Genetics of (Premature) coronary artery disease

Coronary artery disease (CAD) and its major complication myocardial infarction (MI) mark the clinical manifestation of a chronic pathomorphological process in the vascular wall that originates in the interaction of multiple genetic and environmental factors. Likewise, a multifactorial etiology applies to many of the underlying cardiovascular risk factors including hypercholesterolemia, hypertension, diabetes mellitus, and smoking addiction. Thus, endogenous (genetic) and exogenous (nutrition, physical activity, therapy, etc.) mechanisms all affect the development of atherosclerotic lesions either directly in the arterial wall, or indirectly via traditional risk factors, or interactively by augmentation or amelioration of other players in the game. On a cellular level, atherosclerosis is also a complex process characterized by endothelial dysfunction, lipid and matrix accumulation, migration and local transformation of circulating cells, smooth muscle cell (SMC) proliferation, calcification, inflammation, and, finally, thrombus formation. In this scenario, the potential involvement of genetically modulated mechanisms may occur at multiple facets of the disease (Fig. 23.1).