Risk factors associated to disability in primary headaches: a systematic review to inform future iterations of the Global Burden of Disease Study

Abstract

Background Headache disorders are prevalent and disabling conditions. Despite the recent introduction of modern therapies, a large portion of patients are still sub-optimally treated, resulting in a minor or no decrease in health loss nor disability. The Global Burden of Disease (GBD) study classifies 88 risk factors which impact several conditions, thus enabling the estimation of the potential health gain due to addressing these risk factors, but such analysis is not available for headache disorders yet. Objective To address which risk factors, as intended by the taxonomy of the GBD study, are associated to disability in primary headaches. Methods Primary research studies addressing primary headache disorders and disability were searched in PubMed, Web of Science and SCOPUS, in the period between 2000 and 2025. The GBD taxonomy, which classifies risk factors into environmental and occupational, behavioural, and metabolic factors, was used. A descriptive analysis was employed to report the associations between disability measures and the presence/absence of specific risk factors, accounting for diagnoses and the age of patients. Results A total of 64 studies (97,846 patients) were included, and a total of 86 single associations were found. Metabolic risk factors (high BMI, high fasting plasma glucose, and LDL cholesterol), and behavioural risk factors (low physical activity, inadequate dietary habits, tobacco smoking, and alcohol consumption) were the most frequently reported. Conclusions Our results suggest that it is possible to address headache-related disability by acting on a set of modifiable factors, with interventions tailored to the specific needs of patients or addressing the exposed populations as a whole. In particular, targeting dietary aspects and exercise is reasonably expected to promote weight loss, and might have an impact on the reduction in fasting plasma glucose and LDL cholesterol, ultimately improving patients' overall health status and reducing headache-related disability.