Influence of smoking on aneurysm recurrence after endovascular treatment of cerebrovascular aneurysms

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OBJECTIVE

Smoking is a known risk factor for aneurysm development and aneurysmal subarachnoid hemorrhage, as well as subsequent vasospasm in both untreated individuals and patients who have undergone surgical clipping of cerebrovascular aneurysms. However, there is a lack of data in the current scientific literature about the long-term effects that smoking has on the integrity of endovascular repairs of cerebral aneurysms. This study was designed to determine if any smoking history increased the risk of poorer outcomes and/or aneurysm recurrence in patients who have had endovascular repair of cerebral aneurysms.

METHODS

The authors retrospectively analyzed the medical records of patients admitted to the University of Michigan Health System from January 1999 to December 2011 with coiled aneurysms and angiography, CT angiography, or MR angiography follow-up. Patients were identified and organized based on many criteria including age, sex, smoking history, aneurysm recurrence, aneurysm location, and Hunt and Hess grade. Analysis was targeted to the patient population with a history of smoking. Bivariate chi-square tests were used to analyze the association between a positive smoking history and documented aneurysm recurrence and were adjusted for potential confounders by fitting multivariate logistic regression models of recurrence.

RESULTS

A total of 247 patients who had undergone endovascular treatment of 296 documented cerebral aneurysms were included in this study. The recurrence rate among all patients treated with endovascular repair was 24.3%, and the average time to the most recent follow-up imaging studies was 1.62 years. Smokers accounted for 232 aneurysms and were followed up for an average of 1.57 years, with a recurrence rate of 26.3%. Never smokers accounted for the remaining 64 aneurysms and were followed up for an average of 1.82 years, with a recurrence rate of 17.2%. Multivariate analysis revealed that, after controlling for potential confounders, a history of smoking—whether current or former—was associated with a significantly increased risk of aneurysm recurrence. The odds ratios for aneurysm recurrence for current and former smokers were 2.739 (95% CI 1.127–7.095, p = 0.0308) and 2.698 (95% CI 1.078–7.212, p = 0.0395), respectively, compared with never smokers.

CONCLUSIONS

A positive smoking history is associated with a significantly increased risk of aneurysm recurrence in patients who have undergone endovascular repair of a cerebral aneurysm, compared with the risk in patients who have never smoked.

ABBREVIATIONS A1AT = alpha 1–antitrypsin; CTA = CT angiography; HH = Hunt and Hess; MRA = MR angiography; OR = odds ratio; SAH = subarachnoid hemorrhage.

OBJECTIVE

Smoking is a known risk factor for aneurysm development and aneurysmal subarachnoid hemorrhage, as well as subsequent vasospasm in both untreated individuals and patients who have undergone surgical clipping of cerebrovascular aneurysms. However, there is a lack of data in the current scientific literature about the long-term effects that smoking has on the integrity of endovascular repairs of cerebral aneurysms. This study was designed to determine if any smoking history increased the risk of poorer outcomes and/or aneurysm recurrence in patients who have had endovascular repair of cerebral aneurysms.

METHODS

The authors retrospectively analyzed the medical records of patients admitted to the University of Michigan Health System from January 1999 to December 2011 with coiled aneurysms and angiography, CT angiography, or MR angiography follow-up. Patients were identified and organized based on many criteria including age, sex, smoking history, aneurysm recurrence, aneurysm location, and Hunt and Hess grade. Analysis was targeted to the patient population with a history of smoking. Bivariate chi-square tests were used to analyze the association between a positive smoking history and documented aneurysm recurrence and were adjusted for potential confounders by fitting multivariate logistic regression models of recurrence.

RESULTS

A total of 247 patients who had undergone endovascular treatment of 296 documented cerebral aneurysms were included in this study. The recurrence rate among all patients treated with endovascular repair was 24.3%, and the average time to the most recent follow-up imaging studies was 1.62 years. Smokers accounted for 232 aneurysms and were followed up for an average of 1.57 years, with a recurrence rate of 26.3%. Never smokers accounted for the remaining 64 aneurysms and were followed up for an average of 1.82 years, with a recurrence rate of 17.2%. Multivariate analysis revealed that, after controlling for potential confounders, a history of smoking—whether current or former—was associated with a significantly increased risk of aneurysm recurrence. The odds ratios for aneurysm recurrence for current and former smokers were 2.739 (95% CI 1.127–7.095, p = 0.0308) and 2.698 (95% CI 1.078–7.212, p = 0.0395), respectively, compared with never smokers.

CONCLUSIONS

A positive smoking history is associated with a significantly increased risk of aneurysm recurrence in patients who have undergone endovascular repair of a cerebral aneurysm, compared with the risk in patients who have never smoked.

ABBREVIATIONS A1AT = alpha 1–antitrypsin; CTA = CT angiography; HH = Hunt and Hess; MRA = MR angiography; OR = odds ratio; SAH = subarachnoid hemorrhage.

Cerebral arterial aneurysms are relatively common, with a prevalence of 0.4%–6%, and have the potential to cause sudden neurological disability secondary to rupture.7,9,36,39,43 Intracranial aneurysms are the most common nontraumatic etiology of subarachnoid hemorrhage (SAH), accounting for about 85% of spontaneous SAH cases with an estimated incidence of 1 case in 10,000 persons in the United States.8,38,43 After SAH, approximately 10% of patients die before reaching the hospital. Of those who do receive treatment, about 45% will die within 1 month, while another third are left with moderate to severe neurological and cognitive disability.18,21,27

Given this high rate of morbidity and mortality, effective diagnosis and treatment are crucial. Endovascular coiling has become an increasingly popular therapeutic modality for intracranial aneurysms, with lower rates of poor neurological outcomes, morbidity, and mortality compared with those rates following traditional microsurgical reconstruction.1,6,10,42 However, the rate of rebleeding and recurrence of aneurysms following endovascular treatment is approximately 15%–20% higher.11,13,20,28 Risk factors contributing to this high recurrence rate post–coil embolization include larger lumen and aneurysm size, aneurysm location, and incomplete occlusion.15,17,31

Recently, smoking has been implicated as a risk factor for aneurysm recurrence following endovascular coiling. Smoking is already a known risk factor for aneurysm development, SAH, as well as subsequent vasospasm.23,26,40,41 Studies have shown that smoking is associated with a 3- to 6-fold increased risk of SAH compared with the risk in nonsmoking populations and that the quantity of cigarettes smoked also has a positive correlation with the risk of SAH.5

Current literature remains divided on the subject of the effects of smoking on cerebral aneurysm recurrence in patients treated endovascularly. While several studies have suggested that patients with a known smoking history have a higher risk for poor postoperative outcomes and recurrence,14,19,29 a 2015 study by Brinjikji et al. found that tobacco smoking was not significantly associated with aneurysm recurrence or retreatment among patients who had undergone coiling.7 Given this lack of consensus, it was our hope when initially designing this single-institution retrospective study to help elucidate the effects, if any, of smoking on outcomes related to the coiling of cerebrovascular aneurysms.

Methods

This study was reviewed and approved by the Medical Sciences Institutional Review Board of the University of Michigan.

Patient Population

We conducted a retrospective chart review of the electronic medical records of adults admitted to the University of Michigan Health System from January 1, 1999, to December 31, 2011, who had undergone treatment for an intracranial aneurysm. Patients were further identified and grouped based on specific endovascular occlusion modality including endovascular coiling, stent-assisted coiling, or balloon-assisted coiling. Only patients with documented follow-up and imaging examinations including angiography, CT angiography (CTA), or MR angiography (MRA) more than 3 months postcoiling were included in our analysis. Patients whose charts did not include information about smoking history, Hunt and Hess (HH) grade, or aneurysm size and shape were not included in the study. If a patient had more than 1 aneurysm coiled, the history of each aneurysm was followed separately.

Data Collection

Our outcome of interest was aneurysm recurrence following treatment with endovascular coiling. Aneurysm recurrence was defined as inflow into a previously completely occluded aneurysm or growth of an incompletely occluded aneurysm (aneurysm recanalization). Patient charts were reviewed, and common covariates were recognized and analyzed for any possible correlation. Our covariate set for this study included the following categorical variables: age (< 45, 45 to < 65, ≥ 65 years), sex, tobacco use (never smoker, former smoker, current smoker), SAH, HH grade, aneurysm location risk (high-risk locations included anterior communicating, A2/pericallosal, posterior communicating, and basilar arteries),4 aneurysm size (< 7 or ≥ 7 mm),24,25 endovascular technique (coiling, stent coiling, balloon coiling), epilepsy or seizures, diabetes mellitus, coronary artery disease, hypertension, Raymond-Roy occlusion classification (complete obliteration, residual neck, and residual aneurysm),33 follow-up time (0.25–0.75, 0.76–1.25, 1.26–1.75, 1.76–2.25, and > 2.25 years), aspirin use, and statin use. All medication usage was recorded in a binary manner based on whether the medication was prescribed prior to the operation. Follow-up time was determined from the operation date to the most recent angiography, CTA, or MRA. The incidence of aneurysm recurrence in patients with a known history of cigarette smoking was compared with a corresponding control group of patients without any history of smoking.

Statistical Analysis

Univariate statistics were first used to describe our sample. We then employed bivariate chi-square tests to identify significant associations between our selected covariates (as noted above) and recurrence. Any covariates found to be significantly associated with recurrence in the bivariate chi-square tests, aside from those previously recognized as risk factors for aneurysm formation, were adjusted for use in logistic regression. For each group of smokers (never smokers, former smokers, current smokers), multivariate logistic regression models of recurrence were fit and adjusted for potential confounding variables related to smoking history and aneurysm recurrence. Results with a p value less than 0.050 were considered statistically significant. All statistical analyses were run using SYSTAT 13 (Systat Software Inc.).

Results

Overall, 38 patients were omitted due to a lack of medical and/or imaging follow-up, and 30 patients were omitted due to a lack of documented information regarding smoking status at the time of review. A total of 247 patients who had undergone endovascular treatment met the inclusion requirements for this study. Multiple recurrences in a single patient were counted as separate incidences, resulting in 296 documented cerebral aneurysms. While all 296 aneurysms were treated endovascularly, the methods of treatment did differ slightly, as 228 aneurysms (77.0%) were coiled, 66 (22.3%) were stent coiled, and 2 (0.7%) were balloon coiled. Of the 296 aneurysms, 232 (78.4%) occurred in women and 64 (21.6%) in men, whose ages ranged from 18–79 years (mean 56.4 years). According to the medical records, 64 aneurysms (21.6%) occurred in never smokers, 109 (36.8%) in former smokers, and 123 (41.6%) in current smokers, as defined by smoking status at the time of endovascular treatment. Follow-up time, calculated from the most recent imaging, ranged from 0.25 to 12.00 years, with a mean of 1.62 years; the specific breakdown is available in Table 1. Regarding imaging modality at follow-up, 270 aneurysms (91.2%) were followed with angiography, 15 (5.1%) with CTA, and 11 (3.7%) with MRA. Overall, 72 aneurysms (24.3%) recurred among all the patients, with 61 (84.7%) of those recurrences in patients with any reported history of smoking, former or current.

TABLE 1.

Descriptive statistics and results of bivariate chi-square tests between covariates and aneurysm recurrence for all patients

ParameterNo. of Aneurysms, All Patients (%)No. of Aneurysms, Recurrent (%)p Value
Total296 (100)72 (24.3)
Age in yrs0.972
 <4538 (12.8)9 (23.7)
 45 to <65183 (61.8)44 (24.0)
 ≥6575 (25.3)19 (25.3)
Sex0.259
 Male64 (21.6)19 (29.7)
 Female232 (78.4)53 (22.8)
Tobacco use0.232
 Never smoked64 (21.6)11 (17.2)
 Former smoker109 (36.8)26 (23.8)
 Current smoker123 (41.6)35 (28.4)
SAH0.102
 No234 (79.1)52 (22.2)
 Yes62 (20.9)20 (32.2)
HH grade0.197
 0234 (79.0)52 (22.2)
 I8 (2.7)2 (25.0)
 II29 (9.8)7 (24.1)
 III14 (4.7)5 (35.7)
 IV8 (2.7)4 (50.0)
 V3 (1.0)2 (66.7)
Aneurysm location0.781
 Average risk144 (48.6)34 (23.6)
 High risk*152 (51.4)38 (25.0)
Aneurysm size in mm<0.001
 <7175 (59.3)20 (11.4)
 ≥7120 (40.7)51 (42.5)
Endovascular technique0.403
 Balloon coiling2 (0.7)0 (0.0)
 Stent coiling66 (22.3)12 (18.2)
 Coiling228 (77.0)60 (26.3)
Diabetes mellitus0.991
 No263 (88.8)64 (24.3)
 Yes33 (11.1)8 (24.2)
Coronary artery disease0.193
 No268 (90.5)68 (25.4)
 Yes28 (9.4)4 (14.3)
Hypertension0.971
 No131 (44.2)32 (24.4)
 Yes165 (55.7)40 (24.2)
Raymond-Roy classification<0.001
 Class I214 (72.5)36 (16.8)
 Class II60 (20.3)26 (43.3)
 Class III21 (7.1)9 (42.8)
FU time in yrs0.007
 0.25–0.7592 (31.1)34 (37.0)
 0.76–1.2562 (20.9)13 (21.0)
 1.26–1.7525 (8.4)4 (16.0)
 1.76–2.2569 (23.3)9 (13.0)
 >2.2548 (16.2)12 (25.0)
Aspirin0.842
 No104 (35.1)26 (25.0)
 Yes192 (64.9)46 (24.0)
FU = follow-up.

High-risk aneurysm locations: anterior communicating, A2/pericallosal, posterior communicating, and basilar arteries.

One recurrent aneurysm was excluded from this category because it lacked proper intraprocedural imaging documentation regarding this category.

In our search for possible confounders among the covariates, other aspects relating to patient history and clinical course—specifically imaging—were investigated as well (Table 1). Common comorbidities of the patient cohort included hypertension (55.7%), diabetes mellitus (11.1%), and coronary artery disease (9.5%). We also looked at the medication regimens of individual patients at the time of aneurysm presentation and treatment. Per the medical records, aspirin was being taken in 192 cases (64.9%), a statin in 95 cases (32.1%), and β-blockers in 93 cases (31.4%), among many other drugs. On initial presentation to a medical center, 62 of the 296 aneurysms had ruptured, and 91.6% of all aneurysm cases were classified as HH Grades 0–II. Imaging diagnostics at presentation revealed that 152 aneurysms (51.4%) were in the following locations: 83 basilar, 33 anterior communicating, 22 posterior communicating, and 14 A2/pericallosal arteries. Imaging records also revealed that most of the aneurysms (175 [59.3%]) were less than 7 mm in any dimension. Postcoiling imaging demonstrated 214 (72.3%) Raymond-Roy occlusion classification Class I aneurysms, 60 (20.3%) Class II, and 21 (7.1%) Class III. Note that 1 recurrent aneurysm was excluded from calculations regarding aneurysm size and Raymond-Roy classification because it lacked proper intraprocedural imaging documentation regarding these categories.

Table 1 shows the results of bivariate chi-square tests between covariates and recurrence for all cases. While smoker status was the variable of greatest interest in this study, we also wanted to determine if there were any covariates that were also significantly related to aneurysm recurrence rates in this patient population. Analysis revealed that aneurysm size (p < 0.001), Raymond-Roy occlusion classification (p < 0.001), and follow-up time (p = 0.007) were statistically significant for recurrence. These confounders were corrected for with further logistic regression analysis. Of note, parameters that one might hypothesize as playing a role in aneurysm recurrence specifically in this study, such as age, sex, SAH, HH grade, and a comorbidity of hypertension, were not found to be statistically significant for aneurysm recurrence. Moreover, there was no statistically significant difference between different methods of endovascular coiling.

Table 2 is a summary of the odds ratios (ORs) and confidence intervals (CIs) calculated from multivariate models of recurrence by smoking history for all patients. The effects of smoking were adjusted for aneurysm size, postcoiling occlusion status, follow-up time, and statin use. Analysis revealed that those patients currently smoking had an almost 3-fold increased risk of aneurysm recurrence, with an OR of 2.739 for aneurysm recurrence (95% CI 1.127–7.095, p = 0.0308), compared with never smokers. Interestingly, former smokers had an increased risk of recurrence almost identical to that of current smokers, with an OR of 2.698 (95% CI 1.078–7.212, p = 0.0395), compared with never smokers. As in the bivariate analysis, aneurysm size (p < 0.001), follow-up time of at least 1.25 years (p = 0.017), and Raymond-Roy occlusion classification Classes II (p = 0.023) and III (p = 0.0315), specifically residual neck and aneurysm after initial endovascular coiling, were also statistically significant for recurrence.

TABLE 2.

Summary of results from logistic regression models of each smoking class and aneurysm recurrence adjusted for potential confounders for all patients

ParameterRecurrence: All Patients*
OR95% CIp Value
Tobacco use
 Never smokedRefRefRef
 Former smoker2.6981.078–7.2120.0395
 Current smoker2.7391.127–7.0950.0308
Aneurysm size in mm
 <7RefRefRef
 ≥75.4502.764–11.149<0.001
Raymond-Roy classification
 Class IRefRefRef
 Class II3.1541.507–6.6370.0023
 Class III3.4561.102–10.7670.0315
Coronary artery disease
 Yes0.3490.088–1.0970.0956
 NoRefRefRef
HH grade
 0RefRefRef
 I2.7470.352–14.6480.267
 II0.9300.279–2.7850.900
 III1.3100.303–5.2500.707
 IV4.8070.869–28.1750.070
 V6.5490.422–188.2280.197
FU time in yrs
 0.25–0.75RefRefRef
 0.76–1.250.3420.137–0.8070.017
 1.26–1.750.2840.069–0.9490.054
 1.76–2.250.4120.151–1.0400.069
 >2.250.4420.166–1.1120.091
SAH
 NoRefRefRef
 Yes
Ref = reference.

Adjusted for aneurysm size, statin use, postcoiling occlusion status, and follow-up time.

Not calculated due to correlation with another covariate.

Discussion

With improved perioperative outcomes1,6,10,42 and a trend toward minimally invasive surgery, endovascular procedures—specifically endovascular repair of intracranial aneurysms—have become increasingly popular and widespread across the medical community.22 Despite this surge in popularity and positive literature, more recent studies have called into question the long-term efficacy of coiling procedures on aneurysm obliteration. Specifically, an increasing number of studies, most significantly the International Subarachnoid Aneurysm Trial (ISAT), suggest that endovascular treatment is associated with a higher rate of rebleeding and recurrence,11,13,20,28 which tends to increase over time posttreatment.30 Reasons for this finding are still unclear, but several risk factors mentioned above have already been tied to aneurysm recurrence. Although smoking is a known risk factor for aneurysm growth25 and de novo formation,16 probably related to its role in inhibiting alpha 1–antitrypsin (A1AT),34,35,37 there has been a scarcity of data on its association with aneurysm recurrence post–coil embolization. In our study of the relationship between smoking history and aneurysm recurrence in patients treated with endovascular coiling, we found that a history of smoking—either current or former—was significantly and independently related to an increased risk of aneurysm recurrence after endovascular treatment.

To our knowledge, despite the known risk of cigarette smoking in aneurysm growth and formation, only 2 studies in the literature have primarily investigated a potential link between smoking status and aneurysm recurrence in patients who undergo endovascular repair. The first was a 2008 study in which Ortiz and colleagues29 retrospectively analyzed a cohort of more than 100 smokers and reported an OR of 4.53 for recurrence and recanalization of cerebral aneurysms treated via endovascular repair as compared with recurrence among nonsmokers. While this finding is significant, it should be noted that Ortiz et al. stratified their patient cohort into just 2 groups—smokers and nonsmokers—while our cohort was stratified into 3 groups—current smokers, former smokers, and never smokers. Their study also demonstrated an increased risk of recurrence in patients presenting with concurrent low HH grade SAH, which was especially prominent when their study population was split into cohorts by sex, a relationship not seen in our data analysis.

The second, a 2015 study by Brinjikji et al. on 384 patients who had undergone endovascular coiling for the treatment of intracranial aneurysms, found no significant association between tobacco smoking and aneurysm recurrence (OR 1.04, p = 0.878) or retreatment (OR 0.82, p = 0.503).7 Much like us, the authors adjusted for several key demographic, comorbidity, and anatomical variables through multivariate logistic regression analysis and stratified their patient cohort into 3 groups with respect to smoking status—current smokers, former smokers, and nonsmokers. This stratification method was a strength in both our and Brinjikji’s analyses, especially compared with that in the study by Ortiz et al., allowing for a more sophisticated analysis of the potentially pervasive influence that cigarette smoking holds on the surgical outcomes of patients at any point throughout their lives. Some may argue that the negative effects of being a former smoker diminish over time, and it would stand to reason that former smokers would have a lower risk of recurrence. Brinjikji and colleagues showed that former smokers, like current smokers, have odds of aneurysm recurrence similar to nonsmokers. However, our analysis revealed that former smokers not only had an increased risk of recurrence compared with nonsmokers, but also had an odds ratio almost identical to that of current smokers compared with nonsmokers. This suggests two possibilities. First, that whatever physiological effects smoking produces to promote recurrence are probably longstanding in nature. Second, that duration and/or quantity (that is, pack-years) of smoking may have a significant relationship to the risk of aneurysm recurrence as a former smoker could have a greater pack-year than a current smoker in our cohort. However, given the limitations of our retrospective analysis in obtaining complete smoking data, we were unable to further investigate this relationship.

So, what accounts for the difference in our findings compared with those of Brinjikji et al.? Both studies accounted for similar variables across many demographic and comorbidity categories. Both study cohorts had a similar incidence of ruptured and unruptured aneurysms on presentation (33.8% and 66.2%, respectively, in their study compared with 20.9% and 79.1% in our study). And both studies had similar ancillary findings: that both complete posttreatment occlusion (Raymond-Roy classification in our study) and aneurysm size were significantly correlated with an increased risk of aneurysm recurrence. Yet both studies found a fundamentally different relationship between smoking and aneurysm recurrence. One possible explanation may be the difference in the adjunctive devices used; Brinjikji and colleagues almost exclusively used balloon-assisted coiling (98.9% of all device-assisted cases), whereas we heavily favored the use of stent-assisted coiling (97.1% of all device-assisted cases). It is possible that this institutional difference in device use explains the discrepancy in outcomes, as previous studies—while mixed—tend to demonstrate that stent-assisted coiling yields lower rates of retreatment compared with balloon-assisted coiling.12 Ultimately, the contradictory outcomes underscore the need for future multicenter studies with a larger patient population across several different demographic regions.

The pathophysiological reasons for this relationship between smoking and aneurysm recurrence remain unknown; however, there are several possibilities. Smoking is a potent inhibitor of tissue A1AT, which itself acts to regulate the broad activity of the enzyme elastase. This deregulation of elastase may allow for the increased breakdown of elastin protein in vessel walls, decreasing wall elasticity over time and thus making those vessels more susceptible to aneurysm formation. Several murine models have demonstrated the ability to induce aneurysm formation with the use of exogenous elastase.3 It may be this overactivity of elastase in smokers that prevents proper aneurysm obliteration even with coiling—especially when complete obliteration is not achieved. It may also be the ability of smoking to stunt overall healing, as seen in postsurgical wounds,36 through its effects on vascular flow and collagen synthesis that contributes to poor vessel remodeling postcoiling and sac clotting. Whatever the specific reason, it is likely that smoking alters the internal biochemical environment in such a way that both inhibits proper coiling and furthers aneurysm growth.

While more studies investigating the outcome of smokers treated with clip ligation are needed, it may be prudent to consider clip ligation as a viable alternative in smokers with untreated aneurysms. Given our large patient database, examining the difference in outcomes between clip ligation and endovascular repair in smokers may be a task we consider for future study. For now, the decision between clipping and coiling is still one that is dependent on surgeon and patient preference and will likely vary on a case-by-case basis depending on multiple factors such as patient comorbidities, smoking history, and aneurysm anatomy. However, given the results of the present study, these decisions may deserve more risk-benefit analysis of the treatment method to determine whether the better short-term outcomes seen in endovascular repair are worth the increased risk of aneurysm recurrence and the need for possible retreatment, as seen in smokers.

Our multivariate analysis also revealed that aneurysm size and incomplete occlusion, of either the aneurysm or its neck, were significantly associated with an increased risk of aneurysm recurrence. This is well-documented in the current literature,15,17,31 and because it was an expected variable, we were able to properly control and correct for it. One important risk factor for recurrence that we were unable to include in this study was aneurysm neck size. This was a known limitation of our retrospective analysis, as neck size was not consistently documented in the operative records.

Our study did have several other limitations. While we were able to produce a reasonably large patient population, one major limiting factor to our retrospective analysis was the tedious process of reviewing past electronic medical records. Often, patient records were incomplete, inaccurate, or inconsistent—especially with regard to smoking history. Unfortunately, some patients could not be included in the study given the lack of information about smoking history. In total, 38 patients were omitted due to the absence of information regarding smoking status. The absence of such data is probably attributable to patients being less than forthcoming about their history of smoking combined with physicians failing to ask and/or properly record this history in their notes and records. Given the repeated inconsistencies seen in many electronic medical records, we were unable to record and analyze with certainty patient smoking pack-years. Going forward, prospective research with the use of preoperative questionnaires should help to improve this data collection.

We found that the absence of recorded imaging follow-up was the most common exclusion criterion for patients in this study. Overall, 38 patients were lost to follow-up, 18 died soon after their procedure, and 4 underwent imaging at other institutions whose records we could not access. As regards follow-up, another limitation was the unequal duration of follow-up times among patients. While some patients were seen only once at around 6 months, others were seen for multiple follow-ups over the course of years. We attempted to correct for this in our statistical analysis; however, given the fact that the rate of aneurysm recurrence is thought to increase over time,30 it is possible that our data actually underrepresent the rate of aneurysm recurrence in smokers.

We also recognize that there were fewer nonsmokers in our cohort. While this smaller sample size would have probably decreased the statistical power of our analysis to validate any nonsignificant relationships between smoking and aneurysm recurrence, it is unlikely to have interfered with our detection of multiple significant correlations in the data set as regards smoking status and recurrence. Of course, with any retrospective study, there are always unknown or undetermined confounders that can skew the results. Every attempt was made to identify and control for all likely variables based on the current and past literature.

Conclusions

It is clear that, despite several impressive studies, there remains a paucity of data in the scientific literature regarding the effects of smoking on aneurysm formation, growth, and recanalization posttreatment. For now, we recommend that any patient undergoing endovascular repair of an intracranial aneurysm be advised of the risk that their smoking history contributes to poor postoperative outcomes and possible aneurysm recurrence. At the very least, this information should factor into their choice of a treatment modality. Any patient smoking before or after surgery should be instructed by their surgeons to seek help with smoking cessation and should be provided the necessary resources and referrals to do so. As studies show that over one-third of smokers2 continue to smoke after SAH caused by a ruptured intracranial aneurysm, we believe that taking steps to quit smoking is crucial to better long-term outcomes.

Our next step at the University of Michigan is to develop a standardized questionnaire, created in conjunction with the Department of Neurosurgery, to be given to all patients undergoing endovascular treatment. Given the limitations of a retrospective study such as this, we believe that implementing a large-scale prospective cohort study would better allow us to track patient outcomes in correlation with risk factors such as smoking. It is our hope that this continued research further establishes and defines the association between cigarette smoking and aneurysm recurrence in patients after coiling.

Disclosures

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Author Contributions

Conception and design: Thompson, Pandey. Acquisition of data: all authors. Analysis and interpretation of data: Thompson, Futchko, Starr, Lau, Leach, Pandey. Drafting the article: Futchko, Starr, Leach. Critically revising the article: Thompson, Futchko, Pandey. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Thompson. Study supervision: Thompson, Pandey.

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    • Export Citation
  • 13

    Crobeddu ELanzino GKallmes DFCloft HJ: Review of 2 decades of aneurysm-recurrence literature, part 1: reducing recurrence after endovascular coiling. AJNR Am J Neuroradiol 34:2662702013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Fábregas NValero RCarrero ESalvador LCalas AParra L: [Outcome of patients who underwent surgical repair of aneurysm after subarachnoid hemorrhage.] Med Clin (Barc) 111:81871998 (Span)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Ferns SPSprengers MEvan Rooij WJRinkel GJvan Rijn JCBipat S: Coiling of intracranial aneurysms: a systematic review on initial occlusion and reopening and retreatment rates. Stroke 40:e523e5292009

    • Search Google Scholar
    • Export Citation
  • 16

    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

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Ferns SPSprengers MEvan Rooij WJvan Zwam WHde Kort GAVelthuis BK: Late reopening of adequately coiled intracranial aneurysms: frequency and risk factors in 400 patients with 440 aneurysms. Stroke 42:133113372011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Fogelholm RHernesniemi JVapalahti M: Impact of early surgery on outcome after aneurysmal subarachnoid hemorrhage. A population-based study. Stroke 24:164916541993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Jang EWJung JYHong CKJoo JY: Benefits of surgical treatment for unruptured intracranial aneurysms in elderly patients. J Korean Neurosurg Soc 49:20252011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Johnston SCDowd CFHigashida RTLawton MTDuckwiler GRGress DR: Predictors of rehemorrhage after treatment of ruptured intracranial aneurysms: the Cerebral Aneurysm Rerupture After Treatment (CARAT) study. Stroke 39:1201252008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Johnston SCSelvin SGress DR: The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology 50:141314181998

  • 22

    Johnston SCWilson CBHalbach VVHigashida RTDowd CFMcDermott MW: Endovascular and surgical treatment of unruptured cerebral aneurysms: comparison of risks. Ann Neurol 48:11192000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Juvela SHillbom MNumminen HKoskinen P: Cigarette smoking and alcohol consumption as risk factors for aneurysmal subarachnoid hemorrhage. Stroke 24:6396461993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Juvela SPorras MPoussa K: Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture. J Neurosurg 108:105210602008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

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

  • 26

    Lasner TMWeil RJRiina HAKing JT JrZager ELRaps EC: Cigarette smoking-induced increase in the risk of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg 87:3813841997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Longstreth WT JrNelson LMKoepsell TDvan Belle G: Clinical course of spontaneous subarachnoid hemorrhage: a population-based study in King County, Washington. Neurology 43:7127181993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Molyneux AJKerr RSBirks JRamzi NYarnold JSneade M: Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up. Lancet Neurol 8:4274332009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Ortiz RStefanski MRosenwasser RVeznedaroglu E: Cigarette smoking as a risk factor for recurrence of aneurysms treated by endosaccular occlusion. J Neurosurg 108:6726752008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Piotin MSpelle LMounayer CSalles-Rezende MTGiansante-Abud DVanzin-Santos R: Intracranial aneurysms: treatment with bare platinum coils—aneurysm packing, complex coils, and angiographic recurrence. Radiology 243:5005082007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Raymond JGuilbert FWeill AGeorganos SAJuravsky LLambert A: Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke 34:139814032003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Rinkel GJDjibuti MAlgra Avan Gijn J: Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke 29:2512561998

  • 33

    Roy DMilot GRaymond J: Endovascular treatment of unruptured aneurysms. Stroke 32:199820042001

  • 34

    Schievink WIKatzmann JAPiepgras DGSchaid DJ: Alpha-1-antitrypsin phenotypes among patients with intracranial aneurysms. J Neurosurg 84:7817841996

  • 35

    Schievink WIPrakash UBPiepgras DGMokri B: Alpha 1-antitrypsin deficiency in intracranial aneurysms and cervical artery dissection. Lancet 343:4524531994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Sørensen LT: Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg 255:106910792012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    St Jean PHart BWebster MSteed DAdamson JPowell J: Alpha-1-antitrypsin deficiency in aneurysmal disease. Hum Hered 46:92971996

  • 38

    van Gijn JKerr RSRinkel GJ: Subarachnoid haemorrhage. Lancet 369:3063182007

  • 39

    Vernooij MWIkram MATanghe HLVincent AJHofman AKrestin GP: Incidental findings on brain MRI in the general population. N Engl J Med 357:182118282007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Weir BKKongable GLKassell NFSchultz JRTruskowski LLSigrest A: Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and risk for vasospasm: a report of the Cooperative Aneurysm Study. J Neurosurg 89:4054111998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Wermer MJvan der Schaaf ICVelthuis BKAlgra ABuskens ERinkel GJ: Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and enlargement of existing aneurysms. Brain 128:242124292005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Wiebers DOWhisnant JPHuston J IIIMeissner IBrown RD JrPiepgras DG: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:1031102003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Winn HRJane JA SrTaylor JKaiser DBritz GW: Prevalence of asymptomatic incidental aneurysms: review of 4568 arteriograms. J Neurosurg 96:43492002

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Article Information

Contributor Notes

Correspondence B. Gregory Thompson, Department of Neurosurgery, University of Michigan, 1500 E Medical Center Dr., Rm. 3552 TC, Ann Arbor, MI 48109-5338. email: gregthom@umich.edu.INCLUDE WHEN CITING Published online June 23, 2017; DOI: 10.3171/2016.12.JNS161625.Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
Headings
References
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    CARAT Investigators: Rates of delayed rebleeding from intracranial aneurysms are low after surgical and endovascular treatment. Stroke 37:143714422006

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    Chalouhi NStarke RMKoltz MTJabbour PMTjoumakaris SIDumont AS: Stent-assisted coiling versus balloon remodeling of wide-neck aneurysms: comparison of angiographic outcomes. AJNR Am J Neuroradiol 34:198719922013

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    Crobeddu ELanzino GKallmes DFCloft HJ: Review of 2 decades of aneurysm-recurrence literature, part 1: reducing recurrence after endovascular coiling. AJNR Am J Neuroradiol 34:2662702013

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Fábregas NValero RCarrero ESalvador LCalas AParra L: [Outcome of patients who underwent surgical repair of aneurysm after subarachnoid hemorrhage.] Med Clin (Barc) 111:81871998 (Span)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Ferns SPSprengers MEvan Rooij WJRinkel GJvan Rijn JCBipat S: Coiling of intracranial aneurysms: a systematic review on initial occlusion and reopening and retreatment rates. Stroke 40:e523e5292009

    • Search Google Scholar
    • Export Citation
  • 16

    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

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Ferns SPSprengers MEvan Rooij WJvan Zwam WHde Kort GAVelthuis BK: Late reopening of adequately coiled intracranial aneurysms: frequency and risk factors in 400 patients with 440 aneurysms. Stroke 42:133113372011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Fogelholm RHernesniemi JVapalahti M: Impact of early surgery on outcome after aneurysmal subarachnoid hemorrhage. A population-based study. Stroke 24:164916541993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Jang EWJung JYHong CKJoo JY: Benefits of surgical treatment for unruptured intracranial aneurysms in elderly patients. J Korean Neurosurg Soc 49:20252011

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Johnston SCDowd CFHigashida RTLawton MTDuckwiler GRGress DR: Predictors of rehemorrhage after treatment of ruptured intracranial aneurysms: the Cerebral Aneurysm Rerupture After Treatment (CARAT) study. Stroke 39:1201252008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Johnston SCSelvin SGress DR: The burden, trends, and demographics of mortality from subarachnoid hemorrhage. Neurology 50:141314181998

  • 22

    Johnston SCWilson CBHalbach VVHigashida RTDowd CFMcDermott MW: Endovascular and surgical treatment of unruptured cerebral aneurysms: comparison of risks. Ann Neurol 48:11192000

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Juvela SHillbom MNumminen HKoskinen P: Cigarette smoking and alcohol consumption as risk factors for aneurysmal subarachnoid hemorrhage. Stroke 24:6396461993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Juvela SPorras MPoussa K: Natural history of unruptured intracranial aneurysms: probability of and risk factors for aneurysm rupture. J Neurosurg 108:105210602008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

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

  • 26

    Lasner TMWeil RJRiina HAKing JT JrZager ELRaps EC: Cigarette smoking-induced increase in the risk of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg 87:3813841997

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Longstreth WT JrNelson LMKoepsell TDvan Belle G: Clinical course of spontaneous subarachnoid hemorrhage: a population-based study in King County, Washington. Neurology 43:7127181993

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Molyneux AJKerr RSBirks JRamzi NYarnold JSneade M: Risk of recurrent subarachnoid haemorrhage, death, or dependence and standardised mortality ratios after clipping or coiling of an intracranial aneurysm in the International Subarachnoid Aneurysm Trial (ISAT): long-term follow-up. Lancet Neurol 8:4274332009

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Ortiz RStefanski MRosenwasser RVeznedaroglu E: Cigarette smoking as a risk factor for recurrence of aneurysms treated by endosaccular occlusion. J Neurosurg 108:6726752008

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Piotin MSpelle LMounayer CSalles-Rezende MTGiansante-Abud DVanzin-Santos R: Intracranial aneurysms: treatment with bare platinum coils—aneurysm packing, complex coils, and angiographic recurrence. Radiology 243:5005082007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Raymond JGuilbert FWeill AGeorganos SAJuravsky LLambert A: Long-term angiographic recurrences after selective endovascular treatment of aneurysms with detachable coils. Stroke 34:139814032003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Rinkel GJDjibuti MAlgra Avan Gijn J: Prevalence and risk of rupture of intracranial aneurysms: a systematic review. Stroke 29:2512561998

  • 33

    Roy DMilot GRaymond J: Endovascular treatment of unruptured aneurysms. Stroke 32:199820042001

  • 34

    Schievink WIKatzmann JAPiepgras DGSchaid DJ: Alpha-1-antitrypsin phenotypes among patients with intracranial aneurysms. J Neurosurg 84:7817841996

  • 35

    Schievink WIPrakash UBPiepgras DGMokri B: Alpha 1-antitrypsin deficiency in intracranial aneurysms and cervical artery dissection. Lancet 343:4524531994

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 36

    Sørensen LT: Wound healing and infection in surgery: the pathophysiological impact of smoking, smoking cessation, and nicotine replacement therapy: a systematic review. Ann Surg 255:106910792012

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    St Jean PHart BWebster MSteed DAdamson JPowell J: Alpha-1-antitrypsin deficiency in aneurysmal disease. Hum Hered 46:92971996

  • 38

    van Gijn JKerr RSRinkel GJ: Subarachnoid haemorrhage. Lancet 369:3063182007

  • 39

    Vernooij MWIkram MATanghe HLVincent AJHofman AKrestin GP: Incidental findings on brain MRI in the general population. N Engl J Med 357:182118282007

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 40

    Weir BKKongable GLKassell NFSchultz JRTruskowski LLSigrest A: Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and risk for vasospasm: a report of the Cooperative Aneurysm Study. J Neurosurg 89:4054111998

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 41

    Wermer MJvan der Schaaf ICVelthuis BKAlgra ABuskens ERinkel GJ: Follow-up screening after subarachnoid haemorrhage: frequency and determinants of new aneurysms and enlargement of existing aneurysms. Brain 128:242124292005

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 42

    Wiebers DOWhisnant JPHuston J IIIMeissner IBrown RD JrPiepgras DG: Unruptured intracranial aneurysms: natural history, clinical outcome, and risks of surgical and endovascular treatment. Lancet 362:1031102003

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 43

    Winn HRJane JA SrTaylor JKaiser DBritz GW: Prevalence of asymptomatic incidental aneurysms: review of 4568 arteriograms. J Neurosurg 96:43492002

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