Risk Of Aneurysmal Subarachnoid Hemorrhage Research Articles

Higher risk of intracranial aneurysms and subarachnoid haemorrhage in siblings of families with intracranial aneurysms.

IntroductionFirst-degree relatives of patients with familial aneurysmal subarachnoid hemorrhage have an increased risk of unruptured intracranial aneurysms and aneurysmal subarachnoid hemorrhage. We assessed whether the type of kinship of first-degree relatives of aneurysmal subarachnoid hemorrhage patients influences this risk.Patients and methodsWe used all available data from the prospectively collected database of families consulting our outpatient clinic between 1994-2016. We constructed pedigrees for all families with ≥2 first-degree relatives with aneurysmal subarachnoid hemorrhage or unruptured intracranial aneurysms. The proband was defined as the first family member with aneurysmal subarachnoid hemorrhage who sought medical attention. We compared both the proportion of aneurysmal subarachnoid hemorrhage and unruptured intracranial aneurysms in proband's first-degree relatives by calculating relative risks (RR) with children as the reference.ResultsWe studied 154 families with 1,105 first-degree relatives of whom 146 had aneurysmalsubarachnoid hemorrhage. Unruptured intracranial aneurysms were identified in 63 (19%) of the 326 screened relatives. Siblings had a higher risk of aneurysmal subarachnoid hemorrhage (RR:1.62, 95% CI:1.12–2.38) and parents a lower risk (RR:0.44, 95% CI:0.24–0.81) than children. Siblings also had a higher risk of unruptured intracranial aneurysms (RR:2.28, 95% CI:1.23–4.07, age-adjusted RR:2.04, 95% CI:1.07–3.92) than children.Conclusion: Siblings of patients with aneurysmal subarachnoid hemorrhage have a significanthigher risk of both unruptured intracranial aneurysms and aneurysmal subarachnoid hemorrhage and parents have a lower risk of aneurysmal subarachnoid hemorrhage than children. Discussion: Type of kinship is a relevant factor to consider in risk prediction and screening advice in families with familial aneurysmal subarachnoid hemorrhage.

The effectiveness of lumbar cerebrospinal fluid drainage in aneurysmal subarachnoid hemorrhage with different bleeding amounts.

Continuous lumbar drainage (LD) of cerebrospinal fluid can reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH)-related complications. We evaluated the effectiveness of LD in aSAH patients with aneurysmal clipping and the relative benefits of different bleeding amounts. We retrospectively reviewed all consecutive aSAH patients who underwent aneurysm clipping in our hospital between January 1, 2014 and December 31, 2014. Outcomes and incidence of post-operative complications were compared between the LD group and the non-LD group in all patients and further analyzed in patients with the low modified Fisher Scale (mFS) (0-2) and high mFS (3-4). In 193 aSAH patients who underwent clipping, LD reduced the risk of hydrocephalus and improved the Glasgow Outcome Scale (GOS) score at discharge and at 3months of follow-up. In the higher mFS group, patients who received LD had significantly lower risk of cerebral vasospasm, delayed cerebral infarction, and hydrocephalus; the GOS score was significantly higher in the LD group at discharge and at 3months of follow-up. However, LD showed no benefits in terms of post-operative complications and outcome in patients with low mFS. LD for aneurysm clipping surgery after aSAH can reduce the risk of post-operative complications and improve the clinical outcome in patients with mFS grades 3 and 4. It should be considered as an adjunctive but dispensable treatment for aneurysm clipping in aSAH patient with low mFS.

Periodontitis and gingival bleeding associate with intracranial aneurysms and risk of aneurysmal subarachnoid hemorrhage

Oral bacteria DNA has been found in intracranial aneurysms (IA) and a high prevalence of periodontitis was reported in IA patients. We investigated whether periodontitis associates with IA formation and aneurysmal subarachnoid hemorrhage (aSAH). First, we compared in a case-control setting the prevalence of periodontal disease in IA patients (42 unruptured IA, 34 ruptured IA) and in age- and gender-matched controls (n = 70) from the same geographical area (Health 2000 Survey, BRIF8901). Next, we investigated whether periodontitis at baseline associated with aSAH in a 13-year follow-up study of 5170 Health 2000 Survey participants. Follow-up data was obtained from national hospital discharge and cause of death registries. Univariate analysis, logistic regression, and Cox-regression were used. Periodontitis (≥ 4mm gingival pocket) and severe periodontitis (≥ 6mm gingival pocket) were found in 92% and 49% of IA patients respectively and associated with IAs (OR 5.3, 95%CI 1.1–25.9, p < 0.000 and OR 6.3, 95%CI 1.3–31.4, p < 0.001, respectively). Gingival bleeding had an even stronger association, especially if detected in 4–6 teeth sextants (OR 34.4, 95%CI 4.2–281.3). Severe periodontitis in ≥ 3 teeth or gingival bleeding in 4–6 teeth sextants at baseline increased the risk of aSAH during follow-up (HR 22.5, 95%CI 3.6–139.5, p = 0.001 and HR 8.3, 95%CI 1.5–46.1, p = 0.015, respectively). Association of periodontitis and gingival bleeding with risk of IA development and aSAH was independent of gender, smoking status, hypertension, or alcohol abuse. Periodontitis and gingival bleeding associate with increased risk for IA formation and eventual aSAH. Further epidemiological and mechanistic studies are indicated.

Abstract WP122: Risk of Intracranial Hemorrhage and National Trends of Delivery Methods of Pregnant Women With Diagnosis of Unruptured Intracranial Aneurysm

Introduction: Understanding the risk of aneurysmal subarachnoid hemorrhage in pregnant women with known history of Unruptured Intracranial Aneurysm (UICA) could potentially impact the delivery method. Due to presumed risk of intrapartum aneurysm rupture, understanding practice patterns of delivery methods and related complication risk is of importance. Methods: We used Nationwide Inpatient Sample database (1998-2014) to identify all the hospitalizations for childbirth in women with and without history of UICA. Patients with intracranial vascular malformation and traumatic intracranial hemorrhage were excluded. The cohort of pregnant women with known history of UICA was compared with the cohort of those without history of UICA with univariate analysis. Results: A total of 323 patients with known history of UICA were hospitalized for childbirth compared to 13,669,848 with no history of UICA. Higher rates of intracranial hemorrhage was observed in history of UICA group compared to no history of UICA [subarachnoid hemorrhage (0.31% Vs 0.001%, p&lt;0.01), intracerebral hemorrhage (0.94% Vs 0.001%, p&lt;0.01), and non-specific intracranial hemorrhage (0.28% Vs 0.0004%, p&lt;0.01)]. UICA group had higher incidence of essential hypertension (6.9% Vs 1.1%, p&lt;0.01), pre-eclampsia (7.1% Vs 3.5%, p&lt;0.01), and eclampsia (0.6% Vs 0.07%, p&lt;0.01), and prevalence of smoking (8.23% Vs 3.95%, p&lt;0.01). The rate of cesarean section (78.8% Vs 29.6%, p&lt;0.01) and length of average hospital stay (3.76 Vs 2.57 days, p&lt;0.01) was higher in UICA group. UICA group had higher rates of major anesthesia complications (0.32% Vs 0.01%, p&lt;0.01), prolonged mechanical ventilation (1.2% Vs 0.04%, p&lt;0.01), and blood transfusion (3.12% Vs 0.75%, p&lt;0.01). 80% of UICA patients who had intracranial hemorrhage also had cesarean section. Conclusion: Women undergoing childbirth with known history of UICA have higher risk of intracranial hemorrhage, peripartum complications, and longer hospitalizations compared to women without a known UICA. Aggressive management of risk factors for aneurysm rupture including hypertension and smoking could potentially decrease the rupture risk. Further research is needed to understand whether delivery method has an impact on decreasing risk of rupture.

Gender-specific effects of MMP-2 and MMP-9 gene variants and the risk of aneurysmal subarachnoid haemorrhage

Matrix metalloproteinases (MMPs), a family of zinc-dependent proteases, have been linked with the pathogenesis of intracranial aneurysm (IA) formation and rupture. Patients with IA have elevated serum levels of MMP-2 and MMP-9 gene expression has been shown to be increased in aneurysm tissue. In this study, we have evaluated the association between MMP gene variants and aneurysmal subarachnoid hemorrhage (aSAH). The rs243865 in MMP-2 and rs17576 in MMP-9 genes were genotyped using Taqman allelic discrimination assay. Upon gender stratification, the presence of G allele of MMP-9 gene exon variant was found to increase the risk of aSAH by 1.4 fold (p = 0.032), in men. The GG genotype also showed a trend towards association with the risk of aSAH (OR: 1.785, CI: 0.971–3.283, p = 0.062) in men, after adjusting for the vascular risk factors. In women, no association was observed. The MMP-2 gene variants were not associated with aSAH in both genders. Further functional studies are required to describe the exact basis of the association between MMP-9 polymorphism and intracranial aneurysm in men.

Factor XIII polymorphism and risk of aneurysmal subarachnoid haemorrhage in a south Indian population

BackgroundThe rupture of a brain aneurysm causes bleeding in the subarachnoid space and is known as aneurysmal subarachnoid haemorrhage (aSAH). In our study, we evaluated the association of factor XIII polymorphism and the risk of Aneurysmal subarachnoid haemorrhage (aSAH) in South Indian population.MethodsThe study was performed in 200 subjects with aSAH and 205 healthy control subjects. Genotyping of rs5985(c.103G > T (p.Val35Leu)) and rs5982(c.1694C > T (p.Pro564Leu)) polymorphism was performed by Taqman® allelic discrimination assay.ResultsIn our study, Val/Leu genotype frequency was higher in control subjects (18%) compared to aSAH patients (9%).The Val/Leu genotype was associated with lower risk of aSAH (OR = 0.48, 95%CI = 0.26–0.88, p = 0.02). When compared with Val allele, Leu allele was significantly associated with lower risk of aSAH (OR = 0.55, 95%CI = 0.32–0.95, p = 0.03). In subtyping, we found a significant association of Leu/Leu genotype with the Basilar top aneurysm (OR = 3.59, 95%CI = 1.11–11.64, p = 0.03). In c.1694C > T (p.Pro565Leu) variant, Pro/Pro Vs Pro/Leu genotype (OR = 2.06, 95%CI = 1.10–3.85, p = 0.02) was significantly associated with higher risk of aSAH. The 564Leu allelic frequency in aSAH patients (36%) was higher when compared with that in healthy controls (30%) in our study. When allele frequency (Pro Vs Leu) was compared, 564Leu allele was found to be significantly associated with higher aSAH risk (OR = 1.36, 95%CI = 1.01–1.83, p = 0.04). (OR = 1.36, 95%CI = 1.01–1.83, p = 0.04). Regarding rs5985 and rs5982, significant association was found in the log-additive model (OR = 0.57, 95%CI = 0.33–0.97, p = 0.034; OR = 1.32, 95%CI = 1.00–1.72, p = 0.043).ConclusionThese results suggest that 34Leu allele was a protective factor for lower risk of aSAH whereas 564Leu allele was associated with higher risk of aSAH in South Indian population.

Elevated International Normalized Ratio Is Associated With Ruptured Aneurysms.

Background and Purpose- The effects of anticoagulation therapy and elevated international normalized ratio (INR) values on the risk of aneurysmal subarachnoid hemorrhage are unknown. We aimed to investigate the association between anticoagulation therapy, elevated INR values, and rupture of intracranial aneurysms. Methods- We conducted a case-control study of 4696 patients with 6403 intracranial aneurysms, including 1198 prospective patients, diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 who were on no anticoagulant therapy or on warfarin for anticoagulation. Patients were divided into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to evaluate the association of anticoagulation therapy, INR values, and presentation with a ruptured intracranial aneurysm, taking into account the interaction between anticoagulant use and INR. Inverse probability weighting using propensity scores was used to minimize differences in baseline demographics characteristics. The marginal effects of anticoagulant use on rupture risk stratified by INR values were calculated. Results- In unweighted and weighted multivariable analyses, elevated INR values were significantly associated with rupture status among patients who were not anticoagulated (unweighted odds ratio, 22.78; 95% CI, 10.85-47.81 and weighted odds ratio, 28.16; 95% CI, 12.44-63.77). In anticoagulated patients, warfarin use interacts significantly with INR when INR ≥1.2 by decreasing the effects of INR on rupture risk. Conclusions- INR elevation is associated with intracranial aneurysm rupture, but the effects may be moderated by warfarin. INR values should, therefore, be taken into consideration when counseling patients with intracranial aneurysms.

Polymorphism and plasma levels of apolipoprotein E and the risk of aneurysmal subarachnoid hemorrhage in a Chinese population: a case-control study

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) is the most common types of subarachnoid hemorrhage, which is a critical clinical problem with high morbidity, mortality, and economic impact. Recent studies have shown that APOE was a genetic risk factor of aSAH, however, the studies lack consistent conclusions and the evidence from Chinese Han population is rare.ObjectiveTo determine the relationship between APOE polymorphism and the incidence of aSAH in Chinese Fujian Han population and explore the possible mechanism of ApoE in the pathogenesis of aSAH.MethodsA total of 131 patients newly diagnosed with aSAH were selected as aSAH group and 137 healthy subjects were selected as the control group. All the samples were analyzed for blood lipids and serum ApoE levels, and ApoE genotype was determined by a commercial chip and further confirmed with Sanger sequencing. An adjusted multivariate logistic regression analysis was carried out to estimate the effects of APOE polymorphism on the risk of aSAH.ResultsCompared with the controls, the serum TC, HDL-C and ApoA1 levels in aSAH were significantly lower: TC (4.52 ± 1.38 vs. 5.11 ± 0.86 mmol/L, P < 0.001), HDL-C (1.23 ± 0.46 vs. 1.44 ± 0.32 mmol/L, P < 0.001) and ApoA1 (1.20 ± 0.32 vs. 1.38 ± 0.25 g/L, P < 0.001). The distribution of ε2/ε3 genotype (19.08% vs. 9.49%, P = 0.038) and ε2 allele frequency (11.07% vs. 5.84%, P = 0.039) was significantly higher in aSAH than the healthy controls. The multivariate logistic regression identified that ApoE ε2 allele was independently associated with aSAH (OR = 2.083; and 95% CI = 1.045-4.153, P = 0.037). The serum ApoE in aSAH were significantly higher than controls (53.03 ± 24.64 vs. 45.06 ± 12.84 mg/L, P = 0.010).ConclusionAPOE polymorphism might be associated with the incidence of aSAH in Chinese Fujian Han population. ApoE ε2 may be a risk factor for the incidence of aSAH, which may be related with the impacts of ApoE genotypes for the serum lipids, especially for the plasma levels of ApoE.

Abstract TP171: Liver Cirrhosis is Associated With an Increased Risk of Aneurysmal Subarachnoid Hemorrhage

Introduction: Cirrhosis has been associated with non-traumatic subarachnoid hemorrhage (SAH). Additionally, cirrhosis appears to contribute to the development of pulmonary vascular abnormalities. We therefore sought to investigate whether cirrhosis is associated specifically with aneurysmal SAH. Methods: We performed a retrospective cohort study using 2009-2015 inpatient and outpatient claims data from a 5% sample of Medicare beneficiaries ≥66 years of age. Our exposure was cirrhosis as defined by a previously validated algorithm using inpatient and outpatient ICD-9- CM diagnosis codes. The outcome of aneurysmal SAH was identified using a validated approach requiring an inpatient ICD-9-CM diagnosis code for non-traumatic subarachnoid hemorrhage, without concomitant diagnosis codes for trauma or rehabilitation. Additionally, to further ensure we were identifying aneurysmal SAH, we required the presence of an ICD-9-CM procedure code reflecting endovascular or surgical treatment of a cerebral aneurysm during the same hospitalization. Patients were censored at the time of death or end of Medicare coverage or on September 30, 2015. We used survival statistics to calculate incidence rates and Cox proportional hazards models to evaluate the association between cirrhosis and aneurysmal SAH after adjustment for demographics, established SAH risk factors, and Charlson comorbidities. Results: We identified 10,658 (0.6%) patients with cirrhosis from among the 1,778,604 beneficiaries in our sample. The mean age of patients with cirrhosis was 73.2 (±6.5) years, and 48% were female. Over a mean of 4.7 (±2.1) years of follow-up, 4,272 patients were hospitalized with aneurysmal SAH. The annual incidence of aneurysmal SAH in patients with cirrhosis was 0.11% (95% confidence interval [CI], 0.08-0.17%) compared to 0.05% (95% CI, 0.05-0.05%) in patients without cirrhosis. After adjustment for demographics, risk factors, and comorbidities, cirrhosis was independently associated with an increased risk of aneurysmal SAH (hazard ratio, 2.3; 95% CI, 1.5-3.4). Conclusions: We found that cirrhosis was associated with aneurysmal SAH among Medicare beneficiaries. Liver cirrhosis may be an independent risk factor for aneurysmal SAH.

Antihyperglycemic Agents Are Inversely Associated With Intracranial Aneurysm Rupture.

Previous studies have suggested a protective effect of diabetes mellitus on aneurysmal subarachnoid hemorrhage risk. However, reports are inconsistent, and objective measures of hyperglycemia in these studies are lacking. Our aim was to investigate the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agent use and glycated hemoglobin levels. The medical records of 4701 patients with 6411 intracranial aneurysms, including 1201 prospective patients, diagnosed at the Massachusetts General Hospital and Brigham and Women's Hospital between 1990 and 2016 were reviewed and analyzed. Patients were separated into ruptured and nonruptured groups. Univariate and multivariate logistic regression analyses were performed to determine the association between aneurysmal subarachnoid hemorrhage and antihyperglycemic agents and glycated hemoglobin levels. Propensity score weighting was used to account for selection bias. In both unweighted and weighted multivariate analysis, antihyperglycemic agent use was inversely and significantly associated with ruptured aneurysms (unweighted odds ratio, 0.58; 95% confidence interval, 0.39-0.87; weighted odds ratio, 0.57; 95% confidence interval, 0.34-0.96). In contrast, glycated hemoglobin levels were not significantly associated with rupture status. Antihyperglycemic agent use rather than hyperglycemia is associated with decreased risk of aneurysmal subarachnoid hemorrhage, suggesting a possible protective effect of glucose-lowering agents in the pathogenesis of aneurysm rupture.

Apolipoprotein E polymorphism and the risk of aneurysmal subarachnoid hemorrhage in a South Indian population

BackgroundThe rupture of a brain aneurysm causes bleeding in the subarachnoid space. This is known as aneurysmal subarachnoid hemorrhage (aSAH). We evaluated the association of apolipoprotein E (APOE) polymorphism and the risk of aSAH in a South Indian population.MethodsThe study was performed on 200 subjects with aSAH and 253 healthy control subjects. Blood samples (5 ml) were used to isolate DNA and genotyping was performed for rs7412 and rs429358 using a Taqman allelic discrimination assay. Statistical software R.3.0.11 was used to statistically analyze the data and a p value < 0.05 was considered as statistically significant.ResultsWe found a significant association with the risk of aSAH in ε3/ ε4 genetic model (OR = 1.91, 95% CI = 1.16–3.14, p = 0.01). However, in the other genetic models and allele frequency, there was no significant association with the risk of aSAH. In subtyping, we found a significant association of ε2 allele frequency with posterior communicating artery (PCOM) aneurysm (OR = 3.59, 95% CI = 1.11–11.64, p = 0.03).ConclusionOur results suggest that APOE polymorphism has an influence on the risk of aSAH in this South Indian population, specifically in the PCOM subtype.

Association of intracranial aneurysm rupture with smoking duration, intensity, and cessation

Although smoking is a known risk factor for intracranial aneurysm (IA) rupture, the exact relationship between IA rupture and smoking intensity and duration, as well as duration of smoking cessation, remains unknown. In this case-control study, we analyzed 4,701 patients with 6,411 IAs diagnosed at the Brigham and Women's Hospital and Massachusetts General Hospital between 1990 and 2016. We divided individuals into patients with ruptured aneurysms and controls with unruptured aneurysms. We performed univariable and multivariable logistic regression analyses to determine the association between smoking status and ruptured IAs at presentation. In a subgroup analysis among former and current smokers, we assessed the association between ruptured aneurysms and number of packs per day, duration of smoking, and duration since smoking cessation. In multivariable analysis, current (odds ratio [OR] 2.21, 95% confidence interval [CI] 1.89-2.59) and former smoking status (OR 1.56, 95% CI 1.31-1.86) were associated with rupture status at presentation compared with never smokers. In a subgroup analysis among current and former smokers, years smoked (OR 1.02, 95% CI 1.01-1.03) and packs per day (OR 1.46, 95% CI 1.25-1.70) were significantly associated with ruptured aneurysms at presentation, whereas duration since cessation among former smokers was not significant (OR 1.00, 95% CI 0.99-1.02). 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.

Aspirin and Risk of Subarachnoid Hemorrhage: Systematic Review and Meta-Analysis.

Recent studies have suggested that the use of low-dose aspirin may reduce the risk of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to evaluate any association between aspirin use and risk of aSAH based on the literature, and whether this is influenced by duration or frequency of aspirin use. A search of electronic databases was done from inception to September 2016. For each study, data on risk of aSAH in aspirin versus nonaspirin users were used to generate odds ratios and 95% confidence intervals, and combined using inverse variance-weighted averages of logarithmic odds ratios in a random-effects models. From 7 included studies, no significant difference was noted between aspirin use of any duration or frequency and nonaspirin users (odds ratio, 1.00; 95% confidence interval, 0.81-1.24; P=0.99). We found a significant association between short-term use of aspirin (<3 months) and the risk of aSAH (odds ratio, 1.61; 95% confidence interval, 1.20-2.18; P=0.002). No significant difference was found in terms of risk of aSAH for 3 to 12 months, 1 to 3 years, and >3 years of durations of use. No significant association was found between infrequent aspirin use (≤2× per week) or frequent use (≥3× per week) with risk of aSAH. Current evidence suggests that short-term (<3 months) use of aspirin is associated with increased risk of aSAH. Limitations include substantial heterogenity of the included studies. The role of long-term aspirin in reducing risk of aSAH remains unclear and ideally should be addressed by an appropriately designed randomized controlled trial.

Diabetes mellitus and the risk of aneurysmal subarachnoid haemorrhage: A systematic review and meta-analysis of current evidence.

ObjectiveThis systematic review aimed to define the relationship between diabetes mellitus (DM) and the risk of aneurysmal subarachnoid haemorrhage (aSAH).MethodsStudies associated with DM and aSAH published until March 2016 were retrieved from Pubmed, Embase, Web of Science, and Cochrane Library databases. A random-effects model was used to calculate the relative risks (RRs) with 95% confidence intervals (CIs).ResultsEighteen observational studies were retrieved. The overall RRs for DM and aSAH were RRs = 0.59 (0.44, 0.79), with moderate heterogeneity (I2 = 55.7%, Pheterogeneity = 0.000). Subgroup analysis by study quality revealed a reduced association between DM and aSAH risk in high quality studies only (RRs = 0.40, 95% CI: 0.29, 0.56; I2 = 0.0%, Pheterogeneity = 0.549), therefore study quality may be a source of heterogeneity.ConclusionA potential decreased risk of aSAH in DM patients was found in high quality studies. Further studies are required to confirm this causal relationship and to investigate the biological mechanisms.

A cost-effectiveness analysis of screening for intracranial aneurysms in persons with one first-degree relative with subarachnoid haemorrhage.

Although persons with one first-degree relative with aneurysmal subarachnoid haemorrhage have an increased risk of aneurysm formation and aneurysmal subarachnoid haemorrhage, screening them for unruptured intracranial aneurysms was not beneficial in a modelling study from the 1990s. New data on the risk of aneurysmal subarachnoid haemorrhage in these persons and improved treatment techniques call for reassessment of the cost-effectiveness of screening. We used a cost-effectiveness analysis using a Markov model and Monte Carlo simulation comparing screening and preventive aneurysm treatment with no screening in persons with one first-degree relative with aneurysmal subarachnoid haemorrhage. We analyzed the impact on quality-adjusted life years, costs and net health benefit of single screening (at varying screening age) and serial screening (with varying screening age and intervals) using a cost-effectiveness threshold of €20,000/quality-adjusted life year. In 17 of the 24 strategies assessed, additional costs for screening for unruptured intracranial aneurysm were <€20,000 per quality-adjusted life year gained. The strategy with highest net health benefit was screening at age 40 and 55. Screening every five years from age 20 to 70 yielded the highest health benefits at the highest additional costs. Based on current risks of aneurysmal subarachnoid haemorrhage and complications of preventive treatment, several strategies to screen for unruptured intracranial aneurysm in persons with one first-degree relative with aneurysmal subarachnoid haemorrhage are cost effective compared with no screening, when applying a cost-effectiveness threshold of €20,000/quality-adjusted life year. We recommend discussing with persons at risk the option of screening twice, at age 40 and 55, which will result overall in substantial health benefits at acceptable additional costs.

Management of Unruptured Intracranial Aneurysms.

Unruptured intracranial aneurysms (UIA) occur in approximately 2-3% of the population. Most of these lesions are incidentally found, asymptomatic and typically carry a benign course. Although the risk of aneurysmal subarachnoid hemorrhage is low, this complication can result in significant morbidity and mortality, making assessment of this risk the cornerstone of UIA management. This article reviews important factors to consider when managing unruptured intracranial aneurysms including patient demographics, comorbidities, family history, symptom status, and aneurysm characteristics. It also addresses screening, monitoring, medical management and current surgical and endovascular therapies.

Elevated relative risk of aneurysmal subarachnoid hemorrhage with colder weather in the mid-Atlantic region

We have previously reported an increase of 0.6% in the relative risk of aneurysmal subarachnoid hemorrhage (aSAH) in response to every 1°F decrease in the maximum daily temperature (Tmax) in colder seasons from patients presenting to our regional tertiary care center. We hypothesized that this relationship would also be observed in the warmer summer months with ambient temperatures greater than 70°F. From prospectively collected incidence data for aSAH patients, we investigated absolute Tmax, average daily temperatures, intraday temperature ranges, and the variation of daily Tmax relative to 70°F to assess associations with aSAH incidence for patients admitted to our institution between 1991 and 2009 during the hottest months and days on which Tmax>70°F. For all days treated as a group, the mean Tmax (± standard deviation) was lower when aSAH occurred than when it did not (64.4±18.2°F versus 65.8±18.3°F; p=0.016). During summer months, the odds ratio (OR) of aSAH incidence increased with lower mean Tmax (OR 1.019; 95% confidence interval 1.001–1.037; p=0.043). The proportion of days with aSAH admissions was lower on hotter days than the proportion of days with no aSAH (96% versus 98%; p=0.006). aSAH were more likely to occur during the summer and on days with a temperature fluctuation less than 10°F (8% versus 4%; p=0.002). During the hottest months of the year in the mid-Atlantic region, colder maximum daily temperatures, a smaller heat burden above 70°F, and smaller intraday temperature fluctuations are associated with increased aSAH admissions in a similar manner to colder months. These findings support the hypothesis that aSAH incidence is more likely with drops in temperature, even in the warmer months.

Long-term risk of aneurysmal subarachnoid hemorrhage after a negative aneurysm screen.

The objective was to assess the risk of aneurysmal subarachnoid hemorrhage (aSAH) in the initial 15 years after negative aneurysm screening in persons with one first-degree relative with aSAH. From a cohort of first-degree relatives of patients with aSAH who underwent screening between 1995 and 1997 (n = 626), we included those with a negative screening (n = 601). We retrieved all causes of death and sent a questionnaire to screenees who were still alive. If aSAH was reported, we reviewed all medical data. We assessed the incidence of aSAH in this cohort with survival analysis and calculated an incidence ratio by dividing the observed incidence with the age- and sex-adjusted incidence in the general population. Of the 601 screenees, 3 had aSAH during 8,938 follow-up patient-years (mean 14.9 years). After 15 years, the cumulative incidence was 0.50% (95% confidence interval: 0.00%-1.06%) with an incidence rate of 33.6 per 100,000 person-years; the incidence rate ratio was 1.7 (95% confidence interval: 0.3-5.7). In the first 15 years after a negative screening, the risk of aSAH in persons with one first-degree relative with aSAH is not nil, but in the range of that in the general population, or even higher. Whether this finding justifies serial aneurysm screening in this population requires further study.

Independent Risk Factors for Intracranial Aneurysms and Their Joint Effect

Three percent of the population has an unruptured intracranial aneurysm (UIA). We aimed to identify independent risk factors from lifestyle and medical history for the presence of UIAs and to investigate the combined effect of well-established risk factors. We studied 206 patients with an UIA who never had a subarachnoid hemorrhage and 574 controls who were randomly retrieved from general practitioner files. All participants filled in a questionnaire on potential risk factors for UIAs. With logistic regression analysis, we identified independent risk factors for UIA and assessed their combined effect. Independent risk factors were current smoking (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.0-4.5), hypertension (OR, 2.9; 95% CI, 1.9-4.6), family history of stroke other than subarachnoid hemorrhage (OR, 1.6; 95% CI, 1.0-2.5), hypercholesterolemia (OR, 0.5; 95% CI, 0.3-0.9), and regular physical exercise (OR, 0.6; 95% CI, 0.3-0.9). The joint risk of smoking and hypertension was higher (OR, 8.3; 95% CI, 4.5-15.2) than the sum of the risks independently. Current smoking, hypertension, and family history of stroke increase the risk of UIA, with smoking and hypertension having an additive effect, whereas hypercholesterolemia and regular physical exercise decrease this risk. A healthy lifestyle probably reduces the risk of UIA and thereby possibly also that of aneurysmal subarachnoid hemorrhage. Whether smoking and hypertension increase the risk of aneurysmal subarachnoid hemorrhage only through an increased risk of aneurysm formation or also through an increased risk of rupture remains to be established.

Joint Effect of Modifiable Risk Factors on the Risk of Aneurysmal Subarachnoid Hemorrhage

The joint effect of risk factors on the risk of aneurysmal SAH (aSAH) has been studied sparsely. We examined the potential synergism between cigarette smoking, hypertension, and regular alcohol consumption and the risk of aSAH in a prospective, population-based cohort of participants from the Nord-Trøndelag Health Study and the Tromsø Study in Norway. Interaction was assessed on additive and multiplicative scales. We identified 122 cases of aSAH over 977 895 person-years of follow-up. Interaction was observed between current smoking and hypertension on the additive scale, (relative excess risk because of interaction, 6.40; 95% CI, 0.88-11.92, adjusted for sex and age). We found no significant interaction between hypertension and regular alcohol consumption or current cigarette smoking and regular alcohol consumption on the additive scale. No significant interaction was detected on the multiplicative scale. The joint effect of current smoking and hypertension on the risk of aSAH was stronger than was the sum of the independent effects of each factor. Persons at risk of aSAH should be advised of a markedly stronger risk for aSAH with the combination of current smoking and hypertension. In addition, the finding suggests that combining smoking cessation and blood pressure lowering may have an extra risk reduction effect on preventing aSAH.