Concomitant metabolic disorders, for example, diabe- tes mellitus, insulin resistance, and obesity, also lead to the production of vasoactive adipocytokines that promote vaso- constriction, endothelial dysfunction, inflammation, and increased oxidative stress in the vasculature, thus increasing both BP and CVD risk.61,62 These shared pathophysiological mechanisms offer potential novel therapeutic targets for the prevention and treatment of both hypertension and CAD, with benefits that may go beyond BP lowering. Genome-wide association studies have identified multiple genetic susceptibility variants, mostly single-nucleotide poly- morphisms, for atherosclerotic disease.63 It has been suggested the polymorphisms of genes of the RAAS, particularly ACE, angiotensin II receptor type 1, and angiotensinogen, are impli- cated in the development of CAD and MI.64,65 The presence of hypertension further increases the risk of CAD and may explain why some individuals are more predisposed than oth- ers to developing coronary events. Some polymorphisms have also been implicated in the BP response to antihypertensive treatment. For example, genetic polymorphisms coding for the matrix metalloproteinases appear to modify CVD outcomes in hypertensive patients treated with chlorthalidone, amlodipine, These data suggest that, in the future, determi- nation of genetic variants may be of some use for selecting appropriate antihypertensive agents to reduce both BP and the risk for CAD. However, because CAD is polygenic and its causes are multifactorial, genetic studies explain only a small proportion of the heritability of the disease.67 1.2.2. Physical Forces and Hemodynamics Physical forces (pressure and flow) are the primary determi- nants of cardiac structure and function and influence coro- nary arterial remodeling and atherosclerosis. When SBP is elevated, both LV output impedance and intramyocardial wall tension increase, resulting in increased myocardial oxygen demand. 