Rule 1. Don’t sweat the small stuff. Rule 2. It’s all small stuff. Rule 3. If you can’t fight or flee, then FLOW!! Being involved in the field of hypertension, we become so focused on blood pressure that we often forget that the only reason that we have blood pressure and a circulatory system is to provide blood flow to the cells of the body. The flow of blood provides nutrients for cells, respiratory gas transport, thermal regulation, cellular and immunoprotection, and elimination of waste products. The need for blood pressure arises because our circulation is a closed system and we live in a gravitational field. The force necessary to propel the blood through the systemic circulation is provided by the left ventricle, and the distribution of this flow, ie, cardiac output, is regulated by varying the resistance to flow in various vascular beds. Because of the pumping action of the heart, the blood flow is pulsatile in nature. So, it is blood flow that is regulated primarily by the body, not blood pressure. The baroceptors simply ensure that flow will be maintained if changes occur in the gravitational field, eg, going from sitting to standing. If tissues need more blood, then vascular resistance and blood pressure must be modified to meet these needs. The most efficient circulation delivers needed flow at the lowest pressure. Vascular shear forces are of major importance in determining the appropriate pressure/flow relationship. Vascular shear forces are important in endothelial regulation and accommodation of blood flow and, therefore, by necessity, blood pressure. Shear is the frictional force exerted on the vascular wall secondary to the flow of blood. Stated another way, arterial wall shear stress expresses the force per unit area exerted on the wall by the fluid in a direction on the local tangent plane. To understand shear, it is helpful to remember the essentials of fluid flow. where P = pressure, r = radius, η = viscosity, and l = length of the pipe. Another way to calculate shear is the ratio of axial to outer flow times the viscosity of blood, ie, ESS = μ dv/dy. Notice in these equations that the quantitation of blood pressure is no longer present. Yet, the difference between the force of blood pressure and shear is great. Remember, normal shear in the systemic circulation is approximately 10 to 20 dynes/cm2, whereas 1 mm Hg exerts a force of 1133 dynes/cm2. Shear is the main controlling factor for the production of endothelial-derived relaxing factor (nitric oxide) and endothelial-derived hyperpolarizing factors. When flow is laminar, production of nitric oxide and endothelium-derived hyperpolarizing factor are adequate to accommodate flow by vasodilation and protect the vascular bed. These endothelial products allow the circulation to accommodate increased flow and provide autoregulation to ensure flow regardless of perfusion pressure. On the other hand, turbulent or low shear promotes vascular damage and the development of atherosclerosis. So, what does all of this have to do with the optimal goal blood pressure for a patient with hypertension? The answer is that blood pressure, a biomarker of hypertension, participates directly in the production of target organ damage, particularly atherosclerosis. And, the increased stretch associated with increased blood pressure increases the production by the endothelium of endothelin, a potent vasoconstrictor. Thus, the optimal blood pressure to avoid cardiovascular risk is the lowest pressure that can deliver needed perfusion to all of the organs, eg, the heart (Figure). Disease states, eg, atherosclerosis, that may obstruct blood flow, will influence the need for pressure modification. Shear is important for autoregulation. The ideal blood pressure is the lowest pressure that does not compromise blood flow. The autoregulation of coronary flow adjusts flow to match the perfusion pressure. However, note that cardiovascular (CV) risk begins as the perfusion pressure begins to rise at the lower portion of the pressure/flow relationship and rises exponentially after. At critical levels of decreased perfusion, risk also increases, giving rise to the J-shaped curve. Atherosclerosis and ventricular hypertrophy may modify this relationship. Modified from Cruickshank JM. Coronary flow reserve and the J curve relation between diastolic blood pressure and myocardial infarction. BMJ. 1988;297:1227–1230. The pulmonary circulation is an example of high flow (high laminar shear) and low arterial pressure and is essentially devoid of atherosclerosis under normal circumstances. Another example is when the right coronary artery originates from the pulmonary artery; the right coronary does not develop atherosclerosis, while the left coronary originating from the aorta, does. Light automobile traffic does not produce much road damage but heavy trucks do. However, even light traffic does some damage. Although randomized clinical trials are used to assess the proper blood pressure goal for therapy, these trials do not measure the efficiency of the blood pressure/flow relationship. Inclusion and exclusion criteria do narrow the phenotype, and the development of an obvious adverse reaction provides a clue, eg, lowering of blood pressure and dizziness; however, in the end, the inter-individual variability is enormous. In the future, I believe that we will adjust blood pressure based on optimal efficiency as more user-friendly methods become available for measuring blood flow in the office. Until then, we must rely on that most precious of physician skills to select the optimal personal blood pressure, ie, CLINICAL JUDGMENT, based on careful history and physical examinations and attention to basic laboratory investigation. Oh, guidelines can help, but only so much.