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Orthostatic hypotension: new views for an old problem

Casiglia, Edoardoa; Jordan, Jensb

doi: 10.1097/HJH.0000000000001272
Editorial Commentaries

aDepartment of Medicine, Laboratory of Epidemiology, University of Padova, Padova, Italy

bInstitute of Aerospace Medicine, German Aerospace Center (DLR), University of Cologne, Cologne, Germany

Correspondence to Prof Edoardo Casiglia, Department of Medicine, Laboratory of Epidemiology, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. Tel: +39 049 8212277; fax: +39 049 8754179; e-mail: edoardo.casiglia@unipd.it

Measuring blood pressure (BP) and heart rate (HR) in the supine and in the upright position may be the single best test to assess the integrity of human cardiovascular reflex regulation and should be part of routine clinical assessment in the hypertension clinic. Indeed, standing imposes a major burden on the cardiovascular system. Within seconds, 500–1000 ml blood is pooled below the diaphragm. Moreover, hydrostatic pressure forces plasma from the vascular into the interstitial space reaching a maximum of 10–20% after approximately 15-min standing. Despite the marked change in cardiac loading conditions, BP remains surprisingly stable in healthy young persons. BP stabilization is achieved through cardiovascular reflexes, particularly the arterial baroreflex, augmenting sympathetic outflow to vasculature, heart, and kidneys while attenuating cardiac vagal activity. BP decreases with standing when these mechanisms fail or when the hemodynamic stimulus exceeds the counter regulatory capacity. For example, hypovolemia and venous insufficiency may promote orthostatic BP reductions. Orthostatic hypotension is commonly defined as reduction in systolic BP of at least 20 mmHg and/or of diastolic BP by at least 10 mmHg after 3-min standing [1]. Transient reductions in BP in the first minute of standing occur even in perfectly healthy persons but may nevertheless elicit symptoms.

Orthostatic symptoms or frank syncope occurs when the BP reduction exceeds the brain's autoregulatory capacity. Many patients with mild-to-modest orthostatic hypotension remain asymptomatic. Therefore, history taking is no substitute for BP and HR measurements in the supine and in the upright position. Yet, history taking is crucial in identifying the underlying causes of orthostatic hypotension and in deciding whether or not symptomatic treatment is required.

Although measuring orthostatic BP and HR in the supine and in the standing position appears to be a fairly simple and inexpensive test, such measurements are rarely taken in real life. Perhaps, busy schedules in outpatient clinics and hospital wards discourage healthcare professionals from taking such measurements. Sometimes there may be no place to have a patient lie down. Therefore, the article by Shaw et al.[2] in the present issue of the Journal of Hypertension tested whether measurements in the seated and in the standing position could be utilized to diagnose orthostatic hypotension. In fact, physicians and nurses in the clinic as well as patients at home [3] actually tend to measure BP, for the sake of convenience, in the seated posture.

Shaw et al. conducted a retrospective analysis among 831 individuals presenting to a specialized autonomic dysfunction center for the workup of suspected autonomic nervous system disease or for study participation. BP was measured with an oscillometric brachial cuff while supine, seated, and standing. The investigators calculated BP changes from supine-to-standing and from seated-to-standing. Orthostatic hypotension was diagnosed on the basis of supine-to-standing measurements as indicated above. Then, receiver operator characteristic curves were constructed to determine the optimal seated-to-stand BP cutoff for the diagnosis of orthostatic hypotension. Given the highly selected patient cohort, more than 40% exhibited significant orthostatic hypotension. Seated-to-standing systolic BP reduction at least 15 mmHg and DBP reductions at least 7 mmHg had optimal test characteristics with sensitivities, specificities, positive predictive values, and negative predictive well above 80%. The test performed better in the subgroup with more severe orthostatic hypotension.

An important limitation of the study is the highly selected patient group, which could have introduced a bias. We had the opportunity of verifying these diagnostic criteria in an epidemiological setting [3]. In 2940 unselected patients from an Italian cohort, Systolic BP decreased gradually from the supine to the seated to the standing position (Fig. 1). Systolic but not diastolic orthostatic hypotension was rather common. When the established supine-to-standing cutoff values of at least 20 or at least 10 mmHg BP reduction, orthostatic hypotension was detected in 16.9% of the population. When we applied the criteria proposed by Shaw et al. with seated-to-standing BP reductions at least 15/at least 7 mmHg, orthostatic hypotension was diagnosed in 17.3% of the population without any appreciable discrepancy between the two tests (difference 0.5%, 95% confidence intervals 1.62–2.62, χ2 0.19, P = 0.66). Logistic regression analysis revealed that, in addition to advanced age [estimate 0.0013, standard error (SE) 0.003, z-statistics 2.094, P < 0.04], seated-to-standing orthostatic hypotension was more common in those with lower basal HRs (estimate 0.009, SE 0.004, z-statistics 2.447, P < 0.02) likely indicating that impaired baroreflex-mediated HR responses predispose to orthostatic hypotension. These findings extend the validity of the seated-to-standing test in diagnosing orthostatic hypotension from rare patients with autonomic dysfunction to more heterogeneous older populations.

Orthostatic hypotension is the key feature of many diseases affecting autonomic cardiovascular function such as diabetic autonomic neuropathy, amyloidosis, and pure autonomic failure among others. In these relatively rare patients, presence of orthostatic hypotension provides important information regarding prognosis and may inform treatment decisions. For example, medications worsening orthostatic hypotension may be discontinued and measures to treat symptomatic orthostatic hypotension may be initiated [4].

The idea that orthostatic hypotension could predict cardiovascular risk independently of traditional risk factors received much attention in recent years. However, the relationship between orthostatic hypotension and cardiovascular risk appears to be complex as outlined in a recent review [5]. For example, the risk associated with orthostatic hypotension may be greater in younger individuals. In individuals aged 65 years or older at inclusion, orthostatic hypotension did not significantly increase the risk for coronary or cerebrovascular events following adjustment for age, sex, and BP [6]. Yet, a recent analysis showed that in very old institutionalized individuals, orthostatic hypotension relates to increased cardiovascular morbidity and mortality independent of seated BP [7]. In the population-based Rotterdam Study, presence of orthostatic hypotension increased the risk for Alzheimer-type and vascular dementia during follow-up [8]. Participants with attenuated compensatory HR increases were at the highest risk. In contrast, orthostatic hypotension did not predict cognitive decline in another recent study [9]. There is no evidence that orthostatic hypotension acutely triggers cardiovascular or cerebrovascular events. Patients with acute strokes may be an exception.

Regardless of the prognostic implications, orthostatic hypotension complicates the management of arterial hypertension. For example, presence of orthostatic hypotension may indicate increased risk for drug-induced hypotension. Patients with severe orthostatic hypotension and supine hypertension due to autonomic failure are an extreme example with 10–20-fold hypersensitivity to vasodilator drugs [10]. It may be prudent to be particularly careful in escalating antihypertensive medications in hypertensive patients with concomitant orthostatic hypotension and to regularly check for signs and symptoms of worsened hypotension. Yet, given the known benefits of attaining guideline-recommended BP targets, presence of asymptomatic orthostatic hypotension should not lead to therapeutic negligence. In contrast to asymptomatic orthostatic hypotension, hypertension is known to elicit vascular events.

A final and curious note: in some cases orthostatic hypotension may be therapeutically exploited. For example, tilting of the whole bed heads up during the night ameliorates supine hypertension in patients with orthostatic hypotension. During daytime, standing improves BP compared with the seated position, which is typically assumed for office BP measurements.

Overall, the seated-to-standing maneuver could be utilized to test for orthostatic hypotension in settings when supine-to-upright measurements are not feasible. The test may be easier to conduct and does not require an examination table, which might encourage physicians testing for orthostatic hypotension in a larger proportion of their patients. The approach may be particularly useful as screening tool for severe orthostatic hypotension. However, the lower BP threshold compared with the supine-to-upright test mandates particularly careful BP measurements. Finally, the seated-to-standing test misclassified some patients compared with the standard supine-to-upright test. Whenever possible, the supine-to-upright test should be applied, particularly in the hypertension clinic.

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ACKNOWLEDGEMENTS

Conflicts of interest

There are no conflicts of interest.

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