Journal of Human Hypertension (2006) 20, 157–162 & 2006 Nature Publishing Group All rights reserved 0950-9240/06 $30.00 www.nature.com/jhh ORIGINAL ARTICLE Nonspecific dizziness: frequency of supine hypertension associated with hypotensive reactions on head-up tilt

JE Naschitz1, R Mussafia-Priselac1, Y Kovalev1, N Zaigraykina1, G Slobodin1, N Elias1, S Storch2 and I Rosner3 1Department of Internal A, The Bnai-Zion Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; 2Department of , The Bnai-Zion Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel and 3Department of , The Bnai-Zion Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel

The clinical syndrome of supine hypertension asso- The median supine BP was 162/90 mmHg; the median ciated with orthostatic hypotension (OH) in given nadir BP on tilt was 118/78 mmHg. Four SH-HRT patterns individuals is recognized by specialists, but is under- were recognized: (I) SH with typical neurogenic OH diagnosed in the community. The objective of this study (n ¼ 6), (II) SH with vasovagal reaction on tilt (n ¼ 4), (III) was to assess supine hypertension associated with SH with sustained HRT (n ¼ 28), and (IV) SH with mixed hypotensive reactions on head-up tilt (SH-HRT) among orthostatic-vasovagal reaction on tilt (n ¼ 4). Dizziness patients evaluated for nonspecific dizziness. Consecu- on tilt occurred in 25% of patients category III (SH with tive patients with nonspecific dizziness were studied sustained HRT), while appearing universally in other with a 10-min supine 30-min head-up tilt test. Supine SH-HRT patterns. In conclusion, nonspecific dizziness hypertension (SH) was diagnosed when supine systolic may be the chief complaint in patients with SH-HRT, (SBP) was X140 mmHg and/or supine a disorder often unrecognized by clinicians. Different diastolic blood pressure (DBP) was X90 mmHg. Hypo- patterns of SH-HRT on HUTT may reflect different tensive reactions on tilt (HRT) were diagnosed when aberrations in cardiovascular homeostasis and may SBP decreased by X30 mmHg on tilt and/or DBP require differentiated management strategies. decreased by X15 mmHg. Of 430 patients tested, 42 Journal of Human Hypertension (2006) 20, 157–162. (9.8%) had SH-HRT. The median age was 67 years; 37 doi:10.1038/sj.jhh.1001947; published online 20 October 2005 had a pretest diagnosis of hypertension, with treatment.

Keywords: arterial hypertension; postural hypotension; tilt test

Introduction In our experience, some patients with un- explained nonspecific dizziness referred for evalua- The association of supine hypertension (SH) and tion exhibited SH associated with hypotensive orthostatic hypotension (OH) in a given individual reactions on head-up tilt (SH-HRT), which may represents a therapeutic dilemma because treatment have bearing on their symptoms. A retrospective of one of the two aspects of the condition may 1 study was conducted to assess SH-HRT among worsen the other. As expected, published studies patients evaluated for nonspecific dizziness. on SH–OH are to be found by and large in patients with autonomic nervous disorders as well as those with chronic arterial hypertension who present Patients and methods syncope.1–6 In clinical practice, aside from typical OH, a variety of other hypotensive reaction patterns Patients may be recognized in association with diverse The institutional committee for human investigation presenting complaints such as headache and fatigue. at our hospital approved the study. Files of con- secutive patients who underwent a tilt test during the period between January 1999 and January 2004 Correspondence: Professor JE Naschitz, Department of Internal for evaluation of nonspecific dizziness were ana- Medicine A, Bnai-Zion Medical Center, Haifa 31048, P.O. Box lysed. The patients were referred by otorhino- 4940, Israel. E-mail: [email protected] laryngologists or neurologists from a dizziness clinic Received 27 June 2005; revised 23 August 2005; accepted 23 after routine investigation was unrewarding. Pa- August 2005; published online 20 October 2005 tients had neither spontaneous nor gaze nystagmus; Supine hypertension with postural hypotension JE Naschitz et al 158 normal reactions were elicited on head-shaking test, Methods head-impulse test, visual acuity test, Fukuda step- Protocol of the capnography-head-up tilt test ping, Dix-Hallpike and Brandt-Daroff tests.7 Patients (HUTT)15. The tests were carried out from 0800 to with a history of syncope or vertigo were excluded.8 1100 hours, in a quiet environment, at a constant All subjects were fully ambulatory at the time of the room temperature of 22–251C. The subjects had study. Their ages ranged from 18 to 70 years. eaten their usual meals, but smoking and caffeine within 6 h of the examination were restricted. Intake of with sympathomimetic activity was Definitions prohibited. Manual BP readings were taken by Syncope is defined as a transient loss of conscious- a skilled in the technique recommended ness associated with loss of postural tone, occurring by the American Heart Association.16 A mercury in the upright position and followed by a rapid column sphygmomanometer (Baumanometer, stand- spontaneous recovery on assuming the supine by model 0661-0250) was utilized for measurement position.9 Dizziness is a vague term lumping of the BP, since this is the standard method to which together symptoms of vertigo, lightheadedness, other noninvasive devices of BP measurement are disequilibrium and presyncope.8 Vertigo is typically validated.17 The HR was recorded on an electro- experienced as an illusion of motion, such as cardiographic monitor. The respiratory rate and the whirling imbalance or spatial disorientation. Non- end-tidal pressure of CO2 (ETPCO2) were continu- specific dizziness, which is exclusive of vertigo, is ously monitored with a Datex Normacap infrared often difficult for the patient to describe, frequently capnometer (Finland). The patient lay supine on the referred to as giddiness or lightheadedness, with tilt table, secured to the table at chest, hips and consciousness unaffected during the episode.9 knees using adhesive girdles. The cuff of the BP Supine hypertension was defined for purposes of recording device was attached to the left arm, which the study as systolic blood pressure (SBP) values of was supported at the heart level at all times during 140 mmHg or more and/or diastolic blood pressure the study. Measurements in the supine position values (DBP) of 90 mmHg or more on five measure- were recorded three times at 5 min intervals, at ments during the 10 min recumbence phase before each step the BP being determined as the average of beginning of the tilt test. three paired systolic and diastolic readings. The Hypotensive reactions on tilt (HRT) were consid- table was then gently tilted head-up to an angle of ered, utilizing restrictive criteria, when, at any time 701. The duration of the tilt was 30 min. During during head-up tilt, the SBP decreased by the initial 5 min of tilt, measurements were obtained X30 mmHg or the DBP decreased by X15 mmHg at 1 min intervals and, subsequently, measurements relative to the median of the last supine measure- were continued at 5 min intervals. Repeated ments.10 Several patterns of the HRT were defined measurements were taken at 30 s intervals when and served to classify the patients accordingly: (1) dizziness, faintness or loss of consciousness occurred. typical neurogenic OH characterized by early onset In the event of severe symptoms, the test was of the HRT reaction within 3 min of tilting;11 (2) discontinued. vasovagal reaction characterized by increase of heart Patients exhibiting SH-HRT were assigned to one rate of at least 10 beats per minute after the initial of the patterns described above under hypotensive 3 min of the tilt (consistent with steady-state reactions on tilt. Symptoms appearing on tilt were adaptation) followed later on tilt by a precipitated correlated with HRTs. fall in SBP and DBP, usually, with concomitant 9 decrease in heart rate; (3) sustained HRT character- Statistical analysis. The normality of distribution ized by slow and continuous decrease in BP on of values was assessed with the Shapiro-Wilk postural challenge which did not meet the criteria of W-test. Unpaired Student’s t test or Mann–Whitney OH and were not associated with symptoms during U-test were used, when indicated, to compare 1 the first 3 min of tilt; (4) mixed HRT, a sustained between independent groups of observations. Cor- HRT reaction that resulted in a vasovagal reaction relations between variables were assessed with 9 (also called atypical vasovagal reaction). Pearson’s coefficient of correlation. Two-tailed Hyperventilation was diagnosed by hypocarbia, P-values of 0.05 or less were considered to be measured as end-tidal pressure of CO2. Normal statistically significant. values of end-tidal pressure of CO2 in our laboratory are within the range of 36–40 mmHg. In diagnosing hypocarbia, the ETPCO2 cutoff of 30 mmHg was Results accepted by us.12,13 ‘Sustained hyperventilation’ was diagnosed when end-tidal pressures of CO2 Data were extracted from 430 charts of consecutive o30 mmHg were recorded consecutively for patients who underwent the capnography-HUTT for X10 min. When a brief episode of hyperventilation evaluation of nonspecific dizziness. A total of 42 occurred in association with severe hypotension just patients met the proposed criteria of SH-HRT. There prior to study termination, it was designated ‘HRT- were 16 males and 26 women. Their median age hyperventilatory event’.14 was 67 years (range 47–86 years). The diagnoses

Journal of Human Hypertension Supine hypertension with postural hypotension JE Naschitz et al 159 at referral included arterial hypertension in 37 sustained HRT and four patients had mixed HRT. patients, ischaemic heart disease in seven, diabetes Characteristic tracings are shown in Figures 1–4. mellitus in six and cerebrovascular accident in four. Dizziness or syncope on tilt occurred in 54% of A total of 14 patients reported falls without loss of patients presenting sustained HRT, while present in consciousness. Medications at evaluation included all subjects who had any of the other HRT patterns nitrates in seven patients, antihypertensives in 21, (Table 3). Tilt was terminated early in five of six one patient on antiparkinsonian and two patients with typical neurogenic OH (average dura- patients on anxiolytic drugs (Table 1). tion of tilt 15.7 min); in three of four patients with vasovagal reaction (average duration of tilt 21 min); in 10 of 28 patients with sustained HRT (average BP and HR measurements duration of tilt 24 min) and in all four patients with Results of the BP and HR measurements, sitting, mixed HRT (average duration of tilt 15.2 min). ‘HRT- supine and on head-up tilt are shown in Table 2. No hyperventilatory events’ occurred in six patients. statistically significant differences of BP, HR and Sustained hyperventilation was not observed. ETPCO2 measurements were noted between patients exhibiting various SH-HRT patterns. Correlations The BP changes from supine to tilt and HR changes Patterns of SH-HRT from supine to tilt did not correlate significantly Typical neurogenic OH occurred in six patients, four with supine BP. Further, the BP changes from supine patients had vasovagal reaction, 28 patients had to tilt were not significantly different in those

Table 1 Patient characteristics

Neurogenic OH Vasovagal reaction Sustained HRT Mixed HRT

Variables Patients 6 4 28 4 Age (years) 77 (47–84) 68 (52–82) 68 (49–81) 63 (51–84) Males (%) 50 50 30 0 Sit-SBP (mmHg) 144 (90–145) 165 (110–180) 150 (118–230) 160 (140–160) Sit-DBP (mmHg) 83 (54–100) 85 (74–88) 81 (55–113) 90 (85–100)

History HT (%) 83 75 83 100 DM (%) 33 25 17 0 CVA (%) 17 25 10 0

Medications Anti-HT (%) 83 75 77 100 Nitrate (%) 17 0 17 50 Diuretic (%) 33 0 23 25 Antiparkinsonian (%) 17 25 3 0

The numbers represent medians, with minimal and maximal values in parentheses. Neurogenic OH ¼ supine hypertension with typical neurogenic orthostatic hypotension on tilt; vasovagal reaction ¼ supine hypertension with vasovagal reaction on tilt; sustained HYPO ¼ supine hypertension with sustained hypotensive reaction on tilt; mixed ¼ supine hypertension with mixed hypotensive-vasovagal reaction on tilt; HT ¼arterial hypertension; DM ¼ diabetes mellitus; CVA ¼ cerebrovascular accident.

Table 2 Measurements on capnography-HUTT

Variables Neurogenic OH Vasovagal reaction Sustained HYPO Mixed HYPO

Supine-SBP (mmHg) 164 (145–170) 169 (148–180) 164 (140–210) 165 (140–175) Supine-DBP (mmHg) 77 (66–100) 85 (72–100) 88 (66–105) 84 (80–90) Supine-HR (mmHg) 74 (52–91) 69 (57–71) 62 (48–94) 63 (57–76)

Supine-ETPCO2 (mmHg) 34 (31–37) 39 (32–40) 37 (33–42) 36 (32–36) Tilt-SBP (mmHg) 114 (50–119) 100 (50–124) 120 (94–165) 100 (70–115) Tilt-DBP (mmHg) 60 (30–90) 52 (30–75) 78 (60–100) 69 (40–78) Tilt-HR (mmHg) 76 (56–108) 72 (51–110) 66 (40–96) 67 (46–77) a Tilt-ETPCO2 (mmHg) 29 (27–34) 37 (20–37) 33 (30–41) 30 Tilt terminated (min) 10 (1–30) 30 (20–30) 30 (15–30) 16 (10–25)

The numbers represent medians, with minimal and maximal values in parentheses. aMeasurements were available in only one patient. ‘Supine’ values in this table are the median of three measurements after 10 min of recumbence. ‘Tilt’ values are the lowest BP on postural challenge and the concomitant heart rate and ETPCO2.

Journal of Human Hypertension Supine hypertension with postural hypotension JE Naschitz et al 160 180 SBP 200 160 SBP DBP HR 140 DBP HR 120 150 100 80 100 60 40 20 50 0 5 2 3 10

tilt 1 0 5 2 3 4 5 10 10 15 20 25 30 supine 1 tilt 1

Figure 1 Supine hypertension with typical neurogenic ortho- supine 1 static hypotension. Figure 4 Supine hypertension with mixed HRT.

Table 3 Patients presenting dizziness, hypocarbia, presyncope or 160 syncope on tilt

140 SH-HRT Patients Dizziness Hypocarbia Syncope None

120 Neurogenic OH 6 6 2 1 0 Vasovagal 4 3 2 1 0 100 Sustained HYPO 28 7 1 0 21 Mixed 4 3 1 2 0 80 Total 42 17 6 4 21

60 The numbers in the table represent patients presenting the symptom. 40 SBP 20 DBP HR patients taking antihypertensive medications versus 0 those not taking antihypertensive medications. 5 2 3 4 5 10 10 15 20 25 30 tilt 1

supine 1 Discussion Figure 2 Supine hypertension with vasovagal reaction on tilt. This study was motivated by the desire to extend the clinical spectrum of the syndrome of SH and OH. We found SH-HRT in nearly 10% of patients referred for further evaluation of nonspecific dizziness, after 180 results of ENT and neurological examinations were SBP 160 unrewarding. On tilt, symptomatic reactions remi- DBP niscent of the patients’ nonspecific dizziness 140 HR occurred in 69% of the subjects. 120 Dizziness affects over 50% of the elderly popula- 100 tion and is the most common reason for visiting a physician after the age of 75 years.8 Dizziness has 80 been reviewed in the settings of primary care, 60 emergency room and dizziness clinics. The main 40 aetiologies of dizziness include vestibular or central vertigo (45–54%), disequilibrium (2–16%), presyn- 20 cope (4–14%), psychiatric disorders (9–21%), hy- 0 perventilation (1–23%), multiple causes (12–13%)

5 2 3 4 5 7,8,18–20 10 10 15 20 25 30 and unknown (8–19%). In reviewing the tilt 1 literature, we could not find reference to postural

supine 1 BP changes in patients complaining of nonspecific Figure 3 Supine hypertension with sustained HRT. dizziness. Patients in our study were preselected,

Journal of Human Hypertension Supine hypertension with postural hypotension JE Naschitz et al 161 having undergone and neurol- Table 4 What is known and what this study adds on dizziness ogy evaluation for common causes of dizziness, and SH-HRT which was unrewarding. The referral model in our Previously known study being different from the above studies, data K Patients with autonomic failure may display both SH and of the present and other studies in patients with severe OH dizziness may therefore not be strictly comparable. K Orthostatic hypotension may be present in 5–14.6 % of Pointedly, we excluded vertigo which represents patients suffering from chronic hypertension, but only a minority of these have orthostatic symptoms about half of the patients presenting with dizziness K The main symptoms related to OH are weakness, dizziness in other studies. and syncope In the present study, four patterns of SH-HRT were K Typically OH occurs within 3 min of standing but ‘delayed- recognized. These were defined by the time se- onset OH’ has also been described quence of the haemodynamic events during the tilt K The treatment of SH-OH is particularly problematic test. These findings extend beyond the well-recog- In the present study on nonspecific dizziness nized SH-OH described in the literature, which is K 10% of patients evaluated had SH-HRT represented in the present study by the group of K Four patterns of SH-HRT were recognized ‘typical neurogenic OH’. Epidemiologic surveys K Classical neurogenic OH was infrequent K The large majority had progressive and sustained hypotension have found OH in as many as 20% of patients over K Symptoms on test correlated with suddenness of hypotension the age of 65 years.21–27 In the Cardiovascular Health study, the prevalence of OH was 18% in subjects aged 65 years or older, but only 2% of these patients had dizziness when standing. There was a modest patterns of SH-HRT, other than SH–OH, may be association between OH and SH, carotid stenosis identified. The implications of SH-HRT patterns for and use of oral hypoglycemic agents.25 In the patient management remain to be established. present study, those with classical SH–OH make up only a small minority of the patients with SH- HRT, the majority being those with sustained HRT. References 28 In an earlier study, Streeten and Andersen de- 1 Biaggioni I, Robertson RM. Hypertension in orthostatic scribed ‘neurogenic OH with delayed onset’, which hypotension and autonomic dysfunction. Cardiol Clin may be comparable to those with SH-HRT in the 2002; 20: 291–301. present study. 2 Schutzman J, Jaeger F, Maloney J, Fouad-Tarazi F. Dizziness on tilt occurred uniformly in those with Head-up tilt and hemodynamic changes during ortho- a sudden decrease in BP such as typical neurogenic static hypotension in patients with supine hyper- OH, vasovagal reaction and mixed HRT. On the tension. J Am Coll Cardiol 1994; 24: 454–461. other hand, patients with sustained HRT, having a 3 Goldstein DS, Pechnik S, Holmes C, Eldadah B, more gradual decrease in BP, were less symptomatic. Sharabi Y. Association between supine hypertension The linkage between SH-HRT and symptoms on tilt and orthostatic hypotension in autonomic failure. Hypertension 2003; 42: 136–142. suggests a possible cause and effect relationship. 4 Jordan J, Biaggioni I. 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