Pitfalls in understanding how multiple long-term conditions cluster: whole population and age-stratified associations in 7,490,874 people in England

Studies of how multiple long-term conditions (MLTC) cluster together in individuals vary in the populations studied, and whether they age and/or sex stratify, which limits comparison between studies and reproducibility. This study uses a large, UK primary-care dataset to examine how pairwise strength of association between 74 conditions varies by age in both men and women aged 30-99 years, and to explore implications for MLT cluster analyses. Joint prevalence of conditions was lowest in younger age-groups and progressively increased with age, whereas Association Beyond Chance (ABC) was highest in younger age-groups and progressively decreased with age. Condition clustering based on ABC identified different clusters in all men and all women aged 30-99 years, and these clusters differed from those identified in each age-group. Researchers examining how MLTC cluster should consider whether age and sex stratification is appropriate given their study aims and/or would improve comparability and reproducibility, and explicitly justify their choices.