New study finds shared origins for individual chronic diseases in multimorbidity

by UK Research and Innovation

Each segment of the graph depicts the number of small molecules associated with one out 27 diseases. Coloured segments and connections between disease indicate the fraction of small molecules common between at least two diseases. Credit: Dr Maik Pietzner at the MRC Epidemiology Unit

A new study published today in Nature Medicine has identified key risk factors that increase the likelihood of individuals developing not only one but multiple non-communicable diseases, which include cardiovascular disease, cancer, chronic respiratory disease and diabetes.

20 mar 2021--The analysis of over 11,000 people found that rather than being due to chance, there are often underlying biological links in individuals with multimorbidity, which is defined as the co-occurrence of two or more long-term health conditions and is a growing public health challenge.

Multimorbidity, which affects about two thirds of people aged 65 years or over in the UK, impairs an individual's quality of life over and above the cumulative burden from each individual disease. Understanding which diseases co-occur not at random but through common mechanisms can aid the identification of preventive strategies and lead to improvements in health care.

A research team led by Dr. Claudia Langenberg at the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge and Berlin Institute of Health, Charité University Medicine Berlin, Germany, analysed the levels of 1,014 metabolites in more than 11,000 participants in the European Prospective Investigation into Cancer (EPIC)-Norfolk study. These metabolites are small circulating molecules, such as sugars, vitamins, or lipids, which objectively reflect influences and interactions of genetics, lifestyle, environment, medical treatment, and gut microbes, on human physiology.

By integrating all of the available data to gain a holistic view, the team was able to identify and document the association of these metabolites with 27 different non-communicable diseases that are frequently observed in multimorbidity, finding that almost half of the metabolites examined were associated with at least one of the 27 diseases. Two-thirds of the disease associated metabolites were shared by multiple diseases and hence with the onset of multimorbidity, for example elevated plasma levels of the carbohydrate N-acetylneuraminate were associated with a higher risk of 14 diseases.

The researchers then examined the relationship between more than 50 characteristics of EPIC-Norfolk study participants identified when they were enrolled onto the study, ranging from waist-to-hip-ratio to smoking behaviour, to identify to which extend the profound changes in small molecules can explain the effect of common risk factors onto disease risk. This analysis highlighted poor kidney and liver health, blood glucose and lipids, gut microbial diversity, and lifestyle factors as potential targets tor prevention or treatment to lower the burden of multimorbidity.

Dr. Claudia Langenberg, who led the study at the MRC Epidemiology Unit said: "Such a deep understanding of molecular process has the potential to not only improve treatment of disease, but also aid earlier identification of individuals at risk. For example, we found that several metabolites measured were better predictors of future kidney-related disease risk than the current standard clinical tests."

"This work has only been possible because we were able to measure the concentrations of hundreds of small molecules in patient's blood using stored samples taken up to twenty years before the onset of any disease, and the electronic health record linkage of more than 11,000 EPIC-Norfolk study participants."

Dr. Maik Pietzner, co-lead author of the study at the MRC Epidemiology Unit, added: "Our observation that two-thirds of the small molecules were linked to at least two, even seemingly unrelated, diseases strongly contrasts the disease-centric approach still common in biomedical research. People do not usually develop just one long-term disease, so by taking a broader approach rather than just focusing on one disease at a time we can gain a more useful understanding of the underlying biological processes. Treatments that target pathways that are shared by two or more of a patient's conditions may be better able to provide benefit in a more consistent way that avoids increasing the risk of other conditions."

Dr. Ivan Pavlov, programme lead at the Medical Research Council, said: "This study moves us one step further towards understanding the biochemical pathways involved in multimorbidity, which is not just critical for early disease detection and prediction, but identifying these metabolic footprints could help to develop preventive therapeutics in the future. Importantly, the paper discovers possible links between seemingly unrelated diseases opening potential new avenues for research."

More information: Plasma metabolites to profile pathways in noncommunicable disease multimorbidity, Nature Medicine (2021). DOI: 10.1038/s41591-021-01266-0 , dx.doi.org/10.1038/s41591-021-01266-0

Largest ever multimorbidity trial in primary care challenge current thinking

In the largest ever trial of an intervention to treat people with multiple long-term conditions (multimorbidity) in primary care, researchers at the Universities of Bristol, Manchester, Dundee and Glasgow found that the patient-centred approach taken improved patients' experience of their care but did not improve their health-related quality of life. This is a challenge to current thinking on which UK and international guidelines are based.

30 jun 2018--In a study involving 1,546 patients from England and Scotland, they found that by making health reviews more patient-centred, such as involving patients in the planning and delivery of their care, overall patient satisfaction improved significantly. However, their health-related quality of life, which included measures of mobility, self-care, pain and discomfort, and anxiety and depression, did not.
The findings, published in The Lancet today, provide the best evidence to date of the effectiveness of a person-centred approach for multimorbidity, for which there is international consensus but little evidence.
One in four people in the UK and the US have two or more long-term health conditions, increasing to two-thirds for patients aged over 65, placing a major strain on health services. Conditions include diabetes, heart disease and asthma, and can include mental health conditions such as depression and dementia. Multimorbidity is associated with reduced quality of life, worse physical and mental health, and increased mortality. Treatment for multimorbidity places an additional burden on patients, who may have to take large numbers of drugs, make lifestyle changes and attend numerous appointments for health care.
The study, funded by the National Institute for Health Research (NIHR), tested a new approach to caring for people with three or more long-term conditions, which aimed to improve their health-related quality of life and experience of patient-centred care, and reduce their burden of illness and treatment compared with usual care. The '3-D' approach, which encourages clinicians to think broadly about the different dimensions of health, simplify complex drug treatment and consider mental health (depression) as well as physical health, was designed to treat the whole person and overcome the disadvantages of treating individual conditions in isolation.
Professor Chris Salisbury, from the University of Bristol's Centre for Academic Primary Care and lead author of the study, said: "Existing treatment is based on guidelines for each separate condition meaning that patients often have to attend multiple appointments for each disease which can be repetitive, inconvenient and inefficient. They see different nurses and doctors who may give conflicting advice. Patients with multiple physical health problems frequently get depressed and they also sometimes complain that no-one treats them as a 'whole person' or takes their views into account.
"Internationally, there is broad consensus about the key components of an approach to improve care for people with multimorbidity but we found little evidence about their effectiveness. We incorporated these components in the 3-D approach, including a regular review of patients' problems according to their individual circumstances. We were surprised to find no evidence of improved quality of life for patients as a result of the intervention but this was balanced by significant improvements in patients' experience of care.
"The question now is whether improved patient experience is sufficient justification for this approach. Given that improving patient experience is one of the triple arms of health care, alongside improving health and reducing costs, our view is that providing care that significantly improves patients' experience is justification in itself."
Patients from 33 primary care practices in Bristol, Greater Manchester and Ayrshire in Scotland took part in the study. Roughly half of the practices offered the 3-D intervention (to 797 patients) and other half offered usual care (to 749 patients). Patients were aged 18 and older. The 3-D intervention replaced disease-focused reviews of each health condition with one comprehensive 'patient-centred' review every 6 months with a nurse and doctor. These reviews focused on discussing the problems that bothered the patients most, how to improve their quality of life and how to improve management of their health conditions. A pharmacist reviewed the patient's medication. A health care plan was then devised with each patient and reviewed six months later.
All measures of patient experience showed benefits after 15 months, with patients widely reporting that they felt their care was more joined up and attentive to their needs. However, there was no difference between the two groups in their reported quality of life at the end of the study period.

More information: 'Improving the management of multimorbidity using a patient-centred care model: a pragmatic cluster-randomised trial of the 3D approach' by Chris Salisbury et al in The Lancet, www.thelancet.com/journals/lan … (18)31308-4/fulltext


Provided by University of Bristol

Better guidelines needed for multimorbidity

New clinical guidelines need to be developed to help doctors provide better care for people with more than one chronic illness, according to a research team led by the University of Dundee.

10 oct 2012--In an article published in the British Medical Journal, the research team - which includes the Universities of Dundee, Glasgow and Manchester and the National Institute for Health and Clinical Excellence (NICE) - say that existing guidelines which concentrate on individual diseases are not best serving clinicians or patients where a number of chronic conditions have to be treated.

"Doctors and other professionals often use guidelines to inform their clinical decision making, and clinical guidelines have played an important part in making healthcare more consistent, efficient, and systematic," said Professor Bruce Guthrie, of the Medical Research Institute at the University of Dundee.

"Through the National Institute for Health and Clinical Excellence and the Scottish Intercollegiate Guidelines Network (SIGN), the UK is a world leader in guideline methodology, and guideline development and implementation.

"Despite their success, clinical guidelines are almost always focused on making recommendations about the treatment of individual diseases, which can make their use in clinical practice problematic. This is because most people with long term conditions have more than onechronic illness, particularly older people in whom multiple chronic illnesses (multimorbidity) are the norm.

"For example, 93% of people with coronary heart disease (heart attacks or angina) have at least one other chronic condition, and a fifth have five or more other conditions.

"This creates a paradox - every individual guideline recommendation may be rational and strongly evidence based, but the cumulative effect of recommendations for multiple chronic conditions may not be appropriate as recommendations are contradictory or treatments recommended interact, or because the burden imposed on patients in terms of numbers of drugs, non-drug therapies (diet, exercise, physiotherapy and so on), and attendance for investigation or follow-up may be overwhelming and not feasible for some people with multiple conditions.

"There will of course be many situations where all guideline recommendations are non-contradictory and appropriate, but previous studies in the USA have shown that guidelines there only occasionally address multiple conditions and recommendations are frequently inconsistent or would produce undesirable drug interactions if implemented.

"Decision making in this situation is complex for both clinicians and patients, but existing guidelines are not ideal for supporting either in deciding the best course of action because they are disease based."

Working with colleagues at the Universities of Manchester and Glasgow, and NICE, Professor Guthrie is leading a research project to implement a new approach to guideline development to help address these problems, and examine its methodological feasibility.

Professors Katherine Payne and Matt Sutton, from the Centre of Health Economics at The University of Manchester, are leading the economic component of the study.

Professor Payne said: "Economic evidence is often used to inform the development of clinical guidelines to provide decision-makers with information on the relative cost effectiveness of the individual interventions included in the guidelines. This study aims to explore if, and how, it is feasible to generate economic evidence to support the development of clinical guidelines involving multiple interventions for people with multiple chronic conditions."

Professor Guthrie added: "This work is exploratory, but if successful will make guideline recommendations more relevant for people with multimorbidity."

The project follows on from previous research published in The Lancet earlier this year by Professor Guthrie and colleagues which showed that having two or more co-existing conditions is the norm for most people with chronic disease, and although the prevalence increases with age, more than half of all people with multimorbidity are under 65.

That paper claimed that health systems in the UK and other developed countries were not devised to deal with this scenario and must be radically changed to cope.

Provided by University of Dundee