Smoking and aneurysm rupture risk factor

Smoking and aneurysm rupture risk factor

Tobacco smoking is one of the most important risk factors for the formation of intracranial aneurysms and for aneurysmal subarachnoid hemorrhage1) 2) 3).


A dose-response relationship has been noted between intensity and duration of smoking consumption and increased risk of intracranial aneurysm rupture. As smoking is modifiable, this finding is important to managing patients with IAs to quit or reduce smoking prior to life-threatening subarachnoid hemorrhage 4).


Current cigarette smoking, smoking intensity, and smoking duration are significantly associated with ruptured IAs at presentation. However, the significantly increased risk persists after smoking cessation, and smoking cessation does not confer a reduced risk of aneurysmal subarachnoid hemorrhage beyond that of reducing the cumulative dose 5)


Data suggest that smoking, independent of hypertension, plays a critical role in aneurysm development, especially in younger patients, but that physiological mechanism exists for the repair of the damage induced by this toxic insult if cessation is possible 6)


Results suggest that high cotinine levels in smokers with brain aneurysms are significantly associated with high rupture risk, independently of smoker status, age, and sex 7)


The prevalence of smoking in patients who have suffered from SAH is higher than that in general adult population 8) 9).

Smoking has also been suggested to contribute to the recurrence of aneurysms after endovascular coiling.

To improve the understanding of the impact of smoking on long-term outcomes after coil embolization of intracranial aneurysms, Brinjikji et al. studied a consecutive contemporary series of patients treated at their institution. The aims of this study were to determine whether smoking is an independent risk factor for aneurysm recurrence and retreatment after endovascular coiling.

All patients who had received an intrasaccular coil embolization of an intracranial aneurysm, who had undergone a follow-up imaging exam at least 6 months later, and whose smoking history had been recorded from January 2005 through December 2012 were included in this study. Patients were stratified according to smoking status into 3 groups: 1) never a smoker, 2) current smoker (smoked at the time of treatment), and 3) former smoker (quit smoking before treatment). The 2 primary outcomes studied were aneurysm recurrence and aneurysm retreatment after treatment for endovascular aneurysms. Kruskal-Wallis and chi-square tests were used to test statistical significance of differences in the rates of aneurysm recurrence, retreatment, or of both among the 3 groups. A multivariate logistic regression analysis controlling for smoking status and for several characteristics of the aneurysm was also performed.

In total, 384 patients with a combined total of 411 aneurysms were included in this study. The aneurysm recurrence rate was not significantly associated with smoking: both former smokers (OR 1.00, 95% CI 0.61-1.65; p = 0.99) and current smokers (OR 0.58, 95% CI 0.31-1.09; p = 0.09) had odds of recurrence that were similar to those who were never smokers. Former smokers (OR 0.78, 95% CI 0.46-1.35; p = 0.38) had odds of retreatment similar to those of never smokers, and current smokers had a lower odds of undergoing retreatment (OR 0.44, 95% CI 0.21-0.91; p = 0.03) than never smokers. Moreover, an analysis adjusting for aneurysm rupture, diameter, and initial occlusion showed that former smokers (OR 0.65, 95% CI 0.33-1.28; p = 0.21) and current smokers (OR 1.04, 95% CI 0.60-1.81; p = 0.88) had odds of aneurysm recurrence similar to those who were never smokers. Adjusting the analysis for aneurysm rupture, diameter, and occlusion showed that both former smokers (OR 0.49, 95% CI 0.23-1.05; p = 0.07) and current smokers (OR 0.82, 95% CI 0.46-1.46; p = 0.50) had odds of retreatment similar to those of patients who were never smokers.

The results show that smoking was not an independent risk factor for aneurysm recurrence and aneurysm retreatment among patients receiving endovascular treatment for intracranial aneurysms at the authors’ institution. Nonetheless, patients with intracranial aneurysms should continue to be counseled about the risks of tobacco smoking 10).

Tobacco use were not significantly associated with poor outcome after aneurysmal subarachnoid hemorrhage 11).

Previously established risk factors such as hypertension and smoking were identified as the most prevalent comorbidities, with disparity between subgroups, particularly women and African Americans 12).

The duration and timing of tobacco use, rather than the dose of tobacco per se, seem to be risk factors for delayed neurological deterioration after aneurysmal subarachnoid hemorrhage (aSAH). Although Krishnamurthy et al. did not find an association between tobacco use and overall clinical outcome after aneurysmal SAH, these results suggest that the distribution of various patterns of tobacco use within a given data set may influence the overall result 13).

Only 8 studies have investigated the incidence and epidemiology of aneurysmal subarachnoid hemorrhage (aSAH) in the United States. This is the first investigation in Indiana, which has some of the highest rates of tobacco smoking and obesity in the nation. The authors prospectively identified 441 consecutive patients with aSAH from 2005 to 2010 at 2 hospitals where the majority of cases are treated. Incidence calculations were based on US Census populations. Epidemiologic variables included demography; risk factors; Hunt and Hess scale; Fisher grade; number, location, and size of aneurysms; treatment type; and complications. Overall incidence was 21.8 per 100,000 population. Incidence was higher in women, increased with age, and did not vary by race. One third to half of patients were hypertensive and/or smoked cigarettes at the time of ictus. Variations by count were partially explained by Health Factor and Morbidity Rankings. Complications varied by treatment. These findings deviate from estimates that 6-16 per 100,000 people in the United States will develop aSAH and are double the incidence in a Minnesota population between 1945 and 1974. The results also deviate from the worldwide estimate of 9.0 aSAHs per 100,000 person-years. The predictive value of variations in Health Factor and Morbidity Rankings implicates the importance of future research on multivariate biopsychosocial causation of aSAH 14).


1) , 8)

Juvela S, Porras M, Poussa K: Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture. J Neurosurg 93:379-387,2000
2)

Juvela S, Poussa K ,Porras M: Factors affecting formation and growth of intracranial aneurysms: A long term follow-up study. Stroke 32:485-491,2001
3) , 9)

Ruigrok YM, Buskens E, Rinkel GJE: Attributable risk of common and rare determinants of subarachnoid hemorrhage. Stroke 32: 1173-1175,2001
4)

Feng X, Qian Z, Zhang B, Guo E, Wang L, Liu P, Wen X, Xu W, Jiang C, Li Y, Wu Z, Liu A. Number of Cigarettes Smoked Per Day, Smoking Index, and Intracranial Aneurysm Rupture: A Case-Control Study. Front Neurol. 2018 May 31;9:380. doi: 10.3389/fneur.2018.00380. PMID: 29904368; PMCID: PMC5990590.
5)

Can A, Castro VM, Ozdemir YH, Dagen S, Yu S, Dligach D, Finan S, Gainer V, Shadick NA, Murphy S, Cai T, Savova G, Dammers R, Weiss ST, Du R. Association of intracranial aneurysm rupture with smoking duration, intensity, and cessation. Neurology. 2017 Sep 26;89(13):1408-1415. doi: 10.1212/WNL.0000000000004419. Epub 2017 Aug 30. PMID: 28855408; PMCID: PMC5649762.
6)

Connolly ES Jr, Poisik A, Winfree CJ, Kim LJ, Huang J, McMahon DJ, Solomon RA. Cigarette smoking and the development and rupture of cerebral aneurysms in a mixed race population: implications for population screening and smoking cessation. J Stroke Cerebrovasc Dis. 1999 Jul-Aug;8(4):248-53. doi: 10.1016/s1052-3057(99)80074-3. PMID: 17895172.
7)

Missori P, de Sousa DA, Ambrosone A, Currà A, Paolini S, Incarbone G, Amabile E, Biraschi F, Diana F, Peschillo S. Cotinine levels influence the risk of rupture of brain aneurysms. Acta Neurol Scand. 2022 Aug 3. doi: 10.1111/ane.13679. Epub ahead of print. PMID: 35920037.
10)

Brinjikji W, Lingineni RK, Gu CN, Lanzino G, Cloft HJ, Ulsh L, Koeller K, Kallmes DF. Smoking is not associated with recurrence and retreatment of intracranial aneurysms after endovascular coiling. J Neurosurg. 2015 Jan;122(1):95-100. doi: 10.3171/2014.10.JNS141035. PubMed PMID: 25380112.
11)

Moon K, Albuquerque FC, Mitkov M, Ducruet AF, Wilson DA, Crowley RW, Nakaji P, McDougall CG. Methamphetamine use is an independent predictor of poor outcome after aneurysmal subarachnoid hemorrhage. J Neurointerv Surg. 2014 Apr 29. doi: 10.1136/neurintsurg-2014-011161. [Epub ahead of print] PubMed PMID: 24780822.
12)

Larrew T, Pryor W 3rd, Weinberg J, Webb S, Battenhouse H, Turk AS, Chaudry I, Spiotta A, Turner R. Aneurysmal subarachnoid hemorrhage: a statewide assessment of outcome based on risk factors, aneurysm characteristics, and geo-demography. J Neurointerv Surg. 2014 Sep 8. pii: neurintsurg-2014-011359. doi: 10.1136/neurintsurg-2014-011359. [Epub ahead of print] PubMed PMID: 25200246.
13)

Krishnamurthy S, Kelleher JP, Lehman EB, Cockroft KM. Effects of tobacco dose and length of exposure on delayed neurological deterioration and overall clinical outcome after aneurysmal subarachnoid hemorrhage. Neurosurgery. 2007 Sep;61(3):475-80; discussion 480-1. PubMed PMID: 17881958.
14)

Ziemba-Davis M, Bohnstedt BN, Payner TD, Leipzig TJ, Palmer E, Cohen-Gadol AA. Incidence, epidemiology, and treatment of aneurysmal subarachnoid hemorrhage in 12 midwest communities. J Stroke Cerebrovasc Dis. 2014 May-Jun;23(5):1073-82. doi: 10.1016/j.jstrokecerebrovasdis.2013.09.010. Epub 2013 Oct 19. PubMed PMID: 24144595.

Unruptured anterior communicating artery aneurysm rupture risk

Unruptured anterior communicating artery aneurysm rupture risk

Although the research on the risk factors of anterior communicating artery aneurysm has made great progress, the independent effect of each risk factor on the rupture of AComA aneurysm is controversial among different studies. For this answer Xie et al. will present the results employing the random effects model. Quality assessment of the included studies will be evaluated using the Newcastle–Ottawa Scale. Statistical analyses will be performed using Stata16 (Stata Corporation, College Station, TX, USA) software.The findings of this study will be submitted to peer-reviewed journals for publication. This systematic review will provide evidence to determine the risk factors that affect the rupture of the AComA aneurysm and quantify their independent effects 1).


Ma et al. found that larger size, greater size ratio, larger flow angle, irregular shape, and smoking of the patient were associated with the rupture of ACoA aneurysms based on univariate analysis. Size ratio (OR = 3.890, P = 0.003), irregular shape (OR = 1.068, P = 0.001), flow angle (OR = 1.054, P = 0.001), and current smoking (OR = 4.435, P = 0.009) were the strongest factors related to ruptured ACoA aneurysms based on multivariate logistic regression analysis. The areas under the curves for the flow angle and size ratio were 0.742 (95% CI 0.646-0.838; P = 0.001) and 0.736 (95% CI 0.621-0.796; P = 0.001), respectively. The strongest risk factors for rupture include size ratio, irregular shape, flow angle, and current smoking. These features should be taken into consideration to aid in the prediction of the rupture risk of ACoA aneurysms 2).


Multiple logistic regression model revealed that A1 dominance [odds ratio (OR) 3.034], an irregular shape (OR 3.358), and an aspect ratio ≥1.19 (AR; OR 3.163) increased the risk of rupture, while cerebral atherosclerosis (OR 0.080), and mean diameters ≥2.48 mm (OR 0.474) were negatively correlated with ACoAA rupture. Incorporating these five factors, the ROC analysis revealed that the threshold value of the multifactors was one, the sensitivity was 88.3%, and the specificity was 66.0%. The scoring model is a simple method that is based on A1 dominance, irregular shape, aspect ratio, cerebral atherosclerosis, and mean diameters from CTA and is of great value in the prediction of the rupture risk of ACoAAs 3).


According to the International Study of Unruptured Intracranial Aneurysms (ISUIA), anterior circulation (AC) aneurysms of <7 mm in diameter have a minimal risk of rupture. It is general experience, however, that anterior communicating artery (AcoA) aneurysms are frequent and mostly rupture at <7 mm. Bijlenga et al. found that AC aneurysms are not a homogenous group. Aneurysms between 4 and 7 mm located in AcoA or distal anterior cerebral artery present similar rupture odds to posterior circulation aneurysms. Intervention should be recommended for this high-risk lesion group 4).


For Matsukawa et al. the anterior projection of an ACoA aneurysm may be related to rupturing. The authors would perhaps recommend treatment to patients with unruptured ACoA aneurysms that have an anterior dome projection, a bleb(s), and a size ≥ 5 mm 5).


Aneurysms found unruptured in the ACoA show a risk of rupture twice as high as that of other intracranial aneurysms (95% confidence interval, 1.29-3.12). It is the first time this fact has been demonstrated based on the follow-up of unruptured aneurysms.

When deciding whether to operate on UIAs located in the ACoA, surgeons should consider their higher risk of rupture 6).


1)

Xie Y, Tian H, Xiang B, Li D, Liu YZ, Xiang H. Risk factors for anterior communicating artery aneurysm rupture: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2021 Dec 3;100(48):e28088. doi: 10.1097/MD.0000000000028088. PMID: 35049234.
2)

Ma X, Yang Y, Liu D, Zhou Y, Jia W. Demographic and morphological characteristics associated with rupture status of anterior communicating artery aneurysms. Neurosurg Rev. 2020 Apr;43(2):589-595. doi: 10.1007/s10143-019-01080-w. Epub 2019 Jan 31. PMID: 30706157.
3)

Wang GX, Wang S, Liu LL, Gong MF, Zhang D, Yang CY, Wen L. A Simple Scoring Model for Prediction of Rupture Risk of Anterior Communicating Artery Aneurysms. Front Neurol. 2019 May 31;10:520. doi: 10.3389/fneur.2019.00520. PMID: 31214103; PMCID: PMC6554323.
4)

Bijlenga P, Ebeling C, Jaegersberg M, Summers P, Rogers A, Waterworth A, Iavindrasana J, Macho J, Pereira VM, Bukovics P, Vivas E, Sturkenboom MC, Wright J, Friedrich CM, Frangi A, Byrne J, Schaller K, Rufenacht D; @neurIST Investigators. Risk of rupture of small anterior communicating artery aneurysms is similar to posterior circulation aneurysms. Stroke. 2013 Nov;44(11):3018-26. doi: 10.1161/STROKEAHA.113.001667. Epub 2013 Jul 30. PMID: 23899912.
5)

Matsukawa H, Uemura A, Fujii M, Kamo M, Takahashi O, Sumiyoshi S. Morphological and clinical risk factors for the rupture of anterior communicating artery aneurysms. J Neurosurg. 2013 May;118(5):978-83. doi: 10.3171/2012.11.JNS121210. Epub 2012 Dec 14. PMID: 23240701.
6)

Mira JM, Costa FA, Horta BL, Fabião OM. Risk of rupture in unruptured anterior communicating artery aneurysms: meta-analysis of natural history studies. Surg Neurol. 2006;66 Suppl 3:S12-9; discussion S19. doi: 10.1016/j.surneu.2006.06.025. PMID: 17081844.

Book: Brain Aneurysms: Rupture and Unruptured 59 Years' Personal Experience Unexpected Major New Evidence

Brain Aneurysms: Rupture and Unruptured 59 Years’ Personal Experience Unexpected Major New Evidence
By Paul S Slosberg MD

Brain Aneurysms: Rupture and Unruptured 59 Years' Personal Experience Unexpected Major New Evidence

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Medical Hypotensive Therapy (MHT) is a proven effective treatment for brain aneurysms. The evidence of success documented here is over the long term – this essential for any treatment. The focus is on blood pressure control and management. There is no need for expensive surgery, equipment, or hospital stays, and their associated risks. In short, MHT yields better results, with fewer risks, and lower cost.


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  • Published on: 2015-10-02
  • Original language: English
  • Dimensions: 9.00″ h x .45″ w x 6.00″ l,
  • Binding: Paperback
  • 190 pages

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About the Author
Dr. Slosberg practiced clinical neurology for 59 years until his retirement in December 2013. He is an Associate Clinical Professor of Neurology at the Icahn School of Medicine at Mount Sinai; Associate Attending Neurologist at the Mount Sinai Medical Center and Chief of the Brain Aneurysm Clinic at Mount Sinai. He continues his research and writings to this day.
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