Journal Logo


Is essential hypertension sometimes a psychosomatic disorder?

Esler, Murraya; Parati, Gianfrancob

Author Information
  • Free

There has been a recent resurgence of interest in the idea that mental stress and psychological illness might cause cardiovascular disease. Although the question of whether chronic, ongoing stress leads to the development of coronary heart disease remains a debated issue, the evidence establishing depressive illness as a bona fide cardiac risk factor is so strong that some national health policy statements confidently assert the causal link to be undeniable [1]. Similarly, the importance of short-term mental stress as a trigger for the development of myocardial infarction and sudden death in patients with existing heart disease is no longer questioned [2]. This relationship between acute mental stress and the incidence of heart attack has been spectacularly illustrated during natural disasters, such as the 1994 Los Angeles earthquake [3].

Stress and blood pressure

Although the notion that essential hypertension may arise through psychosomatic mechanisms is rather more contentious than the stress–heart disease link, the idea is an old one, originally attributed to Geisbock [4]. The lay public needs no convincing that psychological factors cause high blood pressure although, despite such ready acceptance, proof that essential hypertension can be psychosomatic remains elusive. However, clinical, epidemiological and laboratory research does provide increasingly strong support for the notion that behavioural and psychological factors may be important in pathogenesis. Although a typical hypertensive personality does not exist, as a characteristic behavioural pattern, hypertensive patients have been reported to commonly exhibit subnormal levels of assertiveness and suppression of hostile impulses [5,6]. More important, perhaps, are long-term follow-up studies of human populations. In their celebrated study, Timio et al. [7] conducted a longitudinal investigation of cloistered nuns living in a secluded and unchanging environment in Umbria in whom blood pressure did not demonstrate the expected rise with age. Also important are epidemiological-based observations made in human populations that demonstrate blood pressure elevation soon after migration [8].

In this issue of the journal, Steptoe and Willemsen [9] continue this tradition, showing a blood pressure-raising influence of low job control in the workplace, in concert with increased perceived stress. A possibly surprising finding in their study, which reports results from a Whitehall II Study epidemiological cohort, was the failure to replicate findings from previous investigations [10,11] showing that job strain, defined as the relationship between the demands of a job to the degree of freedom to conduct it as desired (job demands/job control), is directly related to blood pressure during the working day and evening. Blood pressure was specifically related to job control (lower control linked to higher pressure) and the perceived stress of the job. The level of demand in the job was unrelated to blood pressure level. Higher socio-economic status participants, and women, were more stressed by low job control compared to men and people of lower socioeconomic status. As the authors suggest, higher socioeconomic groups are accustomed to greater degrees of control over their life circumstances and may, perhaps, find a lack of control at work particularly aversive and stressful. An unsettled issue is whether the marginally higher pressure in the low job control group might materially increase cardiovascular risk, or escalate over time to a pressure level that met the criteria for a diagnosis of hypertension.

Assessing the cardiovascular effects of stress in humans: methodological aspects

Whether or not repeated exposure to environmental stress, particularly in the workplace, might lead to sustained hypertension has been an issue of debate for some years [12,13]. One reason for the discrepant views is the methodological difficulties encountered when trying to precisely assess, in a quantitative fashion, the effects of stress on cardiac and vascular targets in humans. The traditional approach to this quantification is based on use of laboratory stressors, which are believed to reproduce, in a controlled environment, the effects of either physical or psycho-emotional daily life challenges [13]. The tests most commonly employed include hand-grip exercise (isometric muscle exercise usually applied for 90 s at 30% of the previously checked subject's maximal strength), cold pressor test (hand immersion in ice water for 60 s), mental arithmetics (administering subtractions of numbers of increasing complexity under pressure of time), mirror drawing test (reproduction of a geometrical drawing by observing the pencil-carrying hand only as reflected by a mirror), the Stroop colour-word test (computer-based test requiring the subject under examination to select a coloured object while exposed to conflicting visual and auscultatory stimulation), and public speaking. The accuracy in evaluating the blood pressure response to these manoeuvres has been considerably improved by the availability of systems for continuous blood pressure monitoring, such as the Finapres, the Finometer (Finapres Medical Systems, Arnhem, The Netherlands) and the Task Force Monitor (CNSystem, Graz, Austria), which have offered the possibility to precisely assess, on a beat-by-beat basis and non-invasively, not only the peak changes in blood pressure and heart rate induced by administration of the above laboratory tests, but also the dynamic profile of haemodynamic variations both during test performance and in the recovery phase [14].

However, in spite of such remarkable progress in the technology of cardiovascular monitoring, the ability of laboratory stressors to faithfully reflect the actual blood pressure and heart rate responses to daily life stress in the home or working environment remains a controversial issue. Indeed, we were able to show that the evaluation of the cardiovascular responses to laboratory stressors is affected by a number of limitations [13,15]. First, the observed blood pressure and heart rate changes may be poorly reproducible, displaying coefficients of variation in the range of 15–33% [16]. Second, subjects identified as hyper- or hyporeactive to a given stressors, may be, respectively, hypo- or hyper-reactive to another test [17]. Finally, only a limited relationship could be observed either between the responses to different laboratory tests and between the blood pressure or heart rate changes elicited in the stress laboratory on the one hand and the blood pressure or heart rate response of real life stressful conditions on the other. This was the case when specific types of daily life stressful conditions were considered, as exemplified by the ‘white-coat effect’ induced by a physician's visit. It was also the case when considering the overall quantification of daytime blood pressure and heart rate variability, taken as a global measure of the reactivity to daily challenges and quantified by means of 24-h ambulatory blood pressure monitoring techniques [13,17].

Indeed, the increasing diffusion of systems for ambulatory blood pressure monitoring in daily life represents another major step forward in this field because it has allowed the much easier assessment of blood pressure and heart rate changes induced by physical or emotional stress in the subject's usual environment, either at home or in the workplace [18]. Through this approach, direct information could be obtained in real time on the blood pressure effects of extremely stressful conditions, such as flying a jetfighter aeroplane, or being exposed to the effects of a seismic shock during an earthquake [19]. However, ambulatory blood pressure monitoring has also allowed the quantification of blood pressure effects for more common daily challenges, such as public speaking, undergoing job or university interviews, playing cards or driving a car in city traffic. In particular, for the first time, this approach has allowed the direct quantification of blood pressure and heart rate changes induced by job stress in different working environments [20,21].

This was also the case in the study by Steptoe and Willemsen [9], where the measurement of blood pressure changes induced by job-related stress was coupled with other parameters, with the aim of providing a deeper insight into the mechanisms that lead to blood pressure elevation in the workplace.

Mediating mechanisms of a stress–hypertension link?

What might be the pathophysiological mechanisms by which life stresses within or outside the workplace could generate hypertension? Activation of the sympathetic nervous system, as a mediating mechanism, is seen as central to the stress–hypertension link. This view was formalized in a recent ruling by an Australian Government body, the Specialist Medical Review Council (Commonwealth of Australia Gazette, 27 March 2002), which was charged with evaluating the causal contribution of stress to the development of essential hypertension. Despite the medicolegal implications, the ruling was made that occupational stress is one proven cause of hypertension. The judgement was reached after due consideration of the epidemiological evidence but, perhaps surprisingly, was based in particular on the described neural pathophysiology of essential hypertension: (i) persistent sympathetic nervous activation is commonly present [22,23]; (ii) suprabulbar projections of noradrenergic brainstem neurons are activated [24,25], as is also seen in experimental models of stress; and (iii) adrenaline is released as a cotransmitter in the sympathetic nerves of hypertensive patients [26,27], as it also is in patients with panic disorder [28], who provide a clinical model of ongoing, severe stress response. These were all considered to be presumptive biological markers of stress.

Experimental studies in the spontaneously hypertensive rat suggest that, with chronic mental stress, it may be the long-term activation of the sympathetic nervous outflow to the kidneys that is of particular importance as a blood pressure-elevating mechanism [29]. The causal significance of sympathetic nerve adrenaline co-transmission per se remains uncertain. One theory of the pathogenesis of essential hypertension, the ‘adrenaline hypothesis’ [30], envisages that stress is a major factor in hypertension pathogenesis through stress-induced elevations in the plasma concentration of adrenaline enlarging the pool of adrenaline present in sympathetic nerves, leading to release of adrenaline as a co-transmitter, facilitation of noradrenaline release from sympathetic nerves, resultant cardiovascular stimulation and development of arterial hypertension. In two independent studies, the release of adrenaline from sympathetic nerves was demonstrated in patients with essential hypertension, providing the most direct evidence available to date in support of the adrenaline hypothesis of hypertension pathogenesis [26,27]. Although sympathetic nerve adrenaline co-transmission in essential hypertension can be taken to be a marker of chronic stress, the phenomenon of adrenaline cotransmission does remain unproven as a primary causal mechanism in essential hypertension. This is well exemplified by findings obtained in patients with panic disorder who, commonly, despite having recurrent stress responses during panic attacks that are sufficient to load their cardiac sympathetic nerves with adrenaline, leading to adrenaline co-release, do not have persistently elevated blood pressure [28].

Societal dimensions of the stress–hypertension debate

It has not been easy to integrate the recent evidence linking psychological illness and stress with cardiovascular disease into the clinical practice of medicine. This is partly because the evidence of such a link has been slow in materializing and, in some areas, still remains fragmentary. Perhaps, more importantly, the spectre of workplace litigation hangs over this field, clouding the arguments and polarizing medical opinion. The study by Steptoe and Willemsen [9] will further fuel the debate. It may be that in hypertension, as is the case with coronary heart disease where multiple risk factors interact synergistically to cause the disease, interaction of the hypertension ‘risk factors’ of obesity, high dietary sodium intake, sedentary lifestyle and genetic predisposition occurs, perhaps in concert with chronic mental stress. Should it ever be demonstrated beyond dispute that occupational stress is an important cause of hypertension, it is hoped that the primary outcome would be the implementation of measures to reduce stress in the workplace, such as worker empowerment to end the low job control scenario, rather than a rash of lawsuits.


1. Bunker SJ, Colquhoun DM, Esler MD, Hickie IB, Hunt D, Jelinek M, et al. ‘Stress’ and coronary heart disease: psychological risk factors. National Heart Foundation of Australia position statement update. Med J Aust 2003; 178:272–276.
2. Rozanski A, Blumenthal JA, Kaplan J. Impact of psychosocial factors on the pathogenesis of cardiovascular disease and implications for therapy. Circulation 1999; 99:2192–2217.
3. Leor J, Poole WK, Kloner RA. Sudden cardiac death triggered by an earthquake. N Engl J Med 1996; 334:413–419.
4. Geisbock F. In: Julius S, Esler M (editors): The nervous system in arterial hypertension. Springfield, Illinois: Charles C. Thomas; 1976, p. xii.
5. Harburg E, Erfurt JC, Hauenstein LS, Chape C, Schull WJ, Schork MA. Socio-ecological stress, suppressed hostility, skin colour, and black-white male blood pressure: Detroit. Psychosom Med 1973; 35:276–296.
6. Perini C, Muller FB, Rauchfleisch U, Battegay R, Buhler FR. Hyperadrenergic borderline hypertension is characterized by suppressed aggression. J Cardiovasc Pharmacol 1986; 8 (suppl 5):53–56.
7. Timio M, Verdecchia P, Rononi M, Gentili S, Francucci B, Bichisao E. Age and blood pressure changes: a 20 year follow-up study of nuns of a secluded order. Hypertension 1988; 12:457–461.
8. Poulter NR, Khaw KT, Hopwood BEC, Mugambi M, Peart WS, Rose G, Sever PS. The Kenyan Luo migration study: observations on the initiation of the rise in blood pressure. BMJ 1990; 300:967–972.
9. Steptoe A, Willemsen G. The influence of job control on ambulatory blood pressure and perceived stress over the working day in men and women from the Whitehall II cohort. J Hypertens 2004; 22:915–920.
10. Schnall PL, Landsbergis PA, Baker D. Job strain and cardiovascular disease. Annu Rev Public Health 1994; 15:381–411.
11. Steenland K, Fine L, Belkic K, Landsbergis P, Schnall P, Baker D, et al. Research findings linking workplace factors to CVD outcomes. Occup Med 2000; 15:7–68.
12. Mancia G, Parati G, Casadei R, Groppelli A, Zanchetti A. Effects of stress on diagnosis of hypertension. Hypertension 1991; 17 (suppl III): III56–III60.
13. Mancia G, Parati G. Reactivity to physical and behavioral stress and blood pressure variability in hypertension. In: Julius S, Basset DR (editors): Handbook of hypertension, vol. 9: behavioral factors in hypertension. Amsterdam: Elsevier; 1987, pp. 104–122.
14. Parati G, Casadei R, Groppelli A, Di Rienzo M, Mancia G. Comparison of finger and intra-arterial blood pressure monitoring at rest and during laboratory testing. Hypertension 1989; 13:647–655.
15. Parati G, Trazzi S, Ravogli A, Casadei R, Omboni S, Mancia G. Methodological problems in evaluation of cardiovascular effects of stress in humans. Hypertension 1991; 17 (suppl III):III50–III55.
16. Parati G, Pomidossi G, Ramirez AJ, Cesana B, Mancia G. Variability of the haemodynamic responses to laboratory tests employed in assessment of neural cardiovascular regulation in man. Clin Sci 1985; 69:533–540.
17. Parati G, Pomidossi G, Casadei R, Ravogli A, Groppelli A, Cesana B, Mancia G. Comparison of the cardiovascular effects of different laboratory stressors and their relationship with blood pressure variability. J Hypertens 1988; 6:481–488.
18. Mancia G, Di Rienzo M, Parati G. Ambulatory blood pressure monitoring: use in hypertension research and clinical practice. Hypertension 1993; 21:500–524.
19. Parati G, Antonicelli R, Guazzarotti F, Paciaroni E, Mancia G. Cardiovascular effects of an earthquake. Direct evidence by ambulatory blood pressure monitoring. Hypertension 2001; 38:1093–1095.
20. Mancia G, Parati G, Di Rienzo M, Zanchetti A. Blood pressure variability. In: Zanchetti A, Mancia G (editors): Handbook of hypertension, vol. 17: pathophysiology of hypertension. Amsterdam: Elsevier Science; 1997, pp. 117–169.
21. Steptoe A, Cropley M, Joekes K. Job strain, blood pressure and response to uncontrollable stress. J Hypertens 1999; 17:193–200.
22. Yamada Y, Miyajima E, Tochikubo O, Matsukawa T, Ishii M. Age-related changes in muscle sympathetic nerve activity in essential hypertension. Hypertension 1989; 13:870–877.
23. Esler M, Jennings G, Lambert G, Meredith I, Horne M, Eisenhofer G. Overflow of catecholamine neurotransmitters to the circulation: source, fate and functions. Physiol Rev 1990; 70:963–985.
24. Eide I, Kolloch R, DeQuattro V, Miano L, Dugger R, Van der Meulen J. Raised cerebrospinal fluid norepinephrine in some patients with primary hypertension. Hypertension 1979; 1:255–260.
25. Ferrier C, Jennings GL, Eisenhofer G, Lambert G, Cox HS, Kalff V, et al. Evidence for increased noradrenaline release from subcortical brain regions in essential hypertension. J Hypertens 1993; 11:1217–1227.
26. Johansson M, Rundqvist B, Eisenhofer G, Friberg P. Cardiorenal epinephrine kinetics: evidence for release in the human heart. Am J Physiol 1997; 273:H2178–H2185.
27. Rumantir MS, Jennings GL, Lambert GW, Kaye DM, Seals DR, Esler MD. The ‘adrenaline hypothesis’ of hypertension revisited: evidence for adrenaline release from the heart of patients with essential hypertension. J Hypertens 2000; 18:717–723.
28. Wilkinson DJC, Thompson JM, Lambert GW, Jennings GL, Schwarz RG, Jeffreys D, et al. Sympathetic activity in patients with panic disorder at rest, under laboratory mental stress, and during panic attacks. Arch Gen Psychiatry 1998; 55:511–520.
29. Koepke JP, Jones S, DiBona GF. Stress increases renal nerve activity and decreases sodium excretion in Dahl rats. Hypertension 1988; 11:334–338.
30. Majewski H, Rand MJ, Tung LH. Activation of prejuctional β-adrenoceptors in rat atria by adrenaline applied exogenously or released as a co-transmitter. Br J Pharmacol 1981; 73:669–679.
© 2004 Lippincott Williams & Wilkins, Inc.