Based on prior studies, the hypothesis that hyperventilation (HV) may have a pressor effect and play a causal role in hypertension has been suggested. The objective of this study was to correlate HV with blood pressure (BP)-change during a postural challenge. Consecutive subjects referred for evaluation of syncope, dizziness, chronic fatigue syndrome (CFS), fibromyalgia, or non-CFS fatigue were assessed with a 10-min supine 30-min head-up tilt test combined with capnography. We selected for analysis the records of patients aged 17–70 years, not taking vasoactive medications, having sitting systolic BP (SBP)<140 mmHg, sitting diastolic BP (DBP) <90 mmHg, and who completed 30 min of tilt. HV was diagnosed when end-tidal pressure of CO2 <30 mmHg was recorded consecutively for ⩾10 min. Postural hypertension (PHT) was diagnosed when DBP on tilt ⩾90 mmHg was recorded consecutively for ⩾10 min. DBP-change was computed as (median DBP on tilt) −(median DBP supine). PHT and DBP-change were correlated with HV. A total of 320 patient charts were reviewed. PHT was present in 30 cases. The mean DBP-change in patients with PHT was +9.9 mmHg (s.d. 5.8), with three patients manifesting HV. Of the remaining 290 patients, 56 had HV, their mean DBP-change was -0.3 mmHg (s.d. 7.2). The other 234 patients without HV had a mean DBP-change +0.95 mmHg (s.d. 5.7), comparable to the DBP-change in patients with HV. In, conclusion, posturally induced HV was not associated with an increase in BP, nor was PHT associated with HV, except in a small minority of cases.
The normal homeostatic response to stressful physical or mental stimuli includes increases in systolic and diastolic blood pressure (BP), heart rate (HR) and respiratory rate.1 Hyper-reactive individuals may respond to a stressor of ordinary intensity with excessive increase in BP, HR or with hyperventilation (HV).2, 3 HV is typically involved in the symptoms of panic attacks2 and hypocapnia induced by HV may link between panic disorder and chronic fatigue syndrome (CFS),4 asthma,5 ischaemic heart disease6 and arterial hypertension.7 Among patients whose BP is poorly controlled despite medications, anxiety-induced HV was frequently recognized.7
Assessment of the relationship between HV and BP is made difficult by technical constraints. Ideally, simultaneous monitoring of the BP and CO2 in the patients' natural ambience should be performed. A 24-h ambulatory BP monitoring is feasible, however, because of the slow response time of the electrodes and reflex vasoconstriction of skin vessels transcutaneous blood gas measurements for HV are not reliable.8, 9 The Hyperventilation Provocation Test consists of voluntary HV followed by monitoring the end tidal pressure of CO2 (ETPCO2) in the exhaled air in order to determine the time to recovery from induced hypocapnia. The low specificity of the Hyperventilation Provocation Test has been criticized.10, 11 On the other hand, change in body position from supine to standing triggers HV in patients presenting the HV syndrome, distinguishing these patients from healthy subjects.12, 13, 14 A postural challenge has been repeatedly utilized for the study of HV.8, 13, 14
The fast response of BP and HR to acute stimuli is under autonomic nervous control and thus measurements of the BP and HR during a postural test can be used as one measure of cardiovascular autonomic activity, providing there is no evidence of organic heart disease, venous insufficiency or hypovolaemia.1 Recognized pathological reactions to the head-up tilt test (HUTT) are formally defined as vasodepressor and cardioinhibitory reactions, orthostatic hypotension, postural tachycardia syndrome,1, 15 hyperventilation4 and postural hypertension.16 Hence, the HUTT offers the possibility to assess the interface between BP reactivity and HV.
In the present study, we utilized a 10-min supine–30-min capnography-HUTT to study BP dynamics, assess HV and compare the magnitude of BP change in the presence and absence of HV.
Patients and methods
The institutional committee for human investigation at our hospital approved the study. Technicians carrying out the capnography-HUTT measurements did not know of the intention to compare between the groups; subsequent analysis of charts was conducted by outside investigators who were unaware of the study's design. The study sample consisted of consecutive patients referred to the Syncope Clinic of Bnai-Zion Medical Center between January 1999 and January 2004. The patients were primarily referred for the evaluation by HUTT for one of the following indications: evaluation of unexplained syncope or dizziness, appraisal of occult dysautonomia or as volunteers for the present study. All patients had sitting systolic blood pressure (SBP) <140 mmHg and diastolic blood pressure (DBP) <90 mmHg on three or more consecutive measurements during a 2-week period. All subjects were fully ambulatory at the time of the study. Patients with evidence of organic heart disease, venous insufficiency or hypovolaemia were not included. Patients taking vasoactive medications were excluded from the study. The subjects' ages ranged from 17 to 70 years. Six patient-groups were studied: neurally mediated syncope,15 dizziness,15 CFS,16 fibromyalgia,17 non-CFS fatigue,16 and familial Mediterranean fever.18
Protocol of the capnography-HUTT19
The tests were conducted from 0800 to 1100 hours, in a quiet environment, at a constant room temperature of 22–25°C. The subjects had eaten their usual meals, but smoking and caffeine within 6 h of the examination were restricted. Intake of food products and medications with sympathomimetic activity was prohibited. Manual BP readings were taken by a physician certified in the technique recommended by the American Heart Association.20 A mercury column sphygmomanometer (Baumanometer, standby model 0661-0250) was utilized for measurement of the BP, since this is the standard method to which other noninvasive devices of BP measurement are validated.21 Studies on the accuracy of automated BP measurement devices showed that the majority of measurements overestimated the DBP, the SBP error varied with the device22 and there was no predictable aberration pattern of the automated measurements.23 The HR was recorded on an electrocardiographic monitor. The respiratory rate and the ETPCO2 were continuously monitored with a Datex Normacap infrared capnometer (Finland). For accurate monitoring of breathing and ETPCO2, open-mouth breathing was not permitted and positioning of the nasal cannula 1 cm within the nostrils as well as patency of the cannula were supervised. The patient lay supine on the tilt table, secured to the table at chest, hips and knees using adhesive girdles, the cuff of the BP recording device attached to the left arm, which was supported at heart level at all times during the study.
Measurements in the supine position were recorded three times at 5-min intervals, at each step the BP being determined as the average of three paired systolic and diastolic readings. The table was then gently tilted head-up to an angle of 70°. The duration of the tilt was 30 min. During the initial 5 min of tilt, measurements were obtained at 1-min intervals and subsequently, measurements were continued at 5-min intervals. Repeated measurements were taken at 30-s intervals when dizziness, faintness or loss of consciousness occurred. In the event of a loss of consciousness, the test was discontinued. Patients who could not complete 30 min of tilt were excluded from the analysis so as to permit assessment of the relationship between HV and PHT.
End points on capnography-HUTT
The following end points were determined.
Hyperventilation: Normal values of ETPCO2 in our laboratory are within the range of 36–40 mmHg. In diagnosing HV, a reading below the ETPCO2 cutoff of 30 mmHg is accepted by some authors while a 25 mmHg cutoff is preferred by others because of the alleged poor discriminatory power of the 30 mmHg cutoff.9, 13, 24, 25 In the present study, HV was diagnosed when end-tidal pressure of CO2 <30 mmHg were recorded consecutively for ⩾10 min (Figure 1). Symptoms of HV were recorded when patients volunteered them on their own initiative, but not in response to direct questioning, as follows: paresthesias of fingers or the face, palpitations, hot or cold sensations, lightheadedness, dizziness.
Postural hypertension (PHT): PHT was diagnosed when DBP on tilt ⩾90 mmHg was recorded consecutively for ⩾10 min (Figure 2).
BP-changes: The differences between median BP on tilt and median supine BP were computed as absolute BP-change and per cent BP-change:
The normality of distribution of values was assessed with the Shapiro–Wilk W-test. Unpaired Student's t-test was used to compare two independent groups of observations. P-values <0.05 were considered to be statistically significant.
Three patient groups
Three patient groups were compiled: Group I—PHT (n=30), Group II—HV no PHT (n=56) and Group III—no HV no PHT (n=234). Three patients in Group I also had HV. The patients' ages, gender as well as median BP values are shown in Table 1. The ages did not differ significantly among the groups. There was preponderance of female subjects in all groups. The difference in gender ratio between PHT and the other groups was significant (P<0.0001), but not between the two normotensive groups (Table 1).
SBP values and SBP-change in the different groups
The supine SBP was significantly higher in patients with PHT (group I) compared to other groups (P<0.005) (Figure 3). Patients with PHT was had significantly less absolute SBP-change (P<0.01) and per cent change (P<0.001). PHT group=average SBP change=−0.12 mmHg (s.d. 11.3), per cent SBP-change −0.6% (s.d. 10.9). In only two patients, the SBP increased on tilt by 10 mmHg or more. In group II (HV no PHT)=average SBP-change=−10.1 mmHg (s.d. 9.7), per cent SBP-change −11% (s.d. 12). In group III (no HV no PHT)=average SBP-change –6.1 mmHg (s.d. 6.2), per cent SBP-change −5.4% (s.d. 5). The difference was not significant between the latter two groups (Figure 4).
DBP values and DBP-change in the different groups
The supine DBP was significantly higher in patients with PHT than in the other groups (P<0.0001) (Figure 5) and so were the absolute and the per cent DBP-change (P<0.0001) (Figure 6): PHT group=average DBP change=+9.9 mmHg (s.d. 5.8), per cent DBP-change +12.3% (s.d. 8.6); Group II (HV no PHT)=average DBP-change=+0.9 mmHg (s.d. 5.7), per cent DBP-change +1.3% (s.d. 6.9); group III (no HV no PHT)=average DBP-change −0.3 mmHg (s.d. 7.2), per cent DBP-change −0.4% (s.d. 7.1). The difference was not significant between the latter two groups.
DBP-change related to severity of hypocapnia
Patients with ETPCO2 within the range 26–29 mmHg (n=33) had an average percent DBP-change=−0.34% (s.d. 6.8). Patients with ETPCO2 <26 mmHg (n=23) had an average percent DBP-change=−0.28% (s.d. 5.9), with no significant difference between them.
In our study, normotensive persons were submitted to a standardized nonspecific challenge—the HUTT. On HUTT, hyper-reactive homeostatic mechanisms were expressed either by undue increase in BP, HV or by a mixed hypertensive-HV reaction. There was little overlap between high BP and HV.
The hypothesis that HV may have a pressor effect is based on prior studies. It has been shown that HV may trigger digital artery spasm in Raynaud's disease,26 may cause splanchnic arterial constriction,27 increased coronary resistance and coronary artery spasm,3 decrease of cerebral blood flow and increased risk of cerebral ischemia.28 In one laboratory study, voluntary HV induced significant increased SBP by 8.9 mm Hg (P<0.01) and DBP by 8.2 mm Hg (P<0.05) in healthy persons.29 Similar results were found by others30, 31 (Table 2).
It is widely appreciated that HV is a frequent accompaniment to hypertension in panic attacks.2 Yet, epidemiological studies suggest that anxiety or stress have little role in sustained hypertension. Indeed, anxiety correlates poorly with cardiovascular reactivity and anxiolytics do not sustain BP lowering in subjects with hypertension-associated anxiety. Chronic anxiety disorders are associated with relatively low BP and low prevalence of sustained hypertension.32, 33
Postural challenge can trigger HV or PHT in predisposed subjects.4, 12, 13, 14, 16 Hence, postural challenge offers the possibility to assess the interface between BP reactivity and HV. The HUTT technique applied in this study is extensively utilized for diagnostic purposes in syncope clinics.15 The same protocol was applied in research for the study of disease-specific cardiovascular reactivity patterns in normotensive as well as hypertensive subjects.34, 35
The normal homeostatic response to postural challenge consists in a decrease in SBP by an average of 6.5 mmHg (range −19 to 11 mmHg) and increase in DBP by an average of 5.6 mmHg (range −9 to 22 mmHg).1 An exaggerated increase in BP during postural challenge has been called PHT: however, there are no accepted criteria to establish a diagnosis of PHT. Postural increase in SBP by 10 mmHg or more, indifferent of the absolute BP values, has been proposed as a criterion of PHT by some.16, 36 Other authors have proposed an increase in SBP more than 5 mm Hg.37 The degree of DBP increase on tilt is related to the subsequent development of diastolic hypertension, but has not been utilized as a criterion for diagnosing PHT.29, 38 DBP exceeding 90 mmHg is arbitrarily accepted for office BP in distinguishing hypertension from prehypertension. The same cutoff has not been studied and validated for the diagnosis of PHT. Data of the present study showed that patients classified as PHT according to the DBP 90 mmHg cutoff had indeed an increased BP reactivity.
The clinical diagnosis of HV is based on sudden onset, rapid and deep breathing followed by lightheadedness, weakness and tingling of the extremities as well as the absence of abnormal cardiac or pulmonary findings or hypoxia, and termination of the incident by rebreathing into a paper bag.6 Frequently, however, the HV is not clinically obvious.13, 20, 39 The diagnosis of HV is confirmed by demonstrating the presence of hypocapnia. In diagnosing hypocapnia, the ETPCO2 cutoff 30 mmHg is accepted by some authors while a 25 mmHg cutoff is preferred by others.9, 13, 24, 25 The inconsistency in defining hypocapnia stems from the observations that the clinical consequences of HV are not dependent only on CO2 levels, but also on the competence of the alkaline buffering systems, neuronal reactivity, integrity of the Ca2+/Mg2+ balance in smooth muscle, and the efficacy of habituation.40 Furthermore, symptoms that are typically associated with HV such as paresthesias of fingers or face, lightheadedness, dizziness, palpitations, tachycardia, headache, fatigue, heaviness of arms or legs, tremor of hands, hot or cold sensations, chest pain, nausea, tinnitus, visual blurring are not specific for hypocapnia and may be encountered in a variety of other disease states.6 In our experience, paresthesias, lightheadedness or dizziness occurred with similar frequency whether HV was diagnosed according to ETPCO2 cutoff 30 or 25 mmHg (Naschitz et al, personal communication). Careful supervision of the position of the nasal cannula within the nostril, patency of the cannula and avoidance of open-mouth breathing are mandatory for accurate monitoring of ETPCO2. This technique is preferred by our patients to nasal clip and mouthpiece for gas sampling and is reliable according to our experience.
In our study, no pressor effect was seen during hypocapnia. Patients who had HV on postural challenge had normal BP response to tilt. Patients who developed PHT had no HV, except in a small minority of cases. There was no link between BP reactivity and respiratory reactivity in this patient population having office BP values less than 140/90 mmHg and not receiving BP-lowering medications. These data are at variance with the assumption that HV may have a significant pressor effect in the normotensive subject.
The disparity between HV symptoms and BP reactivity in response to HV may be related to disproportionate constriction of arterioles in different vascular territories.6 Thus, constriction of cerebral arteries resulting in cerebral ischemia can occur without a systemic pressor effect, as has been shown on trans-cranial Doppler and magnetic resonance flow studies.3, 41. Further, the ‘HV symptom complex’7 is only partially caused by cerebral ischemia but is also related to increased neuronal excitability.42, 43 Thus, there is a rationale for the disparity between BP, HV and symptoms of HV.
There are limitations to the applicability of the results of this study. First, our selection included patients with a tendency to HV14, 20, 39 and with often an abnormal cardiovascular reactivity.34, 35 There was also a female gender bias. Therefore, observations of this study cannot be extrapolated to hypertensive patients or patients with anxiety. Second, a test of voluntary HV with the patient seated was not performed and we did not compare the cardiovascular and respiratory reactivity on HUTT with results of a voluntary hyperventilation test. Third, the prognostic significance of PHT and HV during the HUTT on later development of arterial hypertension have barely been investigated.38 Our study did not provide additional data on this subject.
In conclusion, PHT did not correlate with HV in the present study. Similarly, posturally induced HV was not associated with an increase in DBP. These data provide evidence for lack of an obligate correlation of HV with elevated BP and do not support a common pathogenic mechanism for the two.
Wieling W, Karemaker JM . Measurement of heart rate and blood pressure to evaluate disturbances in neurocardiovascular control. In: Mathias ChJ (ed) Autonomic Failure. A Textbook of Clinical Disorders of the Autonomic Nervous System, 4 edn. Oxford Univeristy Press: Oxford, 1999, pp 198–210.
Garssen B, Buikhuisen M, van Dyck R . Hyperventilation and panic attacks. Am J Psychiatry 1996; 153: 513–518.
Fortune JB et al. Cerebral blood flow and blood volume in response to O2 and CO2 changes in normal humans.J Trauma 1995; 39: 463–471.
Saisch SG, Deale A, Gardner WN, Wessely S . Hyperventilation and chronic fatigue syndrome. Q J Med 1994; 87: 63–67.
Lehrer PM . Emotionally triggered asthma: a review of research literature and some hypotheses of self-regulation therapies. Appl Psychophysiol Biofeedback 1998; 23: 13–41.
Laffey JG, Kavanagh BP . Hypocapnia. N Engl J Med 2002; 37: 43–53.
Kaplan NM . Anxiety-induced hyperventilation. A common cause of symptoms in patients with hypertension. Arch Intern Med 1997; 157: 945–948.
Malmberg LP, Tamminen K, Sovijarvi AR . Orthostatic increase of respiratory gas exchange in hyperventilation syndrome. Thorax 2000; 55: 295–301.
Simon M et al. Comparison of transcutaneous and endtidal CO2-monitoring for rigid bronchoscopy during high-frequency jet ventilation. Acta Anaesthesiol Scand 2003; 47: 861–867.
Hornsveld H, Garssen B . The low specificity of the Hyperventilation Provocation Test. J Psychosom Res 1996; 41: 435–449.
Spinhoven P, Onstein EJ, Sterk PJ, Le Haen-Versteijnen D . Discordance between symptom and physiological criteria for the hyperventilation syndrome. J Psychosom Res 1993; 37: 281–289.
Steurer J et al. Changes in arterial and transcutaneous oxygen and carbon dioxide tensions during and after voluntary hyperventilation. Respiration 1997; 64: 200–205.
Gardner W . Orthostatic increase of respiratory gas exchange in hyperventilatory syndrome. Thorax 2000; 55: 257.
Naschitz JE et al. The capnography head-up tilt test for evaluation of chronic fatigue syndrome. Semin Arthritis Rheum 2000; 30: 79–86.
Brignole M et al. Task Force Report. Guidelines on management (diagnosis and treatment) of syncope. Eur Heart J 2001; 22: 1256–1306.
Fukuda K et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Study Group. Ann Intern Med 1994; 121: 953–959.
Wolfe F et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia: Report of the Multicenter Criteria Committee. Arthritis Rheum 1990; 33: 160–172.
Livneh A et al. Criteria for the diagnosis of familial Mediterranean fever. Arthritis Rheum 1997; 40: 1879–1885.
Naschitz JE et al. The capnography-tilt test for the diagnosis of hyperventilation syncope. Q J Med 1997; 90: 139–145.
Curb JD et al. Training and certification of blood pressure observers. Hypertension 1983; 5: 610–614.
O'Brien E et al. British hypertension protocol: evaluation of automated and semi-automated blood pressure measuring devices with special reference to ambulatory systems. J Hypertens 1990; 8: 607–619.
Shuler CL, Allison N, Holcomb S, Harlan M . Accuracy of automatic blood pressure device in stable inpatients. Arch Intern Med 1998; 158: 714–721.
Naschitz JE et al. In-field validation of automatic blood pressure measuring devices. J Hum Hypertens 2000; 14: 37–42.
Gardner WN, Bass C . Controlled study of respiratory response during prolonged measurement in patients with chronic hyperventilation. Lancet 1986; ii: 826–830.
Rosen SD . Hyperventilation and the chronic fatigue syndrome. Q J Med 1994; 87: 373–374.
Williams H, Freeman LJ, Nixon PG . Hyperventilation and Raynaud's disease. Postgrad Med J 1987; 63: 377–379.
Guzman JA, Kruse JA . Gut mucosal-arterial PCO2 gradient as an indicator of splanchnic perfusion during systemic hypo- and hypercapnia. Crit Care Med 1999; 27: 2760–2765.
Kazmaier S et al. Effects of respiratory alkalosis and acidosis on myocardial blood flow and metabolism in patients with coronary artery disease. Anesthesiology 1998; 89: 831–837.
Todd GP et al. Pressor effect of hyperventilation in healthy subjects. J Hum Hypertens 1995; 9: 119–122.
Fontana F et al. Blood pressure response to hyperventilation test reflects daytime pressor profile. Hypertension 2003; 41: 244–248.
Alexopoulos D et al. Hemodynamic response to hyperventilation test in healthy volunteers. Clin Cardiol 1995; 18: 636–641.
Rosenman RH . Does anxiety or CVR have a causal role in hypertension? Integr Physiol Behav Sci 1991; 26: 296–304.
Young EA, Nesse RM, Weder A, Julius S . Anxiety and cardiovascular reactivity in the Tecumseh population. J Hypertens. 1998; 16 (12, Part 1): 1727–1733.
Naschitz JE et al. Disease-related phenotypes of cardiovascular reactivity as assessed by fractal and recurrence quantitative analysis of the heart rate and pulse transit time. Q J Med 2004; 97: 141–151.
Naschitz JE et al. Assessment of cardiovascular reactivity by fractal and recurrence quantification analysis of heart rate and pulse transit time. J Hum Hypertens 2003; 17: 111–118.
Eguchi K et al. Greater change of orthostatic blood pressure is related to silent cerebral infarct and cardiac overload in hypertensive subjects. Hypertens Res 2004; 27: 235–241.
Thomas RJ et al. Positional change in blood pressure and 8-year risk of hypertension: the CARDIA Study. Mayo Clin Proc 2003; 78: 951–958.
Jokinitty J et al. Can blood pressure responses to tests unmask future blood pressure trends and the need for antihypertensive medication? Ten years of follow-up. Clin Physiol Funct Imaging 2002; 22: 125–133.
Saish SGN, Deale A, Gardner WN, Wessely S . Hyperventilation and chronic fatigue syndrome. Q J Med 1994; 87: 63–67.
Nixon PGF . An appraisal of Thomas Lewi's effort syndrome. Q J Med 1995; 88: 741–747.
Wecksser M et al. Functional imaging of the visual cortex with bold-contrast MRI: hyperventilation decreases signal response. Magn Reson Med 1999; 41: 213–216.
Huttunen J et al. Effects of voluntary hyperventilation on cortical sensory responses: electroencephalographic and magnetoencephalographic studies. Exp Brain Res 1999; 125: 248–254.
Graham EM, Apostolou M, Mishra OP, Delivoria-Papadopoulos M . Modification of the N-methyl-D-aspartate (NMDA) receptor in the brain of newborn piglets following hyperventilation induced ischemia. Neurosci Lett 1996; 218: 29–32.
About this article
Cite this article
Naschitz, J., Mussafia-Priselac, R., Peck, E. et al. Hyperventilation and amplified blood pressure response: is there a link?. J Hum Hypertens 19, 381–387 (2005). https://doi.org/10.1038/sj.jhh.1001830
- arterial hypertension
- postural hypertension
- tilt test
Current Hypertension Reports (2014)
Nonspecific dizziness: frequency of supine hypertension associated with hypotensive reactions on head-up tilt
Journal of Human Hypertension (2006)
Patterns of Hypocapnia on Tilt in Patients with Fibromyalgia, Chronic Fatigue Syndrome, Nonspecific Dizziness, and Neurally Mediated Syncope
The American Journal of the Medical Sciences (2006)
Physiological Measurement (2006)