Diogo C. Haussen, MD

Defining which modifiable risk factors enhance the risk of cerebral aneurysm rupture is a critical clinical matter. The modifiable feature that has been more often correlated with development of subarachnoid hemorrhage (SAH) is active cigarette smoking. Other putative factors include alcohol consumption and hypertension; however, accurate data on these variables and on other modifiable factors is scant. Vlak et al. report the results of a case-control study that compared 250 SAH individuals with 206 patients with unruptured aneurysms, attempting to shed more light in this penumbra. Firstly, the results reinforce the consideration that active smoking is solidly associated with ruptured status. Migraine (defined by patient self-report on a questionnaire) was found to be independently associated with rupture. The authors acknowledge that this finding may have been generated by misclassification bias; once migraine was defined by as previous diagnosis documented in the medical chart (a more strict characterization), the association with SAH was lost. Hyperlipidemia was found to be protective from the risk of aneurysm rupture. 

Early epidemiological studies revealed an association between low cholesterol and intracerebral hemorrhage; would this also apply for aneurysms? Once the authors performed sensitivity analysis controlling for potential selection bias, hyperlipidemia became non-significantly associated with SAH. The effect of statins on the risk of aneurysm rupture makes this association even more difficult to interpret, and is certainly an interesting research question that must be addressed in future studies. Finally, hypertension was not found to be differently prevalent between unruptured and ruptured aneurysm cases. This brings us an important point: although ruptured and unruptured aneurysms may have a different biology, it is very unlikely for both conditions to have totally distinct pathophysiological mechanisms. Hypertension simply seems to constitute a shared underlying contributor. This report reflects the difficulties in studying epidemiological factors of such a complex disease, and reminds us of the importance lifestyle modification in patients with cerebral aneurysms.