 hypotheses: distinct driver in each …