How low can you go?

The Systolic Pressure Intervention Trial (SPRINT) was recently terminated early because it reached its endpoint by showing that a systolic blood pressure (SBP) of 120 torr was associated with fewer deaths and myocardial infarcts than a SBP of 140 torr. However, the publicity that this outcome has achieved should give pause not only to neurologists, but also to primary care physicians. The interpretation that is trumpeted in the lay press (there has been no scientific publication of the results yet), that physicians should seek to keep their patients’ SBP below 120 torr, is potentially quite dangerous and could result in a rash of patients seeing neurologists with ischemic brain damage. Many of these patients will not present with frank cerebral infarction, but instead with cognitive impairment, falls, or “dizziness” (i.e., complaints that will span the spectrum of general neurology). The reason I can confidently make this statement is that, in seeing general neurology patients, I already frequently see patients whose SBP is being too aggressively controlled and who present with these complaints. The reason this happens is because so few physicians understand the basic physiology of maintaining cerebral perfusion pressure. First, it is not the SBP, but the mean arterial pressure (MAP) that is important in determining cerebral blood flow. Because MAP 5 2/3 diastolic BP (DBP) 1 1/3 SBP, for the purpose of calculating the effects on brain perfusion, the SBP is the wrong number to look at. This is particularly true in elderly patients with wide pulse pressure, owing to poor arterial compliance. Thus, in 2 people meeting their SBP goal of 120 torr, a young person with good arterial compliance might have a blood pressure (BP) of 120/80, yielding an MAP of 93 torr, whereas an elderly person with a BP of 120/50 would have an MAP of 73 torr. This is dangerous because of the physiology of the autoregulation curve for cerebral blood flow. As we all learn in medical school, the central nervous system regulates cerebral blood flow across a wide range of systemic BPs. What is often forgotten is that there is a sharp drop in cerebral perfusion pressure below a threshold MAP. In healthy young people, that threshold is generally around 60 torr. In people with long--standing hypertension, this curve is shifted to the right, meaning that a precipitous (and disastrous) fall in cerebral blood flow may occur at an MAP of 70 or 80 torr or even higher. Returning to the example above, if the elderly patient had a customary BP of 160/90 (MAP 5 113) and had shifted his or her autoregulation curve 10 torr to the right, an MAP of 73 torr would bring him or her to the edge of not being able to adequately perfuse the brain. Now add to this picture the problem that BP is not static, but fluctuates over the course of the day. One of the most important determinants of MAP experienced by the brain is orthostasis. Most BP readings are taken in a seated position in the physician’s office. The additional pooling of blood in the lower extremities with upright posture can cause a further fall in MAP when standing of 10 torr or more. This may not be symptomatic in someone whose MAP is well above the threshold for brain ischemia, but it can cause neurological symptoms in a person whose MAP is on the edge of adequacy when seated. Other challenges involve fluctuations in blood volume, such as when the patient becomes dehydrated on a hot day, which can exacerbate the fall in MAP when standing. These factors can easily put the cerebral blood flow in an upright patient into the range where there could be substantial cognitive or motor deficits (“brownout symptoms”) and, possibly, an infarct in the distribution of a partially occluded cerebral artery. A transient arrhythmia that suddenly drops cerebral perfusion pressure by 20 torr could cause syncope and, quite possibly, produce widespread brain ischemia with longterm white matter damage. I have seen a number of these patients present as “dementia” with widespread white matter hyperintensities on T2 magnetic resonance imaging (MRI) scan. In some who have not already suffered irreversibly brain injury, their cognitive performance may improve substantially when BP control is liberalized. This situation is eerily similar to the long-standing debate about glycemic control in diabetes. For many years, the long-term vascular complications of diabetes were attributed to the peaks in blood glucose, leading to an attempt to keep it as low as possible. However, recent studies have demonstrated that the autonomic neuropathy that commonly is observed in severe diabetics is more closely associated with the frequent occurrence of hypoglycemia, when attempting to maintain a euglycemic state. Ironically, the ensuing autonomic neuropathy causes severe orthostatic hypotension, which puts this population at severe risk for too tight control of BP as well. What can a neurologist do? The first thing is to make sure that when we see patients with transient nonlocalizing deficits (confused, dizzy, or forgetful), we remember the possibility that tight BP control may cause such symptoms, especially if they occur in relationship to orthostasis, dehydration,