A matched cohort study investigating premature, accentuated, and accelerated aging in people living with HIV.

INTRODUCTION: The impact of HIV infection on the aging process is disputed and largely unknown. We aimed to identify whether people living with HIV experience premature, accelerated, and/or accentuated aging by investigating the development of four age-related non-communicable diseases in people living with versus without HIV. METHODS: This population-based matched cohort study design used UK-based primary care electronic health records from the IQVIA Medical Research Database. Between January 2000 and January 2020, all people living with and without HIV aged ≥18 years were eligible. Outcomes included cardiovascular disease (CVD), hypertension, type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), which were identified by Read codes. We used age at diagnosis to investigate premature aging and age at exit date to investigate accentuation and acceleration. For each outcome, people with and without HIV were excluded if they had the outcome of interest at baseline. Participants were matched based on propensity scores (1:1 ratio). Linear regression was used to report any difference in age at diagnosis between the two groups and to report the prevalence trends for age at exit date. RESULTS: In total, 8880 people living with HIV were matched with 8880 people without HIV and were found to have an earlier onset of CVD (54.5 vs. 56.8; p = 0.002). Similarly, people living with HIV had an earlier onset of hypertension (49.7 vs. 51.4; p = 0.002). No difference was found for T2DM or CKD (53.4 vs. 52.6; p = 0.368 and 57.6 vs. 58.1; p = 0.483, respectively). The burden of CKD increased over time, whereas no difference in the burden was found for the other conditions. CONCLUSION: The earlier development of CVD and hypertension in people living with HIV than in those without HIV indicates premature aging, whereas the increased burden of CKD indicates accelerated aging.

Early onset of immune-mediated diseases in minority ethnic groups in the UK.

BACKGROUND: The prevalence of some immune-mediated diseases (IMDs) shows distinct differences between populations of different ethnicities. The aim of this study was to determine if the age at diagnosis of common IMDs also differed between different ethnic groups in the UK, suggestive of distinct influences of ethnicity on disease pathogenesis. METHODS: This was a population-based retrospective primary care study. Linear regression provided unadjusted and adjusted estimates of age at diagnosis for common IMDs within the following ethnic groups: White, South Asian, African-Caribbean and Mixed-race/Other. Potential disease risk confounders in the association between ethnicity and diagnosis age including sex, smoking, body mass index and social deprivation (Townsend quintiles) were adjusted for. The analysis was replicated using data from UK Biobank (UKB). RESULTS: After adjusting for risk confounders, we observed that individuals from South Asian, African-Caribbean and Mixed-race/Other ethnicities were diagnosed with IMDs at a significantly younger age than their White counterparts for almost all IMDs. The difference in the diagnosis age (ranging from 2 to 30 years earlier) varied for each disease and by ethnicity. For example, rheumatoid arthritis was diagnosed at age 49, 48 and 47 years in individuals of African-Caribbean, South Asian and Mixed-race/Other ethnicities respectively, compared to 56 years in White ethnicities. The earlier diagnosis of most IMDs observed was validated in UKB although with a smaller effect size. CONCLUSION: Individuals from non-White ethnic groups in the UK had an earlier age at diagnosis for several IMDs than White adults.

Predictors of interest in predictive testing for rheumatoid arthritis among first degree relatives of rheumatoid arthritis patients.

OBJECTIVES: There is increasing interest in prediction and prevention of RA. It is important to understand the views of those at risk to inform the development of effective approaches. First-degree relatives (FDRs) of RA patients are at increased risk of RA. This study assessed predictors of their interest in predictive testing for RA. METHODS: Questionnaires were completed by RA patients (provided with their questionnaire by a healthcare professional) and their FDRs (provided with their questionnaire by their RA proband). FDR surveys assessed interest in taking a predictive test, demographic variables, perceived RA risk, attitudes about predictive testing, autonomy preferences, illness perceptions, avoidance coping and health anxiety. Patient surveys included demographic variables, disease impact, RA duration and treatment. Ordinal logistic regression examined the association between FDRs' characteristics and their interest in predictive testing. Generalized estimating equations assessed associations between patient characteristics and FDRs' interest in predictive testing. RESULTS: Three hundred and ninety-six FDRs responded. Paired data from the RA proband were available for 292. The proportion of FDRs interested in predictive testing was 91.3%. Information-seeking preferences, beliefs that predictive testing can increase empowerment over health and positive attitudes about risk knowledge were associated with increased interest. Beliefs that predictive testing could cause psychological harm predicted lower interest. Patient characteristics of the proband were not associated with FDRs' interest. CONCLUSIONS: FDRs' interest in predictive testing for RA was high, and factors associated with interest were identified. These findings will inform the development of predictive strategies and informational resources for those at risk.

Angiotensin-converting enzyme inhibitors and risk of age-related macular degeneration in individuals with hypertension.

AIMS: Several observational studies have examined the potential protective effect of angiotensin-converting enzyme inhibitor (ACE-I) use on the risk of age-related macular degeneration (AMD) and have reported contradictory results owing to confounding and time-related biases. We aimed to assess the risk of AMD in a base cohort of patients aged 40 years and above with hypertension among new users of ACE-I compared to an active comparator cohort of new users of calcium channel blockers (CCB) using data obtained from IQVIA Medical Research Data, a primary care database in the UK. METHODS: In this study, 53 832 and 43 106 new users of ACE-I and CCB were included between 1995 and 2019, respectively. In an on-treatment analysis, patients were followed up from the time of index drug initiation to the date of AMD diagnosis, loss to follow-up, discontinuation or switch to the comparator drug. A comprehensive range of covariates were used to estimate propensity scores to weight and match new users of ACE-I and CCB. Standardized mortality ratio weighted Cox proportional hazards model was used to estimate hazard ratios of developing AMD. RESULTS: During a median follow-up of 2 years (interquartile range 1-5 years), the incidence rate of AMD was 2.4 (95% confidence interval 2.2-2.6) and 2.2 (2.0-2.4) per 1000 person-years among the weighted new users of ACE-I and CCB, respectively. There was no association of ACE-I use on the risk of AMD compared to CCB use in either the propensity score weighted or matched, on-treatment analysis (adjusted hazard ratio: 1.07 [95% confidence interval 0.90-1.27] and 0.87 [0.71-1.07], respectively). CONCLUSION: We found no evidence that the use of ACE-I is associated with risk of AMD in patients with hypertension.

Type 2 diabetes mellitus, glycaemic control, associated therapies and risk of rheumatoid arthritis: a retrospective cohort study.

OBJECTIVE: To compare the incident risk of RA in patients with type 2 diabetes mellitus (T2DM) and to explore the role of glycaemic control and associated therapeutic use in the onset of RA. METHODS: This study was a retrospective cohort study using patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 1995 and 2019. A total of 224 551 newly diagnosed patients with T2DM were matched to 449 101 patients without T2DM and followed up to assess their risk of RA. Further analyses investigated the effect of glycaemic control, statin use and anti-diabetic drugs on the relationship between T2DM and RA using a time-dependent Cox regression model. RESULTS: During the study period, the incidence of RA was 8.1 and 10.6 per 10 000 person-years in the exposed and unexposed groups, respectively. The adjusted hazard ratio (aHR) was 0.73 (95% CI 0.67, 0.79). In patients who had not used statins in their lifetime, the aHR was 0.89 (95% CI 0.69, 1.14). When quantifying the effects of glycaemic control, anti-diabetic drugs and statins using time-varying analyses, there was no association with glycaemic control [aHR 1.00 (95% CI 0.99, 1.00)], use of metformin [aHR 1.00 (95% CI 0.82, 1.22)], dipeptidyl peptidase-4 inhibitors [DPP4is; aHR 0.94 (95% CI 0.71, 1.24)] and the development of RA. However, statins demonstrated a protective effect for progression of RA in those with T2DM [aHR 0.76 (95% CI 0.66, 0.88)], with evidence of a duration-response relationship. CONCLUSION: There is a reduced risk of RA in patients with T2DM that may be attributable to the use of statins.

Allergic diseases and long-term risk of autoimmune disorders: longitudinal cohort study and cluster analysis.

INTRODUCTION: The association between allergic diseases and autoimmune disorders is not well established. Our objective was to determine incidence rates of autoimmune disorders in allergic rhinitis/conjunctivitis (ARC), atopic eczema and asthma, and to investigate for co-occurring patterns. METHODS: This was a retrospective cohort study (1990-2018) employing data extracted from The Health Improvement Network (UK primary care database). The exposure group comprised ARC, atopic eczema and asthma (all ages). For each exposed patient, up to two randomly selected age- and sex-matched controls with no documented allergic disease were used. Adjusted incidence rate ratios (aIRRs) were calculated using Poisson regression. A cross-sectional study was also conducted employing Association Rule Mining (ARM) to investigate disease clusters. RESULTS: 782 320, 1 393 570 and 1 049 868 patients with ARC, atopic eczema and asthma, respectively, were included. aIRRs of systemic lupus erythematosus (SLE), Sjögren's syndrome, vitiligo, rheumatoid arthritis, psoriasis, pernicious anaemia, inflammatory bowel disease, coeliac disease and autoimmune thyroiditis were uniformly higher in the three allergic diseases compared with controls. Specifically, aIRRs of SLE (1.45) and Sjögren's syndrome (1.88) were higher in ARC; aIRRs of SLE (1.44), Sjögren's syndrome (1.61) and myasthenia (1.56) were higher in asthma; and aIRRs of SLE (1.86), Sjögren's syndrome (1.48), vitiligo (1.54) and psoriasis (2.41) were higher in atopic eczema. There was no significant effect of the three allergic diseases on multiple sclerosis or of ARC and atopic eczema on myasthenia. Using ARM, allergic diseases clustered with multiple autoimmune disorders. Three age- and sex-related clusters were identified, with a relatively complex pattern in females ≥55 years old. CONCLUSIONS: The long-term risks of autoimmune disorders are significantly higher in patients with allergic diseases. Allergic diseases and autoimmune disorders show age- and sex-related clustering patterns.

Healthcare resource utilisation and economic burden attributable to back pain in primary care: A matched case-control study in the United Kingdom.

Objective: Incremental healthcare costs attributed to back pain, and characterisation by patient and clinical factors have rarely been documented. This study aimed to assess annual healthcare resource utilisation and costs associated with back pain in primary care. Methods: Using the IQVIA Medical Research Data (IMRD), patients with back pain were identified (study period: 01 January 2006 to 31 December 2015) using diagnostic records and analgesics prescriptions (n = 133,341), and propensity score matched 1:1 to patients without back pain. The annual incremental costs of back pain associated with consultations and prescriptions were estimated and extrapolated to a national level. Sensitivity analysis was conducted by restricting the study population to the most recent diagnosis of back pain. Variations in cost were assessed stratified by gender, age-groups, deprivation, and comorbidity categories. Results: The mean age was 57 years, and 62% were females in both the case and control groups. The total incremental healthcare costs associated with back pain was £32.5 million in 2015 (£35.9 million in 2020), with per-patient cost of £244 (£265 in 2020) per year. On a national level, this translated to an estimated £3.2 billion (£3.5 billion in 2020). Eighty percent of the costs were attributed to consultations; and female gender, older age, higher deprivation, and higher comorbidity were all associated with increased mean healthcare costs of patients with back pain. Conclusion: Our findings confirm the substantial healthcare costs attributed to back pain, even with primacy care costs only. The data also revealed significant cost variations across socio-demographic and clinical factors.

Predictors of the likelihood that patients with rheumatoid arthritis will communicate information about rheumatoid arthritis risk to relatives: A quantitative assessment.

First-degree relatives (FDRs) of people with rheumatoid arthritis (RA) are increasingly recruited to prediction and prevention studies. Access to FDRs is usually via their proband with RA. Quantitative data on predictors of family risk communication are lacking. RA patients completed a questionnaire assessing likelihood of communicating RA risk information to their FDRs, demographic variables, disease impact, illness perceptions, autonomy preferences, interest in FDRs taking a predictive test for RA, dispositional openness, family functioning, and attitudes towards predictive testing. Ordinal regression examined associations between patients' characteristics and their median likelihood of communicating RA risk to FDRs. Questionnaires were completed by 482 patients. The majority (75.1%) were likely/extremely likely to communicate RA risk information to FDRs, especially their children. Decision-making preferences, interest in FDRs taking a predictive test, and beliefs that risk knowledge would increase people's empowerment over their health increased patients' odds of being likely to communicate RA risk information to FDRs. Beliefs that risk information would cause stress to their relatives decreased odds that patients would be likely to communicate RA risk. These findings will inform the development of resources to support family communication about RA risk.

The cost of primary care consultations associated with long COVID in non-hospitalised adults: a retrospective cohort study using UK primary care data.

BACKGROUND: The economic impact of managing long COVID in primary care is unknown. We estimated the costs of primary care consultations associated with long COVID and explored the relationship between risk factors and costs. METHODS: Data were obtained on non-hospitalised adults from the Clinical Practice Research Datalink Aurum primary care database. We used propensity score matching with an incremental cost method to estimate additional primary care consultation costs associated with long COVID (12 weeks after COVID-19) at an individual and UK national level. We applied multivariable regression models to estimate the association between risk factors and consultations costs beyond 12 weeks from acute COVID-19. RESULTS: Based on an analysis of 472,173 patients with COVID-19 and 472,173 unexposed individuals, the annual incremental cost of primary care consultations associated with long COVID was £2.44 per patient and £23,382,452 at the national level. Among patients with COVID-19, a long COVID diagnosis and reporting of longer-term symptoms were associated with a 43% and 44% increase in primary care consultation costs respectively, compared to patients without long COVID symptoms. Older age, female sex, obesity, being from a white ethnic group, comorbidities and prior consultation frequency were all associated with increased primary care consultation costs. CONCLUSIONS: The costs of primary care consultations associated with long COVID in non-hospitalised adults are substantial. Costs are significantly higher among those diagnosed with long COVID, those with long COVID symptoms, older adults, females, and those with obesity and comorbidities.

Comorbidity phenotypes and risk of mortality in patients with osteoarthritis in the UK: a latent class analysis.

BACKGROUND: Osteoarthritis (OA) is a common chronic condition but its association with other chronic conditions and mortality is largely unknown. This study aimed to use latent class analysis (LCA) of 30 comorbidities in patients with OA and matched controls without OA to identify clusters of comorbidities and examine the associations between the clusters, opioid use, and mortality. METHODS: A matched cohort analysis of patients derived from the IQVIA Medical Research Data (IMRD-UK) database between 2000 and 2019. 418,329 patients with newly diagnosed OA were matched to 243,170 patients without OA to identify comorbidity phenotypes. Further analysis investigated the effect of opioid use on mortality in individuals with OA and their matched controls. RESULTS: The median (interquartile range (IQR)) number of comorbidities was 2 (1-4) and 1 (0-3) in the OA and control groups respectively. LCA identified six comorbidity phenotypes in individuals with and without OA. Clusters with a high prevalence of comorbidities were characterised by hypertension, circulatory, and metabolic diseases. We identified a comorbidity cluster with the aforementioned comorbidities plus a high prevalence of chronic kidney disease, which was associated with twice the hazard of mortality in hand OA with a hazard ratio (HR) (95% CI) of 2.53 (2.05-3.13) compared to the hazard observed in hip/knee OA subtype 1.33 (1.24-1.42). The impact of opioid use in the first 12 months on hazards of mortality was significantly greater for weak opioids and strong opioids across all groups HR (95% CI) ranging from 1.11 (1.07-11.6) to 1.80 (1.69-1.92)). There was however no evidence of association between NSAID use and altered risk of mortality. CONCLUSION: This study identified six comorbidity clusters in individuals with OA and matched controls within this cohort. Opioid use and comorbidity clusters were differentially associated with the risk of mortality. The analyses may help shape the development of future interventions or health services that take into account the impact of these comorbidity clusters.

The association between inflammatory bowel disease and mental ill health: a retrospective cohort study using data from UK primary care.

BACKGROUND: Patients with active inflammatory bowel disease (IBD) and mental illnesses experience worse IBD outcomes. AIM: To describe the incidence of mental illnesses, including deliberate self-harm, in IBD patients. METHODS: A population-based retrospective cohort study using IQVIA medical research data of a primary care database covering the whole UK, between January 1995 and January 2021. IBD patients of all ages were matched 4:1 by demographics and primary care practice to unexposed controls. Following exclusion of patients with mental ill health at study entry, adjusted hazard ratios (HR) of developing depression, anxiety, deliberate self-harm, severe mental illness and insomnia were calculated using a Cox proportional hazards model. RESULTS: We included 48,799 incident IBD patients: 28,352 with ulcerative colitis and 20,447 with Crohn's disease. Incidence rate ratios of mental illness were higher in IBD patients than controls (all p < 0.001): deliberate self-harm 1.31 (95% CI 1.16-1.47), anxiety 1.17 (1.11-1.24), depression 1.36 (1.31-1.42) and insomnia 1.62 (1.54-1.69). Patients with Crohn's disease were more likely to develop deliberate self-harm HR 1.51 (95% CI 1.28-1.78), anxiety 1.38 (1.16-1.65), depression 1.36 (1.26-1.47) and insomnia 1.74 (1.62-1.86). Patients with IBD are at increased risk of deliberate self-harm (HR 1.20 [1.07-1.35]). The incidence rate ratios of mental illnesses were particularly high during the first year following IBD diagnosis: anxiety 1.28 (1.13-1.46), depression 1.62 (1.48-1.77) and insomnia 1.99 (1.78-2.21). CONCLUSION: Deliberate self-harm, depression, anxiety and insomnia were more frequent among patients with IBD. IBD is independently associated with an increased risk of deliberate self-harm.

Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study).

INTRODUCTION: Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4-12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies. METHODS AND ANALYSIS: A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers. TRIAL REGISTRATION NUMBER: 1567490.

Methodological considerations in the assessment of direct and indirect costs of back pain: A systematic scoping review.

BACKGROUND: Back pain is a common and costly health problem worldwide. There is yet a lack of consistent methodologies to estimate the economic burden of back pain to society. OBJECTIVE: To systematically evaluate the methodologies used in the published cost of illness (COI) literature for estimating the direct and indirect costs attributed to back pain, and to present a summary of the estimated cost burden. METHODS: Six electronic databases were searched to identify COI studies of back pain published in English up to February 2021. A total of 1,588 abstracts were screened, and 55 full-text studies were subsequently reviewed. After applying the inclusion criteria, 45 studies pertaining to the direct and indirect costs of back pain were analysed. RESULTS: The studies reported data on 15 industrialised countries. The national cost estimates of back pain in 2015 USD ranged from $259 million ($29.1 per capita) in Sweden to $71.6 billion ($868.4 per capita) in Germany. There was high heterogeneity among the studies in terms of the methodologies used for analysis and the resulting costs reported. Most of the studies assessed costs from a societal perspective (n = 29). The magnitude and accuracy of the reported costs were influenced by the case definition of back pain, the source of data used, the cost components included and the analysis method. Among the studies that provided both direct and indirect cost estimates (n = 15), indirect costs resulting from lost or reduced work productivity far outweighed the direct costs. CONCLUSION: Back pain imposes substantial economic burden on society. This review demonstrated that existing published COI studies of back pain used heterogeneous approaches reflecting a lack of consensus on methodology. A standardised methodological approach is required to increase credibility of the findings of COI studies and improve comparison of estimates across studies.

Burden of chronic diseases associated with periodontal diseases: a retrospective cohort study using UK primary care data.

OBJECTIVES: To identify the association between periodontal diseases (gingivitis and periodontitis) and chronic diseases including cardiovascular disease, cardiometabolic disease, autoimmune disease and mental ill health. DESIGN: Retrospective cohort. SETTING: IQVIA Medical Research Data-UK between 1 January 1995 and 1 January 2019. PARTICIPANTS: 64 379 adult patients with a general practitioner recorded diagnosis of periodontal disease (exposed patients) were matched to 251 161 unexposed patients by age, sex, deprivation and registration date. MAIN OUTCOME MEASURES: Logistic regression models accounting for covariates of clinical importance were undertaken to estimate the adjusted OR (aOR) of having chronic diseases at baseline in the exposed compared with the unexposed group. Incidence rates for each outcome of interest were then provided followed by the calculation of adjusted HRs using cox regression modelling to describe the risk of outcome development in each group. RESULTS: The average age at cohort entry was 45 years and the median follow-up was 3.4 years. At study entry, the exposed cohort had an increased likelihood of having a diagnosis of cardiovascular disease (aOR 1.43; 95% CI 1.38 to 1.48), cardiometabolic disease (aOR 1.16; 95% CI 1.13 to 1.19), autoimmune disease (aOR 1.33; 95% CI 1.28 to 1.37) and mental ill health (aOR 1.79; 95% CI 1.75 to 1.83) compared with the unexposed group. During the follow-up of individuals without pre-existing outcomes of interest, the exposed group had an increased risk of developing cardiovascular disease (HR 1.18; 95% CI 1.13 to 1.23), cardiometabolic disease (HR 1.07; 95% CI 1.03 to 1.10), autoimmune disease (HR 1.33; 95% CI 1.26 to 1.40) and mental ill health (HR 1.37; 95% CI 1.33 to 1.42) compared with the unexposed group. CONCLUSIONS: In this cohort, periodontal diseases appeared to be associated with an increased risk of developing cardiovascular, cardiometabolic, autoimmune diseases and mental ill health. Periodontal diseases are very common; therefore, an increased risk of other chronic diseases represent a substantial public health burden.

Comorbidity phenotypes and risk of mortality in patients with ischaemic heart disease in the UK.

OBJECTIVES: The objective of this study is to use latent class analysis of up to 20 comorbidities in patients with a diagnosis of ischaemic heart disease (IHD) to identify clusters of comorbidities and to examine the associations between these clusters and mortality. METHODS: Longitudinal analysis of electronic health records in the health improvement network (THIN), a UK primary care database including 92 186 men and women aged ≥18 years with IHD and a median of 2 (IQR 1-3) comorbidities. RESULTS: Latent class analysis revealed five clusters with half categorised as a low-burden comorbidity group. After a median follow-up of 3.2 (IQR 1.4-5.8) years, 17 645 patients died. Compared with the low-burden comorbidity group, two groups of patients with a high-burden of comorbidities had the highest adjusted HR for mortality: those with vascular and musculoskeletal conditions, HR 2.38 (95% CI 2.28 to 2.49) and those with respiratory and musculoskeletal conditions, HR 2.62 (95% CI 2.45 to 2.79). Hazards of mortality in two other groups of patients characterised by cardiometabolic and mental health comorbidities were also higher than the low-burden comorbidity group; HR 1.46 (95% CI 1.39 to 1.52) and 1.55 (95% CI 1.46 to 1.64), respectively. CONCLUSIONS: This analysis has identified five distinct comorbidity clusters in patients with IHD that were differentially associated with risk of mortality. These analyses should be replicated in other large datasets, and this may help shape the development of future interventions or health services that take into account the impact of these comorbidity clusters.

Patterns of Multimorbidity in Middle-Aged and Older Adults: An Analysis of the UK Biobank Data.

OBJECTIVE: To assess the prevalence, disease clusters, and patterns of multimorbidity using a novel 2-stage approach in middle-aged and older adults from the United Kingdom. PATIENTS AND METHODS: Data on 36 chronic conditions from 502,643 participants aged 40 to 69 years with baseline measurements between March 13, 2006, and October 1, 2010, from the UK Biobank were extracted. We combined cluster analysis and association rule mining to assess patterns of multimorbidity overall and by age, sex, and ethnicity. A maximum of 3 clusters and 30 disease patterns were mined. Comparisons were made using lift as the main measure of association. RESULTS: Ninety-five thousand seven hundred-ten participants (19%) had 2 or more chronic conditions. The first cluster included only myocardial infarction and angina (lift=13.3), indicating that the likelihood of co-occurrence of these conditions is 13 times higher than in isolation. The second cluster consisted of 26 conditions, including cardiovascular, musculoskeletal, respiratory, and neurodegenerative diseases. The strongest association was found between heart failure and atrial fibrillation (lift=23.6). Diabetes was at the center of this cluster with strong associations with heart failure, chronic kidney disease, liver failure, and stroke (lift>2). The third cluster contained 8 highly prevalent conditions, including cancer, hypertension, asthma, and depression, and the strongest association was observed between anxiety and depression (lift=5.0). CONCLUSION: Conditions such as diabetes, hypertension, and asthma are the epicenter of disease clusters for multimorbidity. A more integrative multidisciplinary approach focusing on better management and prevention of these conditions may help prevent other conditions in the clusters.