Subarachnoid hemorrhage (SAH) caused by brain aneurysm rupture is an infrequent subtype of stroke that carries high morbidity and mortality. There are only a few preventive strategies that are currently available for this disease, so there is a pressing need to better understand the biological mechanisms that lead to brain aneurysm formation and rupture. A team of Yale investigators is evaluating whether elevated lipid levels – generally considered to be detrimental to human health due to their effect on cardiovascular disease – can have protective effects on the brain. The rationale for this hypothesis is that compared to other tissues, the brain contains a significantly higher proportion of cholesterol content in the form of lipid membranes, a key component of cell structure and integrity.
Julian N. Acosta, MD, and Cameron Both, two research fellows working in the Falcone Lab, led a study recently published in Annals of Neurology, which evaluated the role of genetically-elevated low density cholesterol levels in the prevalence and risk of rupture of brain aneurysms. The study used publicly available genetic association data coming from large consortia and employed Mendelian randomization, a powerful analytical tool that analyzes the random assortment of genetic information during meiosis to allow researchers to draw causal conclusions from observational data. The study found that one mmol/L increase of genetically-instrumented low density cholesterol was associated with a 17% lower risk of a composite of intracranial aneurysm presence and aneurysm rupture. Although the exact function of low density cholesterol in preventing SAH is still undetermined, these results were consistent when considering persons from any race/ethnicity or European ancestry only.
This research was suppodrted by the National Institutes of Health and the American Heart Association, and the results were presented at the annual meeting of the European Stroke Organization. In addition to Acosta and Both, the other members of the research team were Natalia Szejko, MD, PhD, Audrey C. Leasure, Safa Abdelhakim, MD, Victor Torres Lopez, Stacy C. Brown, MD, Charles C. Matouk, MD, Murat Gunel, MD, Kevin N. Sheth, MD, and Guido J. Falcone, MD, ScD.