Identification of the Risk Factors for Complex-Multiple Long-term Conditions (C-MLTC): A Scoping Review

Background Complex multiple long-term conditions (C-MLTC) is commonly defined as the presence of four or more long-term conditions, and its prevalence is projected to increase significantly over the next decade. Methods We undertook a scoping review of the literature to identify the available evidence on the risk factors for C-MLTC as well as to map out the potential clusters. We focussed on a subset of 18 chronic conditions because they include the most commonly reported and prevalent conditions in the general population. We searched NICE Clinical Knowledge Summaries (CKS) and PubMed, Register of Controlled Trials (Cochrane CENTRAL), Google Scholar and TRIP database for guidelines and reports. Results We found 53 risk factors associated with 18 long-term conditions. Sixteen of these are linked to C-MLTC, with 11 being modifiable. Although we reviewed 35 systematic reviews, inconsistent reporting made it difficult to quantify the risk factors and conditions associated with C-MLTC. Diabetes mellitus is a risk factor for most other conditions (10), followed by coronary heart disease, hypertension, and chronic kidney disease (each associated with 8 long-term conditions). Additionally, depression and anxiety are commonly associated with other long-term conditions, with 14 and 17 conditions, respectively. Conclusion Several risks and conditions contribute to the development of multimorbidity. Anxiety and depression are nearly associated with all long-term conditions. Reporting problems within the existing evidence and a lack of clear definitions prevent adequate quantification of the risks associated with C-MLTC. ### Competing Interest Statement CH receives funding support from the NIHR (National Institute for Health Research) School for Primary Care Research Evidence Synthesis Working Group: NIHR SPCR ESWG project 390 and NIHR Program Grant NIHR204406. He is an NHS urgent care GP (full declaration at www.phc.ox.ac.uk/team/carl-Heneghan). JPS receives funding from the Wellcome Trust/Royal Society via a Sir Henry Dale Fellowship (ref: 211182/Z/18/Z), the National Institute for Health and Care Research (NIHR) and the British Heart Foundation (refs: PG/21/10341; FS/19/13/34235). This research was funded, in part, by the Wellcome Trust [211182/Z/18/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. JB is a major shareholder in the Trip Database search engine (www.tripdatabase.com) as well as being an employee. RP receives funding support from the NIHR Programme Grants for Applied Research, NIHR Applied Research Collaboration Oxford and Thames Valley and the NIHR Community Healthcare MedTech and in-Vitro Diagnostic Cooperative. AT receives funding support from the NIHR Oxford BRC, NIHR Oxford HealthTech Research Centre and the NIHR-ARC Oxford and Thames Valley. IO, KB and DB have no conflicts to declare. ### Clinical Protocols ### Funding Statement This project is funded by the NIHR Programme Grants for Applied Research Programme (NIHR204406). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data are made available online on the Open Science Framework