Genomic Reflections of Coronary Artery Disease

Abstract

Coronary artery disease (CAD) is a multistaged process leading to a wide spectrum of pathoanatomic and clinical presentations.1 Given the diversity of underlying mechanisms, it is reasonable to involve distinct genetic modifiers along the cascade of events. Yet, molecular genetic association studies usually admix patients with stable and acute presentation, stenotic and ectatic forms of CAD, as well as proximal, distal or bifurcational lesions. In this issue of Circulation: Cardiovascular Genetics , Kitsios et al2 address this issue by analyzing the impact of phenotype heterogeneity on the strength of association at previously identified risk loci for CAD. Perhaps surprisingly, the authors found little evidence for a contribution of phenotype definition to between-study heterogeneity of association signals at already known genomic CAD loci. Article see p 58 This meta-analysis clustered 965 individual studies into 3 groups: those involving patients with (1) acute coronary syndromes (ie, myocardial infarction [MI] and unstable angina), (2) angiographically diagnosed CAD, or (3) “broadly defined” CAD.2 The later group included association studies that combined patients with MI, revascularization procedures (angioplasty or bypass surgery), positive exercise test findings, symptomatic angina, history of hospitalization for CAD-related diagnoses, or …