Comorbidity and Multimorbidity - Synthesis

Comorbidity and Multimorbidity - Synthesis


Almost two thirds of older adults over 80 years of age have three or more chronic diseases or comorbidities/multimorbidities. [1] Definitions of multimorbidity vary but a pragmatic approach adopted in the Australian RACGP aged care clinical guide is based on “people with multiple conditions where these present significant problems to everyday functioning, or the management of their care has become burdensome to the patient and/or involves a number of services working in an uncoordinated way”. [2] People with multimorbidity have a greater risk of premature death than people without multimorbidity. [3-7]

Although often used interchangeably within published literature to describe a state of multiple chronic conditions, the terms multimorbidity and comorbidity differ. In comorbidity, an index condition takes priority e.g. diabetes, stroke and cancer are index conditions that will often dominate treatment and management decisions. [8] In contrast, multimorbidity is not dominated by an index condition so that all co-existing conditions are regarded equally with none taking priority.[8] This distinction is now recognised in the research literature database PubMed but it is often not made in the literature. Given the difficulty of determining retrospectively which term would have been appropriate, in the following text any distinction between the two should be regarded with caution.

It is also worth noting that some but not all chronic conditions are life-limiting. The Australian Institute of Health and Welfare reports data on ten chronic conditions [9] including conditions that are not recognised as life-limiting, and the National Strategic Framework for Chronic Conditions [10] uses the following definition for chronic conditions:

  • have complex and multiple causes;
  • may affect individuals either alone or as comorbidities;
  • usually have a gradual onset, although they can have sudden onset and acute stages;
  • occur across the life cycle, although they become more prevalent with older age;
  • can compromise quality of life and create limitations and disability;
  • are long-term and persistent, and often lead to a gradual deterioration of health and loss of independence; and
  • while not usually immediately life-threatening, are the most common and leading cause of premature mortality

Quality Statement

A total of 26 systematic reviews, [1,3-7,11-35] a realist review, [36] an integrative review [37] and a scoping review [38] are included in this synthesis of evidence for multimorbidity and comorbidity. Six were specific to older adults and palliative care in an aged care context, [12,20,26-28,30] whereas 20 were pertinent to older adults some of which included an aged care setting but not necessarily with a palliative focus. [1,3-7,11,13,15-17,19,21,23-24,29,32,34,36,38] Four did not limit to older adult cohorts or an aged care setting but were pertinent to an end-of-life context. [14,18,22,37] Meta-analysis was performed in ten reviews. [3-6,11,15,21,32,34-35]

The included papers were of acceptable to high quality, [1,3-7,11-13,18-21,23,24,27,29,31,34] although twelve studies scored poorly [14-17,22,25,26,28,30,32-33,35-38] due to the lack of reporting on methodology and quality of included studies.

Other papers, guidelines, and reports have been included as they provide context. [2,8-10,39-57] These include clinical guidelines relating to multimorbidity in older Australians [2] and UK guidelines for the assessment, prioritisation and management of care for people with commonly occurring multimorbidity. [44]

Evidence Synthesis

Comorbidity and particularly multimorbidity are associated with poorer quality of life, increased use of health services and hospitalisation, and polypharmacy. [1,5,8] For many older people with multimorbidity, it is likely that at least one of their chronic diseases will be life-limiting and progressive. [42] The presentation and severity of symptoms will be varied but produce cumulative effects. [1,5,41] In Australia, the prevalence of chronic conditions in addition to a life-limiting condition ranges from 82% for cancer, [42] 90% for chronic obstructive pulmonary disease (COPD), [42] and 99.1% for heart failure. [47] While evidence-based guidelines exist for the management of a single disease, few address comorbidity or multimorbidity, particularly in a palliative care context. [1,18] There is a low inclusion rate of older adults in multimorbidity randomised clinical trials and this reinforces the difficulty in creating appropriate clinical protocols for their management. [5] Available guidelines for multimorbidity include:

Clinicians may need to pursue more flexible approaches to care of older adults with comorbidities in a palliative care context. [41] Some proposed adjustments in line with person-focused care aim more at fulfilment and quality of life rather an improvement in health status. [18]

The Ariadne principles, a consensus framework for primary care consultations to guide the care of people presenting with multimorbidity, lacks a strong evidence base but serves to encourage a broader approach to care that is consistent with general practice settings and patient need. [49] The principles are:

  • assess potential interactions – the person’s conditions and treatment, constitution, and context
  • elicit preferences and priorities – the person’s most and least desired outcomes
  • individualise management to reach the negotiated treatment goals.

This framework is used here to structure the following sections.

Potential interactions

Prognosis and conditions

Older people with life-limiting illness and multimorbidity may have considerable palliative care needs associated with the cumulative impact of their disease symptoms and functional impairments. [50] These needs are similar to those of people referred to specialist palliative care. [53] Therefore, timely identification of palliative care needs is important for improving symptom burden and overall quality of life. It is also important for timely discussion of changing goals of care and patient and family priorities as a life-limiting illness progresses. Determining the appropriate time relies on a degree of prognostication, with the clinician recognising certain indicators of life expectancy and where the person is likely to be in their illness trajectory.

Prognostic factors are often used to determine the start of palliative care and subsequent discussions for end-of-life planning. Tools such as Supportive and Palliative Care Indicators Tool (SPICT) and the Gold Standards Framework Prognostic indicator Guidance are available to help with prognostication, [30] as are established trajectories of decline for major life-limiting illnesses. [14] However, the dynamic, fluctuating nature of multimorbidity can complicate decision making based on an estimation of life expectancy. [49]

The RACGP Silver Book identifies three possible trajectories for illness and palliative care. (See Figure 1, page 7 of Part A. Palliative and end-of-life care). A diagnosis such as cancer often causes a clear and sudden deterioration in a person’s physical health in the last weeks of life and makes referral to palliative care services a clear option. In organ system failure (e.g. chronic heart failure), the person’s health deteriorates more gradually punctuated with symptom flare-ups. In advanced dementia or frailty, the person’s health declines slowly over a long period. This slow rate of decline and lack of a single life-limiting condition can put frail patients at risk of being excluded from palliative care services. [8,14] Importantly, frailty may unintentionally marginalise the person’s views and wishes in the decision-making process. [38] A process of supported decision making can facilitate incorporation of the person’s wishes even in the presence of cognitive impairment. [57]

In the systematic review by Brown et al [12] looking at prognosticators for advanced dementia. Overall, there was no consensus on the best indicator or scale to use. The presence of one or more comorbid conditions, including cancer and heart failure, was identified as a significant prognosticator indicating a more rapid decline. [12] Comorbidities were especially indicative of decline if more than one was present. Other significant prognosticators related to nutrition, functional impairment, and scores on cognitive function tests. [12]

In a systematic review by Salpeter et al, [22] the authors concluded that common end-of-life clinical presentations in advanced non-cancer illnesses that are consistent with an approximate 6-month prognosis include poor functional performance, advanced age, malnutrition, comorbid illness, organ dysfunction and hospitalisation for acute deterioration in health. Despite the therapeutic resistance of chronic illnesses in their late stage, clinical practice still appears to be biased towards treatment and gives rise to older adults receiving invasive procedures and polypharmacy despite it not prolonging survival. [22] A palliative approach would appear preferable.

Prognosis has traditionally focused on remaining life expectancy; functional disability and quality of life represent additional outcomes of particular relevance for older persons with multimorbidity. [1,41] Each person’s prognosis informs, but does not dictate, clinical management decisions within the context of their preferences. It is estimated that approximately 40% of deaths are associated with multiple comorbidities and a degree of cognitive impairment but without an overriding diagnosis which can make prognostication particularly difficult. [24] In such cases, the Ariadne principles may provide additional guidance. [49]

Treatment complexity

Evidence is emerging that older people with multimorbidity may experience pain and emotional distress similar to that of patients with cancer at the end of life. [53] The patterns of symptoms, rather than overall level of need itself, may be different between older people with multimorbidity and standard specialist palliative care patients. [53] For example, considering symptoms of 'deficit' e.g. lack of energy, poor functional status, may be more useful for older adults with multimorbidity rather than a focus on distinct symptoms e.g. pain. [53] More work is needed to understand whether there are specific palliative care symptom clusters which are commonly associated with older people with multimorbidity. For example, the cluster of increasing weakness, poor mobility, and poor appetite. [53]

The clinician needs to be aware of all the person’s co-existing illnesses as well as the interdependent ways in which they and their respective treatments interact. [48,52] For example, a treatment with known benefits for one condition (e.g. thiazolidinediones for diabetes) may cause a worsening of another (heart failure). [45] Some conditions also share symptoms (e.g. acute breathlessness in heart failure and COPD), which can make it hard to determine which condition to prioritise. [32]

Assessment of interaction relating to the disease and treatments is guided by principles that include assessing clinical and functional status, including frailty, as well as treatment burden for the person. Patients preferences for care should be regularly reviewed and contribute to treatment choices.

Regular medication and care plan reviews should also take place with the aim of identifying and reducing unnecessary medications in light of life expectancy, trajectory, and ‘time horizon to benefit’. [48] Preventative drugs with a long horizon to benefit may be easy targets for deprescribing, examples being statins, antihypertensive agents, antihyperglycaemic agents and anticoagulants. [37] However, critical evaluation of preventative drugs such warfarin is essential as studies have associated discontinuation with adverse outcomes. [20] Several useful tools are available to help with deprescribing. [26] These include the Screening Tool of Older People’s Prescriptions (STOPP) and Screening Tool to Alert to Right Treatment (START). [2]

Older adults are more prone to adverse drug reactions but despite this, polypharmacy (>5 medications) in the management of multimorbidity is common. [1,28] Single disease clinical practice guidelines cannot incorporate decisions related to multimorbidity and strict adherence to all of these in a single patient may lead to the undesirable side effects of polypharmacy including functional impairment, falls and cognitive impairment. [28] Medications may be therapeutically omitted where burden outweighs benefits, [18,41] taking into account the palliative care context.

The review by Tjia et al. [27] of interventions where medications were ceased in frail older adults found, of the 36 studies included, only three were in a palliative care or hospice context and only one of these used limited life expectancy as a factor in prescribing.

The review by Stewart et al [1] concluded that there are many challenges in implementing appropriate prescribing for older adults with multimorbidity and the approach should be person-centred, clinically robust, multidisciplinary, and designed to fit the healthcare system in which it is delivered. It references a European 7-step process for a person-specific and holistic review of medicines [1] similar to a five-step process of reducing inappropriate polypharmacy through deprescribing developed in Australia. [56] Both these guidelines advocate consideration of the person’s specific needs and the Australian guidelines encourage consideration of 'benefit over the person’s remaining lifespan', which would include the palliative context. [56]

Similarly, screening procedures such as prostate-specific antigen testing, mammography, and colonoscopy may not be beneficial or may be even harmful if the time horizon to benefit is longer than remaining life expectancy, especially because the harms and burdens associated with many of these tests increase with age and multimorbidity. [41]

Finally, the decision to not resuscitate 'DNR’ has implications for older adults with multimorbidity and already poor functional status. [15] In the systematic review by de Decker et al [15] the authors conclude that DNR orders are already more likely to be in place for older adults with multimorbidity, in particular for people with cognitive impairment particularly where decisions have been influenced by prognosis and quality of life.

Eliciting Preferences and Priorities

As a person-centred approach to care is central to the Aged Care Quality Standards, [40] discussions about prognosis can serve as a springboard for difficult conversations with older people with multimorbidity, and may thus facilitate shared or supported decision-making and advance care planning. [41]

This means providing patients with opportunities to discuss the difficulties they are having in meeting their treatment goals in light of any competing priorities in their life. [44] The Instrument for Patient Capacity Assessment (ICAN) Discussion Aid [51] is a tool which can help patients to discuss treatment burden. It has also been shown to help health professionals understand patient capacity, workload, and treatment burden. [25]

This means identifying older peoples’ priorities, goals and preferences through discussion and then incorporating them into shared decisions. [49] As Boyd states, ‘specific health priorities give clinicians an anchor for decision making and communication in the face of uncertainty variability’. [48] This process was seen as especially important for preference-sensitive decisions such as when there may be more than one reasonable option. [41] More research is needed to understand the effectiveness of this approach which aligns with palliative care principles of person-centred care. Two reviews conclude that patient and clinician priorities are often poorly aligned and unreconciled, [23,36] while another suggests that the concepts involved in collaboratively prioritising and setting goals remains underdeveloped. [25,29] A further systematic review found ‘surprisingly few relevant tools’ to help clinicians elicit patient preferences. [18] However, one large systematic review (152 studies) looking at care preferences of older people with multimorbidity identified end-of-life care, in particular advance care planning, as the main priority for this group. [17] Self-management, treatment options, involvement in shared decision-making, goal setting, service delivery and screening/diagnostic testing were also identified as preferences for this group. The only intervention study within this review highlighted the fluctuating nature of prioritising preferences of care, with priorities changing as chronic conditions progressed, new conditions occurred, or contexts changed. [17]

While shared decision-making has been highlighted as a preference for this group of older people, structured processes to facilitate this appear to be lacking. A Cochrane review examining the effectiveness of interventions for including older people with multimorbidity in decision-making identified only three studies and none with this as the primary outcome of interest. [13] However, patient involvement was apparent in those interventions although no impact of this on health-related quality of life was found. A newer approach termed “supported decision-making” is being developed in Australia and is being increasingly used. It is defined as: “the process of enabling a person who requires decision-making support to make, and/or communicate, decisions about their own life. The decision-making is supported, but the decision is theirs.” [57]

Common morbidities associated with specific life-limiting conditions

Older people with a life-limiting condition and multimorbidity or comorbidity may present with diverse combinations of morbidities of varying type and severity. Some of the more common conditions include diabetes, heart disease, cancer, hypertension, depression, COPD, stroke, arthritis/osteoarthritis, osteoporosis, and asthma. [31] Ongoing research is finding, however, that some conditions tend to co-occur more frequently than others which may be due to shared causal pathways or risk factors. [39]

This section lists some of the more common comorbidities to expect with prevalent life-limiting conditions.


Comorbidities are very common with COPD. [35] They include cardiovascular disease, arrhythmia, heart failure, lung cancer, diabetes, depression, mobility issues, obesity, and osteoporosis. [32] More recently, research has identified a strong association between COPD and rheumatoid arthritis. [33] However, heart failure is particularly prevalent with COPD (20-32%) and shares symptoms with it such as acute breathlessness. [32] It is also a strong predictor of unscheduled rehospitalisation and mortality. [3]

COPD makes people vulnerable to accidental falls. As they are also more prone to osteoporosis due to taking high doses of corticosteroids, this can put them at increased risk of osteoporotic fractures. [32] The combination of COPD and obstructive sleep apnoea (the ‘overlap syndrome’) is particularly important as a predictor of more frequent COPD exacerbations and increased mortality. [39,46]

Heart failure

Comorbidities are also common in heart failure. [47] They increase the person’s risk of mortality [6] and necessitate an adjustment to standard heart failure management protocols. [45] The most common heart failure comorbidities are diabetes and COPD, [6] however, the list also includes atrial fibrillation, central sleep apnoea, COPD, anaemia, and chronic kidney disease. [45] Depression is common and should be considered an adverse prognostic marker for hospitalisation and mortality. As frailty is also especially prevalent with heart failure (40-50%), a comprehensive frailty assessment may provide additional prognostic information. [45]


Australian clinical practice guidelines for dementia recommend regular assessment of comorbidities with a special mention of depression. [43] Cancer and dementia appear to be an uncommon comorbidity. [19,55] However, the presence of cancer or other comorbid conditions such as heart failure has been identified as a significant prognosticator of 6-month mortality in dementia although nutrition, nourishment and eating habits were stronger indicators. [12] Underreported cancer-related pain, comorbid with dementia, leading to lack of analgesia, is a concern in the nursing home setting. [16] Furthermore, sarcopenia is an under-recognised age-related syndrome common in dementia characterised by progressive loss of muscle mass and strength. It is associated with poor health outcomes such as cognitive and functional decline and depression. [21]

An Australian evidence-based guideline for deprescribing cholinesterase inhibitors and memantine for dementia is available. [54] This guideline stresses that decisions to deprescribe for dementia should balance patient and carer values and preferences against any likely benefits and harms of continuing these therapies in light of anticipated changes in patient pharmacokinetics and pharmacodynamics with advanced illness.

Colorectal cancer

As colorectal cancer is usually diagnosed in older age, it commonly coincides with comorbidities and frailty. Furthermore, both comorbidity and frailty have been shown to be strong prognostic factors of accelerated decline and increased mortality in colorectal cancer. [11] Screening for cancer via colonoscopy may lack benefit or be harmful for older adults if the time horizon to benefit is longer than life expectancy. [41]

Evidence gaps

  • Prognostication in older adults with multimorbidity remains poorly understood. Measures need to be developed, refined, externally validated, and tested for feasibility and effect on clinical outcomes for older people receiving palliative care.
  • More research is needed to identify the 'best' structured approaches for establishing and documenting discussions around patient preferences, priorities, and goals in the context of multimorbidity with life-limiting illness.
  • ‘Guiding principles of care’ have emerged to fill the gap left by a lack of research evidence on multimorbidity and its management. To date, there is no evidence of the effectiveness of these alternative approaches in terms of improved outcomes for older patients with multimorbidity.
  • More research is also needed to identify the 'best' approaches for incorporating prognosis into clinical decision-making for older adults with multimorbidity.

Page updated 10 May 2022

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