The causes of postural cardiovascular disorders.

In this issue of Hypertension, Shibao et al 1 describe a series of tests that elucidate mast cell activation as a novel cause of postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). Because blood pressure control systems are redundant, patients with OH often have more than a single cause of their postural symptoms, and elucidating these causes can be challenging. The study by Shibao et al illustrates this because all but one of their subjects were premenopausal females. Estrogen2 and histamine1 vasodilate, and the patients who developed POTS were predominantly those made more susceptible to excessive vasodilation by age and sex.3 There are so many syndromes that cause orthostatic symptoms that approaching the problem through differential diagnosis is needlessly difficult. Analysis of the cardiovascular physiology of patients with OH is a better way to elucidate etiology and is also more likely to reveal when there are multiple reasons for impaired blood pressure control. The cardiovascular systems used to maintain blood pressure during upright posture are most simply pictured as a volume of fluid, a pump, vessels that resist fluid flow, and a system that regulates pump speed and resistance to flow. The corresponding anatomic parts of this system are blood volume, the heart, resistance blood vessels, and the autonomic nervous system. It is possible to test each of these components responsible for maintenance of blood pressure to determine the defect(s) causing POTS or OH. This simple physiological approach is useful in the outpatient setting to diagnose a single patient and in the clinical research laboratory. Blood volume must be adequate for maintenance of blood pressure. When we stand, 300 to 600 mL of blood pools in our legs. When sympathetic innervation is impaired, an even greater volume of blood pools in the legs. Continued upright posture causes fluid to transude into our legs and feet, causing a 10% hemoconcentration. This rapid loss of blood volume into the legs diminishes cardiac preload and decreases cardiac output by half because the heart can only pump blood delivered by the veins. When blood volume is diminished by anemia, hypoalbuminemia, or dehydration, cardiac preload may fall critically low. Diminished blood volume presents a characteristic clinical picture with increased norepinephrine, renin, and aldosterone levels, a tachycardic response to standing and diminished pulse pressure on standing. All of these characteristics can be seen in the mast cell activation plus OH group of Shibao et al.1 In contrast to the other groups, that group decreased pulse pressure from 35 to 19 mm Hg on standing. Pulse pressure typically falls in patients with low blood volume because standing causes heart rate to increase while cardiac filling decreases, leading to a much smaller stroke volume. The sympathetic nervous response elicits tachycardia, vasoconstriction, and cool blue fingertips. If a vasodilator such as histamine is present, then reflex vasoconstriction may not be able to compensate for the low cardiac output, leading to OH. Low volume can be treated with salt, water, fludrocortisone, erythropoetin, desmopressin, or, in the case of hypoalbuminemia, with food.4 Cardiac output is directly proportional to blood pressure, so it is surprising that congestive heart failure is an uncommon cause of OH. The poor cardiac output in heart failure usually does not cause OH because it is accompanied by increased peripheral vascular resistance, in part driven by increased sympathetic nervous activity. Cardiac preload is increased in congestive heart failure so that preload is adequate even during upright posture. However, when patients with congestive heart failure are treated with diuretics or nitrates, preload falls and they may develop OH. Patients with heart failure have taught us that when OH is caused by diminished cardiac output, the problem usually lies with diminished cardiac preload and not with impaired cardiac contractility. The autonomic nervous system provides the major reflex mechanism that allows maintenance of blood pressure on standing. Autonomic failure usually divides into central nervous system diseases such as multiple system atrophy (Shy-Drager Syndrome) and peripheral neuropathies. Peripheral neuropathies are often seen with diabetes mellitus or uremia and tend to cause deterioration of the longest autonomic nerves. The vagus and sympathetic nerves to the legs show first damage. The vasovagal reflex can cause a brief withdrawal of sympathetic nervous tone with increased vagal activity.5 Because central and peripheral causes of autonomic defects generally have diffuse effects, they can be recognized by the many signs and symptoms they cause. Patients with autonomic defects may have defective sweating, poor temperature control, impaired papillary constriction, and poor sphincter tone. They tend to have constipation, difficult urination, impotence, impaired gastric motility, and diminished heart rate variability. When normal subjects stand, heart rate increases and pulse pressure decreases as a consequence of higher diastolic and lower systolic blood pressure. Blood flow to the hands and feet decreases, and this leads to a change in the color of the palms and fingertips from pink toward blue that becomes visible after 3 minutes of standing. In contrast, when subjects with autonomic insufficiency stand, they decrease The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association. From the University of California, San Diego (M.G.Z.); and the United States Navy Regional Medical Center (D.P.R.), San Diego, Calif. Correspondence to Michael Ziegler, MD, UCSD Medical Center, 200 W Arbor Dr, San Diego, CA 92103-8341. E-mail [email protected] (Hypertension. 2005;45:354-355.) © 2005 American Heart Association, Inc.