The consensus statement on the definition of orthostatic hypotension: a revisit after 13 years

Abstract

Orthostatic hypotension is a physical sign that reflects a final common pathway of various forms of disordered physiology. As such, it stimulates particular interest among clinical physiologists, especially those interested in hemodynamic homeostasis. It has very little clinical significance until it creates symptoms of hypoperfusion of the brain and retina. Pain in the neck and shoulder (‘coat hanger pain’) that resolves quickly on lying down may be another diagnostic clue. In unusual circumstances, stenosis of certain arteries (cardiac, cerebral), coupled with a sudden decline in standing blood pressure leads to clinically expressed ischemia [1]. Studies dealing with the significance of postural changes in blood pressure have a long history. At the beginning of the twentieth century, Crampton [2] explored the changes in heart rate and blood pressure upon standing (the blood ptosis test) as an index of ‘the gravity-resisting ability’ of the circulation. In patients with a large variety of conditions, the increase in systolic pressure was thought to connote efficiency and the increase in heart rate deficiency. Around the same time, Schneider and Truesdell [3] applied orthostatic stress testing for estimating physical fitness in aviators. Prevention of gravitational accumulation of blood within the abdomen by an increase in vascular tone of the splanchnic vessels and of tension in the retaining abdominal wall was considered the key factor in maintaining postural normotension. A systemic course of graduated exercises such as furnished by drills of increasing severity was advised in patients with orthostatic intolerance [4]. In 1996, a consensus committee of the American Autonomic Society and the American Academy of Neurology met to define the neurologic causes of orthostatic hypotension and to decide on a precise definition [5]. Prior to this, investigators and clinicians used varying numbers to denote the presence of orthostatic hypotension, creating confusion. The combined clinical wisdom of this group of experts proclaimed that a 20 mmHg systolic and/or 10 mmHg diastolic decline in blood pressure from lying to standing, after 3 min of observation, should be the standard. This was based on clinical judgment, as epidemiologic data were unavailable at the time. This definition quelled the preceding chaos. Thirteen years later, it is clear that the time has come to revisit this issue. Clinical correlations that are now available are much more extensive and meaningful. Abundant data have accumulated that explores the precise hemodynamic disturbances that occur with orthostatic hypotension. Continuous noninvasive measurement of finger arterial blood pressure and computation of changes in stroke volume have contributed importantly to our understanding of the hemodynamic mechanisms underlying orthostatic adjustments [6,7]. Data about the prognosis of orthostatic hypotension are beginning to appear, particularly in the elderly individuals [8–10]. In this issue of the journal, Federowski et al. [11] profitably explore this issue. They suggest that the previous criteria for the diagnosis of orthostatic hypotension be modified in patients with high or low blood pressures. Their data confirm that the older 20/10 mmHg standard for the definition of orthostatic hypotension is an excellent cutoff for normotensive persons. However, using the 20/10 mmHg standard, they detected that almost 10% of their participants with resting systolic blood pressures above 160 mmHg had significant orthostatic hypotension. Upon examination of their evidence, they suggest that in their hypertensive participants, instead of using the previous standard of 20/10 mmHg, we should adopt 30 mmHg as a practical single absolute systolic criterion. Furthermore, they also recommend that in those with systolic blood pressures under 120 mmHg, the decline in standing blood pressure be 15 mmHg rather than 20 mmHg as an indicator of orthostatic hypotension. On examination, their data suggest that these conclusions have merit. They are in accordance with previous observations. In the classical study by Schneider and Truesdell [3] in aviators mentioned above, a fall of more than 20 mmHg in systolic pressure occurred in less than 2.5% of 2000 unselected normotensive individuals aged 18–42 years. In 542 patients with diabetes mellitus, van Dijk et al.[12] have documented that the supine systolic blood pressure level accounts for about 20% of the systolic blood pressure fall. In 75 normotensive controls, abnormality thresholds of 20.5 mmHg for systolic and 9.4 mmHg for diastolic blood pressure falls after 1 min standing were calculated. Aging per se has little effect on circulatory regulation of arterial pressure during orthostasis; in upright, arterial pressure in well hydrated normotensive elderly individuals is maintained just as well as in young individuals [13,14]. The adjustment to acute stress in healthy elderly individuals appears, however, to be easily deranged if circulatory homeostasis is heavily taxed, as occurs for instance during periods of hypovolemia. This tendency to orthostatic hypotension may reflect diminished arterial baroreceptor reserve. As our understanding of orthostatic hypotension evolves, the clinical utility of detecting it has become more and more important. Although common reversible events (hypovolemia, deconditioning, drugs, among others) cause orthostatic hypotension, the onset of this sign in individuals without any of these disorders merits careful investigation and substantial clinical judgment for both diagnosis and therapy. It becomes clear that the presence of orthostatic hypotension may reflect an autonomic imbalance, which may just be the tip of the iceberg of homeostatic maladjustment. In fact, one may compare the current status of our understanding of orthostatic hypotension with the data on elevated blood pressure levels in the 1940s and 1950s. In that era, levels of blood pressure above 160/90 mmHg might have been considered interesting clinical phenomena, but they evoked little clinical or investigational curiosity. As it became apparent that the sequelae of elevated blood pressure were strikingly important and that the pathophysiologic disorders responsible for it were varied and complex, intensive interest in these phenomena grew exponentially. Clearly, our knowledge of hypertensive disease spurred the development of an enormous new industry in the search for antihypertensive agents. We have come a long way since then; one might predict that similar prospects will occur with respect to orthostatic hypotension. For example, Federowski et al. [11] provide interesting data suggesting that two forms of antihypertensive therapy have differing effects on orthostatic hypotension: angiotensin-converting enzyme (ACE) inhibition appeared to protect their hypertensive individuals from this condition and spironolactone seemed to enhance it. Although these are clearly observational data, which require validation upon repeat investigation, one may speculate on the possible mechanisms induced by these agents. Are there effects on the renin–aldosterone system blunting the development of orthostatic hypotension in those who take ACE inhibitors? Mechanistic theories can emerge, but they are theories nonetheless and, until these observations are confirmed by other studies, the potential causes responsible for these data remain speculative. In the study by Federowski et al.[11], the arm was supported at heart level both in the supine and standing positions and the differences between supine and standing blood pressures they report can be assumed to be the real changes that occur on standing. Accurate measurement of orthostatic blood pressure changes is crucial in research protocols dealing with orthostatic hypotension. The reference for the measurement of the blood pressure is the right atrium, mostly referred to as ‘at heart level’. It is usually taken as the level of the fourth intercostal space or the level of the midsternum. Midcuff level is usually used [15]. The position of the arm is important, as it has a direct influence on the magnitude of orthostatic changes in blood pressure. Blood pressure readings taken while allowing the arm to hang vertically during the blood pressure measurement (i.e., below heart level), instead of supporting it at the level of the midsternum, will result in systolic and diastolic blood pressures that are about 10 mmHg higher [15]. The difference is a direct hydrostatic effect and depends on the length of the arm, but not on the level of blood pressure. Orthostatic hypotension will thus be underestimated with the arm vertical and parallel to the body. In clinical practice, the 10 mmHg underestimation of blood pressure will be less, as in supine position with the arm on the bed (i.e., also below heart level), the pressure will be about 5 mmHg higher than at heart level. In patients with symptomatic orthostatic hypotension, the fall in blood pressure usually exceeds the 20 mmHg systolic and/or 10 mmHg diastolic decline in blood pressure. Consequently, a routine upright measurement in daily practice with the arm vertical and parallel to the body will usually suffice in symptomatic patients. The larger systolic blood pressure fall is easier to account for than the diastolic fall. As far as the timing of the orthostatic blood pressure measurement is concerned, the 1996 consensus statement recommends an observation period of 3 min after a change in posture from lying to active standing or head-up tilt on a tilt table at an angle of at least 60° [5]. For routine clinical assessments and research purposes, this 3 min observation period seems a generally accepted standard [16,17]. However, from a physiological point of view, it is important to realize that active or passive changes in posture evoke different initial (first 30 s) cardiovascular effects. A transient pronounced initial fall in arterial pressure is only observed immediately after active standing up. It is useful to classify the orthostatic response in laboratory conditions according to the following criteria: the initial response (the first 30 s), the early phase of stabilization (1–3 min upright), and prolonged orthostatic stress (>5 min upright), as well as according to the active (standing up) or passive (head-up tilt) nature of orthostasis [6,18]. The circulatory adjustment to postural change in the initial phase and the early phase of stabilization is governed exclusively by the neural system [6,19]. The integrity of sympathetic vasomotor outflow to the resistance and splanchnic capacitance vessels, rather than cardiac effector mechanisms, is essential. A large ‘vasomotor reserve’ is an important factor for determining orthostatic tolerance [20]. Under normal circumstances, activation of the sympathetic nervous system and renin–angiotensin vasoconstriction are involved in the maintenance of blood pressure during prolonged orthostasis. The vasopressin plasma level only increases markedly during hypotensive orthostatic stress. The arterial (and especially carotid) baroreceptor control of sympathetic vasomotor tone of resistance and splanchnic capacitance vessels in combination with the magnitude of the central blood volume are the most important components in the maintenance of postural normotension in humans. Activation of the skeletal muscle pump of the lower body can compensate in part for defects in control of vasomotor tone and a reduction of central blood volume. The physiological classification of the orthostatic adjustment in an initial response, an early phase of stabilization and prolonged orthostasis is of direct clinical relevance [6]. First, complaints of a brief feeling of light-headedness and some visual blurring upon arising suddenly after prolonged supine rest or after arising from the squatted position are very common. Symptoms typically resolve spontaneously within 20 s [21]. In some, the symptoms are severe and syncope may occur upon standing in otherwise healthy individuals. In a recent study in 394 young adults (i.e., medical students), standing up was reported as the trigger for transient loss of consciousness in 8% [22]. The underlying mechanism is a mismatch between cardiac output and systemic vascular resistance [21]. Initial orthostatic hypotension can be strongly suggested by the medical history, but documented only by beat-to-beat blood pressure monitoring. A transient fall of more than 40 mmHg systolic or more than 20 mmHg diastolic is considered abnormally large. Second, as discussed above, blood pressure measurements in the early phase of stabilization are commonly used to assess orthostatic hypotension in the office or at the bedside. Depending on the clinical setting, early orthostatic hypotension will be detected in at least 50% of patients with autonomic disturbances within 3 min in the upright posture [23,24]. Third, prolonged orthostasis is applied to evaluate delayed orthostatic hypotension [24,25], the postural tachycardia syndrome [26] and a tendency to vasovagal fainting [7]. The clinical significance of delayed orthostatic hypotension remains to be determined [27]. With increasingly sophisticated epidemiologic and biostatistical techniques, one can tease out the clear-cut added impact of orthostatic hypotension on subsequent morbidity and mortality in the middle-aged and elderly individuals. That such occurs presently is now clear, despite somewhat pessimistic assessment of this issue by Federowski et al. In fact, abundant evidence exists that orthostatic hypotension independent of other risk factors significantly impairs survival and independently in elderly individuals [8–10]. That all-cause mortality is increased in these individuals is strongly suggested. The questions remain why does this happen and what are the implications for prophylaxis and therapy in its presence? Another methodological question that needs be addressed are the number of measurements required in order to establish a clinical diagnosis of orthostatic hypotension [27]. Finally, the recognition that deconditioning in the bed-bound elderly patients leads to orthostatic hypotension is a clear clinical fact. The common clinical scenario is that of an older individual, in hospital for an unrelated reason, who develops orthostatic hypotension while bedridden. Almost certainly, these are individuals who have clinically inapparent, asymptomatic orthostatic hypotension prior to hospitalization. In elderly individuals, deconditioning occurs rapidly while in bed, with a loss of muscle mass of the antigravity muscles, decrease in plasma volume, and decline in baroreflex function [28], precipitating significant orthostatic hypotension. This leads to a vicious cycle of bedrest, further deconditioning, a worsening of orthostatic hypotension, and so on. This clinical fact is often unrecognized by practitioners and represents an important and frequent source of disability and morbidity, if not mortality, in hospitalized elderly patients.