Associations between multimorbidity and adverse health outcomes in UK Biobank and the SAIL Databank: A comparison of longitudinal cohort studies

Abstract

Background: Cohorts such as UK Biobank are increasingly used to study multimorbidity; however, there are concerns that lack of representativeness may lead to biased results. This study aims to compare associations between multimorbidity and adverse health outcomes in UK Biobank and a nationally representative sample.

Methods and findings: These are observational analyses of cohorts identified from linked routine healthcare data from UK Biobank participants (n = 211,597 from England, Scotland, and Wales with linked primary care data, age 40 to 70, mean age 56.5 years, 54.6% women, baseline assessment 2006 to 2010) and from the Secure Anonymised Information Linkage (SAIL) databank (n = 852,055 from Wales, age 40 to 70, mean age 54.2, 50.0% women, baseline January 2011). Multimorbidity (n = 40 long-term conditions [LTCs]) was identified from primary care Read codes and quantified using a simple count and a weighted score. Individual LTCs and LTC combinations were also assessed. Associations with all-cause mortality, unscheduled hospitalisation, and major adverse cardiovascular events (MACEs) were assessed using Weibull or negative binomial models adjusted for age, sex, and socioeconomic status, over 7.5 years follow-up for both datasets. Multimorbidity was less common in UK Biobank than SAIL (26.9% and 33.0% with ≥2 LTCs in UK Biobank and SAIL, respectively). This difference was attenuated, but persisted, after standardising by age, sex, and socioeconomic status. The association between increasing multimorbidity count and mortality, hospitalisation, and MACE was similar between both datasets at LTC counts of ≤3; however, above this level, UK Biobank underestimated the risk associated with multimorbidity (e.g., mortality hazard ratio for 2 LTCs 1.62 (95% confidence interval 1.57 to 1.68) in SAIL and 1.51 (1.43 to 1.59) in UK Biobank, hazard ratio for 5 LTCs was 3.46 (3.31 to 3.61) in SAIL and 2.88 (2.63 to 3.15) in UK Biobank). Absolute risk of mortality, hospitalisation, and MACE, at all levels of multimorbidity, was lower in UK Biobank than SAIL (adjusting for age, sex, and socioeconomic status). Both cohorts produced similar hazard ratios for some LTCs (e.g., hypertension and coronary heart disease), but UK Biobank underestimated the risk for others (e.g., alcohol-related disorders or mental health conditions). Hazard ratios for some LTC combinations were similar between the cohorts (e.g., cardiovascular conditions); however, UK Biobank underestimated the risk for combinations including other conditions (e.g., mental health conditions). The main limitations are that SAIL databank represents only part of the UK (Wales only) and that in both cohorts we lacked data on severity of the LTCs included.

Conclusions: In this study, we observed that UK Biobank accurately estimates relative risk of mortality, unscheduled hospitalisation, and MACE associated with LTC counts ≤3. However, for counts ≥4, and for some LTC combinations, estimates of magnitude of association from UK Biobank are likely to be conservative. Researchers should be mindful of these limitations of UK Biobank when conducting and interpreting analyses of multimorbidity. Nonetheless, the richness of data available in UK Biobank does offers opportunities to better understand multimorbidity, particularly where complementary data sources less susceptible to selection bias can be used to inform and qualify analyses of UK Biobank.

Fig 1. Distribution of counts in UK Biobank and SAIL.

Bar plot showing the percentage of participants at baseline with each LTC count for UK Biobank and SAIL, respectively. LTC, long-term condition; SAIL, Secure Anonymised Information Linkage.

Fig 2. Observed and expected LTC counts in UK Biobank.

The grey bars show the observed LTC counts in UK Biobank. The blue line shows the expected LTC counts in UK Biobank based on the age and sex adjusted regression models fitted in SAIL. The red line shows the expected LTC counts in UK Biobank based on age, sex, and socioeconomic status adjusted regression models fitted in SAIL. Observed and expected counts, with 95% confidence intervals, are also shown in S2 Table. LTC, long-term condition; SAIL, Secure Anonymised Information Linkage; SES, socioeconomic status.

Fig 3. Relationship between LTC count and absolute mortality risk for UK Biobank and SAIL.

Lines indicate the modelled 5-year mortality rate. Shaded area indicates 95% confidence interval. Predicted values are modelled at mean age for UK Biobank (56.5 years) and UK national mean Townsend score for socioeconomic status. LTC, long-term condition; SAIL, Secure Anonymised Information Linkage.

Fig 4. Relationship between LTC count and hazard ratio for mortality in UK Biobank and SAIL.

Points indicate hazard ratios adjusted for age, sex, and socioeconomic status. Whiskers indicate 95% CIs. N = total number of participants per LTC count, n events = number of events. CI, confidence interval; HR, hazard ratio; LTC, long-term condition; SAIL, Secure Anonymised Information Linkage.

Fig 5. Relationship between LTC count and absolute risk of unscheduled hospitalisation for UK Biobank and SAIL.

Lines indicate the modelled rate of unscheduled hospitalisations per 1,000 person years observation. Shaded area indicates 95% confidence interval. Predicted values are modelled at mean age for UK Biobank (56.5 years) and UK national mean Townsend score for socioeconomic status. LTC, long-term condition; SAIL, Secure Anonymised Information Linkage.

Fig 6. Relationship between LTC count and IRR for unscheduled hospitalisation in UK Biobank and SAIL.

Points indicate IRRs adjusted for age, sex, and socioeconomic status. Whiskers indicate 95% CIs. N = total number of participants per LTC count, n events = number of events. CI, confidence interval; IRR, incidence rate ratio; LTC, long-term condition; SAIL, Secure Anonymised Information Linkage.

Fig 7. Relationship between LTC count and absolute risk of MACE for UK Biobank and SAIL.

Lines indicate the modelled 5-year risk of MACE. Shaded area indicates 95% confidence interval. Predicted values are modelled at mean age for UK Biobank (56.5 years) and UK national mean Townsend score for socioeconomic status. LTC, long-term condition; MACE, major adverse cardiovascular event; SAIL, Secure Anonymised Information Linkage.

Fig 8. Relationship between LTC count and incident rate ratio for unscheduled hospitalisation in UK Biobank and SAIL.

Points indicate HRs adjusted for age, sex, and socioeconomic status. Whiskers indicate 95% CIs. N = total number of participants per LTC count, n events = number of events. CI, confidence interval; HR, hazard ratio; LTC, long-term condition; SAIL, Secure Anonymised Information Linkage.

Fig 9. Relationship between each LTC and all-cause mortality in UK Biobank and SAIL.

Points indicate HRs adjusted for age, sex, and socioeconomic status. Whiskers indicate 95% CIs. Conditions are ordered by the mean HR (of UK Biobank and SAIL) for each condition. CI, confidence interval; COPD, chronic obstructive pulmonary disease; HR, hazard ratio; LTC, long-term condition; SAIL, Secure Anonymised Information Linkage; TIA, transient ischaemic attack.