The increase in SBP increases cardiac metabolic require- ments and predisposes to the development of LV hypertro- phy and HF. Pulse pressure is closely related to SBP and is linked to CVD events, including MI and stroke. Aortic stiff- ness is an independent predictor of all-cause and cardiovas- cular mortality, fatal and nonfatal coronary events, and fatal stroke in patients with hypertension, type 2 diabetes mel- litus, and end-stage renal disease.73 1.2.3. Endothelial Dysfunction Endothelial dysfunction, characterized by an unfavorable balance between vasodilators, for example, nitric oxide and , and vasoconstrictors, for example, endo- thelin and angiotensin II, is an important contributor to BP elevation in people with vascular disease. The injured endothelium loses its vasodilator capacity and contributes to thrombosis and vascular occlusion. Release of chemotac- tic cytokines and adhesion molecules at the luminal surface of the injured endothelium promotes adhesion of circulat- ing mononuclear leukocytes to the vessel wall. This low- grade, self-perpetuating vascular inflammation underlies the atherosclerotic process. Inflammatory mediators activate medial smooth muscle cells, causing them to proliferate and migrate into the subintimal space. In the presence of dyslip- idemia, monocytes in the vessel wall incorporate oxidized low-density lipoprotein cholesterol and become lipid-laden macrophages, the core of the atherosclerotic plaque. In established lesions, resident macrophages secrete metal- loproteinases and cathepsins, destabilizing the fibrous cap of the plaque, which may result in plaque rupture and the release of tissue factor to cause thrombosis, coronary occlu- sion, and acute MI. 