Female sex as a risk factor for the growth of asymptomatic unruptured cerebral saccular aneurysms in elderly patients

Clinical article

Restricted access

Object

The prevalence of patients with asymptomatic unruptured intracranial aneurysms (UIAs) increases with the advancing age of the general population. The goal of the present study was to identify risk factors for the growth of UIAs detected with serial MR angiography (MRA) in patients 70 years of age or older.

Methods

This prospective study enrolled 79 patients (age range 70–84 years) with 98 UIAs. Patients were followed up every 4 months, including an assessment of the aneurysm diameter and morphological changes on MRA, neurological status, and other medical conditions. Aneurysm growth was categorized into two different patterns on the basis of the MRA findings: 1) maximum increase in aneurysm diameter of 2 mm or more; and 2) obvious morphological change, such as the appearance of a bleb.

Results

The mean duration of follow-up was 38.5 months (250.2 patient-years). Aneurysm rupture did not occur, but aneurysm growth was observed in 8 aneurysms (8 patients) during the study period. Univariate analysis showed that female sex, patient age ≥ 75 years, and an aneurysm location in the internal carotid artery (ICA) or middle cerebral artery (MCA) were associated with aneurysm growth (p = 0.04, p = 0.04, and p < 0.001, respectively). Multivariate analysis demonstrated that female sex was the only independent predictor of aneurysm growth (p = 0.0313, OR 2.3, 95% CI 1.3–30.2).

Conclusions

Female sex is an independent risk factor for the growth of UIAs in elderly patients. In addition, an age ≥ 75 years and aneurysm location in the ICA or MCA are characteristics that may warrant additional attention during follow-up imaging.

Abbreviations used in this paper:ACA = anterior cerebral artery; ACoA = anterior communicating artery; CTA = CT angiography; HICH = hypertensive intracerebral hemorrhage; ICA = internal carotid artery; MCA = middle cerebral artery; MRA = MR angiography; PCoA = posterior communicating artery; SAH = subarachnoid hemorrhage; UIA = unruptured intracranial saccular aneurysm.
Article Information

Contributor Notes

Address correspondence to: Yoshitaka Kubo, M.D., Ph.D., Department of Neurosurgery, Iwate Medical University, 19-1 Uchimaru, Morioka 020-8505, Japan. email: yokubo@iwate-med.ac.jp.Please include this information when citing this paper: published online June 27, 2014; DOI: 10.3171/2014.5.JNS132048.

© AANS, except where prohibited by US copyright law.

Headings
References
  • 1

    Aoki TKataoka HIshibashi RNakagami HNozaki KMorishita R: Pitavastatin suppresses formation and progression of cerebral aneurysms through inhibition of the nuclear factor ϰB pathway. Neurosurgery 64:3573662009

    • Search Google Scholar
    • Export Citation
  • 2

    Burns JDHuston J IIILayton KFPiepgras DGBrown RD Jr: Intracranial aneurysm enlargement on serial magnetic resonance angiography: frequency and risk factors. Stroke 40:4064112009

    • Search Google Scholar
    • Export Citation
  • 3

    Chien ALiang FSayre JSalamon NVillablanca PViñuela F: Enlargement of small, asymptomatic, unruptured intracranial aneurysms in patients with no history of subarachnoid hemorrhage: the different factors related to the growth of single and multiple aneurysms. Clinical article. J Neurosurg 119:1901972013

    • Search Google Scholar
    • Export Citation
  • 4

    Chmayssani MRebeiz JGRebeiz TJBatjer HHBendok BR: Relationship of growth to aneurysm rupture in asymptomatic aneurysms ≤ 7 mm: a systematic analysis of the literature. Neurosurgery 68:116411712011

    • Search Google Scholar
    • Export Citation
  • 5

    Chung RYCarter BSNorbash ABudzik RPutnam COgilvy CS: Management outcomes for ruptured and unruptured aneurysms in the elderly. Neurosurgery 47:8278332000

    • Search Google Scholar
    • Export Citation
  • 6

    Ferns SPSprengers MEvan Rooij WJvan den Berg RVelthuis BKde Kort GA: De novo aneurysm formation and growth of untreated aneurysms: a 5-year MRA follow-up in a large cohort of patients with coiled aneurysms and review of the literature. Stroke 42:3133182011

    • Search Google Scholar
    • Export Citation
  • 7

    Ferreri NR: Estrogen-TNF interactions and vascular inflammation. Am J Physiol Heart Circ Physiol 292:H2566H25692007

  • 8

    Hasan DMMahaney KBBrown RD JrMeissner IPiepgras DGHuston J: Aspirin as a promising agent for decreasing incidence of cerebral aneurysm rupture. Stroke 42:315631622011

    • Search Google Scholar
    • Export Citation
  • 9

    Inoue TShimizu HFujimura MSaito ATominaga T: Annual rupture risk of growing unruptured cerebral aneurysms detected by magnetic resonance angiography. Clinical article. J Neurosurg 117:20252012

    • Search Google Scholar
    • Export Citation
  • 10

    Ishibashi TMurayama YUrashima MSaguchi TEbara MArakawa H: Unruptured intracranial aneurysms: incidence of rupture and risk factors. Stroke 40:3133162009

    • Search Google Scholar
    • Export Citation
  • 11

    Iwamoto HKiyohara YFujishima MKato INakayama KSueishi K: Prevalence of intracranial saccular aneurysms in a Japanese community based on a consecutive autopsy series during a 30-year observation period. The Hisayama study. Stroke 30:139013951999

    • Search Google Scholar
    • Export Citation
  • 12

    Jamous MANagahiro SKitazato KTTamura TKuwayama KSatoh K: Role of estrogen deficiency in the formation and progression of cerebral aneurysms. Part II: experimental study of the effects of hormone replacement therapy in rats. J Neurosurg 103:105210572005

    • Search Google Scholar
    • Export Citation
  • 13

    Juvela SPoussa KPorras M: Factors affecting formation and growth of intracranial aneurysms: a long-term follow-up study. Stroke 32:4854912001

    • Search Google Scholar
    • Export Citation
  • 14

    Kongable GLLanzino GGermanson TPTruskowski LLAlves WMTorner JC: Gender-related differences in aneurysmal subarachnoid hemorrhage. J Neurosurg 84:43481996

    • Search Google Scholar
    • Export Citation
  • 15

    Kubo YOgasawara KKashimura HOtawara YKakino SSugawara A: Cognitive function and anxiety before and after surgery for asymptomatic unruptured intracranial aneurysms in elderly patients. World Neurosurg 73:3503532010

    • Search Google Scholar
    • Export Citation
  • 16

    Matsubara SHadeishi HSuzuki AYasui NNishimura H: Incidence and risk factors for the growth of unruptured cerebral aneurysms: observation using serial computerized tomography angiography. J Neurosurg 101:9089142004

    • Search Google Scholar
    • Export Citation
  • 17

    Matsumoto EMasuzawa TNakamura Y: Long-term outcome of unruptured cerebral aneurysms. J Epidemiol 13:2892952003

  • 18

    Miyazawa NAkiyama IYamagata Z: Risk factors for growth of unruptured intracranial aneurysms: follow-up study by serial 0.5-T magnetic resonance angiography. Neurosurgery 58:104710532006

    • Search Google Scholar
    • Export Citation
  • 19

    Morita AFujiwara SHashi KOhtsu HKirino T: Risk of rupture associated with intact cerebral aneurysms in the Japanese population: a systematic review of the literature from Japan. J Neurosurg 102:6016062005

    • Search Google Scholar
    • Export Citation
  • 20

    Morita AKirino THashi KAoki NFukuhara SHashimoto N: The natural course of unruptured cerebral aneurysms in a Japanese cohort. N Engl J Med 366:247424822012

    • Search Google Scholar
    • Export Citation
  • 21

    Otawara YOgasawara KKubo YTomitsuka NWatanabe MOgawa A: Anxiety before and after surgical repair in patients with asymptomatic unruptured intracranial aneurysm. Surg Neurol 62:28312004

    • Search Google Scholar
    • Export Citation
  • 22

    Otawara YOgasawara KOgawa AYamadate K: Cognitive function before and after surgery in patients with unruptured intracranial aneurysm. Stroke 36:1421432005

    • Search Google Scholar
    • Export Citation
  • 23

    Sacco RLWolf PABharucha NEMeeks SLKannel WBCharette LJ: Subarachnoid and intracerebral hemorrhage: natural history, prognosis, and precursive factors in the Framingham Study. Neurology 34:8478541984

    • Search Google Scholar
    • Export Citation
  • 24

    Shinohara YNagayama MOrigasa H: Postpublication external review of the Japanese Guidelines for the Management of Stroke 2004. Stroke 40:143914432009

    • Search Google Scholar
    • Export Citation
  • 25

    Sonobe MYamazaki TYonekura MKikuchi H: Small unruptured intracranial aneurysm verification study: SUAVe study, Japan. Stroke 41:196919772010

    • Search Google Scholar
    • Export Citation
  • 26

    Srivastava SWeitzmann MNCenci SRoss FPAdler SPacifici R: Estrogen decreases TNF gene expression by blocking JNK activity and the resulting production of c-Jun and JunD. J Clin Invest 104:5035131999

    • Search Google Scholar
    • Export Citation
  • 27

    Tamura TJamous MAKitazato KTYagi KTada YUno M: Endothelial damage due to impaired nitric oxide bioavailability triggers cerebral aneurysm formation in female rats. J Hypertens 27:128412922009

    • Search Google Scholar
    • Export Citation
  • 28

    Tsutsumi KUeki KMorita AKirino T: Risk of rupture from incidental cerebral aneurysms. J Neurosurg 93:5505532000

  • 29

    Tulamo RFrösen JPaetau ASeitsonen SHernesniemi JNiemelä M: Lack of complement inhibitors in the outer intracranial artery aneurysm wall associates with complement terminal pathway activation. Am J Pathol 177:322432322010

    • Search Google Scholar
    • Export Citation
  • 30

    Vlak MHRinkel GJGreebe PAlgra A: Risk of rupture of an intracranial aneurysm based on patient characteristics: a case-control study. Stroke 44:125612592013

    • Search Google Scholar
    • Export Citation
  • 31

    Wermer MJvan der Schaaf ICAlgra ARinkel GJ: Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. Stroke 38:140414102007

    • Search Google Scholar
    • Export Citation
  • 32

    Yamashita KKashiwagi SKato STakasago TIto H: Cerebral aneurysms in the elderly in Yamaguchi, Japan. Analysis of the Yamaguchi Data Bank of Cerebral Aneurysm from 1985 to 1995. Stroke 28:192619311997

    • Search Google Scholar
    • Export Citation
TrendMD
Cited By
Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 298 237 11
PDF Downloads 183 135 5
EPUB Downloads 0 0 0
PubMed
Google Scholar