Correspondence
Unruptured Cerebral Aneurysms in a Japanese Cohort
N Engl J Med 2012; 367:1267-1269September 27, 2012DOI: 10.1056/NEJMc1208985
- Article
To the Editor:
In their article on the Unruptured Cerebral Aneurysm Study of Japan (UCAS Japan) (June 28 issue),1 the investigators provide information regarding the natural history of such aneurysms with a 3-year follow-up of patients. By analyzing data from 6413 patients from January 2001 through April 2004, the authors attempted to delineate the risk factors that predispose patients to the rupture of cerebral aneurysms. In line with other studies, they regarded the location of the aneurysm as an independent risk factor. However, in contrast to the findings of the International Study of Unruptured Intracranial Aneurysms (ISUIA),2 the UCAS Japan investigators found that posterior-circulation aneurysms had a lower rupture rate than anterior-circulation aneurysms, except for those in the posterior communication artery. The diagnosis of a cerebral aneurysm partially relies on noninvasive testing, such as computed tomographic (CT) or magnetic resonance angiography, which can result in a data-collection bias. Owing to limitations in the spatial resolution of CT units with 4 or 16 detector rows or magnetic resonance imaging units, heterogeneous sensitivities for depicting cerebral aneurysms have been documented,3,4 especially in depicting aneurysms smaller than 5 mm, which account for the majority of those that occurred in this Japanese cohort. In regard to location, false negative results with CT angiography were commonly found in the posterior circulation arteries.3,4 Thus, these factors may have caused the elevated rate of rupture of intracranial aneurysms shown in this study.
Fei Peng Zhu, M.D.
Long Jiang Zhang, M.D.
Guang Ming Lu, M.D.
Jinling Hospital, Nanjing, China
cjr.luguangming@vip. 163. com No potential conflict of interest relevant to this letter was reported.
4 References1
The UCAS Japan Investigators
Free Full Text | Web of Science | Medline2
Wiebers DO ,Whisnant JP ,Huston J III , et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362:103-110
CrossRef | Web of Science | Medline3
Westerlaan HE ,van Dijk JM ,Jansen-van der Weide MC , et al. Intracranial aneurysms in patients with subarachnoid hemorrhage: CT angiography as a primary examination tool for diagnosis -- systematic review and meta-analysis. Radiology 2011;258:134-145
CrossRef | Web of Science4
Lu L ,Zhang LJ ,Poon CS , et al. Digital subtraction CT angiography for detection of intracranial aneurysms: comparison with three-dimensional digital subtraction angiography. Radiology 2012;262:605-612
CrossRef | Web of Science
To the Editor:
The main message of the UCAS Japan investigators is quite similar to the findings of the criticized ISUIA report1: only size, location, and shape of the aneurysms matter. However, the Japanese study has some major problems. The follow-up group (patients who had aneurysms that were not surgically treated before rupture) does not represent the general Japanese population but is highly selected, since almost 40% of the patients were 70 years of age or older, 68% were women, and only 15% were former or current smokers. Moreover, current and former smokers were grouped together, the criteria for hypertension were not described, the numbers of patients with treated and untreated hypertension were not provided, and blood-pressure values were not recorded or reported.
Diagnosed hypertension is a less important risk factor than high blood-pressure values that occur before subarachnoid hemorrhage,2 and former smoking is also a less significant risk factor than current smoking.2,3 Do the authors suggest that smoking and high blood pressure, which have been shown to be the most important risk factors for subarachnoid hemorrhage,2-4 including in the Asia–Pacific region,5 are less important risk factors than the size, location, and shape of the aneurysms?
Miikka Korja, M.D., Ph.D.
Helsinki University Central Hospital, Helsinki, Finland
miikka.korja@hus. fi Seppo Juvela, M.D., Ph.D.
University of Helsinki, Helsinki, FinlandJuha Hernesniemi, M.D., Ph.D.
Helsinki University Central Hospital, Helsinki, FinlandNo potential conflict of interest relevant to this letter was reported.
5 References1
Wiebers DO ,Whisnant JP ,Huston J III , et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362:103-110
CrossRef | Web of Science | Medline2
Korja M ,Silventoinen K ,Jousilahti P ,Kaprio J . Subarachnoid hemorrhage risk factors: Finnish population-based prospective longitudinal cohort study. Neurology 2011;76:A361-A361
CrossRef | Web of Science3
Sandvei MS ,Romundstad PR ,Muller TB ,Vatten L ,Vik A . Risk factors for aneurysmal subarachnoid hemorrhage in a prospective population study: the HUNT study in Norway. Stroke 2009;40:1958-1962
CrossRef | Web of Science4
Knekt P ,Reunanen A ,Aho K , et al. Risk factors for subarachnoid hemorrhage in a longitudinal population study. J Clin Epidemiol 1991;44:933-939
CrossRef | Web of Science | Medline5
Feigin V ,Parag V ,Lawes CM , et al. Smoking and elevated blood pressure are the most important risk factors for subarachnoid hemorrhage in the Asia-Pacific region: an overview of 26 cohorts involving 306,620 participants. Stroke 2005;36:1360-1365
CrossRef | Web of Science
Author/Editor Response
In response to the comments of Zhu et al.: we admit that we cannot eliminate a case-selection bias. Nonetheless, the correspondents inappropriately claim that the rupture rate reported in our study is elevated owing to a failure to detect small (<5 mm) posterior-circulation aneurysms by means of CT angiography. We did not find that the rupture rate of small posterior-circulation aneurysms (excluding aneurysms located at the internal carotid–posterior communicating artery) was lower than that of aneurysms in the anterior circulation (Table 3 of our article; and Table 4S in the Supplementary Appendix, available with the full text of our article at NEJM.org). Therefore, a failure to detect these aneurysms did not elevate the rupture rate. In our study, 16.2% of aneurysms were detected only with CT angiography. There was no significant difference in the percentage of small posterior-circulation aneurysms among all locations detected only with CT angiography, as compared with other methods (7.3% with CT angiography and 6.9% with other methods). Moreover, our aim was to clarify the natural course of aneurysms already diagnosed by means of routine methods, not to identify the real rupture risk of all existing unruptured aneurysms.
To Korja and colleagues, we can say that we do not agree with the concern regarding case selection. Our study, like the ISUIA,1 was fundamentally different from population-based epidemiologic studies of subarachnoid hemorrhage. We attempted to find risk factors for the rupture of unruptured aneurysms that have already been detected. Therefore, our cohort is influenced by factors related to aneurysm development, perhaps similar to those causing rupture. Factors causing subarachnoid hemorrhage might already be incorporated into case selection. Nevertheless, we agree that smoking and hypertension are important causes of subarachnoid hemorrhage. Adjustment for smoking history and hypertension can be made during follow-up, but we did not record information regarding changes in those factors, as discussed in the article. Thus, although these factors did not significantly influence the overall risk of rupture, we believe they can never be negligible.2 Our article presents important findings; aneurysmal factors such as size, location, and shape do influence the risk of aneurysmal rupture independently of the status of patient factors, such as hypertension or smoking history, and we wish to stress the importance of combining results from multiple studies to clarify the true risk factors for the rupture of cerebral aneurysms.
Akio Morita, M.D., Ph.D.
Coordinating Office of UCAS Japan, Tokyo, Japan
ucasj-head@umin.ac. jp Shinjiro Tominari, M.D., M.P.H.
Kyoto University School of Public Health, Kyoto, JapanTakaaki Kirino, M.D., Ph.D.
National Hospital Organization, Tokyo, JapanSince publication of their article, the authors report no further potential conflict of interest.
2 References1
Wiebers DO ,Whisnant JP ,Huston J III , et al. Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 2003;362:103-110
CrossRef | Web of Science | Medline2
Juvela S ,Porras M ,Poussa K . Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture. J Neurosurg 2000;93:379-387
CrossRef | Web of Science | Medline
