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Orthostatic hypotension

is it a predictor of total and cardiovascular mortality in the elderly?

Grossman, Ehuda,b

doi: 10.1097/HJH.0000000000001919
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aInternal Medicine D and Hypertension Unit, The Chaim Sheba Medical Center, Tel HaShomer, Ramat Gan

bThe Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

Correspondence to Ehud Grossman, MD, Professor of Medicine, Chief of Medicine, The Chaim Sheba Medical Center, Tel Hashomer, Floor 1, Room 132, 526601 Ramat Gan, Israel. Tel: +972 3 5303175; fax: +972 3 5305288; e-mail: grosse@tauex.tau.ac.il

Orthostatic hypotension is defined as sustained reduction of SBP of at least 20 mmHg or DBP of 10 mmHg within 3 min of standing [1].

There are several additional variants to the classic definition of orthostatic hypotension.

Initial orthostatic hypotension which is defined as a transient exaggerated blood pressure (BP) decrease (>40 mmHg SBP and/or >20 mmHg DBP) within 15 s of standing. This BP fall can only be diagnosed with continuous beat-to-beat BP monitoring.

Delayed orthostatic hypotension occurs beyond 3 min of standing. This disorder can be diagnosed by extending the period of orthostatic stress beyond 3 min.

In patients with supine hypertension, a reduction in SBP of 30 mmHg may be a more appropriate criterion for orthostatic hypotension because the magnitude of the orthostatic BP fall is dependent on the baseline BP [1].

Most studies define orthostatic hypotension according the change in BP when moving from supine to standing position. However, there are situations in which a supine-to-standing manoeuvre cannot be easily performed. In this case, a sitting-to-standing manoeuvre with lower diagnostic cut-offs for orthostatic hypotension provides a simple screening test for orthostatic hypotension. A recent analysis suggested that a SBP drop of at least 15 mmHg or a DBP drop of at least 7 mmHg best optimizes sensitivity and specificity of this sit-to-stand test [2]. In a previous study, we have shown that even intermediate postural BP drop below the orthostatic hypotension range may be an important finding in the geriatric population [3].

The finding of orthostatic hypotension may not be consistent. It is more common during the morning and during summer time [4,5]. Orthostatic BP fall is also influenced by hydration, cardiac and vascular stiffness, ambient temperature, sex, prolonged recumbence and deconditioning. Age, food intake, medication may also affect orthostatic fall in BP. We performed orthostatic test three times during the day (morning, noon and evening) in 489 elderly patients who were hospitalized in a geriatric department. Three hundred and thirty-two (67.9%) patients experienced orthostatic hypotension at least once during the day. Of these, only 170 patients (34.8%) had orthostatic hypotension at least twice and 162 patients (33.1%) experienced orthostatic hypotension only once. Therefore, the diagnosis of orthostatic hypotension should be based on repeated orthostatic tests. The study by Syzyndler et al.[6] used the classic definition of orthostatic hypotension. In their study, the diagnosis of orthostatic hypotension was based on the change in BP from sitting to standing position only one time. As mentioned above the criteria for change in BP from sitting to standing may be different from the change from lying to standing, and one measurement may not be reproducible and it may overestimate the prevalence of orthostatic hypotension.

The prevalence of orthostatic hypotension is age related [7]. The Atherosclerosis Risk in Communities (ARIC) study of middle-aged American men and women reported a prevalence of 5% [8]. In the Cardiovascular Health Study of 5201 American men and women more than 65 years old, 16.2% had asymptomatic orthostatic hypotension [9]. Stratified by age, the overall prevalence of orthostatic hypotension increased from 14.8% among persons 65–69 years old to 26.0% among persons at least 85 years old. Among 342 patients at least 75 years old who attended a US Veterans Administration geriatric clinic 55% had orthostatic hypotension [10]. Among 489 elderly patients who were hospitalized in a geriatric department we observed a prevalence of 34.8% [5]. Among 209 very elderly individuals (mean age 83.9 years) Syzyndler et al.[6] found orthostatic hypotension, 3 min after standing, in 38.3%. It is clear that orthostatic hypotension is very common in very elderly individuals. Patients with orthostatic hypotension may experience symptoms due to inadequate perfusion of the brain and other vital organs. The symptoms depend on the BP levels during standing. In patients with hypertension, a fall of SBP from 160 to 130 mmHg may be asymptomatic. In the study by Syzyndler et al.[6], individuals with orthostatic hypotension were asymptomatic and therefore not necessarily represent the typical elderly patient with symptomatic orthostatic hypotension.

Several studies have shown an association between orthostatic hypotension and mortality. In the ARIC study individuals with orthostatic hypotension had a two-fold higher risk of cardiovascular death and other deaths [8]. In a recent study, orthostatic hypotension was related to all-cause mortality in the most frail group of nursing home patients [11]. In the Action to Control Cardiovascular Risk in Diabetes BP trial, orthostatic hypotension was common, and predicted increased mortality and heart failure events in patients with type 2 diabetes mellitus and hypertension [12].

A recent meta-analysis showed an association between orthostatic hypotension and all-cause death, incident coronary heart disease, heart failure and stroke. However, the association was significant mainly in patients younger than 65 years [13]. It seems that young patients have mainly neurogenic orthostatic hypotension and in them there is an association between orthostatic hypotension and mortality, whereas in the elderly the results are not consistent. We showed in very elderly hospitalized patients no association between orthostatic hypotension and mortality [14]. Veronese et al.[15] showed in elderly patients with orthostatic hypotension an association only between orthostatic hypotension and noncardiovascular mortality. The study by Syzyndler et al.[6] also showed no association between orthostatic hypotension and mortality, but they evaluated a small group of very elderly community-dwelling population who had asymptomatic orthostatic hypotension and followed them for a relatively short time. It is unclear how much their study applies to elderly patients with symptomatic orthostatic hypotension. When considering the impact of orthostatic hypotension on mortality we need to understand why we expect orthostatic hypotension to affect life expectancy. What is the normal response to standing and what is abnormal in individuals with orthostatic hypotension. Immediately after standing, there is a pooling of 300–800 ml of blood in the lower extremities and splanchnic venous capacitance system. As a consequence, venous return to the heart falls and cardiac filling pressure is reduced. This results in diminished stroke volume (SV) and cardiac output (CO). In response, sympathetic outflow to the heart and blood vessels increases and cardiac vagal nerve activity decreases. These autonomic adjustments increase vascular tone, heart rate and cardiac contractility, and stabilize arterial pressure. Thus, cardiac decompensation or inadequate sympathetic activation leading to vasoconstrictor failure may cause orthostatic hypotension. We showed that orthostatic stress causes an exaggerated decrease in SV and CO in hypertensive patients with impaired left ventricular filling [16]. Orthostatic hypotension may be a sign of underlying disease or condition. It is very common in elderly patients with Parkinson's disease or multiple system atrophy and in other conditions of autonomic neuropathy. Orthostatic hypotension may be a marker of nondipping or reverse-dipping pattern of diurnal BP [17], and this may explain the increased risk for cardiovascular disease in patients with orthostatic hypotension [18].

Several studies have identified associations between orthostatic hypotension and antihypertensive polypharmacy. In a study of American veterans attending a geriatric clinic the percentage of patients with orthostatic hypotension was 35, 58, 60 and 65% among patients using 0, 1, 2 and at least three antihypertensive agents, respectively [10]. Similarly, a British study of elderly women found orthostatic hypotension to be significantly more prevalent among users of three or more antihypertensive patients than among nonusers [19]. Recently, Press et al.[20] found in geriatric individuals an association between drug therapy and orthostatic hypotension. Syzyndler et al.[6] found no association between the number of antihypertensive drugs used and the rate of orthostatic hypotension. On the contrary, intensive hypertension treatment (more than two drugs versus none) was associated with longer survival. These findings support the data from the recent large Systolic Blood Pressure Intervention Trial [21]. In this study patients in the more intensive arm received more BP-lowering agents (2.9) than in the standard treatment (1.9) but experienced less orthostatic hypotension (16.6 versus 18.3%) and had less primary endpoints. It still remains a challenge how to treat hypertensive patients with supine hypertension and symptomatic orthostatic hypotension. There are no guidelines to answer this dilemma, but it is clear that one has to weigh the balance between the long-term benefit of lowering BP versus the short-term risk of symptomatic orthostatic hypotension [22]. Sleeping with the head of the bed tilted upright and using short-acting antihypertensive agents before sleep may be beneficial [22,23].

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ACKNOWLEDGEMENTS

Conflicts of interest

There are no conflicts of interest.

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