The natural course of unruptured cerebral aneurysms in a Japanese cohort

UCAS Japan Investigators; Akio Morita; Takaaki Kirino; Kazuo Hashi; Noriaki Aoki; Shunichi Fukuhara; Nobuo Hashimoto; Takeo Nakayama; Michi Sakai; Akira Teramoto; Shinjiro Tominari; Takashi Yoshimoto

doi:10.1056/NEJMoa1113260

The natural course of unruptured cerebral aneurysms in a Japanese cohort

N Engl J Med. 2012 Jun 28;366(26):2474-82. doi: 10.1056/NEJMoa1113260.

Authors

UCAS Japan Investigators; Akio Morita, Takaaki Kirino, Kazuo Hashi, Noriaki Aoki, Shunichi Fukuhara, Nobuo Hashimoto, Takeo Nakayama, Michi Sakai, Akira Teramoto, Shinjiro Tominari, Takashi Yoshimoto

Collaborators

UCAS Japan Investigators:
T Kirino, K Hashi, A Morita, N Aoki, I Date, S Fukuhara, T Fukui, N Hashimoto, K Houkin, T Kawase, T Kiuchi, T Nakayama, Y Ohashi, T Ohmoto, I Saito, N Saito, M Sakai, T Sakurai, Y Shiokawa, A Teramoto, T Tominaga, S Tominari, T Yamaki, T Yoshimoto, H Arai, Y Iwasaki, H Kajikawa, Y Katayama, T Kanno, N Kodama, K Kurisu, C Ochiai, A Ogawa, K Saito, N Sakai, T Sasaki, T Sasaki, H Sano, H Segawa, A Takahashi, W Taki, S Nagao, T Nakagawa, I Nagata, M Negoro, S Fujiwara, T Hori, T Matsushima, M Matsutani, S Miyamoto, A Yamaura, N Yasui, T Yasui, J Yoshida, T Yoshimine, K Watanabe, E Watanabe, N Aoki, S Fukuhara, T Fukui, T Nakayama, Y Ohashi, M Sakai, T Sakurai, K Takakura, Y Fukuuchi, T Fukui, T Sakura, T Maehara, S Tanabe, S Aoki, A Morita, T Kiuchi, N Sato, M Uchida, M Yamamoto, R Tanikawa, H Kamiyama, T Nakamura, Y Hirose, H Sano, M Hayakawa, A Sadato, T Hatano, Y Tokuriki, K Hosotani, K Saito, M Matsumoto, K Yokoyama, K Miyamoto, S Takaya, S Suzuki, K Mukada, T Yano, K Ogasawara, Y Otawara, Y Kubo, H Seki, T Sugawara, K Yoshida, T Kawase, S Onozuka, T Kohno, T Izumidani, T Inoue, Y Nagamine, S Irie, K Saito, S Miyamoto, K Nozaki, N Mikuni, K Watanabe, J Koizumi, O Tone, H Tomita, I Nagata, N Kitagawa, H Nakamura, T Sasaki, T Morinaga, H Nakase, S Kawaguchi, A Fukamachi, Y Ohashi, H Yoshioka, K Iihara, S Miyamoto, K Sako, N Tokumitsu, Y Matsumoto, Y Inoue, H Sato, T Ohmoto, I Date, K Tokunaga, M Komiyama, T Yasui, S Nakajima, T Ishikawa, N Yasui, H Hadeishi, T Nishi, K Koga, S Fujioka, J Murata, N Nakayama, T Tanaka, K Shibawaki, H Karibe, T Onuma, M Kameyama, H Niizuma, H Ohyama, T Nakagawa, A Yamamura, S Fukazawa, K Shimizu, Y Okada, H Ujiie, T Higa, T Kirino, A Morita, N Saito, H Kinouchi, H Nukui, T Yagishita, K Zenke, T Hatakeyama, N Nakao, T Itakura, Y Oiwa, K Houkin, T Kuroda, Y Akiyama, K Mizoi, Y Otawara, Y Kubo, T Yoshimoto, H Karibe, T Kayama, Y Kokubo, M Matsumoto, E Watanabe, M Hashimoto, E Matsumoto, Y Yoshimoto, Y Matsumaru, K Shima, S Tsuzuki, A Yamaura, H Kobayashi, H Arai, N Ishii, T Kawase, S Onozuka, Y Katayama, A Hirayama, A Teramoto, Y Haraoka, H Nishioka, H Ujiie, T Hiki, T Abe, H Matsumoto, K Oono, T Nariai, N Saito, A Morita, Y Shiokawa, H Kurita, T Nakagomi, K Tanaka, K Fujii, A Kurata, M Yamada, I Yuzawa, M Oda, J Tominaga, H Sugano, N Kawahara, H Nanba, N Sugiyama, R Tanaka, Y Ito, H Kiuchi, T Yagishita, M Sugita, K Hongo, K Sakai, T Endo, Y Hirashima, N Kuwayama, S Yamashita, S Kida, S Miyaji, T Kojima, J Umemura, K Mase, K Cho, T Watabe, K Sano, M Hayakawa, T Iwama, Y Kaku, K Taki, F Asakura, S Kawaguchi, M Matsuda, K Oohashi, K Nozaki, S Mikuni, K Mineura, H Sasajima, R Inagaki, A Miura, T Kuroiwa, A Nishio, T Goto, T Yoshimine, Y Nakajima, K Kataoka, T Itakura, Y Oiwa, N Arita, H Hayashi, K Sato, S Matsubara, S Kawai, S Fukumoto, Y Kumon, I Date, K Tokunaga, R Ishii, N Ishii, A Tominaga, T Watanabe, T Tabuchi, H Nagai, M Suzuki, S Kato, E Urasaki, M Hashimoto, M Shigemori, Y Hirohata, T Sasaki, Miyazono, T Fukushima, K Hirakawa, Y Mineta, N Hagiwara, N Kitagawa, H Kobayashi, M Fujiki, S Nakano, H Tsuranuki, M Shinno, T Shimotsuru, N Yasui, H Hadeishi, H Seki, T Sugawara, H Ootsuki, M Ito, S Sato, N Sato, M Ishikawa, A Okumura, N Ogata, N Matsuura, N Sakai, S Nakajima, T Miyamaoto, K Iihara, M Nakatsukasa, H Kakumu, H Miyake, M Oono, Y Ueno, F Igawa, A Tanaka, K Shibawaki, Y Ozawa, K Ikeda, S Inoue, Y Akiyama, F Isaka, H Hondo, M Kouno, T Sasaki, T Morinaga, U Toyama, T Saito, I Ezuka, T Kito, J Ranto, T Kawamura, T Tanaka, H Nakayama, Y Tokuriki, K Hosoya, K Kashiwabara, Y Suzuki, K Akaji, S Takayama, H Tomita, O Tone, N Takeda, H Yamazaki, M Nakano, T Imaizumi, E Ichihashi, H Nokura, C Maruki, A Tsunoda, K Yamamoto, H Yamamoto, H Sameshima, S Iwabuchi, Y Inoue, H Sato, K Yamane, C Yamanaka, M Okazaki, A Miyaki, K Watanabe, H Koizumi, T Souma, M Takigami, Y Yamamoto, M Suga, M Miyazaki, T Tsukakoshi, M Ochiai, K Nagata, M Saito, T Shigeno, J Kumai, T Shishido, T Yoshimoto, R Suzuki, G Nagashima, T Kawaguchi, H Oda, Y Nikaido, Y Yamada, S Nakagawa, O Sato, K Kouno, H Watanabe, H Tanaka, S Wakabayashi, K Yamamura, H Kamiyama, T Nakamura, T Onuma, M Kameyama, H Kon, Y Nagamine, Y Abiko, Y Kurokawa, I Suzuki, H Miyauchi, Y Miyahara, K Hara, H Miyazaki, N Takenaka, T Imanishi, H Hisamura, K Abe, A Nakahara, S Hamazaki, S Nagata, S Fujimoto, Y Terai, H Wanibuchi, A Oikawa, H Ooishi, T Kawaguchi, T Kouno, H Matuzaki, K Sahimazaki, S Masui, S Oki, N Isobe, T Yasui, K Tsutsumi, S Kawamoto, Y Ito, H Kawai, H Fukuoka, A Yamamura, T Hirakuri, T Saito, S Irie, K Aida, T Sugimura, Y Takazato, Y Kawamo, I Kamei, T Kuwata, Y Fu, T Morisako, J Karasawa, T Inoue, A Hirayama, H Ogawa, F Ishida, H Sato, M Ito, H Nakamura, M Nakanishi, K Morikawa, K Ichihara, Y Itoh, K Morikawa, Y Kawamoto, T Handa, K Watanabe, Y Kawamoto, A Kou, M Taibou, S Kashiwabara, J Sakai, T Araya, M Takeda, K Nonaka, K Sako, N Tokumitsu, N Yamamoto, T Mizutani, M Amagasa, M Kitahara, S Ishikawa, T Hattori, T Iwai, H Yamakawa, S Mori, S Takehara, M Tomita, K Shimizu, S Suzuki, Y Komatsu, K Zenke, T Hatayama, K Onoda, S Nakajima, M Oosawa, S Suda, K Maeda, S Noguchi, S Itoh, Y Saito, T Fujii, F Marusumi, H Oki, A Kito, H Manabe, H Itoh, S Ohara, K Takenaka, T Aki, O Hirai, M Matsumoto, T Kokuuchi, H Motofuji, K Takase, K Muneta, I Takeshita, M Ohota, K Koga, H Fujioka, K Takasaki, Y Hiiragi, M Kawakami, T Fujita, H Sato, R Kimura, K Kusaka, K Kyoushima, N Tsuda, T Nakano, Y Honda, T Watanabe, K Futami, S Ootsuka, H Yasui, K Koide, Y Mitsuhashi, T Watanabe, R Nakajima, A Ono, T Shimomura, K Seki, M Domoto, H Nagaseki, O Oda, H Ogawa, M Koichi, Y Okuda, T Wada, K Umemura, K Muraishi, T Matsuda, S Tsuruoka, S Kawasaki, T Kondo, K Suma, S Kaku, T Iwamoto, T Moriyama, H Ohta, T Kawazoe, T Asano, T Tsuruno, R Miyahara, O Fukuda, M Takaba, M Ougi, H Hirose, T Kodera, H Kim, N Sato, H Fujimori, H Ueda, H Tsukamoto, H Matsumoto, I Nakahara, K Tougemoto, H Sawa, M Kurino, H Watanabe, M Hisanaga, T Koike, I Aoyama, M Kojima, Y Iwai, K Tsumura, K Yamamoto, M Ohno, T Kubota, N Shirakawa, T Tsuda, M Agawa, T Kouno, T Izumiya, S Ishihara, H Yasuda, T Tashiro, H Nakayama, A Kimura, M Souma, N Itoh, M Hokari, K Komatsu, Y Takahashi, Y Araki, H Nogura, K Tokoro, H Shimamura, T Otoh, Y Ohashi, Y Yoshioka, S Azuma, N Uchiyama, K Mukada, T Yano, T Okada, H Ohyama, H Matsuzawa, N Ando, H Yamakawa, K Horikawa, H Seto, T Matsuki, A Marushima, M Takehara, N Tsuchiya, M Ueda, H Itoho, N Kamizato, S Kim, H Okamoto, A Kondo, N Kato, A Takahashi, A Awane, K Nitta, Y Sinho, H Joshita, A Takamuro, H Tokimura, H Yamahata, T Kamiguchi, T Tokuma, H Takahashi, K Waseda, T Iwai, K Wakai, T Katsuki, H Igawa, K Okada, S Ohmori, M Ichikawa, S Ito, S Ueda, K Nishitani, K Hiramatsu, A Harada, H Miyake, M Tsuji, M Kunimoto, J Ono, S Hirai, N Hashimoto, K Yokoyama, K Miyamoto, Y Watanabe, T Oikawa, H Sato, S Takatou, I Akiyama, I Isobe, K Tsuruta, K Aoki, H Ohnishi, T Monobe, T Mori, S Gondo, R Oka, H Fujioka, I Sakaguchi

PMID: 22738097
DOI: 10.1056/NEJMoa1113260

Abstract

Background: The natural history of unruptured cerebral aneurysms has not been clearly defined.

Methods: From January 2001 through April 2004, we enrolled patients with newly identified, unruptured cerebral aneurysms in Japan. Information on the rupture of aneurysms, deaths, and the results of periodic follow-up examinations were recorded. We included 5720 patients 20 years of age or older (mean age, 62.5 years; 68% women) who had saccular aneurysms that were 3 mm or more in the largest dimension and who initially presented with no more than a slight disability.

Results: Of the 6697 aneurysms studied, 91% were discovered incidentally. Most aneurysms were in the middle cerebral arteries (36%) and the internal carotid arteries (34%). The mean (±SD) size of the aneurysms was 5.7±3.6 mm. During a follow-up period that included 11,660 aneurysm-years, ruptures were documented in 111 patients, with an annual rate of rupture of 0.95% (95% confidence interval [CI], 0.79 to 1.15). The risk of rupture increased with increasing size of the aneurysm. With aneurysms that were 3 to 4 mm in size as the reference, the hazard ratios for size categories were as follows: 5 to 6 mm, 1.13 (95% CI, 0.58 to 2.22); 7 to 9 mm, 3.35 (95% CI, 1.87 to 6.00); 10 to 24 mm, 9.09 (95% CI, 5.25 to 15.74); and 25 mm or larger, 76.26 (95% CI, 32.76 to 177.54). As compared with aneurysms in the middle cerebral arteries, those in the posterior and anterior communicating arteries were more likely to rupture (hazard ratio, 1.90 [95% CI, 1.12 to 3.21] and 2.02 [95% CI, 1.13 to 3.58], respectively). Aneurysms with a daughter sac (an irregular protrusion of the wall of the aneurysm) were also more likely to rupture (hazard ratio, 1.63; 95% CI, 1.08 to 2.48).

Conclusions: This study showed that the natural course of unruptured cerebral aneurysms varies according to the size, location, and shape of the aneurysm. (Funded by the Ministry of Health, Labor, and Welfare in Japan and others; UCAS Japan UMIN-CTR number, C000000418.).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aneurysm, Ruptured*
Carotid Artery, Internal / pathology
Cerebral Arteries / pathology*
Disease Progression
Female
Humans
Intracranial Aneurysm* / pathology
Male
Middle Aged
Middle Cerebral Artery / pathology
Observation
Proportional Hazards Models
Prospective Studies
Risk Factors
Rupture, Spontaneous
Sex Factors