Population-based studies of risk factors for subarachnoid hemorrhage

Subarachnoid hemorrhage (SAH), the least common type of stroke, is a highly fatal vascular disease, in most cases caused by a rupture of an arterial intracranial aneurysm. SAH is more common in women than in men and the mean age at SAH is lower compared to other strokes, often affecting people of working ages. However, the causes of SAH are not fully elucidated. The aim was to study potential risk factors for SAH in population-based settings. Lung volumes assessed in spirometry was studied in association to incidence of SAH in 28,000 subjects from the general population (150 SAH events). Stroke incidence was also evaluated in 100,000 patients with chronic obstructive pulmonary disease (COPD) based on nation-wide register data, comparing the rates to the general population. Leukocyte count was studied for SAH incidence in a cohort study. In nested case control studies, we studied serum levels of fibroblast growth factor 23 (FGF23), and exome-wide coding genetic variation, in relation to SAH risk. Subjects with moderately reduced lung function had increased incidence of SAH, even after adjusting for smoking and in non-smokers. COPD patients had an increased risk of all stroke subtypes; ischemic stroke, intracerebral hemorrhage, and SAH. High leukocyte count and high levels of FGF23, which both may indicate systemic inflammation, was associated with risk of incident SAH. No coding genetic variants were strongly associated with SAH, but a few previously reported common loci for intracranial aneurysms were detected also for SAH. The results suggest that mechanisms related to reduced lung function, and low-grade inflammation may be involved in development of SAH. It is still not known if the association between COPD and stroke is due to shared risk factors or if there is a causal relationship. However, risk factor interventions in COPD patients seem important to reduce stroke risk.