Psychosocial factors in the aetiology and prognosis of coronary heart disease: systematic review of prospective cohort studiesBMJ 1999; 318 doi: http://dx.doi.org/10.1136/bmj.318.7196.1460 (Published 29 May 1999) Cite this as: BMJ 1999;318:1460
- Harry Hemingway, senior lecturer in epidemiology,
- Michael Marmot, professor of epidemiology and public health ()
- International Centre for Health and Society, Department of Epidemiology and Public Health, University College London Medical School, London WC1E 6BT
- Correspondence to: Dr H Hemingway, Department of Research and Development, Kensington and Chelsea and Westminster Health Authority, London W2 6LX
Do psychosocial factors cause coronary heart disease or affect survival among patients with coronary heart disease? Here we use an explicit methodological quality filter to review systematically the prospective cohort studies testing specific psychosocial hypotheses. This review of the epidemiological literature identifies the psychosocial factors that have been most rigorously tested. Only four psychosocial factors met the quality filter: type A/hostility, depression and anxiety, work characteristics, and social supports. The importance of other study designs—for example, ecological1 or nested case-control2–4 studies—is acknowledged. The review should be seen as complementary to existing reviews5–8 on single psychosocial factors and as a challenge to investigators in the field to ensure that the systematic review is made unbiased, kept up to date, and used to guide future hypothesis testing.
In healthy populations, prospective cohort studies show a possible aetiological role for type A/hostility (6/14 studies), depression and anxiety (11/11 studies), psychosocial work characteristics (6/10 studies), social support (5/8 studies)
In populations of patients with coronary heart disease, prospective studies show a prognostic role for depression and anxiety (6/6 studies), psychosocial work characteristics (1/2 studies), and social support (9/10 studies); none of five studies showed a prognostic role for type A/hostility
Although this review can not discount the possibility of publication bias, prospective cohort studies provide strong evidence that psychosocial factors, particularly depression and social support, are independent aetiological and prognostic factors for coronary heart disease
What is a psychosocial factor?
A psychosocial factor may be defined as a measurement that potentially relates psychological phenomena to the social environment and to pathophysiological changes. The validity and reliability (precision) of the questionnaire based instruments used to measure psychosocial factors has been improved through the use of psychometric techniques. By avoiding the unhelpful general term of “stress,” recent work has developed theoretical models—for example, the job control-demands-support model of psychosocial work characteristics—which generate specific hypotheses that can be tested.
How might psychosocial factors be linked to coronary heart disease?
Evidence of mechanisms linking psychosocial factors with coronary heart disease (reviewed elsewhere 9 10 ) is important in making causal inferences and therefore in designing preventive interventions. Psychosocial factors may act alone or combine in clusters11 and may exert effects at different stages of the life course.12 Broadly, three interrelated pathways may be considered. Firstly, psychosocial factors may affect health related behaviours such as smoking, diet, alcohol consumption, or physical activity, which in turn may influence the risk of coronary heart disease.13 If such behaviours do lie on the causal pathway between psychosocial factors and coronary heart disease, then treating them as confounding variables, as some studies do, must be questioned. Secondly, psychosocial factors may cause direct acute or chronic pathophysiological changes. Thirdly, access to and content of medical care may plausibly be influenced by, for example, social supports (but there is little direct evidence for this). Although it is beyond the scope of this review to consider the determinants of adverse psychosocial factors, socioeconomic status is inversely associated with coronary heart disease14 and also with certain psychosocial factors, and it has been proposed that psychosocial pathways may play a mediating role. 15 16
Method of systematic review
A methodological quality filter was used to select studies for inclusion in the systematic review, so that the strength of evidence could be compared across psychosocial factors. Prospective cohort studies are the best observational design for questions of aetiology and prognosis. The studies included had a prospective cohort design; a population based sample (aetiological studies in healthy populations); at least 500 participants (aetiological studies) or 100 participants (prognostic studies in populations of patients with coronary heart disease); measurements of a psychosocial factor used in at least two different study populations; outcomes of fatal coronary heart disease or non-fatal myocardial infarction or (prognostic studies only) all cause mortality.
Articles were identified by Medline search (1966-97), manual searching of the bibliographies ofretrieved articles, previous review articles, writing to researchersin the field, and an in-house bibliographic database. No register of published and unpublished studies with psychosocial exposures exists, and hand searching of journals was not performed, so there is a serious potential for publication bias. For this reason as well as the lack of standardised methods of measurement of psychosocial factors, we carried out a narrative, rather than quantitative, systematic review. Given that randomised controlled trials, at least for primary prevention, are rarely feasible, observational studies are likely to remain the main type of evidence on which to base preventive action.
Evidence for specific psychosocial factors
Largely on the basis of studies in middle aged men (table 1), four groups of psychosocial factors were identified by using the predefined quality filter: psychological traits (type A behaviour, hostility), psychological states (depression, anxiety), psychological interaction with the organisation of work (job control-demands-support), and social networks and social support. In simple terms this corresponds to a spectrum with mainly psychological components at one end and a stronger social component at the other. The box summarises the key results.
Studies showing role of psychosocial factors
In healthy populations, prospective cohort studies suggest a possible aetiological role for:
Type A/hostility (6/14 studies)
Depression and anxiety (11/11 studies)
Psychosocial work characteristics (6/10 studies)
Social support (5/8 studies)
In coronary heart disease patient populations, prospective studies suggest a prognostic role for:
Type A/hostility (0/5 studies)
Depression and anxiety (6/6 studies)
Psychosocial work characteristics (1/2 studies)
Social support (9/10 studies)
Although this review cannot discount the possibility of publication bias, prospective cohort studies provide strong evidence that psychosocial factors, particularly depression and social support, are independent aetiological and prognostic factors for coronary heart disease.
Hostility and type A behaviour
Type A behaviour pattern—the only personality trait which met the criteria of our review—is characterised by hard driving and competitive behaviour, a potential for hostility, pronounced impatience, and vigorous speech stylistics. The instruments for measurement of type A behaviour and hostility—the Jenkins activity scale, the structured interview, the Minnesota multiphasic personality inventory (MMPI), the Bortner hostility scale—have been subjected to psychometric testing and incorporated into many cardiovascular cohort studies, including some that have not reported results. Unlike other psychosocial factors, type A is distinguished by being the subject of numerous intervention trials.17 On the basis of early positive findings in the Framingham study18 and the Western Collaborative Group's eight year follow up,19 among other evidence, the National Institutes of Health declared type A an independent risk factor for coronary heart disease. However, with the publication of negative findings20–22 it was proposed that a more specific component of type A, namely hostility, might be aetiological, although there are conflicting studies. None of the five studies that examined type A or hostility in relation to prognosis among patients with coronary heart disease showed an increased risk; indeed, one suggested a protective effect.
Depression and anxiety
The relation between depression and anxiety and coronary heart disease differs from those of other psychosocial factors for several reasons. Firstly, unlike other psychosocial factors, depression and anxiety represent well defined psychiatric disorders, with standardised instruments for measurement. Secondly, depression and anxiety are commonly the consequence of coronary heart disease, and the extent to which they are also the cause poses important methodological issues. Thirdly, the ability to diagnose and treat such disorders makes them attractive points for intervention. Finally, depression and coronary heart disease could share common antecedents—for example, environmental stressors and social supports.
Table 2 shows the results from the 11 prospective studies that investigated depression or anxiety in the aetiology of coronary heart disease, all of which were positive. All three of the prospective studies examining the effect of anxiety in the aetiology of coronary heart disease had positive results. Intriguingly, there is some evidence that this effect is strongest specifically for phobic anxiety and sudden cardiac death. Wassertheil-Smoller23 reported the effect of depression in relation to cardiovascular events among 4367 healthy older people. An increase in depression symptoms (but not the baseline scores) predicted events, even when multiple covariates were controlled for. Such findings are compatible with the hypothesis that premonitory signs of coronary heart disease such as angina or breathlessness may have led to the increase in depression. Studies with longer periods of follow up are less likely to be confounded by the possibility of early disease causing depression, but raise further questions about the time course of exposure. For example, it is possible that there is a common trigger (such as viral illness) that precipitates both symptoms of depression and atherothrombotic processes. By examination of subclinical manifestations of coronary heart disease (using non-invasive measures of arterial structure and function, for example) before the onset of symptoms, the temporal sequence of the relation might be better understood.
Depression in patients after myocardial infarction seems to be of prognostic importance beyond the severity of coronary artery disease. Although discrete major depressive episodes are not uncommon after a myocardial infarction, depressive symptoms are more prevalent. Given the graded relation between depression scores and risk, the long lasting nature of the effect, and the stability of the depression measured across time, it has been proposed that depression is a continuously distributed chronic psychological characteristic.
Psychosocial work characteristics
The longstanding observation that rates of coronary heart disease vary markedly among occupations—more than can be accounted for by conventional risk factors for coronary heart disease—has generated a quest for specific components of work that might be of aetiological importance. The dominant “job strain” model of psychosocial work characteristics, as proposed by Karasek and Theorell, grew out of secondary analyses of existing survey data on the labour force. This model proposes that people in jobs characterised by low control over work and high conflicting demands might be high strain. A subsequent addition to the model was that social support might buffer this effect. The advantage of the model is that it generates specific hypotheses for testing.
Table 3 shows prospective cohort studies that have examined the relation between job strain and coronary heart disease. Both self reports and ecological measurements (assigning a score on the basis of job title) of job strain have been made. Self reports may be biased by early manifestations of disease, and ecological measurements may lack precision. The finding that these methods tend to give reasonably consistent results suggests that they are complementary. Six of the 10 studies were had positive results. There is growing emphasis on the importance of low job control rather than on conflicting demands,24 and it seems likely that these empirical results will lead to a reformulation of the model. Alternative models of psychosocial work characteristics involve an imbalance between the effort at work and rewards received. 25 26
Social network structure and quality of social support
Social supports and networks relate to both the number of a person's social contacts and their quality (including emotional support and confiding support). Marital status—information routinely sought in clinical practice—is a simple measure of social support, and the ability of low social support to predict all cause mortality has long been recognised. It has been proposed that social supports may act to buffer the effect of various environmental stressors and hence increase susceptibility to disease,27 but most of the evidence supports a direct role.
Five of the eight prospective cohort studies that investigated aspects of social support in relation to the incidence of coronary heart disease were positive (table 4). Nine of the 10 prognostic studies were positive, and the relative risks for three of these studies exceeded 3. Despite the strength and consistency of these findings, the relative effect of structural and functional aspects of social supports has yet to be delineated.
Modification of psychosocial factors
The main implications of these findings for clinical practice are summarised in the box. A recent meta-analysis found that psychosocial interventions are associated with improved survival after myocardial infarction.28 However, two recent large randomised controlled trials of psychological rehabilitation after myocardial infarction found no difference in anxiety and depression, and this may in part explain the lack of effect on mortality. 29 30 Randomised controlled trials of modification of social supports after myocardial infarction show a decrease in cardiac death or reinfarction rates.31 A patient's social circumstances should be elicited as part of the history, and the doctor may have a role in mobilising social support. A multicentre trial of 3000 patients after myocardial infarction (ENRICHD—enhancing recovery in coronary heart disease) is currently under way in the United States. It will target patients at high psychosocial risk (those who are depressed or socially isolated) and enrol large numbers of women and ethnic minorities.
Psychosocial components of secondary prevention
Clinicians should consider
Detecting and treating depression
Mobilising social support
Using socioeconomic status and psychosocial factors to risk stratify patients
The potential for primary prevention in relation to psychosocial factors lies largely outside the remit of clinicians. Psychosocial factors themselves are determined largely by social, political, and economic factors and it is therefore policy makers who influence the structure and function of communities—in the public and private domains—who may have scope for primary prevention.
Of the large number of psychosocial factors that have been studied, only four met the quality filter: type A/hostility, depression and anxiety, work characteristics, and social supports. While this review cannot discount the possibility of publication bias, the prospective observational studies show aetiological roles for social supports, depression and anxiety, and work characteristics and prognostic roles for social supports and depression. Further evidence of a causal role is provided by human and other primate evidence of biological and behavioural pathways mediating these effects. However, conflicting data exist on whether psychosocial interventions reduce mortality after myocardial infarction. This systematic review should be updated and expanded to include other observational study designs and other endpoints (for example, all cause mortality) in order to focus future research and, ultimately, policy. In this expanding area, future primary research might investigate the:
Interrelationships between different psychosocial factors
Effect of change in and cumulative exposure to psychosocial factors
Short and long term effects thoughout the life course
Differences by sex, ethnic group, and country
Behavioural and biological mechanisms involved
Effect of psychosocial factors on different clinical and subclinical outcomes
Appropriate primary and secondary preventive measures.
The comments of Lisa Berkman, Ichiro Kawachi, Redford Williams, and Mandy Feeney are gratefully acknowledged. To keep this review complete and up to date, we would be grateful to be informed of studies which we may have missed.
Contributors: HH designed and conducted the review in discussion with MM. HH wrote the first draft of the manuscript and incorporated MM's revisions.
This is the third of four articles
Funding MM is supported by an MRC research professorship; his group investigating pyschosocial factors and health has been supported by the Agency for Health Care Policy and Research (5 RO1 HS06516); the New England Medical Centre-Division of Health Improvement; the National Heart Lung and Blood Institute (2RO1 HL36310); National Institute on Aging (RO1 AG13196-02); the John D and Catherine T MacArthur Foundation Research Network on Successful Midlife Development; the Institute for Work and Health, Ontario, Canada; the Volvo Research Foundation, Sweden; Medical Research Council; Health and Safety Executive; and British Heart Foundation (RG/28).
website extra: References in the tables are given on the BMJ website www.bmj.com