Analysis of aneurysmal subarachnoid hemorrhage as a multistep process

Background and purpose: Aneurysmal subarachnoid hemorrhage (ASAH) is a complex disease with higher incidence in women compared to men and in Japan compared to other countries. It was hypothesized that ASAH is consistent with a multistep model of disease. The following assessments were made: (1) the number of steps needed for the disease to occur and (2) whether this number may be different in female versus male and in Japanese versus non-Japanese patients. Methods: Incidence data were generated from a meta-analysis on ASAH incidence until 2017, which was supplemented with a literature search from 2017 to April 2023. Age- and sex-adjusted incidences per 10-year age groups were calculated and the logarithm of age-specific incidence against the logarithm of age was regressed with least-squares regression. Results: In 2317 ASAH patients a linear relationship between logarithm of incidence and logarithm of age was found with a slope estimate of 3.13 (95% confidence interval 2.60–3.65), consistent with a four-step process. Similar estimates were found for female, male, Japanese and non-Japanese patients. Conclusions: Our results suggest that ASAH is a four-step process, also in subgroups with higher ASAH incidence. Elucidation of the exact nature of these steps can provide important clues for identification of disease mechanisms underlying ASAH.