Many patients with several concurrent medical conditions (multimorbidity) are seen in the primary care setting. A thorough understanding of outcomes associated with multimorbidity would benefit primary care workers of all disciplines. The purpose of this systematic review was to clarify the relationship between the presence of multimorbidity and the quality of life (QOL) or health-related quality of life (HRQOL) of patients seen, or likely to be seen, in the primary care setting.
Medline and Embase electronic databases were screened using the following search terms for the reference period 1990 to 2003: multimorbidity, comorbidity, chronic disease, and their spelling variations, along with quality of life and health-related quality of life. Only descriptive studies relevant to primary care were selected.
Of 753 articles screened, 108 were critically assessed for compliance with study inclusion and exclusion criteria. Thirty of these studies were ultimately selected for this review, including 7 in which the relationship between multimorbidity or comorbidity and QOL or HRQOL was the main outcome measure. Major limitations of these studies include the lack of a uniform definition for multimorbidity or comorbidity and the absence of assessment of disease severity. The use of self-reported diagnoses may also be a weakness. The frequent exclusion of psychiatric diagnoses and presence of potential confounding variables are other limitations. Nonetheless, we did find an inverse relationship between the number of medical conditions and QOL related to physical domains. For social and psychological dimensions of QOL, some studies reveal a similar inverse relationship in patients with 4 or more diagnoses.
Our findings confirm the existence of an inverse relationship between multimorbidity or comorbidy and QOL. However, additional studies are needed to clarify this relationship, including the various dimensions of QOL affected. Those studies must employ a clear definition of multimorbidity or comorbidity and valid ways to measure these concepts in a primary care setting. Pursuit of this research will help to better understand the impact of chronic diseases on patients.
With technological advances and improvements in medical care and public health policy, an increasingly large number of patients survive medical conditions that used to be fatal. As a result of this phenomenon, and parallel to the aging of the population, a growing proportion of primary care patients presents with multiple coexisting medical conditions. From available data, it was estimated that 57 million Americans had multiple chronic conditions in 2000 and that this number will rise to 81 million by 2020 . Epidemiological data from several countries support this estimate [2-8]. On average, patients aged 65 years and older present with 2.34 chronic medical conditions . In fact, 50% of patients with a chronic disease have more than one condition .
The terms "comorbidity" and "multimorbidity" have been used to describe this phenomenon. Feinstein  originally described comorbidity as "any distinct additional entity that has existed or may occur during the clinical course of a patient who has the index disease under study." Kraemer  later referred to comorbidity in studying specific pairs of diseases. Van den Akker and colleagues  further refined both concepts, reserving the term "multimorbidity" to describe the co-occurrence of two or more chronic conditions; they also proposed some qualifiers to better classify the type of multimorbidity (simple, associative and causal). Unfortunately, much confusion still exists in the literature, where the 2 terms often seem to be used interchangeably. For the purpose of this paper, the term "multimorbidity" will be used according to Van den Akker and colleagues' definition and the focus will be solely on chronic diseases.
Previous reports on multimorbidity or comorbidity have documented that this phenomenon influences outcomes in many areas of health care [13-19]. Outcome measures that have been related to multimorbidity include mortality, length of hospital stay, and readmission. An association between disability and multimorbidity in elderly patients has also been described [14,20-22].
Quality of life (QOL) is an outcome measure that is increasingly being used to evaluate outcomes in clinical studies of patients with chronic diseases [23-26]. QOL represents a subjective concept, with a multidimensional perspective encompassing physical, emotional, and social functioning . It is important to address QOL as it has been associated with health and social outcomes  which may contribute to the worsening of the course of the diseases. In research and the medical literature, there is little distinction between health-related quality of life (HRQOL) and overall QOL (the latter encompasses not only health-related factors but also many non medical phenomena such as employment, family relationships, and spirituality) . In practice, the terms are often used interchangeably. Different evaluation scales have been proposed to measure QOL or HRQOL. Some focus on a specific disease [30,31], while others have wider applications (i.e., generic measurements) [32-34].
Little is known about the impact of multimorbidity on QOL of primary care patients , although this is where most patients receive their care. Thus, the purpose of this systematic review is to clarify the association between the presence of several concurrent medical conditions and the QOL or HRQOL of patients seen or likely to be seen in a primary care setting.
For this review, we consulted Medline and Embase electronic databases for the reference period 1990 to 2003. Figure 1 illustrates the search strategy. Since the term "multimorbidity" does not have any equivalent in the thesaurus, databases were searched for the following terms: multimorbidity, comorbidity, and their spelling variations. The term "multimorbidity" was searched as a keyword, while "comorbidity" was searched as a Medical Subject Heading (MeSH). The term "chronic disease" was used to increase the sensitivity of the search. We also used the MeSH "quality of life" and the keyword "health-related quality of life" to help target pertinent literature.
Figure 1. Selection of articles: Medline (Embase), years 1990–2003
To identify studies pertinent to the primary care setting, the following search terms were used: general practice, family practice, family medicine, family physician, and primary health care. A parallel strategy was used to identify all descriptive studies, regardless of the context of care, and the results were then combined. For the initial screening, the search was restricted to studies on human subjects, published in French or English. To be complete, we directly searched the Quality of Life Research and Health and Quality of Life Outcomes journals. We also screened references from key articles retrieved (hand searching).
One researcher (LL) performed the initial screening. Any ambiguous findings were discussed with the lead investigator (MF) and a consensus was reached.
Inclusion and exclusion criteria
For the purpose of this systematic review, we selected original, cross-sectional, and longitudinal descriptive studies that had evaluated the relationship between multimorbidity or comorbidity and QOL or HRQOL as the main outcome of interest. As stated earlier, we focused on the population of patients seen, or likely to be seen, in the primary care setting including members of the general population and residents of nursing homes and home healthcare facilities. We also selected original descriptive studies that had examined the relationship between multimorbidity or comorbidity and QOL or HRQOL as a secondary outcome.
Figure 1 shows our exclusion criteria. In keeping with our objectives, we did not include studies on specific diseases (e.g., acquired immunodeficiency disease) or populations unlikely to represent a large part of primary care practice. We also excluded any studies that did not address physical comorbidities, including those that exclusively examined mental disorders and associated mental comorbidities. Finally, we excluded studies in which the main outcome of interest was not QOL or HRQOL as well as those that used a nonstandard approach to measuring QOL or HRQOL.
Assessment of study quality
Before being included in the synthesis, the quality of each article selected was critically analyzed. For this assessment, we devised a scale in which points were assigned for study parameters indicative of good quality (e.g., well-defined populations, clear definitions, valid measures). Using this scale (Table 1), 2 researchers independently determined a global quality score for each article. The scores for each article were then compared and adjusted by consensus. To ensure adequate methodological quality, the cut-off score for an article to be included in the synthesis was 10 out of a maximum of 20 points.
Table 1. Evaluation criteria
Synthesis or results
Figure 1 shows the number of articles found at each stage of the selection process. Of the 753 articles screened, 108 were evaluated according to the study's inclusion and exclusion criteria. We also assessed the quality of each study before selecting 30 for inclusion in the synthesis: 7 that had evaluated the relationship between multimorbidity or comorbidity and QOL as the main outcome (Table 2) and 23, as a secondary outcome.
Quality of life as the main outcome measure
Of the 7 studies that featured QOL as a primary outcome [36-42], 5 had been conducted in European populations. We analyzed theses studies in detail. Quality scores for these studies ranged from 10 to 18 (out of a maximum of 20 points) and were highest in 2 studies from the Netherlands, one from the United States, and another study from Sweden. Table 2 presents a synthesis of the various studies.
All studies came to the same conclusion, namely that there is an inverse relationship between the number of medical conditions and QOL or HRQOL. This association may be affected by the patient's age or gender. Whereas multimorbidity mostly affects physical dimensions of QOL or HRQOL [36,37,41], data from one study suggest that social and psychological dimensions may be affected in patients with 4 or more diagnoses .
In each study, investigators relied on simple count of chronic diseases from a limited list to measure multimorbidity. The chronic conditions included in this list varied among the studies, and no attempt was ever made to assess or account for the severity of each condition. Furthermore, 5 of the 7 studies did not consider psychiatric comorbidity, either because the illnesses considered did not include psychiatric diagnoses or because patients presenting with psychiatric diagnoses were excluded from the QOL evaluation. In most cases, the diagnostic information was obtained by a questionnaire that was completed by a nurse or a doctor or sometimes self-administered. One study assessed comorbidity via chart review.
To measure QOL, a variety of scales were used. Most studies (5/7) used tools from the Medical Outcomes Study i.e., the Short-Form-36 Health Survey (SF-36) and Short-Form-20 Health Survey (SF-20). However, the Nottingham Health Profile (NHP) was used in one study and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) was used in another. Although the number of domains explored varied from one study to the next, the measuring instruments used have excellent psychometric properties and validity.
The 4 studies associated with the highest quality scores explored only a limited number of potential confounders, namely age [37,38], gender [36,41], and socio-demographic and economic factors . Effects of these confounders are reported in Table 2. The other 3 studies did not investigate potential confounders.
Quality of life as a secondary outcome measure
Of the 23 studies that evaluated the relationship between multimorbidity or comorbidity and QOL as a secondary outcome measure [43-65], most were done in Europe (9 studies) and the United States (12 studies). As with the main outcome studies, each used a simple count of a limited and varying number of chronic medical conditions to evaluate multimorbidity. While there was generally no attempt to assess or account for the severity of individual conditions, one study used a comorbidity index, the Duke Severity of Illness (DUSOI), for this purpose . Diagnostic information was obtained from chart reviews and clinical evaluations (9 studies), from self-report questionnaires (13 studies), or both sources (1 study). Psychiatric comorbidity was evaluated in 13 studies.
As with the results from the main outcome studies, we found an inverse relationship between the number of medical conditions and the QOL relating to physical domains in all studies. However, the relationship between multimorbidity and QOL relating to psychological or social domains was less clear. Some investigators reported an effect of multimorbidity on these domains in patients with 3 or more diagnoses , while others reported no effect [48,55].
As in the main outcome studies, tools from the Medical Outcomes Study, including the SF-36 (17 studies), SF-20 (3 studies), and Short-Form-12 Health Survey (SF-12) (1 study), were used to evaluate QOL in most of these studies. However, the NHP was used in one study and the Quality of Well-Being Scale (QWB), in another. In the majority of studies, all of the QOL domains were explored.
Table 2. Synthesis of studies on multimorbidity with quality of life as the main outcome measure