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Rheumatology Advance Access originally published online on December 22, 2006
Rheumatology 2007 46(5):805-807; doi:10.1093/rheumatology/kel403
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Is the report of widespread body pain associated with long-term increased mortality? Data from the Mini-Finland Health Survey

G. J. Macfarlane, G. T. Jones, P. Knekt1, A. Aromaa1, J. McBeth2, M. Mikkelsson3 and M. Heliovaara1

Aberdeen Pain Research Collaboration (Epidemiology Group), University of Aberdeen, Scotland, UK, 1National Public Health Institute, Helsinki, Finland, 2Arthritis Research Campaign Epidemiology Unit, Division of Epidemiology and Health Sciences, University of Manchester, England, UK and 3Department of Rehabilitation, The Rheumatism Foundation Hospital, Heinola, Finland

Correspondence to: Prof. Gary J. Macfarlane, Epidemiology Group, Department of Public Health, School of Medicine, Polwarth Building, Forresterhill, Aberdeen, Scotland, AB25 2ZD, UK. E-mail: g.j.macfarlane{at}abdn.ac.uk


   Abstract
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 Abstract
Introduction
 Methods
 Results
 Discussion
 References
 
Objective. To determine whether an observation in a UK study, that persons with chronic widespread pain are at long-term increased risk of cancer mortality, can be replicated in a different setting.

Methods. Subjects were participants aged ≥30 yrs in the Mini-Finland Health Survey conducted between 1979 and 1980. Information collected included prevalent pains at different joints throughout the body, demographic, anthropometric, lifestyle and occupational factors. During follow-up, until 1994, information on vital status and cause of death was obtained.

Results. 7182 persons participated (89.8%). The prevalence of widespread body pain (pain at four or more sites) was 20% in females and 12% in males, and during follow-up there were a total of 1647 deaths. The risk of death was not elevated amongst those with widespread pain [relative risk (RR): 0.86; 95% confidence interval (CI): 0.74–1.00], and in particular, those with widespread pain were at a slightly lower risk of several disease-specific causes of death and cancer death (RR: 0.64; 95% CI: 0.46–0.91).

Conclusions. This study of multiple pains has not confirmed a previous observation of an association between the reporting of widespread pain and subsequent increased risk of cancer death. Differences in the definitions used or, more probably, the population studied, in particular, a larger rural population with more multiple pains related to physical activity may account for the differences.

KEY WORDS: Widespread pain, Mortality, Cohort study, Cancer


   Introduction
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 Abstract
 Introduction
Methods
 Results
 Discussion
 References
 
Chronic widespread body pain is the clinical hallmark of the syndrome known to rheumatologists as fibromyalgia. Evidence strongly suggests that fibromyalgia is not a distinct clinical entity but one end of a spectrum of pain and tender points [1]. Chronic widespread pain has a population prevalence of 10–13% and its onset is predicted by individual factors, such as psychological distress, aspects of illness behaviour and by previous reports of other somatic symptoms [1]. Aspects of the social environment, which have been particularly studied in a workplace setting, also influence the likelihood of symptom onset [2]. A variety of abnormalities in biology have been investigated in patients with fibromyalgia, although consistent evidence for many are lacking.

Chronic widespread pain is associated with persistent symptoms and high levels of disability [4]; however, until recently it was not believed that they resulted in premature mortality. A population-based prospective cohort study from the UK, however, demonstrated that persons reporting chronic widespread pain were twice as likely to die over the next 9 yrs (compared with persons reporting no pain) and that this excess risk of death was principally related to cancer deaths [5]. These results, if true, would have important implications for management. Preliminary results from a further study conducted in the same geographical area confirm some of the previous results [6]. No other studies examining this issue directly have reported, and the available related indirect evidence provides only weak supporting evidence. In addition, there is no clear biological mechanism linking the report of pain with a long-term increase in disease-related deaths.

It is therefore important, before placing too much emphasis on this observation, to try to replicate these findings, and in doing so it would be particularly advantageous to do so in a diverse setting from the original observation. We, therefore, took advantage of available information from the Mini-Finland Health Survey to determine whether persons reporting multiple bodily pains subsequently experience increased mortality either overall or from specific causes of death.


   Methods
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 Abstract
 Introduction
 Methods
Results
 Discussion
 References
 
The methods of the Mini-Finland Health Survey, conducted between 1978 and 1980, have been described in detail previously [7]. In brief, the study population was a stratified two-stage cluster sample drawn from the Finnish population aged ≥30 yrs. In the first stage, areas of the country were selected which were considered representative in terms of geographical area, urbanization and employment. In the second stage, a sample of inhabitants was drawn from the population register of each area. Of the 8000 persons selected, all the data necessary for the current study were obtained for 7182 (89.8%). The distributions of the participants with respect to age, sex, marital status and level of education corresponded closely with the whole Finnish population [8].

Information was collected in the study using interviews within a mobile clinic. Subjects were asked, ‘Have you had a pain, ache or tenderness on movement in one or more joints during the last month? Can you identify these joints on the body manikin?’ Respondents were also specifically asked about neck and back pain. The number of painful sites and joints were then summed. We defined widespread pain as pain present in at least four sites, since examination of the data distribution showed that this resulted in a prevalence of widespread pain similar to other prevalence studies, and since it had face validity with respect to the American College of Rheumatology (ACR) definition of widespread pain in their criteria for fibromyalgia [9]. Pain reported in between one and three sites was defined as regional pain. Information was also collected on age, sex, years of education, present or most recent occupation, current alcohol consumption and tobacco habits. Height and weight were measured allowing body mass index (BMI) to be derived.

Information was collected on physical and mental work stress. The presence of physically stressful features was recorded in the present or in the previous occupation of longest duration as dichotomies (no = 0, yes = 1) (lifting or carrying heavy objects; stooped, twisted or otherwise awkward work posture; shaking of the whole body or use of vibrating equipment; a constantly repeated series of movements; and work paced by a machine) and summed to form an index (0–5). Similarly mental stress features (uninteresting or monotonous work, a hurried or tight work schedule, and worry about making mistakes) were recorded at three levels of severity (none = 0, mild = 1, severe = 2) and summed to form an index of mental stress at work (0–6) [10].

During follow-up, the vital status of the participating subjects was determined by obtaining information from the Central Statistical Office of Finland. Principal causes of death were coded according to the 8th revision of the International Standard Classification of Disease, Injuries and Causes of Death (ISD-8). Follow-up for this analysis was continued until 31 December 1994, equivalent to a follow-up between 14 yrs and 16 yrs, and providing a total of 88 870 person-years.

Statistical methods
The relationship between pain reporting and subsequent mortality was analysed using Cox proportional hazard models, with adjustment for potential confounding variables. Hazard ratios were derived from the model (i.e. the ratio of probability of death in the pain groups compared with those with no pain) and are expressed as relative risks (RR) with 95% confidence intervals (CIs). Assumptions of proportionality were not violated.


   Results
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 Abstract
 Introduction
 Methods
 Results
Discussion
 References
 
The socio-demographic characteristics and reported lifestyle of the participants is shown in Table 1: 46% were male, most had elementary level of education (68%), and most were never smokers (56%). In terms of their jobs, 6% were never employed while for the remainder their current or longest-serving jobs (if currently not employed) were evenly split between professional (22%), agricultural (23%), industrial (25%) and the service sector (23%). An intermediate or high physical work stress was more common (45%) than an intermediate or high mental work stress (34%) (Table 1). Older age, low number of years of education, obesity and a high mental or physical workload were all significantly associated with the reporting of widespread pain.


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  		TABLE 1. Characteristics of participants and their relationship to the report of widespread pain

 
Males were more likely to report no pain (39 vs 30%) and less likely to report widespread pain (four or more body sites: 12 vs 20%). Regional pain exhibited a similar prevalence (pain at 1–3 body sites: 49 vs 50%). During the follow-up period there were a total of 856 and 791 deaths amongst male and female participants, respectively. The risk of death was unrelated to the number of pain sites reported on the recruitment screening survey in either males or females. Neither for overall mortality nor for any of the disease-related deaths was there an excess risk of death in those reporting regional or widespread pain. Indeed for cardiovascular, respiratory and cancer deaths, and all other disease-related deaths (combined), there was reduced risk of death for those reporting widespread pain which for cancer death was statistically significant (Table 2).


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  		TABLE 2. Pain report and subsequent specific cause of death

 

   Discussion
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 Abstract
 Introduction
 Methods
 Results
 Discussion
References
 
This population-based prospective study from Finland has not supported an initial observation in a UK study that widespread body pain is associated with an increased risk of death and, in particular, cancer death. There are a number of methodological issues which are relevant to consider:
  1. Unlike the original observation, the study was unable to define widespread pain according to the definition used in the ACR criteria for fibromyalgia [9]. Instead the study used a count of painful joints of the body. It is possible therefore that the relationship with increased mortality is only with widespread pain rather than multiple joint pains. Against this, however, is the fact that the most common areas for pain to be reported on the body manikins is in the axial skeleton and major joints (i.e. shoulder, knee and hip) [11], that the ACR criteria are most commonly satisfied by multiple regional pains rather than pain over the whole body and that when an alternative definition of widespread pain is applied in population studies (Manchester criteria) which requires the pain to be more truly widespread, prevalence is considerably lower [12, 13].
  2. Information is not available about the duration of pain reported at multiple sites. However, data from other studies has shown that in 80–90% of persons reporting widespread body pain, the pain has been present for >3 months [5].
Therefore, how can we reconcile this observation of no relationship between multiple joint pain reports and subsequent mortality experience with our previous study showing a strong relationship between widespread pain, death from cancer and deaths from suicides and accidents? Firstly it may be that the original observation is wrong and that although strong, the relationship was observed by chance. This may be the case, although initial results from a second prospective study in the UK have confirmed the initial results and shown a doubling of risk of both cardiovascular and cancer death over the 8 yrs after pain reports [6]. Interestingly, this second UK study was also not able to use the ACR definition of widespread pain, but instead had a count of painful joint areas in the body, more similar to the definition used in the current study—thus suggesting that the different results are not due to different definitions of widespread pain. Alternatively, it may be that we are studying different types of populations and whose symptoms have a diverse aetiology. The populations in the two studies showing a strong relationship between pain and cancer death have both been from the Greater Manchester area of the UK. This is a densely populated conurbation, with employment in either industrial or service sectors, and including areas of social deprivation. There have been many studies of chronic widespread pain conducted in this geographical area—and they have shown that the reports of widespread pain are associated with a psychological (rather than mechanical) aetiology and social factors. In contrast, a much greater proportion of the population in the Mini-Finland Health Survey lived in rural settings, the majority finished education at the elementary level and roughly equal proportions of persons were employed across professional, agricultural, industrial and service industries. The development from a poor agricultural society to an industrialized one and, later on, to the post-industrial stage has been more rapid and drastic than elsewhere. In Finland in 1980, consequently, a substantial proportion of people had been exposed to very heavy manual labour, a risk factor for widespread pain. A previous report from this study on the prevalence and associated features of fibromyalgia (which has widespread pain as one of its primary symptoms) demonstrated that fibromyalgia was significantly more common in those employed in the agriculture sector, was strongly related to high physical work stress, but not with level of mental work stress [14]. A particularly strong relationship between physical work stress and widespread pain is shown in the current analysis. It could, therefore, be that the multiple pains reported in this study are more likely to be as a result of mechanical load and injury than is the case in urban populations. If so, the conclusion would be that if there is an increased risk of cancer (and perhaps cardiovascular) death it is not linked to the reporting of multiple pains per se, but to the chronicity of symptoms and the commonly associated comorbid features. This hypothesis will need to be tested in future studies.

In conclusion, the data on whether there is a link between the experience of widespread body pain and premature mortality is contradictory. This study (of multiple joint pains) has found no relationship. This suggests that, if there is a link, it is not a simple biological link triggered by the experience of multiple pains. We, therefore, should remain cautious about whether a link exists but studies currently underway will allow us to determine whether the link is specific to pain that is truly ‘widespread’ (with its common comorbidities) and/or whether behavioural and lifestyle changes consequent upon the experience of chronic symptoms may explain the relationship. Understanding any potential link is important for the many patients who present to primary and secondary care with widespread body pain symptoms.

The authors have declared no conflicts of interest.

Formula


   References
Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 

  1. Macfarlane GJ. (1999) Fibromyalgia, Chronic widespread pain. In Crombie IK, Croft PR, Linton SJ, LeResche L, von Korff M (Eds.). Epidemiology of painInternational Association for the Study of Pain, IASP Press.
  2. Clauw DJ and Crofford LJ. (2003) Chronic widespread pain and fibromyalgia: what we know, and what we need to know. Best Pract Res Clin Rheumatol 17:685–701.[CrossRef][Medline]
  3. Bennett R. (2005) Fibromyalgia: present to future. Curr Rheumatol Rep 7:371–6.[Medline]
  4. Papageorgiou AC, Silman AJ, Macfarlane GJ. (2002) Chronic widespread pain in the population: a seven year follow-up study. Ann Rheum Dis 61:1071–4.[Abstract/Free Full Text]
  5. Macfarlane GJ, McBeth J, Silman AJ. (2001) Widespread body pain and mortality: prospective population-based study. Brit Med J 323:1–5.[Abstract/Free Full Text]
  6. Macfarlane GJ, Symmons DPM, Silman AJ, et al. (2005) Widespread pain is associated with a long-term increased risk of cancer death. Arthritis Rheum 52:Suppl, S77.
  7. Mäkelä M, Heliovaara M, Sievers K, Knekt P, Maatela J, Aromaa A. (1993) Musculoskeletal disorders as determinants of disability in Finns aged 30 years or more. J Clin Epidemiol 46:549–59.[CrossRef][ISI][Medline]
  8. Aromaa A, Heliövaara M, Impivaara O, Knekt P, Maatela J. (1989) The execution of the mini-Finland health survey (Social Insurance Institution, Helsinki, Turku) Part 1: (In Finnish with English summary).
  9. Wolfe F, Smythe HA, Yunus MB, et al. (1990) The American College of Rheumatology, 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum 33:160–72.[ISI][Medline]
  10. Mäkelä M, Heliövaara M, Sievers K, Impivaara O, Knekt P, Aromaa A. (1991) Prevalence, determinants and consequences of chronic neck pain in Finland. Am J Epidemiol 1356–67.
  11. Macfarlane GJ, Jones GT, McBeth J. (2005) Epidemiology of pain. In McMahon SB and Koltzenburg M (Eds.). Wall and Melzack's textbook of pain 5th edn. (Chapter 76) (Elsevier Churchill, Livingstone).
  12. Hunt IM, Silman AJ, Benjamin S, McBeth J, Macfarlane GJ. (1999) The prevalence and associated features of chronic widespread pain in the community using the ‘Manchester’ definition of chronic widespread pain. Rheumatology 38:275–9.[Abstract/Free Full Text]
  13. Macfarlane GJ, Croft PR, Schollum J, Silman AJ. (1996) Widespread pain: is an improved classification possible? J Rheumatol 23:1628–32.[ISI][Medline]
  14. Mäkelä M and Heliövaara M. (1991) Prevalence of primary fibromyalgia in the Finnish population. Brit Med J 303:216–9.[ISI][Medline]
Submitted 19 May 2006; revised version accepted 31 October 2006.
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