Early dynamics of multimorbidity in 17.4 million people in Spain: onset patterns and prognostic value

Multimorbidity, the coexistence of two or more chronic diseases, has become a defining challenge for ageing societies. Yet evidence on when and how chronic diseases begin to cluster, and on the prognostic importance of this timing, remains limited. We used nationwide primary care electronic health records covering 17.4 million people in Spain to reconstruct the onset and progression of chronic disease over the life course. The first recorded diagnosis was used to trace temporal trajectories of multimorbidity by age and sex. We examined how the first condition, age at diagnosis, and time since that diagnosis were associated with advanced (≥3 diseases), multisystem (≥2 organ systems), and complex multimorbidity (≥3 organ systems), as well as premature mortality (<50 and <65 years) and outcomes related to polypharmacy and high-risk prescribing, using multivariable regression and gradient boosting models. By 2021, more than one in three Spaniards lived with a chronic condition, and over half of adults aged 45 years or older had multimorbidity. Among them, nearly 60% had complex multimorbidity. The time elapsed since the first diagnosis showed the closest link to further accumulation, followed by age at first diagnosis and current age. Later onset, particularly after the mid-50s, was associated with faster decline once disease emerged. The timing of the first chronic condition is a powerful but often overlooked prognostic marker. Public health strategies delaying onset and integrating early management could substantially reduce the long-term burden of multimorbidity in European populations.