In the presence of occlusive CAD, the hemodynamics are much more complicated. Significant CAD will shift the lower autoregulatory limit upward. However, because myocardial blood flow is very heterogeneous,130 the consequences of cor- onary underperfusion are unpredictable and may depend on intramyocardial wall stress (which in turn is increased by a high arterial pressure but decreased by LV hypertrophy), the effects of antihypertensive medications on these variables, and, of course, the severity of the occlusive coronary disease. There is also a reduced coronary flow reserve (defined as the difference between resting flow and flow through a maxi- mally dilated coronary circulation at any level of perfusion pressure) in patients with LV hypertrophy, coronary athero- sclerosis, or microangiopathy, with a reduced functional or structural capacity of coronary resistance vessels to dilate.131 This potential for impairment of myocardial oxygen supply may be compounded by an increased myocardial oxygen demand resulting from exercise, LV hypertrophy, and the increase in the output impedance of the LV caused by the increased SBP. This combination of a decreased oxygen sup- ply and an increased oxygen demand, especially during exer- cise, is particularly pernicious in the heart because the heart is an aerobic organ that can develop only a small oxygen debt, and oxygen extraction is almost maximal even at rest and can increase little with increased demand. It is theoretically possible, therefore, that although lower- ing BP improves cardiovascular outcomes in hypertensive patients (as long as coronary perfusion is maintained above the lower autoregulatory limit for coronary blood flow), any further reduction of DBP to levels below the lower autoregu- latory limit could reduce coronary blood flow. 