The effect of disease onset chronology on mortality among patients with multimorbidity: A Danish nationwide register study.

Background: Multimorbidity is associated with increased mortality. Certain combinations of diseases are known to be more lethal than others, but the limited knowledge of how the chronology in which diseases develop impacts mortality may impair the development of effective clinical interventions for patients with multimorbidity. Objective: To explore if in multimorbidity the chronology of disease onset is associated with mortality. Design: A prospective nationwide cohort study, including 3,986,209 people aged ≥18 years on 1 January 2000, was performed. We included ten diagnosis groups: lung, musculoskeletal, endocrine, mental, cancer, neurological, gastrointestinal, cardiovascular, kidney, and sensory organs. We defined multimorbidity as the presence of at least two diagnoses from two diagnosis groups (out of ten). To determine mortality, logistic regression models were used to calculate odds ratios (OR) and ratio of ORs (RORs). Results: For most combinations of multimorbidity, the chronology of disease onset does not change mortality. However, when multimorbidity included mental health diagnoses, mortality was in general higher if the mental health diagnosis appeared first. If multimorbidity included heart and sensory diagnoses, mortality was higher if these developed second. For the majority of multimorbidity combinations, there was excess mortality if multimorbidity was diagnosed simultaneously, rather than consecutively, for example, heart and kidney (3.58 ROR; CI 2.39-5.36), or mental health and musculoskeletal diagnoses (2.38 ROR; CI 1.70-3.32). Conclusions: Overall, in multimorbidity, the chronology in which diseases develop is not associated with mortality, with few exceptions. For almost all combinations of multimorbidity, diagnoses act synergistically in relation to mortality if diagnosed simultaneously.