UPBEAT-UK: a programme of research into the relationship between coronary heart disease and depression in primary care patients

Coronary heart disease

Coronary heart disease, especially when chest pain is present, often causes functional limitation, distressing symptoms, is often life-threatening and requires long-term management, mostly in primary care. Many patients with CHD have a documented history of myocardial infarction (MI) or coronary artery disease shown at angiography. CHD also causes 70% of heart failure with fatigue and shortness of breath. CHD mainly comprises three groups of patients with: chronic stable angina (with exertional chest pain), post MI, and heart failure with a hierarchy of physical and emotional effects. The researchers at Imperial College London, on behalf of the Public Health Observatories of England, have developed a prevalence model. 8 They estimate the prevalence of CHD in primary care trusts and at local authority level to be 5.80%, although this number rises to 16.08% in people aged 65–74 years, and 21.91% in those ≥ 75 years. In the south London primary care trusts of Lambeth, Southwark and Lewisham, the prevalence is 3.30%, 3.50%, and 3.85%, respectively (≥ 15% in those aged 65–74 years and ≥ 22% in those ≥ 75 years). 8

Depression

Depression is a major public health problem responsible for around 100 million lost working days in England and Wales each year and costing £9B per annum. 9 In the UK, depression is a common reason for consulting a general practitioner (GP). Up to one-third of people who visit the GP have mental health problems, and 90% of those are treated only in primary care. 10

Depression incurs a 50% increase in the cost of long-term medical care after controlling for the severity of the physical illness,11 and this may relate to the link between depression and adverse health risk behaviours such as smoking, diet, lack of exercise and poor self-care. Depression may exacerbate the perceived severity of symptoms and this, in turn, can bring about an increase in health service utilisation. Treating depression and improving outcomes for depression has been shown to reduce health costs in people with physical illness. 11 Furthermore, collaborative care and individualised management of patients with depression and chronic conditions, such as diabetes and CHD, has shown to improve both medical outcomes and depression. 12

Depression and coronary heart disease comorbidity

Depression occurs in up to 20% of patients with CHD and depression increases the incidence and recurrence of CHD, acute coronary syndromes and mortality. 5 A systematic review by Nicholson et al. 13 places the pooled relative risk (RR) of future CHD associated with depression at 1.81; however, the authors stop short of calling depression an independent risk factor for developing CHD, owing to the heterogeneity of studies.

The clear association that exists between these two conditions has led to a long discussion about the precise nature of the relationship. Ageing (which increases the odds of both conditions), lifestyle factors, inflammation pathways, heart rate variability, impaired arterial repair and several genes, are just some of the mechanisms that could play a role. 14 Nevertheless, the link is well established. A review by the American Heart Association15 recently recommended that depression be considered an independent risk factor for adverse outcomes in patients with acute coronary syndrome, given the strength of the evidence in the current literature.

The presence of concurrent physical illness, such as CHD, is known to reduce the likelihood of major depression being recognised by GPs. 16 Diagnosing depression in elderly primary care patients is hampered by conditions such as heart disease and the drugs to treat these conditions, which can have mood-destabilising effects. 17 The natural history, morbidity and mortality of depression in primary care CHD populations are unknown.

As GP practices keep separate registers for their patients with heart failure, this programme of research is solely concerned with CHD and patients on CHD registers rather than patients on heart failure registers. This also means that the focus of research in terms of physical symptoms is purely on chest pain rather than on fatigue and dyspnoea.

Managing depression and coronary heart disease

Although there are several treatment options for managing depression in primary care that are endorsed by the National Institute for Health and Care Excellence (NICE)18 [e.g. antidepressant medication, supervised exercise, guided self-help, problem-solving, computerised cognitive–behavioural therapy (CBT), group or individual CBT or interpersonal therapy], the treatment preferences of CHD patients are unknown, as are primary care professional treatment preferences. A recent US working party on the management of depression in CHD concluded that RCTs comparing stepped depression care with treatment as usual (TAU) for patients with CHD and depression are needed. 5

It remains unclear how GPs and practice nurses (PNs) should best manage patients with depression and CHD. Previous research, which has been largely from the USA, has focused on treating depression with antidepressant medication, psychological treatment, case management and collaborative care. Because of the absence of available evidence in this area, we decided to conduct a systematic review and metasynthesis of available evidence in work package 1.

Medication and psychological treatment

Two large US-based trials19,20 have also provided an indication in post-hoc subgroup analyses that there may have been cardiovascular benefit from the management of the depression using antidepressant medication and it has been suggested that this may be owing to an effect on platelet activation. 21,22 Mortality seems to have been reduced in those whose depression improved or in those who took sertraline (Zoloft^®, Pfizer) in one study. 23,24 This evidence was influential in the introduction of financial incentive payments to English GPs for screening consecutive CHD patients for comorbid depressive disorder under the General Medical Services Quality and Outcomes Framework (QOF), although this was abandoned in 2013.

Case management

Case management has been shown to improve outcomes for depression in primary health-care settings,25 but there has been no research to determine the cost-effectiveness in patients with CHD. Case management is ‘taking responsibility for following-up patients; determining whether patients were continuing the prescribed treatment as intended; assessing whether depressive symptoms were improving; taking action when patients were not adhering to guideline-based treatment or were not showing expected improvement’. 26 It consists of five essential components:25

1. identification of patients in need of services

2. assessing individual patient’s needs

3. developing personalised treatment plans

4. co-ordination of care

5. monitoring outcomes and altering care when favourable outcomes are not achieved.

Collaborative care

An early, large US-based multicentre study of stepped collaborative depression care showed positive results regarding depression in older people as did another US trial of collaborative depression care in diabetics in motivated patients. 27,28 However, the latter trial did not improve diabetic outcome. 28 Subsequently, during the life of the UPBEAT-UK programme, Katon et al. ,12 using collaborative care, were able to demonstrate in a groundbreaking study the improvement of depression, systolic hypertension, glycosylated haemoglobin and blood lipids. As they applied rigorous nurse care to the depression, hypertension, diabetes and lipid abnormalities, it is not clear to what extent the management of depression contributed to the improvement of the physical outcome measures. Since then, and again in the lifetime of the UPBEAT-UK programme, it has been demonstrated that collaborative care as a model works in an English setting for depressive disorder, albeit with a modest effect size. 29 Collaborative care usually requires the collaboration of psychiatrists or other mental health professionals working together with their primary care colleagues to supervise case management by dedicated case workers. These care workers are usually mental health professionals brought in for the purpose of overseeing the case management and liaising with the patient’s primary and secondary care workers.

The overall design of the UPBEAT-UK programme led to a pilot RCT in order to inform a future definitive RCT of the cost-effectiveness of PN-led personalised case management in primary care for patients with CHD and depression. A pilot RCT was necessary to determine whether or not case management by PNs for this population would be a feasible and acceptable intervention compared with TAU in terms of both depression and cardiac outcomes.

The first step was to judge the acceptability, feasibility and likely effect of case management to inform whether or not to conduct a future definitive RCT. As any future potential definitive RCT would be a complex intervention, it was necessary to follow Medical Research Council (MRC) guidelines30 for the development of a complex intervention using a programme of related work packages to develop and test a new nurse-led personalised case management practice for depression and CHD in primary care. The overall scientific framework for the UPBEAT-UK programme was the MRC framework for the development and testing of complex interventions. 30 This framework has four stages:

Stage 1: development concerns the identification of existing evidence in order to develop the intervention to a point where it can be expected to have a beneficial effect. Conducting a systematic literature review or metasynthesis is recommended if such a review does not already exist. This is followed by the identification and development of theory with a rationale for the proposed intervention and likely change process. The development of theory may build on existing evidence and be supplemented with new (often qualitative) research. This should then lead to a testable model with a specific intervention, process and likely outcomes.

Stage 2: feasibility and piloting involves assessing the feasibility and acceptability of the new complex intervention and of the evaluation methods, including acceptability, compliance, delivery, randomisation, recruitment, retention, and observed variability around changes in the primary outcome to inform the power calculation for a subsequent definitive RCT. The pilot RCT examines key criteria for a definitive RCT.

Stage 3: evaluation involves the evaluation of the intervention using appropriate design usually by a definitive RCT.

Stage 4: implementation involves the routine implementation of the new intervention, surveillance, monitoring and long-term follow-up.

Stages 1–4 should be seen as cyclical rather than linear, with results from any stage informing not just subsequent stages but previous stages in continuous improvement and increasingly higher-level evaluation. 30 The UPBEAT-UK programme mainly involves stages 1 and 2 outlined above.

The four inter-related UPBEAT-UK work packages are:

1. a review of previous work in the area and qualitative study of GP and PN treatment preferences for this patient group

2. a qualitative study of patients with CHD and comorbid depression treatment preferences

3. a pilot RCT of nurse-led case management for depressed primary care patients with CHD

4. a 4-year cohort study of patients with CHD.

In this introductory chapter, the detailed methods will be described in each work package chapter.

Work package 1

A review and metasynthesis of the existing literature and a qualitative study of health professionals’ perceptions of distress and depression in patients with CHD.

Work package 2

Study of patients’ perceptions of distress and depression in patients with CHD.

Work package 3

Pilot RCT of primary care case management for depressed patients with symptomatic CHD (sCHD).

Work package 4

Metasynthesis of published qualitative and quantitative research

Review results

Our first finding was that no relevant paper concerning GP or PN views about depression and comorbid physical illness of any kind was identified, despite our use of a comprehensive search strategy. Seven qualitative37–43 and 10 quantitative studies of the management of primary depression were included. 44–53 Figure 1 shows the flow of studies through the review process.

FIGURE 1.

Flow of studies through review process. Reproduced from Barley et al. 31 © 2011 Barley et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Qualitative interview study of general practitioners’ and practice nurses’ views and experience of managing depression in coronary heart disease

Summary of study results

Summary: what we learned from reviewing existing literature and conducting our own qualitative study

The findings of our metasynthesis of studies of primary care management of depression in general and our qualitative study of primary care management of depression comorbid with CHD were complementary. On balance, GPs and PNs expressed uncertainty in the management of depression, citing lack of time, training and available management options that are acceptable to patients. That these findings were similar for our metasynthesis and this qualitative study indicates that GPs and PNs have similar struggles when managing depression whether or not it is comorbid with CHD. Social problems, in both studies, were seen as important contributing factors, which should be addressed; our qualitative study indicated that these might be especially important in CHD patients who often come from low socioeconomic groups. However, GPs and PNs are uncertain in their role in and responsibility for addressing social problems and existing resources are underused; a finding from both our review and this qualitative study which highlights the need for a new intervention to help address this. Nurses’ attitudes towards and confidence in managing depression varied enormously. This was a finding of both our review and qualitative study, and, as primary care patients with CHD commonly receive most of their care through nurse-led clinics, suggests that the development of interventions for depression in these patients should include sensitive consideration of nurses’ views.

By asking clinicians, in our qualitative study, to consider depression comorbid with CHD, we not only confirmed that the findings of our review were relevant when managing people with CHD, but also identified issues that may be particularly important to people living with CHD. For instance, erectile dysfunction is a common problem that is not addressed routinely despite clinician awareness that this can contribute to depression and that if people with CHD become housebound, they are unlikely to receive any help for depression.

Strengths and limitations

Through the inclusion of only recent studies conducted in the UK, we ensured that our metasynthesis produced findings relevant to current practice within the NHS; findings may be less relevant to those wishing to develop interventions in other health-care systems. The aim of our review was to identify broad themes concerning depression management in order to inform our qualitative study focusing on managing depression when it is comorbid with CHD and hence we excluded studies focusing on specific aspects of the management of major depression such as antidepressant use. These more specific aspects of management were, however, addressed in our qualitative study focusing on their relevance to people with comorbid CHD. As is the case with all metasyntheses, we had to make decisions concerning which studies to include; we have detailed our methods clearly but others conducting the same review may have selected different studies. The findings of our review and qualitative study were, however, concordant, indicating that our choices were appropriate and that we produced robust findings to inform our intervention.

The findings of our metasynthesis were extremely useful in ensuring that our qualitative interviews were focused on known barriers and facilitators to managing depression in the UK; this information was essential in ensuring that our intervention would be feasible to deliver in primary care. However, we also used an iterative process of data collection and analysis so that new topics could be explored in subsequent interviews. For instance, the idea that depression in some people with CHD may be compounded by erectile dysfunction or by being housebound had not been identified in our review. Such findings emphasised the need for a future intervention to be personalised in order to address the varying needs of individuals. A potential weakness is that our participants were all practising within south-east London; however, we were careful to recruit from areas of contrasting deprivation and affluence in order to elicit a range of experiences.

It should also be noted that, as in the case of all qualitative research, it is possible that our positionality influenced our final findings. For instance, the UPBEAT-UK programme was funded to consider the ‘problem’ of depression comorbid with CHD and this informed our methodology. Had we conducted a study about the impact of illness on well-being and health as a resource for daily living, our findings may have been different.

Finally, since we conducted our study, guidelines for the management of depression with a chronic physical health problem have been issued;18 these may impact on attitudes and practice in the future.

Conclusion

Our systematic review of existing literature describing GPs’ and PNs’ experience of managing depression in UK primary care identified a range of barriers and facilitators to delivering care that need to be considered when designing future interventions for depression. We were then able to determine whether or not similar barriers and facilitators were experienced by GPs and PNs when managing depression in patients who also have CHD by conducting our own qualitative study. This work addressed a gap in the literature highlighted by our review and helped us to determine GPs’ and PNs’ views concerning what an intervention for people with sCHD and comorbid depression should consist of. By seeking clinicians’ views directly, we were able to identify elements (such as the need for a flexible, personalised intervention which allowed clinicians to use both their clinical judgement and existing tools and resources) of a future intervention, which would make it not only effective (in terms of addressing care needs identified as unaddressed in these patients) but, importantly, feasible to deliver in current practice.

The following chapter describes how we also sought the views of patients with CHD and comorbid depression to inform our intervention. How this work was synthesised to develop an intervention to test is then detailed in Chapter 4.

Aims

The study aimed to explore (1) primary care patients’ perceptions of links between their physical condition and mental health; (2) their experiences of living with depression and CHD; and (3) their own self-help strategies and attitudes to current personalised care (PC) interventions for depression.

Methods

The sampling frame was the UPBEAT-UK cohort study database of primary care patients with CHD. At the time of recruitment (November 2008–January 2009) this numbered 376. On recruitment to the cohort, study participants were given the option of being interviewed in depth about their experiences of CHD and how this affected them emotionally. From participants who agreed to be contacted, we purposively sampled for positive scores on the PHQ-9,80 which indicates symptoms of depression. We also sampled for maximum variation on sociodemographic factors: age, sex, ethnicity and occupational status.

At the time of sampling, 42 patients screened positive for symptoms of depression and of these, five were included in the pilot interview study. Of the remaining 37, one patient declined and three could not be contacted or had died. Of the remaining 33 patients, 30 were interviewed, at which point interviewing was stopped as data saturation had been reached.

We conducted five individual unstructured pilot interviews and 30 semistructured interviews. Topic guides were informed by the aims of the research, review of the literature, discussion with coauthors and findings from the pilot interview study. We audio-recorded all interviews and transcribed them verbatim following written informed consent. Transcribed interviews were entered into NVivo 8 qualitative software for analysis and data management.

All transcripts were analysed using a thematic approach81 involving a process of constant comparison between cases. 82 Analysis began alongside data collection, with ideas from early analysis informing later data collection in an iterative process. Analysis of individual transcripts commenced with open coding grounded in the data. This generated an initial coding framework, which was added to and refined, with material regrouped and recoded as new data were gathered. Codes were gradually built into broader categories through comparison across transcripts and higher-level recurring themes were developed. Data were scrutinised for disconfirming and confirming views across the range of participants. Discrepancies were resolved by discussion at regular UPBEAT-UK research meetings to ensure consistency.

Study results

Taking control and individual coping strategies

Analysis of pilot interviews revealed the ways in which patients tried to gain control of their health and emotional well-being and the individual coping strategies they used. These included:

• devising own fitness regime

• going to the gym

• studying health issues and alternative or complementary medicine

• meditating

• praying and being an active member of a religious community

• learning specific relaxation techniques based on yoga and Buddhist philosophy

• fishing and being in the natural environment (described as a yoga-like experience)

• being able to drive

• setting goals for exercise and pacing performance

• getting an allotment and growing vegetables

• volunteering at a hospital.

The following are illustrations of strategies used by participants: devising own fitness regime, going fishing and going to the gym. These examples not only illustrate the most cited strategies used but also individual differences in participant preferences for individual or group approaches to self-help.

Geoff described his fitness regime; he has a mini-gym in his sitting room and also goes fishing. He explained:

I’ve got equipment where I train, I’ve got the balls, I’ve got the weights, I’ve got a track that I run on, and I got legs . . . because of this operation, because I have got arthritis I got to strengthen my legs . . . and I got a thing to do my upper body. Yeah I train at least once per week.

When exercising and out walking, Geoff also wears a heart rate watch and he finds this source of ‘biofeedback’ helps him to pace and monitor his exercise, particularly when climbing hills. Geoff finds that being by the river, fishing and enjoying the natural environment a therapeutic experience in itself, he said:

Yeah, yeah, it’s like a yoga, you can go into your own trance can’t you, you can sit by the river and just imagine you’re doing anything, it’s like yoga.

Geoff had worked as a porter in the various Covent Garden markets for most of his life but since retiring he had built up a sizeable collection of books on alternative and complementary approaches to health. Geoff may have symptoms of depression, as detected by his PHQ score, but he is actively taking control of his health.

Another participant, June, talked about the ‘psychosocial’ benefits she gained from her regular trips to a gym where there was a special programme for heart disease patients:

. . . there is a group there [at the gym] and nine times out of ten we spend most of our time laughing!

This participant clearly enjoyed the fun she had with other people who had similar health problems and were trying to cope with the gym equipment and exercises through laughter.

The significance of having heart problems

For all five participants, having heart problems was not the health condition that concerned them the most. Three out of the five participants suffered from arthritis and this condition appeared to be causing more problems than heart disease owing to chronic pain and impaired mobility. One participant, June, was unable to work because of arthritis in her shoulder, arms, legs and ankles. She had already undergone five operations for arthritis.

Out of the five participants, Gurch seemed the most depressed or unhappy. Gentle probing about his heart problems (bypass surgery and a number of heart attacks) and how this had affected his feelings almost immediately led onto the topic that dominated the interview: his unhappy marriage and home life and his abuse of alcohol. The following exchange illustrates the problems Gurch had experienced:

But how did it [heart bypass surgery] affect you emotionally, what did you think and what did you feel?

At that time there are family problems.

Did you have family problems?

Yes family problems you know then I just take so much whisky you know drank you know.

All right so I understand that you were saying that you had family problems and that was why you were drinking a lot.

It was one of the causes you know, the family problem you know I don’t know (. . .) my wife is but I do not know at that time you know, what are right what are wrong, anyhow it were due to my family quarrelling.

A little later in the interview he reflected that at the time of his heart bypass surgery, nearly 23 years ago, he was ‘totally unhappy, just spending my time you know just passing my time’.

Like Gurch, four out of the five participants had experienced problems in their marital relationships that seemed to have affected them over a long period of time and caused them unhappiness, anxiety and depression. In comparison with their relationship issues, participants seemed almost blasé about their heart problems.

Ambivalence about accessing mental health services

The next theme explored participants’ ambivalence about accessing mental health services through their GP and these included:

• cultural perceptions of depression can act as barrier to accessing help, for example in South Asian and Sikh communities

• not knowing the meaning of ‘depression’

• suffering seen as Karmic – in the hands of God

• cannot talk to anyone in community (stigma?)

• fearing negative perceptions of GPs as always ‘moaning and groaning’ (this idea is reinforced when doctor praises client for not moaning)

• discomfort in talking about emotional issues

• low self-esteem and a sense that their problems are not worthy of attention

• the perception that their health is relatively good and that there are people in far worse situations

• some people do not want to go down that path because it frightens them.

Excerpts from interviews with June and Ivy illustrated how health stoicism and fear of being viewed negatively by their GP acted as an inhibitor to accessing primary care health services. Although June suffered from asthma, arthritis, heart disease and possible depression she seemed reluctant to visit her GP other than for her regular 2-monthly check-ups. June explained ‘. . . there are some times when you are thinking to yourself that there are people a lot worse off than you!’.

Ivy had also adopted this approach – even though she was 79 years old and had heart disease, arthritis, balance problems and symptoms of depression. She explained:

To be honest, I hardly go near them [GP surgeries] . . . I mean they have got enough to do when they have got a whole lot of patients who are worse off than I am.

OK so do you think of yourself as being in quite good health?

Yeah.

You think ‘I’m OK I’m much better off than some people’?

Yeah, yeah.

And does that make you feel better?

Sometimes it does.

Although the strategies of stoicism and ‘counting your blessings’ that Ivy used can have some positive benefits (putting problems into perspective to combat feelings of anxiety about health) it can also act as an inhibiter to accessing health care.

June was concerned that her GP might perceive her negatively by making more frequent visits to the surgery. June explained:

I don’t want to come in too often!

Too often?

Even though they say they don’t get fed up, you don’t want them to get fed up, you know?

In relation to depression, a study by Priest et al. 83 found that stigma was still associated with depression, and patients felt ambivalent about consulting a family doctor. Some feared the GP would make negative evaluations of them or would be irritated or annoyed. With this in mind, June might be similarly reluctant to disclose her feelings of depression to her GP.

Services participants would like for heart disease and depression

In relation to the services participants would like for heart disease and depression, participants seemed more interested and comfortable in talking about services they would like for heart disease. The following suggestions were made:

• more frequent (physical) check-ups at the GP surgery with specialist nurse and improved feedback

• being able to request a check-up when needed

• access to a gym with specialist cardiac trainer for attention, guidance and reassurance

• the promotion of wrist heart rate monitors

• some people were interested in having counselling

• one participant had counselling and found it helpful.

Three out of the five participants had used a gym as part of their aftercare but only one participant, June, seemed to have attended sessions that were designed for people with heart problems. The other participants attended general fitness centres where they were assessed by a trainer and then given a set of exercises and left to get on with these on their own. These three participants all felt that a dedicated session would be preferable, particularly in the period immediately after their coronary incident when they needed the most reassurance about symptoms and safety while exercising. June’s experience of going to a dedicated gym session was an enjoyable one because there were a group of people ‘in the same boat’ and they had a good laugh. She also felt safe and reassured by the trainer when she had some cardiac symptoms. Even though this kind of CR might not be considered a psychological intervention, in the strictest sense, it may have some positive outcomes for patients suffering from mild depression and may also help to prevent a ‘cardiac invalid’ mind set.

Only two out of the five participants had received help for depression from their GP. None of the participants had received antidepressant medication, June had received information and Ivy had attended counselling sessions. Geoff had been offered group therapy but did not want to attend. Generally participants seemed cautiously positive about the idea of receiving one-to-one counselling while less positive about group therapy.

Future orientation (having achievable hopes and dreams for the future)

When asked if there was anything the participants enjoyed or were looking forward to doing with their lives, the following topics were discussed:

• planning for a holiday with a friend

• gaining skills needed for a new way of life

• planning to retire and live abroad

• wanting to learn how to use a laptop

• volunteering at a hospital.

In a critical literature review of the relevance of hope in the trajectory of heart failure illness, Davidson et al. 84 explained:

. . . hope . . .  defend[s] against despair by focusing on the future. Expectations can be directed toward relief from a difficult situation. To achieve this relief, people must have a sense of control over their environment and feel that they are capable of making decisions that alter their life circumstances.

In relation to hope, four out of the five participants gave examples of achievable personal goals. When talking about their personal dreams, participants looked relaxed and animated, and their body language changed. Even the unhappiest participant, Gurch, seemed a different person when talking about his activities as a volunteer with Parkinson disease patients at a London hospital. Besides a lot of other benefits, being a volunteer had given Gurch some future orientation. Gurch explains how this has affected him as follows:

It makes me feel good, when I help a person and I can see that they are suffering like that you know and I help ladies and gentlemen who are suffering from this disease how to do step by step.

You are looking a lot happier while you are talking to me about doing the volunteering you look quite happy.

Yes I am happy.

Another participant, James, talked about his hopes and dreams for the future as follows:

. . . we’ve got friends in Portugal that are living in a very beautiful kind of place and it is very nice to go and visit them and I think ‘this will do me fine’ nothing grand, just something with a bit of land. Errrh, yeah and this is why I am doing the allotment because I need to know that I can do it, if I want to.

James was close to retirement age and was seriously considering starting a new life abroad. He was taking some practical steps in preparation for his goal of having some land of his own to cultivate.

Similarly, June talked about her wish to go travelling as follows:

What I want to do at the moment is to go travelling and I can’t at the moment, I want to go away for a holiday but I will have to wait. That is what I want; I really, really want to go away.

June and a friend were hoping to go to Jamaica in a year’s time, health permitting.

Maintaining hope and encouraging a future orientation may be important factors to consider in devising interventions for patients with CHD and depression. Patients with CHD may need some help in either finding a future goal or in taking practical steps to achieve something they want to do.

The positives

Although all five participants had positive scores for the PHQ-280 and had suffered from periods of ‘unhappiness’ over the course of their lives, participants spoke about the positive aspects of their lives, their friendships, interests, hopes and dreams or about how they had successfully tackled personal problems, such as alcohol abuse. Of the five participants:

• four had a close friend, group of friends and contact with family members

• four mentioned things that they enjoyed doing

• one participant had used his experience of heart disease as an opportunity for personal growth and improved care of self

• the unhappiest participant was trying to improve his situation by volunteering and by trying to understand his unhappy relationship

• two participants with alcohol problems had managed to either abstain or moderate their drinking behaviour.

One participant, James, thought that his heart disease had given him the opportunity for change and personal growth. James explained as follows:

I started the yoga and the Buddhism and a couple of the meditation techniques. It did change me quite a lot and I was quite happy about that change . . . I used to be somebody I didn’t like very much and now I am somebody who is OK, as far as I’m concerned. I used to treat people very badly and I used to argue about anything and would drink a lot and I have stopped doing a lot of those things really.

In the excerpt above James explained how having a heart attack had been a catalyst for change in his life. He had also changed his diet and lost 5 stone in weight.

Participants’ perceptions of what caused or contributed to feelings of distress and depression

Participants talked about the issues that they felt had contributed to or caused their depression and these included fear of dying, boredom, unhappy relationships, chronic pain and disability, low self-confidence, alcohol abuse, being bullied and being bereaved.

In the interview with Geoff, dying and fear of dying was a topic touched on in different ways. Geoff was understandably scared when he realised he was about to undergo open-heart surgery. Geoff also referred to his sense of frustration with other heart disease sufferers who were becoming ‘cardiac invalids’ because of their fear of dying and he gave examples of friends who had suddenly died from a heart attack, reminding him of his own mortality.

The following extract describes Geoff’s reaction when he first realised he was going to have a heart operation.

So I went up the hospital earlier about me stomach he looked at me diagrams and me sheets and all that and he said ‘do you want us to do this one first’ and I thought ‘what one is that?’ He said sort out yer valves in your artery and so I said Oh . . . !

So that was news to you was it?

Scary and all. So I said ‘OK then’ he said ‘do you want to know what the chances are of dying?’ and he said ‘six to one′ so I said ‘all right then.’ So he said it will be a little while before we get a spare bed so I come home here and then I got a phone call to say could you come in. So that’s when the scary part went in!

Geoff’s interview provided examples of how the reality of dying had affected and distressed him. Indeed, since his operation some years ago he had become very interested in health matters and had devised his own fitness regime that involved monitoring his heart rate, using a wrist monitor. One could speculate that Geoff’s anxieties had been channelled into monitoring his heart rate, as the following extracts might suggest:

You go fishing yeah and what does going fishing do for you? Why do you prefer going fishing to group therapy?

Because I can train. I got a hill like that (tilts hand) and I go up the hill but I don’t do that straight away but that’s a little bit of training that is getting me heart pumping I do it and when I reach the 120 heart murmurs I stop because I have to watch . . . that’s a good idea if you can get them free, a heart watch so if people are training and have just had open heart surgery and the doctor said ‘if you want your heart rate to be 120 you should look at your watch and if it says 120 and then I stop, stop going up the hill work it to about 112 and then I will carry on back up the hill, don’t forget I’ve got all me fishing gear with me and a barra [barrow].

And later in the interview he continued . . .

So when I go fishing there is a hill and it is a hill, but I want to work me heart so going up this hill is errh when I get to 120 . . . I done 130 actually and then I did stop. I wasn’t out of breath but I just thought ‘well that’s too much for me’ so I went and I looked at me clock and it was 130 and I thought ‘that’s quite good’, it went down to 112 and when it goes down to 112 the heart is (makes pumping sounds) just nicely beating . . .

Although Geoff was doing something positive about his health, his need for reassurance through biofeedback could be a manifestation of the anxiety he was experiencing. Geoff was not interested in attending group therapy sessions because he felt that listening to everyone’s symptoms of heart disease would make him worried for them (or perhaps remind him of his own health issues).

Discussion

The themes explored in this pilot study have revealed more similarities than differences among five participants who were purposively sampled for contrasting demographic backgrounds.

The participants did not want to be perceived as ‘moaning and groaning’ in relation to accessing health care and were mostly uncomfortable in talking about their feelings and ambivalent about accessing mental health services.

Although all of the participants had experienced unhappiness in their lives (mainly owing to relationship problems) they were all still trying to do the best they could and seemed to prefer taking their own courses of action to improve their lives, thereby preserving a sense of agency, control and future orientation.

For all of the participants, having heart disease and the symptoms of heart disease did not seem to be their main health concern. In contrast, chronic pain and impaired mobility caused by conditions such as arthritis seemed to affect participants the most.

Most participants would like to be able to attend dedicated gym sessions for people with heart problems so that they feel safe and supported. As dedicated sessions provide an opportunity for social interaction with other people with heart problems there is also an opportunity to make these fun and enjoyable and thereby emotionally therapeutic.

The main difference between the responses of the participants was evident with one participant, James, who seemed more comfortable about introspecting and talking about his feelings. James occupied the highest occupational status of the five participants and this difference in socioeconomic status/social class might indicate that he has access to and is familiar with psychological discourses, whereas the other four participants appeared to refer to ideas of stoicism in preference to introspection. There may well be issues of social class influencing the importance patients place on their feelings and whether or not these are appropriate and safe topics to discuss, either with a researcher or a health-care professional.

How the pilot study informed the main interview study

For the pilot study, an unfocused interview approach was adopted to allow participants to raise issues that were salient to them around the topic of CHD and depression. Findings from the pilot interviews and UPBEAT-UK literature reviews were used to inform the topic guide for the main interview study. This approach allowed us to balance topics identified in academic literature with patient-centred perspectives.

The researcher commenced the interviews by asking the following question: ‘So, if you wouldn’t mind just starting by telling me about when you first knew that you had some problems with your heart.’ Participants responded to this request by recounting personal accounts of their lives in the context of CHD and depression. This narrative approach worked well in the pilot study; it provided an opportunity to assess how participants perceived the connections between their physical, social and emotional worlds, in the context of illness. For this reason a narrative-based topic guide was developed for use in the main interview study.

Study results

RS interviewed 30 patients with CHD and symptoms of depression. The main findings from this study have been published in an open access journal paper by Simmonds et al. 85

The interviews were conducted using a narrative approach guided by topics informed by findings from the pilot interview study.

While recounting their stories of CHD and depression the following topics were explored:

1. participants’ perceptions of the relationship between their physical and mental health

2. participants’ experiences of living with depression

3. participants’ own self-help strategies for coping with depression

4. participants’ views and experiences of primary care interventions for depression

5. participants’ ideas for primary care-based interventions for depression that they would like to be made available.

Direct links made between coronary heart disease and depression

Of the 30 participants interviewed, 63% (19 participants) were male. Nearly half of these male participants (30% of the sample) reported feeling depressed, very depressed or suicidal after having a heart attack and explicitly stated a link between feeling depressed and having CHD.

The way men described their feelings was closely connected to the loss of perceived manliness (emasculation) and gender roles, which included loss of ability to work, erectile dysfunction and generally feeling ‘useless’.

Indirect links made between coronary heart disease and depression

Fewer direct links were made between CHD and depression by participants who reported a history of negative life events.

Factors contributing to or causing depression in this category were underpinned by feelings of interpersonal loss. The main issues that participants reported as ‘getting them down the most’ were:

• marriage and partnership breakdown/unhappiness, problems with access to children after marital breakdown, loss of home/homelessness

• bereavement issues through the death of a child, partner, parents and friends

• being a full-time carer for wife, not having any support or respite and not being able to visit children in America.

Although partnership breakdown was reported as being a major, long-term, stressful experience by male and female participants alike, more male participants talked about the added stress of either losing touch or being denied access to their children. Destructive family politics were mentioned by a number of participants, both male and female, and these corrosive situations had caused a great deal of stress.

For participants who had talked about marital or relationship breakdown the breakdown had preceded CHD and participants partly attributed their feelings of distress or depression to this experience and partly to their physical condition. Experiencing stressful life events was seen more as a factor that caused participants’ heart disease rather than heart disease causing them to feel depressed. 86

Participants experienced bereavement as a severe loss and the source of ongoing distress. Some participants believed that there was a causal link between experiencing grief and heart disease. Parkes et al. 87 argued that the association between heart disease and bereavement is one that cuts across social class difference. Patients with CHD may need particular help in the case of bereavement.

One participant was a full-time carer for his wife, who was incapacitated through rheumatoid arthritis. Although this participant was in his eighties and had suffered a heart attack, he did all the housework, washing, cooking, shopping and personal care for this wife.

This participant reported feeling depressed about being trapped in the daily grind of being a carer and not being able to visit his children in America. His wife refused any respite care and her family were unsupportive. The loss that this participant was experiencing centred round a loss of freedom, which included the freedom to visit his children in America.

Weak links made between coronary heart disease and depression

A number of participants were coping with CHD and comorbid conditions including: asthma, psoriasis, chronic obstructive pulmonary disease (COPD), arthritis, diabetes, thrombosis, sarcoidosis, stroke, hearing loss, poor eyesight, diabetic blindness, memory loss, prostate problems, kidney problems, paroxysmal positional vertigo, morbid obesity, underactive thyroid and restless leg syndrome. Chronic painful conditions limited mobility and interfered with the daily activities of participants.

Conditions that caused pain, such as arthritis, seemed to distress participants the most. As there are no ‘cures’ for some health conditions participants were faced with a seemingly never-ending illness trajectory. These factors, coupled with the realities of ageing, made the future seem bleak for some participants. Links made between depression and CHD were weaker in participants coping with other painful health conditions. Participants with comorbidities seemed more depressed and attributed low mood to physical conditions that were painful and disabling, such as arthritis.

NHS interventions and services participants found helpful or unhelpful

NHS services for depression that participants did not find helpful

Discussion

Most participants in this study had suffered heart attack(s) and other health/personal traumas that had impacted on every area of their lives. The losses experienced by participants were complex and multiple. For this reason the association participants made between CHD and depression varied substantially.

Male participants in the study made the strongest links between their physical state and mental health. Charmaz88 (p. 268) observed ‘illness can reduce a man’s status in masculine hierarchies, shift his power relations with women and raise his self-doubt about masculinity’. These observations were reflected in our study of men who felt emasculated by CHD. Men who suffer serious cardiac disease may need specific therapeutic support to help them find new ‘scripts’ through which they can perform positive masculine identities.

Participants who had suffered losses in their personal relationships through divorce and bereavement made weaker causal links between CHD and depression. These participants attributed depression mainly to the unhappiness and upheaval they had experienced in their lives. Together with patients who had multiple health conditions, these participants felt that they needed someone to talk to, who would get to know them, rather than take antidepressant medications. Patients who have lost a partner through death or divorce might find the experience of ageing and ill health a lonely process. These participants do not want to ‘burden’ their children with their concerns and they are reluctant to talk to their GP because they generally do not want to be perceived as ‘moaning and groaning’. Older CHD patients, living alone, may be more susceptible to depression if they lack an intimate confidante and someone they can share age-related anxieties with.

The theme of resistance underpinning reasons participants gave for not wanting to take antidepressants may be reflecting one way in which patients can reclaim some control. These patients may have been demonstrating resistance to the medicalisation of their lives and perhaps the resulting feelings of disempowerment this engendered. As a number of participants felt that their lives were already dominated by ‘taking pills’ perhaps they felt they could say ‘no’ to antidepressants, in contrast to the rest of their medication, which was probably essential to the functioning of their hearts. A diagnosis for depression as a ‘mental illness’ is a culturally powerful label that can have serious implications for how a person is perceived. Resisting antidepressants could be a way of resisting the meaning given to ‘depression’ via medical records and biomedical discourse. 89–92

Barriers to accessing care provided by GPs, such as an overly bureaucratic GP appointment system, a lack of patient privacy when upset and a lack of continuity of care can affect the quality of care for patients with mild to moderate depression. 93 Continuity of care, that allows the patient to develop a relationship over time with one GP, might also have the benefit of improving facilitation of conversations about emotions and feelings for patients who are distressed or depressed. Privacy and continuity of care may be important elements to consider when designing a primary care intervention for CHD and depression.

From care currently provided by the NHS for patients with CHD, CR courses and appropriately supervised exercise were rated highly by participants. However, the fact that participants enjoyed CR may not equate with a significant improvement in their depressive symptoms. A longitudinal study on the effect of CR on depressive symptomatology94 concluded that exercise itself is not effective in alleviating depression and that CR programmes should provide specific screening and treatment for depression. Doing something enjoyable or useful is important to most people and perhaps this should be seen as just one important ingredient in a holistic approach to improving mental health rather than a treatment for depression per se.

Although a theme of ‘loss’ underpins participants’ accounts of CHD and depression, this does not mean that participants’ lives were totally devoid of happiness and pleasure. Participants talked about enjoying rewarding relationships with grandchildren, going on holidays and day trips, doing voluntary work and in self-development. Despite having symptoms of distress/depression, most participants had hopes and dreams for the future, some of which could be achieved through support in goal-setting and realistic pacing. A primary care intervention that includes a mentoring approach, as part of a stepped care model for treating depression, could help patients identify and achieve some of their goals while enhancing a sense of self-determination and control over their lives. Table 4 summarises participants’ ideas and preferences for interventions that could be delivered in primary care.

How findings from the interview studies informed the pilot intervention

A clear finding from the patient interview studies was that (1) participants were experiencing a range of social, physical and gender identity (erectile dysfunction) losses; (2) some participants preferred to do things on their own, whereas others preferred group activities; (3) most participants had hopes and dreams for the future or enjoyed some aspect of their lives; (4) participants felt disempowered by ill health and the medicalisation of their lives; (5) participants preferred therapeutic treatment approaches for depression; (6) participants were not enthusiastic about antidepressant medication; and (7) loneliness was a problem for a number of participants.

Given the diverse needs of the sample (older people with chronic health conditions who feel lonely, men who felt emasculated and/or want to work again and participants who had experienced a number of adverse life events) an intervention for patients with CHD and depression may need to adopt an individual approach that can accommodate the specific sociocultural and personal needs of patients. A holistic, case management/mentoring approach to depression in CHD could help patients to feel more empowered and in control of their lives, especially if they are supported to achieve personal and health goals.

While conducting the patient interview study, interim findings, participant suggestions and final conclusions were discussed iteratively with the UPBEAT-UK team. The final design of a primary care, nurse-led complex intervention was informed by both the GP and PN (see Chapter 2), and patient qualitative studies together with the UPBEAT-UK literature reviews.

Plans for the content and structure of a nurse-led complex intervention were discussed in-depth with patients (suffering from sCHD and depression) during a series of two focus groups. Adjustments to the design and content of the intervention were made according to recommendations from the focus groups.

Ethical approval

Bexley and Greenwich Ethics Committee gave ethical permission for the study (reference 07/H0809/38), and approval was obtained from NHS trust research governance offices in south-east and south-west London. The researcher (RS) consented the participants.

Phase 1: gathering evidence

This phase included the qualitative studies of patients and primary care clinicians, and the metasynthesis of published literature detailed in Chapters 2 and 3. Essentially, all three studies led to the conclusion that the needs of patients with CHD and depression are diverse and include psychosocial problems involving interpersonal and health/control losses that primary care staff are uncertain how to manage.

Phase 2: synthesis of findings from previous work packages and iterative literature review

Multidisciplinary team discussions involving GPs, psychiatrists, psychologists, nurses and a cardiologist, of our earlier studies led to agreement that the UPBEAT-UK intervention should:

• improve depression, quality of life and cardiac outcomes in patients with CHD

• help patients and clinicians to manage an individualised range of problems, including social problems

• be nurse-led and feasible for delivery in primary care.

These conclusions were used to guide literature searches focused on identifying high-quality systematic reviews and evidence-based guidelines: we searched the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effectiveness and the NICE website. We also looked for evidence published subsequently to the reviews and guidelines using MEDLINE, EMBASE and PsycINFO. Findings from the evidence reviews were discussed and used to support choices for the intervention content. This is detailed in Table 5 (first published in our RCT development paper). 2

We discussed the meaning of these findings in the context of UK primary care, where an established component of chronic disease management is the provision of self-management support; this means enabling patients to take better care of themselves, for instance by providing information and helping them to change unhealthy behaviours.

Two important factors for behaviour change are known to be belief in the importance of an outcome and belief in capacity to succeed (self-efficacy). 105 This suggested to us that instead of focusing on generic CHD or depression risk factors, the new intervention should enable patients to specify their own goals, for instance stopping smoking or increasing social contact, so that work is directed towards outcomes important to patients.

Informed by our evidence review a ‘toolkit’ of behaviour change skills and existing local resources was developed to facilitate nurses, acting as case managers, to help the patient to increase their self-efficacy and achieve their desired outcomes.

The intervention we developed therefore was a PN-led PC intervention. It comprises the following:

Personalised care planning: the nurse acting as case manager conducts a standardised biopsychosocial assessment (including physical and mental health, difficulties with current treatment regimens, problems with daily activities and social problems) face to face with the patient either at the patient’s GP surgery or at their home, according to patient preference. Patients are helped to identify up to three problems that they consider contribute to their depression and which they most want to address. The nurse case managers, as applicable, provide information, signpost patients to existing resources (e.g. leisure centres, social clubs, IAPT services) and use evidence-based behaviour change techniques to help patients set and achieve goals. The underlying intention of the intervention is to increase the patient’s self-efficacy to achieve their desired goals (as opposed to goals determined by others such as symptom management or reduction of cardiac risk factors, a primary aim of many previous collaborative care projects). Details of the assessment and action plan are recorded in a ‘personalised health plan’, which the patient holds.

Follow-up care: follow-up interviews to determine progress and/or set new goals are conducted via telephone to conserve nurse time. This is initially weekly and then the frequency of contact is agreed between the patient and nurse case manager. Calls are planned to last 15 minutes.

The intervention process is detailed in Figures 4 and 5 (first published in our RCT development paper). 2

FIGURE 4.

Personalised care planning. The UPBEAT-UK intervention assessment stage and initial care planning. Reproduced from Barley et al. 2 © 2012 Barley et al. ; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

FIGURE 5.

Follow-up care. The UPBEAT-UK intervention follow-up care stage. Reproduced from Barley et al. 2 © 2012 Barley et al. ; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Phase 3: modelling

Having developed the intervention, and following MRC guidance,30 we now wanted to explore its acceptability among people with sCHD and depressive symptoms. Using maximum variation sampling to select patients varying by sex, age, ethnicity and borough of residence, we invited participants of the UPBEAT-UK cohort study to attend two focus groups.

In a short presentation, two researchers (RS and Zoe Fortune) explained the proposed intervention and the intervention materials (patient information leaflet, assessment form, personalised health plan) were provided. All participants gave informed consent and ethical approval was granted, along with that for the other qualitative studies, by Bexley and Greenwich Research Ethics Committee (07/H0809/38).

Sixteen patients agreed to take part. Thirteen actually participated; five out of six came for the first group and eight out of 10 came for the second group. Reasons for not attending were not elicited. Those who participated (53% male) were aged between 48 and 86 years (mean 71 years). All but two, who were African Caribbean, described themselves as white British.

Discussions were tape-recorded and transcribed by RS. Transcripts were entered into NVivo 8 qualitative software. Coding was informed by the aims of the study. The coding frame and themes were discussed within the research team; we used notes of key discussion points (verified by participants) to guide our analysis.

Key findings of the discussion and modifications to the intervention

The participants were very focused on their need for someone to confide in and felt that a case manager would help with this.

The concept of self-management, in which the case manager would help them to solve their own problems, did not seem to be well understood. We planned to examine this in our exploratory study.

Participants agreed that PNs were the correct people to act as case managers because of their understanding of heart disease and its associated problems. Nurses should also be able to provide the continuity of care that participants emphasised as important.

Some participants disliked the planned use of goal-setting. Rather, participants were focused on wanting case managers to be a source of social contact. Based on our work with PNs, who complained of lack of time to manage these patients, this did not seem feasible. Instead, we felt that goal-setting and action-planning could be used to help patients obtain social contact. Furthermore, our literature searches identified good evidence for the feasibility of goal-setting in primary care. 106 This highlighted to us the importance, when designing interventions, of utilising multiple sources of evidence. We planned to explore the acceptability of goal-setting further in our exploratory study.

Finally, a minor point was that some of the wording used on the assessment form was not clear. We had developed our care plan format from the framework proposed by the Department of Health as the standard assessment for adults;107,108 this grouped health-related domains such as ‘activities of daily living and mobility’ under headings such as ‘improved personal dignity and autonomy’. These higher-level headings appeared to confuse patients, so they were removed from intervention documents.

Discussion

Informed by the MRC framework for the design of complex interventions,30 we conducted empirical studies and iterative literature searching to identify evidence and theory to develop and model a new PN-led PC intervention to improve mood and cardiac outcomes in sCHD patients with depressive symptoms.

Our approach is only one possible approach to developing a complex intervention using the MRC framework. 30 For instance, others109 have drafted an intervention around a specific psychological theory and have tested theory-related hypotheses. However, we feel that a strength of our approach is that the intervention development was driven by the patients who will receive it and by the clinicians who will deliver it, with theory (i.e. self-efficacy theory and behaviour change theory) and evidence used to support choices concerning its content. The fact that all the studies reported here were funded by a single programme grant facilitated access to patients and allowed subsequent work to build on earlier findings in a timely fashion.

Furthermore, our approach led us to change our initial plans, which, as we have explained in Chapter 1, were to develop a nurse-led stepped care intervention. Our intervention development work clearly demonstrated a need for an intervention that could be tailored to the differing needs of individual patients; this could be included within a stepped care approach. It was also clear from this work that some PNs will need support to deliver an intervention for depression and that, since their workload is already very high, they would need convincing that any new intervention is feasible for them to deliver as well as effective for patients. Hence, with so much uncertainty around the feasibility of PN-led interventions for depression, we changed our plan to conduct a definitive RCT and decided to conduct an exploratory study which would provide this evidence and inform the best methods of a future definitive RCT.

Aims and objectives

1. To examine the rate of participant recruitment and reasons for non-participation.

2. To examine research procedures such as consent, randomisation/blinding and data collection.

3. To explore possible differences between primary outcome measurements and explore the most appropriate secondary outcome measures in relation to patients’ reported problems.

4. To identify any trends between the groups in changes in self-efficacy and the impact of this on depression outcomes.

5. To determine the acceptability and feasibility of the intervention to practices and participants.

6. To explore whether or not the intervention can be standardised and whether or not therapist effects are likely to be important.

7. To explore potential costs of the intervention.

Methods

Analysis

We conducted exploratory analyses using Stata version 11.2 (StataCorp LP, College Station, TX, USA). The intention-to-treat principle was used for all analyses. Owing to the exploratory nature of the analysis, p-values are reported for the preliminary primary outcome (HADS-D) only. We were fortunate to have a National Institute for Health Research-funded statistical fellow attached to our programme and were therefore able to conduct detailed exploratory analyses; these are explained fully in the published report of this study. 110 Essentially, we developed a single statistical model to estimate the difference in mean scores between participants randomised to PC and TAU across the three follow-up points (1, 6 and 12 months). Other exploratory analyses compared the median number of responders (≥ 50% decrease in score from baseline at follow-up) and remitters (score of < 8 at follow-up) according to the HADS-D score between groups and explored changes in self-efficacy, the effect of nurse contact time and therapist effects using t-tests and chi-squared tests.

A health economics analysis used multiple regression, incremental cost-effectiveness ratios and the net benefit approach to estimate mean differences in costs and QALYs. Non-parametric bootstrap analyses were conducted to account for the highly skewed distribution of the cost data; results were plotted on a cost-effectiveness plane and used to estimate cost-effectiveness acceptability curves.

Aim 1: examining recruitment

Seventeen practices were approached by the PCRN-GL and agreed to participate. Practices were recruited between October 2010 and June 2011; practice recruitment was therefore completed in considerably less than the 12 months planned in the study proposal, indicating that recruitment of practices for a definitive trial would be feasible.

We have published patient recruitment details in a paper by Tylee et al. 111 We summarise it briefly here. Of the 3325 people on the 17 GP CHD registers, 1001 consented to be contacted by returning a letter to their GP. A brief screen by telephone found that 126 were eligible for assessment (PHQ-9 score of ≥ 3 and reporting current chest pain on the modified Rose angina questionnaire). Of the 126 who were eligible, 40 had a HADS score of < 8, two had experienced hallucinations, two had no current chest pain and one did not have sufficient English, therefore, 81 were found to be eligible. These were consented and randomised (41 to intervention, 40 to control). The screening process involved minimal effort (return of a letter and a brief telephone screen). Target recruitment was achieved within 8 months, which was considerably faster than expected (we had planned a 12-month recruitment period based on experience of other studies); recruitment of patients for a definitive RCT, therefore, seems promising.

Baseline demographic and lifestyle data are reported elsewhere. 110 There were 27 (66%) males in the PC group and 25 (63%) in the TAU group; mean age was 64.2 years (SD 13.0 years) in the PC group and 64.9 years (SD 8.5 years) in the TAU group. Any differences between the groups on the recorded demographic, lifestyle and outcome variables appeared small and the randomisation process appears to have produced balanced groups.

Aim 2: examining study procedures

Attrition

The Consolidated Standards of Reporting Trials diagram for the study is shown in Figure 6 and has been published. 110 By 12 months, six people in the intervention group had dropped out (two because they found participation upsetting, two because they felt too physically unwell to continue and two gave no reason) and one from the control group had dropped out (because they found participation upsetting). Two intervention group participants received baseline assessment but no intervention, as the nurses were unable to contact them. Overall, attrition was low (7/81 = 9%), with data collected at one or more follow-up points for 79 people (98%).

FIGURE 6.

The UPBEAT-UK pilot study Consolidated Standards of Reporting Trials diagram. Uncontactable means lost to follow-up. Reproduced from Barley et al. 111 © 2014 Barley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Across the study period, completion was better for the TAU group than the PC group (Table 6). Completion was better among non-drinkers and those that drank the most (> 11 units per week), as well as those who were retired compared with being in paid employment across time points. Characteristics of completers are described in Table 7, which lists the demographics of those who completed follow-up and those who did not. HADS-D scores (Table 8) were marginally lower at 1 and 6 months among non-completers; however, they evened out by 12 months. We compared the models from our analyses with an additional model that controlled for any variables that were associated with missing follow-ups; these analyses did not give us any reason to alter any of our conclusions.

TABLE 6 - Demographics of those who complete follow-up and those who do not

BMI, body mass index.

Measure	1-month follow-up completed, n (%)	6-month follow-up completed, n (%)	12-month follow-up completed, n (%)
Randomisation
PC	37 (90)	35 (85)	32 (78)
TAU	40 (100)	39 (98)	37 (93)
Sex
Male	48 (92)	46 (88)	44 (85)
Female	29 (100)	28 (97)	25 (86)
Ethnicity
White	64 (96)	61 (91)	57 (85)
Black	3 (100)	3 (100)	3 (100)
Asian	5 (100)	4 (80)	4 (80)
Other	5 (83)	6 (100)	5 (83)
BMI
Underweight	3 (100)	3 (100)	2 (67)
Normal	19 (100)	17 (90)	15 (79)
Overweight	22 (96)	21 (91)	21 (91)
Obese	27 (90)	28 (93)	25 (83)
Smoke
Never	20 (91)	20 (91)	18 (82)
Ex-smoker	39 (98)	37 (93)	35 (88)
Current	18 (95)	17 (89)	16 (84)
Units of alcohol
Does not drink	38 (97)	37 (95)	35 (90)
1–10	26 (90)	24 (83)	21 (72)
≥ 11	13 (100)	13 (100)	13 (100)
Employment status
Paid employment	10 (83)	10 (83)	10 (83)
Retired	55 (100)	52 (95)	49 (89)
Housewife/husband	4 (100)	3 (75)	3 (75)
Unemployed/student	6 (86)	7 (100)	5 (71)
Relationship status
Married	38 (95)	37 (93)	37 (93)
Cohabiting	6 (75)	7 (88)	5 (63)
Widowed	12 (100)	12 (100)	10 (83)
Separated	4 (100)	4 (100)	4 (100)
Divorced	11 (100)	8 (73)	8 (73)
Single/non-cohabiting partner	6 (100)	6 (100)	5 (83)
Live with
Spouse	26 (93)	27 (96)	25 (89)
Spouse and children	14 (88)	13 (81)	13 (81)
Children	7 (100)	7 (100)	6 (86)
Alone	28 (100)	25 (89)	23 (82)
Other	2 (100)	2 (100)	2 (100)
Place of residence
Owner occupied house/flat	32 (97)	32 (97)	29 (88)
Privately rented house/flat	8 (100)	8 (100)	7 (88)
House/flat rented from local authority	32 (91)	30 (86)	29 (83)
Sheltered housing/warden control	4 (100)	3 (75)	3 (75)
Other	1 (100)	1 (100)	1 (100)

TABLE 7 - Continuous demographics of those who complete follow-up and those who do not

BMI, body mass index; IMD, Index of Multiple Deprivation.

Measure	Completed			Not completed
	n	Mean	SD	n	Mean	SD
1-month follow-up
Age (years)	77	65.1	10.8	4	53.8	7.1
IMD score	77	26	13.9	4	26.6	10.2
BMI (kg/m2)	71	29.5	7.1	4	32.3	5.3
Years in education	74	12.7	8.4	4	14.3	5.3
6-month follow-up
Age (years)	74	65.4	10.5	7	55.1	11.6
IMD score	74	26.1	14	7	25.6	10.8
BMI (kg/m2)	69	29.8	7.2	6	28	3.8
Years in education	72	12.0	4	6	11.8	3.1
12-month follow-up
Age (years)	69	64.9	10.4	12	62.4	13.9
IMD score	69	26.3	14.4	12	24.2	8.6
BMI (kg/m2)	63	30	7	12	27.7	6.6
Years in education	67	12	4	11	11.7	3.2

TABLE 8 - Comparison of psychiatric baseline scores between completers and non-completers of follow-ups

Measure	Completed			Not completed
	n	Mean	SD	n	Mean	SD
1-month follow-up
HADS-D score	77	11.6	3.2	4	10.0	2.3
HADS-A score	77	12.4	5	4	15.5	1.3
PHQ-9 score	76	15.7	5.4	4	16.3	5.2
6-month follow-up
HADS-D score	74	11.7	3.2	7	10.3	2.4
HADS-A score	74	12.5	4.9	7	13.3	4.5
PHQ-9 score	73	15.9	5.4	7	13.6	5.1
12-month follow-up
HADS-D score	69	11.5	3.1	12	11.6	3.4
HADS-A score	69	12.3	4.8	12	14.4	5.4
PHQ-9 score	68	15.8	5.2	12	15.4	6.6

Aim 3: validity of outcome measures in comparison with participant-reported problems

Using the BIPQ, participants were asked to list the three most important problems that caused their illness (CHD). Sixty-one participants gave at least one reason (these data are published online as an appendix110). The most common reason given was ‘genetics or heredity’, followed by lifestyle factors such as smoking, poor diet and lack of exercise. Mood problems, especially stress and work-related stress were also mentioned, and comorbid or past health problems were also blamed. Four patients mentioned relationship problems and one mentioned financial problems.

Participants in the PC group (n = 41) identified 21 types of problem as contributing to their depression and which were addressed during the intervention (up to three problems per patient); most common were pain (chest and other pain, e.g. arthritis) (n = 18), lack of exercise (n = 17), difficulty sleeping (n = 13), anxiety (n = 11) and being overweight (n = 11). Reported problems and whether or not they were addressed during the intervention are published online as an appendix. 110

Participants therefore explained both their CHD and their depression in terms of wide-ranging problems that appeared similar for the two conditions; lifestyle problems in particular were associated with both.

Within our study, mood outcomes were assessed using the HADS (depression and anxiety) and the PHQ-9 (depression); however, we had no measure of change in lifestyle-related outcomes. The PC intervention was aimed at tackling the problems that each participant felt were important rather than addressing specific cardiac risk factors; however, in view of our current finding that patients do consider lifestyle factors known to be associated with CHD as contributing to their depression, inclusion of a measure of change in cardiac risk factors should be considered for a definitive trial of PC. It will be important to select a measure that captures the variation between participants in terms of which risk factors they want to address; a validated measure of goal attainment may therefore be appropriate.

Aim 4: exploring changes in self-efficacy

Self-efficacy improved over the course of the study (see Table 11). At 12 months, the PC group had a mean increase of 2.5 points versus 0.9 points in the TAU group, suggesting a greater increase in self-efficacy in the PC group; however, the mixed-effects model indicated no difference between groups over time (adjusting for baseline self-efficacy): mean difference –0.58 (95% CI –3.05 to 1.89).

At 6 and 12 months the overall illness perceptions score and most measured dimensions showed improvement in both groups, though differences between groups were small (Table 12). The mean improvement in overall score from baseline to 12 months was greater in the PC group than in the TAU group: 7.8 points versus 2.5 points. As expected, the biggest difference in mean improvement between the PC and TAU groups in dimension scores was in personal control (mean change in BIPQ from baseline = 1.5 for PC group vs. 1.1 for TAU at 6 months; and 1.1 for PC vs. 0.1 for TAU at 12 months); however, the mixed-effects model suggested no difference between groups over time (adjusting for baseline total BIPQ score): mean difference –0.42 (95% CI –4.57 to 3.72).

Controlling for changes in self-efficacy or overall illness perceptions had little effect on change in depression over time, whether or not considering depression severity, remission or response (Table 13). Since CIs were wide, change in favour of either PC or TAU cannot be ruled out.

Aim 5: exploring acceptability and feasibility of personalised care

Aim 6: exploring standardisation and therapist effects

Aim 7: examine the potential cost of personalised care

The average EQ-5D utility scores at baseline were slightly higher for the PC group (see Figure 7, which is also published elsewhere110), although the difference between groups was not statistically significant (95% CI –0.98 to 0.25; p = 0.40). By the 1-month follow-up, the TAU group had a higher utility score, and this difference was maintained up to the 12-month follow-up [95% CI –0.26 to 0.11; p = 0.422 (at 6-month follow-up: 95% CI –0.27 to 0.11, p = 0.408)]. In terms of QALYs, the TAU group showed an incremental QALY gain of 0.038 compared with PC over the 12-month treatment period. In Figure 7 the area between the two curves represents the QALY gain for the control group.

FIGURE 7.

European Quality of Life-5 Dimensions score and QALY gain. CM, nurse-led case management. Reproduced from Barley et al. 110 © 2014 Barley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Cost–utility analysis

Of the total 81 participants, cost and QALY data at each time point were available for 68 patients (84%). Cost–utility results yielded an incremental cost-effectiveness ratio of £29,921 per additional QALY. Cost-effectiveness plane and cost-effectiveness acceptability curves were produced from bootstrapped resamples. The distribution of the cost-effectiveness point estimates on the cost-effectiveness plane (Figure 8, which can also be found in Barley et al. 110) indicated a strong likelihood of cost savings for the PC group compared with the TAU group. The point estimate of the incremental cost-effectiveness ratio falls in the south-western quadrant, representing the situation where the PC group has reduced costs and worse outcomes. The second most likely result is that PC results in lower costs and better outcomes (south-east quadrant).

FIGURE 8.

Distribution of the cost-effectiveness point estimates on the cost-effectiveness plane. NE, north-east; NW, north-west; SE, south-east; SW, south-west. Source: reproduced from Barley et al. 110 © 2014 Barley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The cost-effectiveness acceptability curves (Figure 9) for the PC group compared with the TAU group was downward sloping. There is a greater likelihood of PC being the most cost-effective option up to a QALY threshold of £3035.

FIGURE 9.

Cost-effectiveness acceptability curves. c-e, cost-effective; p, probability. Source: reproduced from Barley et al. 110 © 2014 barley et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Discussion

We developed a PN-led PC intervention, which was designed to be easily implemented within practice in order to improve current primary care. In this patient-randomised pilot trial we explored the acceptability, feasibility and potential costs of the intervention for primary care CHD patients who have probable concurrent depression and current chest pain. We also explored the feasibility of the trial protocol to inform the methods of a definitive trial.

Objectives

The objectives of the cohort study were to:

1. determine the prevalence, incidence rate and risk factors of depressive disorders in primary care patients with CHD

2. explore and describe the course and prognosis of physical and depressive symptoms among primary care patients with CHD over a 3-year period

3. determine the effect of depression on mortality, symptom severity and pain in primary care patients with CHD.

Service use, service costs and lost employment costs will be described separately.

Methods

The cohort study methods, instruments and analysis plan have been described elsewhere. 1 This was a naturalistic cohort study of primary care patients recruited from QOF CHD registers held by GP practices in south London. All participants on these registers were eligible for inclusion in the study as long as they were > 18 years of age and not temporarily registered with their GP. Eligible consenting patients were assessed at baseline and then followed up at 6-monthly intervals for a period of up to 4 years. We report on the 3-year follow-up data here. All patients were eligible for 36 months follow-up at the end of the study. A smaller population was eligible for a 4-year follow-up (and will be analysed in the future). The measures used at baseline and follow-up are shown in Table 16, previously published as table 1 in Tylee et al. 1 Not all measures have been used in the analyses presented here. For more details on the instruments used, see Appendix 4.

The reporting of chest pain by cohort members was recorded at each wave of follow-up. Chest pain is the cardinal symptom of CHD and the key to a clinical diagnosis of angina pectoris. We report here the prevalence rate of this physical symptom at baseline and the outcome in terms of cardiovascular events (e.g. MI) or continued exertional chest pain (i.e. patients reporting exertional pain on most occasions). We have analysed the relative roles of depression, anxiety and quality-of-life scores for these outcomes.

Chest pain assessment

We used the Rose questionnaire113 to assess the severity of the symptomatology (i.e. chest pain) of CHD. Devised in the 1960s for the purpose of detecting angina pectoris in field studies, it has been widely used since. The original validation criterion was agreement with CHD diagnosis in GP medical notes but since then it has been used as a useful predictor of subsequent cardiovascular events in the longer term. 157–160 On the other hand, the agreement between a positive response on the Rose and concurrent clinical testing for evidence of CHD can be poor. 161,162 It is used in both a long form in field studies and, as the short form of the Rose questionnaire has equivalent predictive power, the short form is often preferred. We describe how both the short form and the long form are rated below. Pain on exertion seems to be the key symptom to predict subsequent problems. 163

The short form is outlined in Table 17 below and the additional questions for the long form are shown in Table 18.

To assess cardiac outcomes, all cardiology notes, investigations and interventions were collected from the GP notes by a medical doctor on the team (JP) and entered into an encrypted Microsoft Access^® 2007 database (Microsoft Corporation, Redmond, WA, USA). The dates of each visit to a cardiologist, each investigation for a cardiac-related problem and each visit to a rapid access chest pain clinic, A&E or hospital admission for a cardiac investigation or intervention (e.g. bypass graft, angioplasty) were recorded. We also recorded any GP visit for cardiac-related problems or regular follow-ups. The data to be inputted and the specific definitions of cardiac investigations were decided before the hard copies were examined, with exception to the ‘rapid access chest pain clinic’ category. The GP notes were re-examined to gather this extra information and all data were entered into the Access database before any analysis of cardiac investigation data occurred. Numerous records per individual were condensed into variables that denoted: (a) the first cardiac investigation to occur within two time points would be recorded per person; and (b) the most severe cardiac investigation to occur within two time points would be recorded per person.

Thus, a cardiac outcome variable with seven hierarchical categories was created using a combination of the short form of the Rose angina questionnaire, the GP medical notes and publicly available mortality records:

• no chest pain: score of 0 on the short Rose angina questionnaire

• chest pain: positive response to the Rose angina questionnaire item

• exertional chest pain: positive classification of grade 1 or grade 2 angina as defined by the short form Rose angina questionnaire

• rapid access: any visit to the rapid access chest pain clinic, or any visit to A&E or emergency hospital admittance where cardiac-related chest pain was the diagnosis

• bypass graft or angioplasty: intervention reported on GP medical notes or cardiologist/cardiology service notes

• MI: occurring at any point during the follow-up period

• death: any cardiovascular-related cause of death included (i.e. cardiovascular and cerebrovascular).

For the purpose of the longitudinal analysis, the most severe outcome was assigned to the time point at the end of the period where the outcome occurred. MIs and deaths had to be combined for some analyses, when there were insufficient numbers to fit full models. When linking cardiac investigation and mortality data with interview data at specific time points, deaths and cardiac investigations were coded into time points at the end of the 6-month window between interviews. If a participant had a recorded cardiac investigation within the 6 months before baseline, this was recorded in the baseline time point. All cardiac investigation data as described, with dates of the investigations, were merged into the cohort data set. The aim of this time assignment was to produce data where mental health status could be clearly identified in its temporal relation to cardiac outcomes (the actual date of death was, however, used for a more detailed and specific study of mortality).

Mortality data was gathered from a number of sources, including case notes and publicly available records. The deaths of the cohort participants were tracked in the first instance via the practice manager at the different GP surgeries, where we asked for date and cause of death. In those cases in which the participant had moved away from the surgery, we contacted the primary care support services within the specific boroughs. Further to this, we purchased death certificates through the health authorities relating to the specific boroughs. Where consent had been withdrawn we recorded the fact of death if known but not the reason. The censoring date was the date of death, the final interview date or the date when the interview would have taken place for those who were lost to follow-up. For the latter group, deaths were monitored using public sources up to their censoring date. If the reason for loss to follow-up was withdrawal of consent, the reasons for death were not sought unless available as part of the public record. An intermediate censoring date was also created, based on the 36-month interview date. Only deaths that occurred before that date were used when analysing the 36-month data.

A sample size of at least 800 participants was calculated to be adequate to allow modelling of associations between physical and mental illness. 1

Results

Recruitment and retention of the study population

Recruitment

Recruitment into the cohort study is shown in Figure 10. Sixteen general practices from south London participated in the research programme, and from these practices 803 participants were recruited into the cohort study from the practice-held CHD registers. The study population represented 27% of those eligible to be included in the cohort study. 164

FIGURE 10.

Recruitment profile of the UPBEAT-UK cohort study.

Baseline characteristics of the study population

The baseline characteristics of the cohort population have been published in detail. 164 Tables 20–22 show the demographic, social and clinical characteristics of participants. Essentially, this was an older population (average age 71 years), predominantly male (70%), with 87.3% classifying themselves as ‘white’. Black and ethnic minorities made up 13% of participants. As would be expected, the majority were retired (77%). The average length of time since a diagnosis of CHD was made in the GP records was 10 years, and 44% reported ongoing chest pain. Social problems were common, with relationship problems being the most common reported social problem (38%). Levels of disability were also high in this population, with 53% reporting problems with pain or discomfort and 49% with mobility problems.

Table 23 shows that our cohort study population contains approximately equal proportions of those with a completed MI and a current GP diagnosis of ischaemic heart disease with no history of MI. Similarly, equal proportions have and have not received some kind of surgical intervention.

Cardiac status at baseline is shown in Table 24.

Using the short Rose angina questionnaire, just over one-quarter of the cohort report exertional pain, which could indicate angina. Using the more stringent full Rose angina questionnaire criteria, 13.9% are likely to have a clinical diagnosis of angina (grade 1 or 2).

Discussion

A total of 44% of the sample stated that they currently experience chest pain. If this pain reflected just current angina pectoris, this figure would be very high, given that angina typically accounts for 4% of GP consultations and, in community samples of older people in Scotland, rates of angina pectoris using the Rose angina questionnaire are reported as 2.5% for men and 2.7% for women. 169 A meta-analysis of prevalence rates of angina in community samples in 31 countries showed a weighted mean of 5.7% for men and 6.7% for women – the highest rates from any of the countries were 14.4% for men and 15.7% for women. 170 Rates of angina following infarction are reported at 19%171 and there should not be any in the aftermath of successful revascularisation.

In fact, chest pain is commonly reported as a symptom in representative epidemiological studies, along with other types of pain. In one study, 12% of participants reported chest pain, compared with 41% reporting backache and 26% reporting headache. 172 The most common explanatory physical diagnosis for chest pain is oesophageal reflux. 173,174 There has been one epidemiological study in Australia of those with non-cardiac chest pain. 175 The authors noted that (1) the most common accompanying symptom was heartburn that suggests oesophageal disorder; (2) many did not seek help for it; and (3) quality of life was reduced for those reporting it with. 175,176 Non-specific chest pain is associated with an increased mortality rate. 177

It has long been recognised that many patients referred for investigation of chest pain have concurrent anxiety and depression syndromes. 173 Chest pain is indeed a recognised symptom for the diagnosis of a panic attack. 178 Case-level anxiety or depression has been stated to be a contraindication to expensive cardiology investigation, as few patients are found to have coronary disease. 179

Most of the work on the association of chest pain with psychiatric disorders has been carried out in cardiology patients. Our study population is different in that we have recruited our patients from a primary care-based register of CHD patients, some of whom are under the care of cardiologists. To our knowledge, there are no previously published studies on this topic based on GP register patients.

We are mainly reporting on the group identified as ‘exertional pain’ from the short Rose angina questionnaire, as there is adequate indication from published studies that this symptom is the most prognostically important for future events as described above. 163 The distribution of the data when classified by the short Rose angina questionnaire data also allows greater power in our analyses, and there are fewer missing responses than when using the long version. Multivariate analyses have been conducted to investigate baseline associations of short Rose classification.

Exertional pain versus non-exertional pain (risk factors)

The next analysis (Table 25) simultaneously compares those with chest pain with those with non-specific pain, and with those with exertional chest pain. Each paired analysis takes into account the third group.

The variables entered were those baseline variables describing cohort members set out in the paper on baseline analyses. 164 They concern sociodemographic status, cardiac variables, self-reported cardiac risk factors, physical disease comorbidity and social problems.

Variables were included in the model if they provided information to an alpha threshold of p < 0.2. Variables in the model were age, sex, ethnicity, Index of Multiple Deprivation (IMD) score, smoking status, comorbidity of COPD, depression (positive on the HADS-D scale), anxiety (positive on the HADS-A scale), total number of SPQ social problems and ‘How much bodily pain’ (i.e. non-specific pain) in the past 4 weeks? (Question 21 on the Short Form Questionnaire 36-items quality-of-life scale.) Only those variables contributing with a significance threshold of p < 0.05 are reported above.

For continuous variables (age, IMD score and total SPQ social problems): with every one unit increase in IMD deprivation, the RR of being in the chest pain group compared with the no chest pain group increases by 3% (RR 1.03; p > 1).

For the categorical variables (sex, ethnicity, depression, COPD and primary GP coded CHD diagnosis): for those classified by the HADS as having depression compared with those without HADS depression, the RR of being in the chest pain group was 2.87, and being in the exertional pain group was 2.92, both compared with the no chest pain group.

The analysis in Table 25 was repeated using the full (long) Rose angina questionnaire classification variables: no pain (n = 447), pain in chest (n = 171), grade 1 and grade 2 angina (n = 111). The results, which are not reported here, were very similar.

Discussion

Notable in the results of this analysis is the absence of any of the cardiac variables or cardiac risk factors that we recorded as associations of chest pain (whether or not the chest pain was exertional) – in particular whether or not there is a history of a revascularisation procedure. The association with GP diagnosis of ischemic heart disease and exertional pain is compatible with the validation criteria of the Rose angina questionnaire. The association with COPD has clinical face validity – sufferers may experience discomfort when they exert themselves.

Depression, anxiety and social factors are the evident associations. The most potent association is the number of social problems rather than any individual social problem. For every additional social problem reported, the risk of exertional pain increases by 36%. Depression and anxiety are both associated with complaints of non-specific and exertional pain – the RR being higher for the exertional pain. Experience of panic and bodily pain remain independently associated with chest pain. Increasing report of bodily pain is associated with increased risk of being in both of the two chest pain categories.

The data from this cohort strongly suggest a psychosocial context for the complaint of chest pain whether or not it is anginal in type. As this is a cross-sectional analysis, direction of causality cannot be assumed. It is possible that having chest pain limits life to the extent that multiple social problems result, for example less social contact.

Baseline analysis

The literature suggests that quality of life is impaired many years after MI for those with persisting symptoms,180 the effect being more marked in younger than older people. The same is reported for those with non-cardiac chest pain. 175 The EQ-5D is used in these analyses as a measure of health-related quality of life, a score can be obtained by summing the response to the five questions asked or from the accompanying visual analogue, in which the respondent makes a judgement of their quality of life now. We have chosen the latter, as one of the five questions asks about anxiety and depression and we wish to examine quality of life separately from mental state so far as is possible.

Examination of associations of baseline European Quality of Life-5 Dimensions visual analogue scale

Quality of life was thus recorded using the EQ-5D questionnaire visual analogue scale (EQ-5D-VAS). To examine the factors associated with quality of life, we used a multiple linear regression model and selected variables from a large pool of sociodemographic and clinical factors. Variables were selected using a stepwise selection procedure that retained all predictors if evidence for their association with the visual analogue scale was lower than p = 0.2.

The outcome, as well as all predictors used in this analysis, was collected by self-report questionnaire and at the same time point (baseline), and so this analysis can be seen as an examination into the factors associated with quality of life and, on an exploratory basis, an examination into the potential predictors of quality of life in our cohort. Owing to the positively skewed distribution of the EQ-5D-VAS, non-parametric bootstrapping using 200 replications was used in the analyses.

The results of this analysis are shown in Table 26–28.

The data in Table 27 show high correlation between anxiety and depression scores, and between EQ-5D scores and both. In the latter, high depression anxiety scores (bad) correlate inversely with high EQ-5D sores (good). Table 28 shows analyses that explore, at baseline, what factors influence the EQ-5D-VAS score in this cohort.

Summary of results

The following variables associated with baseline quality of life:

• Ethnicity: white ethnic group had a 4.74 unit higher score (p = 0.024). This is a small standardised effect size (0.1).

• Current smokers: current smokers scored, on average, lower by 5.19 units (p = 0.022).

• Exertional chest pain: those with exertional chest pain had a lower quality-of-life score by 3.90 units (p = 0.020), a small effect size (0.09).

• Bodily pain: those reporting bodily pain (an item taken from the SF-12) had, on average, a 3.85-point lower score on the EQ-5D-VAS (p < 0.001). This was a moderate effect size (0.28).

• Treatment for heart problem: people who had received a treatment for their heart problem in the past had a lower quality-of-life score by –2.75 units (p = 0.021). This was a small effect size (0.07).

• Cancer: cancer was associated with lower quality of life by 5.63 points (p = 0.013). This was a small effect size (0.1).

• Depression: HADS-D (scoring ≥ 8 on the HADS-D scale) was associated with a 9.71-unit lower quality of life (p < 0.001). This was a small effect (0.17).

• Anxiety: HADS-A (score of ≥ 8) was also associated with a lower score on the EQ-5D-VAS scale by 4.8 units (p = 0.003). This was a small effect (0.11).

Depression, anxiety and chest pain all impair quality of life at baseline.

Prevalence of depression

The prevalence of depressive and anxiety disorders and the risk factors associated with a depressive disorder at baseline have been presented in detail elsewhere31 and will be summarised here. The prevalence of depressive and anxiety disorders in this population at baseline is shown in Table 29.

The proportion of the population who had depression recorded as an active problem in GP records at recruitment into the cohort was 7%, whereas 4.6% of the population had an International Classification of Diseases, 10th edition, diagnosis of a depressive disorder (mild, moderate or severe) as defined by the Clinical Interview Schedule – Revised (CIS-R). According to the HADS-D scale, 12.8% of the population suffered from a depressive disorder at baseline (i.e. scored > 7 on the depression subscale).

The statistically significant associations between predictor variables and CIS-R-defined depression at baseline fell into three domains: living alone, disability and pain, and age (problems with living alone: adjusted OR for a CIS-R diagnosis of mild, moderate or severe depressive episode 5.49, 95% CI 2.11 to 13.40; p < 0.001; experiencing chest pain: adjusted OR for a CIS-R diagnosis of mild, moderate or severe depressive episode 3.27, 95% CI 1.58 to 6.76; p = 0.001; being disabled by pain or discomfort: adjusted OR for a CIS-R diagnosis of mild, moderate or severe depressive episode 3.39, 95% CI 1.42 to 8.10; p < 0.006; having problems carrying out usual activities: adjusted OR for a CIS-R diagnosis of mild, moderate or severe depressive episode 3.71, 95% CI 1.93 to 7.14; p < 0.001; and age: adjusted OR per year for a CIS-R diagnosis of mild, moderate or severe depressive episode 0.95, 95% CI 0.92 to 0.98; p < 0.001) (see Walters et al. 164). Chest pain was significantly associated with depression independently of other pains and discomfort.

Participants had an increased odds of having a GP-recorded diagnosis of depression if they reported problems with close relationships (adjusted OR for a GP diagnosis of depression 2.51, 95% CI 1.40 to 4.52; p = 0.002), reported having diabetes mellitus (adjusted OR for a GP diagnosis of depression 2.01, 95% CI 1.11 to 3.63; p = 0.02), were disabled by pain and discomfort (adjusted OR for a GP diagnosis of depression 1.95, 95% CI 1.04 to 3.68, p = 0.037), or were female (adjusted OR for a GP diagnosis of depression 1.88, 95% CI 1.04 to 3.37; p = 0.035) (see Walters et al. 164).

Incidence of depression and risk factors for incident depression

The incidence risk of developing a depressive disorder (as defined by scoring ≥ 8 on the HADS-D subscale) is shown in Table 30. The proportion of new cases of depression was similar at each time point for those who were not depressed at baseline. However, the proportion of incident cases of depression decreased across time points for those who were depressed at baseline. The cohort followed participants for a total 1942.3 years at risk. During this period there were 240 incident cases of depression giving an incident rate ratio of 123.6 per 1000 person-years at risk.

The risk factors associated with the incidence of depression are shown in Table 31. The strongest predictor of incident depression was having had a documented MI at some point before the incident depression. Other predictors of incident depression were: suffering with depression at baseline or having a past history of depression, self-reported exertional chest pain, problems with disability and living alone.

[Exertional pain was initially considered as a possible type 3 variable. However, in the final model it was better treated as a time-invariant (baseline only) predictor because of uncertainties in the longitudinal data recording. It was not always possible to establish the time sequence of the incidence of pain and depression and there were a large number of missing values, which greatly reduced the sample size.]

The course of depression in cohort participants is described in Table 32.

Of the 12.9% of participants depressed at baseline, 42.7% remained depressed throughout the 36-month follow-up period. Only 35% were not depressed at final follow-up. Of those not depressed at baseline, 23.6% developed depression at some point over the follow-up period.

The incidence and effect of depression and anxiety on cardiac outcomes and mortality

The incidence of cardiac outcomes is reported in two ways – first, the incidence of cardiac events over the follow-up period (and the effect of depression and anxiety) and, second, the continuing reporting of chest pain over that same period.

Table 33 shows the incidence of cardiac events over the 36-month follow-up. There were 44 total deaths that had a cardiovascular cause. Sixteen patients in the cohort had a MI during the follow-up period.

Table 34 shows the percentage of cardiac outcomes that were related to depression and anxiety. Although our initial analysis was done with depression, we found that for every cardiac outcome anxiety was more strongly related, especially in MI and cardiovascular death.

Table 35 shows the predictors of cardiac outcome with ‘no chest pain’ as comparator.

Discussion

In terms of predictors of cardiac outcome status, chest pain and exertional chest pain were not associated with baseline depression status but were statistically significantly associated with baseline anxiety. There were no associations between attendance at a rapid access cardiac clinic for a cardiac reason and either baseline depression or anxiety.

There was no evidence of an association between baseline depression and having a MI or dying from a cardiac cause, but there was a statistically significant association with baseline anxiety and having a MI or dying from a cardiac cause. Rose angina questionnaire categories for chest pain at baseline were significantly and strongly associated with subsequent chest pain and exertional chest pain, especially the latter, and in the direction that would be expected, that is, both were associated with all cardiac outcome status compared with no chest pain with exertional chest pain having a stronger association with cardiac status (apart from attendance at a rapid access cardiac clinic) than chest pain. Women have an increased risk of chest pain and exertional pain (but no evidence for higher risk of other cardiac outcomes). Age was a significant predictor only of MI/death. The effect of adding covariates to an unadjusted mode, leading to the full model reported above, is shown in Table 36.

Sensitivity analyses

General practitioner practice was also included in the model as a sensitivity analysis as the practices were situated in areas with different sociodemographic characteristics and also had varying levels of loss to follow-up. The results did not differ significantly from the original model, apart from the exertional chest pain outcome, in which depression and anxiety had similar relative risk ratios (RRRs), both of which were significant (depression: RRR 1.702, 95% CI 1.025 to 2.827; p = 0.040; anxiety: RRR 1.573, 95% CI 1.027 to 2.411; p = 0.037).

The baseline number of comorbid medical illnesses and social problems as measured by the SPQ was added to the model. Depression was now no longer significant for chest pain (RRR 1.177, 95% CI 0.650 to 2.130; p = 0.591), although anxiety remained significant (RRR 1.730, 95% CI 1.132 to 2.643; p = 0.011). Total number of social problems was also related to chest pain (p = 0.001), but not the number of comorbidities. In terms of exertional chest pain, in this model, depression was no longer statistically significant (RRR 1.424, 95% CI 0.560 to 2.373; p = 0.174) although, again, anxiety remained statistically significant (RRR 1.600, 95% CI 1.059 to 2.413; p = 0.026). There was no change in associations for rapid access chest clinic or for cardiac interventions (neither significant), but social problems were significant for chest pain and exertional chest pain (p = 0.001 for both) and for cardiac interventions (p = 0.005), but not for other outcomes.

Two alternative definitions of depression were analysed:

1. Depression in the 6 months before the index cardiac event. The results of this analysis were similar to the main model, except that both depression and anxiety were statistically significantly associated with exertional chest pain (depression: RRR 1.85, 95% CI 1.291 to 2.663; p = 0.001; anxiety: RRR 1.867, 95% CI 1.349 to 2.585; p < 0.001). For other outcomes, the model could not be fitted owing to small sample sizes.

2. Cumulative burden of depression using the sum of follow-up periods, occurring before the index cardiac outcome, in which the patient had been depressed. Chest pain and exertional chest pain were both associated with depression and anxiety (depression: RRR 1.217, 95% CI 1.000 to 1.482; p = 0.05; anxiety: RRR 1.239, 95% CI 1.041 to 1.474; p = 0.016). However, other outcomes were similar to the main model except that cumulative anxiety was associated with attendance at a rapid access chest clinic (RRR 1.350, 95% CI 1.059 to 1.722; p = 0.015).

Redefining the cardiac outcome with rapid access chest clinic combined with any other interventions did not show any association with baseline depression or anxiety.

Mortality

There were 72 deaths altogether, of which 22 were from cardiac disease, 22 from vascular disease, 16 from cancer and eight were attributable to other causes; in four cases, the cause of death was not ascertainable. Of the 22 cardiac deaths, 14 were of men (2.5% of 561) and eight of women (3.3% of 242). Incidence rates of cardiac death were 12.7 per 1000 person-years for men and 9.3 per 1000 person-years for women. Standardised mortality ratios compared with the general population were 1.13 (95% CI 0.62 to 1.90) and 1.87 (95% CI 0.81 to 3.70), for men and women, respectively.

Table 37 shows a Poisson regression model for the rates of cardiovascular deaths. Only risk ratios for increasing age and a higher baseline anxiety were significant at p = 0.05. A sensitivity analysis using the CIS-R definition of depression and anxiety was similar, except that the risk ratio for depression was increased to 1.260 (95% CI 0.274 to 5.796; p = 0.766) and that for anxiety decreased (risk ratio 2.001, 95% CI 0.694 to 5.774, p = 0.199) and was no longer significant.

Table 38 shows a Poisson regression model for the rates of non-cardiovascular deaths. Only RRs for increasing age, male sex and higher baseline total comorbidities were significant at p = 0.05.

The effect of depression on continuing chest pain

This next series of analyses use data from the five-wave follow-up. We report on the frequency of cardiac events, the persistence of chest pain reported by respondents and the predictive power of depression and other psychosocial factors.

Chest pain type and frequency of report

As shown in Table 39, the amount of chest pain is reported, ranging from 0 to 100%, of the occasions when patients were interviewed using the Rose angina questionnaire. These proportions became the outcome variable to contrast with baseline predictors between those with no chest pain and those with non-exertional pain only.

In contrast to Table 39, which takes into account the whole cohort, subsequent analyses report on those who remained under follow-up who did not experience any of the events mentioned above. In addition, only those who had, at most, two missing chest pain responses out of the five possible over the follow-up period were included. Those with more than two missing responses were excluded. (Sensitivity analysis was carried out restricting it to one or fewer missing responses, and no differences were found, thus we selected this analysis, which includes a larger portion of the sample.) These two exclusions reduced the sample for analysis to n = 568. Baseline depression and anxiety scores were examined separately, and then quality of life, as measured by the EQ-5D-VAS, was entered into the analysis.

Predictors of non-exertional pain

Females and those with asthma comorbidity were most at risk of reporting non-exertional chest pain (Tables 40 and 41). Shorter amount of time on the GP CHD register is also predictive. Anxiety and depression, counterintuitively, do not have an effect. The addition of the quality-of-life measure does produce a significant finding, with a lower score being predictive of more pain report.

Exertional pain

The situation with exertional pain is quite different (Tables 42 and 43). Exertional pain reported at baseline had a massive effect in predicting subsequent reports of chest pain, as did, to a lesser extent, non-exertional pain. Depression and anxiety each had an additional effect on baseline pain. The length of time on the register was predictive, but in the opposite direction to non-exertional pain, meaning the longer time spent on the register, the more likely they were to report exertional pain. Older age was a weak risk factor. Addition of the quality-of-life measure eliminated the effect of depression, and weakened that of anxiety.

Objectives

To:

1. assess the long-term costs of care for a sample of patients with CHD and comorbid (a) baseline, and (b) subsequent depression compared with those without comorbid depression

2. identify predictors of these costs.

Methods

Sample characteristics

Differences in sociodemographic variables between CHD patients with/without comorbid baseline depression were analysed using a two-sided t-test and chi-squared test. Depression status was measured by the HADS-D at baseline and at each follow-up point. Patients were classified into depressed and non-depressed, using a cut-off score of ≥ 8 for possible depression. 114 At baseline, 13% of patients had depression.

Sociodemographic characteristics of the sample are shown in Table 44. Approximately two-thirds were male in both groups and the average age was 66 years and 71 years for the depressed and the non-depressed group, respectively. The majority of patients were married and retired, with only a small proportion (< 5%) cohabiting. In the non-depressed group, 53% received > 11 years of education while a similar proportion in the depressed group received < 10 years of education. Approximately half of either group were ex-smokers and consumed, on average, between 0 and 10 units of alcohol per week. The mean IMD score was 20 and 23, for the non-depressed and depressed group, respectively. The vast majority of the depressed patients reported chest pain, while most of the non-depressed patients did not have chest pain. Both groups had an average number of two additional comorbidities, with the most frequent ones being hypertension and diabetes. Approximately 65% of patients had depression when assessed by the CIS-R instrument. It is noticeable that approximately 80% of the depressed patients also had anxiety when measured by the HADS-A. Most of the differences were statistically significant at a 10% level (see Table 44).

Statistical analyses

Statistical analyses were carried out using Stata version 11. Regression analysis was used to estimate mean differences in service use and costs between groups. Baseline and follow-up costs were used as the dependent variables and the group identifier as the independent variable. To estimate whether or not the difference in costs between depressed and non-depressed patients was present at each time point, the HADS-D status was also assessed at consecutive follow-up times (Figure 11).

FIGURE 11.

Mean depression score (HADS-D) across time.

Sociodemographic and clinical baseline variables were tested for significance using simple ordinary least squares regression models. Each variable was regressed on the cumulative 3-year hospital care costs, community care costs, informal care costs, total health-care costs and total societal costs. Those variables with statistical significance at the 10% level (p < 0.10) in at least one of the above mentioned dependent variables were included in the final multivariate model to identify predictors of costs (Table 45). Certain other variables that were of interest, although not statistically significant in the first stage, were also included in the final models. Of the statistically significant variables, those with high numbers of missing values were excluded from the final models. The remaining variables were checked for correlation and those that were highly correlated (r ≥ 0.7) with each other were removed, one at a time, from the model. Two models were constructed using the cumulative health-care and societal costs as the dependent variables. The models included the following baseline covariates: sex, ethnicity, relationship status, age at referral, health literacy status, years in education, family history of depression or cardiac problems, smoking status, average units of alcohol per week, the body mass index score, number of CHD risk factors, depressive disorder assessed by the CIS-R, currently being treated for depression, anxiety status measured by the HADS, the IMD score, housing, working or financial problems, social contact and relationship problems, currently active comorbidities such as diabetes, arthritis, cancer, asthma, hypertension, COPD and chronic kidney disease. The models were also adjusted for informal care costs and total health-care costs at baseline. Approximately 100 observations had missing data on the health literacy variable. Thus, two additional models including all the above covariates except the health literacy variable were also run. To produce a more parsimonious model that aids interpretation, the backward elimination stepwise method was used. This method involved starting with all independent variables and then sequentially removing variables with the highest p-values until only those with p-values < 0.1 were included.

It is commonly known that health-care data often violate the assumptions underlying ordinary least squares. Therefore, the models were run to test for the assumptions of normality and homoscedasticity of residuals. Both assumptions were violated and generalised linear models were used. The use of log transformation is common practice for dealing with skewed data, such as costs. However, log-scale results are of little interest in decision-making, while actual values (i.e. GBPs) are meaningful. Generalised linear models overcome the shortcomings of (log) ordinary least squares using the original scale of costs. 182 To use generalised linear models, the distribution of cost data and a function that specifies the relationship between the mean and the linear specification of the covariates (the so-called link function) must be specified. 182 The appropriate distribution of costs was identified by implementing the modified Park test. 183 The gamma distribution, with a log-link function, was applied to the final model. The log-link function means that the value of the exponentiated coefficients is interpreted as proportional changes of the 3-year total health-care and societal costs (Tables 46–49).

Results