Risk Of Aneurysmal Subarachnoid Hemorrhage Research Articles

Causal relationships between gut microbiota and Aneurysmal Subarachnoid Hemorrhage: A Bidirectional Mendelian Randomization Study

Background and PurposeAneurysmal Subarachnoid Hemorrhage (aSAH) poses a significant health burden globally, necessitating a deeper understanding of its etiology and potential preventive strategies. Recent research has suggested a possible link between gut microbiota composition and the risk of vascularity, prompting investigation into this association using Mendelian Randomization (MR) analysis. Here, we aimed to elucidate the causal relationship between gut microbiota composition and aSAH risk utilizing MR analysis. MethodsWe employed four distinct MR methodologies, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, to assess the causal nexus between gut microbiota composition and aSAH risk. Genetic instrumental variables (IVs) associated with gut microbiome composition were selected from a comprehensive multiethnic genome-wide association study (GWAS) involving 18,473 individuals across diverse geographic regions. Sensitivity analyses were conducted to detect potential heterogeneity and pleiotropy. ResultsOur Mendelian Randomization (MR) analyses unveiled a substantial and statistically significant causal relationship between gut microbiota composition and the risk of Aneurysmal Subarachnoid Hemorrhage (aSAH). Employing the Inverse Variance Weighted (IVW) method, we observed negative associations between aSAH and specific taxonomic levels of gut microbiota. Specifically, the IVW approach identified significant associations with one order, Victivallales (PIVW=0.047, OR: 0.78, 95% CI: 0.62-0.99), one family, Porphyromonadaceae (PIVW=0.03, OR: 0.64, 95% CI: 0.43-0.95), one class, Lentisphaeria (PIVW=0.047, OR: 0.78, 95% CI: 0.62-0.99), and three genera: Bilophila (PIVW=0.02, OR: 0.68, 95% CI: 0.50-0.93), Fusicatenibacter (PIVW=0.04, OR: 0.69, 95% CI: 0.49-0.98), and Ruminococcus1 (PIVW=0.01, OR: 0.51, 95% CI: 0.32-0.84). These findings were consistent across various MR methodologies, underscoring the robustness of our results. Sensitivity analyses further validated the stability of our findings, with no evidence of heterogeneity or pleiotropy detected. ConclusionOur study provides compelling evidence supporting a causal relationship between gut microbiota composition and the risk of aSAH. These findings underscore the potential therapeutic implications of modulating gut microbiota to prevent and manage aSAH. Further research is warranted to explore the underlying mechanisms and develop targeted interventions aimed at mitigating aSAH risk through gut microbiota modulation.

Screening for intracranial aneurysms in persons ⩾35 years with hypertension and atherosclerotic disease who smoke(d).

Lifetime risk of aneurysmal subarachnoid haemorrhage (aSAH) is high (7%) in persons ⩾35 years with hypertension who smoke(d). Whether screening for intracranial aneurysms (IAs) to prevent aSAH is effective in these patients is unknown. Participants were retrieved from a cohort of patients with clinically manifest atherosclerotic vascular disease included between 2012 and 2019 at the University Medical Centre Utrecht (SMART-ORACLE, NCT01932671) in whom CT-angiography (CTA) of intracranial arteries was performed. We selected patients ⩾35 years with hypertension who smoke(d). CTAs were reviewed for the presence of IAs by experienced neuroradiologists. Patients with IAs were offered follow-up imaging to detect aneurysmal growth. We determined aneurysm prevalence and developed a diagnostic model for IA risk at screening using multivariable logistic regression. IA were found in 25 of 500 patients (5.0% prevalence, 95%CI: 3.3%-7.3%). Median 5 year risk of rupture assessed with the PHASES score was 0.9% (IQR: 0.7%-1.3%). During a median follow-up of 57 months (IQR: 39-83 months) no patients suffered from aSAH. Aneurysmal growth was detected in one patient for whom preventive treatment was advised. IA risk at screening ranged between 1.6% and 13.4% with predictors being age, female sex and current smoking. IA prevalence in persons ⩾35 years with hypertension and atherosclerotic vascular disease who smoke(d) was 5%. Given the very small proportion of IA that needed preventive treatment, we currently do not advise screening for Caucasian persons older than 35 years of age who smoke and have hypertension in general. Whether screening may be effective for certain subgroups (e.g. women older than 50 years of age) or other ethnic populations should be the subject of future studies.

Several Risk Factors for Aneurysmal Subarachnoid Hemorrhage

We reviewed current literature on the role of seasonal, meteorological, or circadian factors in ruptured cerebral aneurysms. We found that cerebral aneurysm rupture most frequently occurs in winter and spring, and less frequently in summer. The highest number of ruptured cerebral aneurysms happens in the morning, between 8 am and 12 pm. The data regarding meteorological factors' effect on the risk of cerebral aneurysm rupture are conflicting. However, it should be noted that changes in barometric pressure and falling temperature are associated with the risk of aneurysmal subarachnoid hemorrhage.

Serum Calcium, 25-Hydroxyvitamin D, and Parathyroid Hormone Levels in Relation to Aneurysmal Subarachnoid Hemorrhage.

Elevated serum calcium (S-Ca), 25-hydroxyvitamin D (S-25OHD), and parathyroid hormone (S-PTH) levels have been associated with risk of aneurysmal subarachnoid hemorrhage (SAH) in observational studies. However, whether these associations are causal is unclear. The objective of the present study was to determine whether genetically predicted S-Ca, S-25OHD, and S-PTH levels are causally associated with aneurysmal SAH using a Mendelian randomization design. Analyses were performed using summary-level data for genetic variants associated with S-Ca, S-25OHD, and S-PTH concentrations. Summary data for aneurysmal SAH were adopted from a genome-wide association study (GWAS) on intracranial aneurysm (n = 79,429 individuals, 69% of the cases had aneurysmal SAH). The inverse variance-weighted approach was adopted as the primary analyses. For sensitivity analyses, the weighted median and MR-Egger approaches were adopted. Genetically predicted S-Ca and S-PTH levels were associated with aneurysmal SAH in the primary analyses. The odds ratios (ORs) of aneurysmal SAH were 1.96 (95% CI: 1.003-3.812; P = 0.049) and 1.495 (95% CI: 1.058-2.114; P = 0.023) for one SD increase of genetically predicted S-Ca and S-PTH levels, respectively. Genetically predicted S-25OHD concentration was not associated with aneurysmal SAH (per 1 SD increase in S-25OHD: OR = 0.92; 95% CI, 0.78-1.09; P = 0.332). Sensitivity analysis yielded similar results, and no evidence of pleiotropy was observed. Our results indicated that higher genetically predicted S-Ca and S-PTH levels may increase the risk of aneurysmal SAH.

Associations Between Drug Treatments and the Risk of Aneurysmal Subarachnoid Hemorrhage: a Systematic Review and Meta-analysis.

There is increasing interest in drug therapy for preventing aneurysmal subarachnoid hemorrhage (aSAH). We aimed to comprehensively evaluate the association between drug use and the risk of aSAH. We searched PubMed and Scopus from the databases' inception until December 2021. Observational studies reporting the association between any drug therapy and aSAH were included. The odds ratios (ORs) for each drug used in aSAH were meta-analyzed with a random-effect model. According to the systematic review, 25 observational studies were eligible for the present study. Four therapeutic purpose-based classes (e.g., lipid-lowering agents) and 14 mechanism-based classes (e.g., statins) were meta-analyzed. Anti-hypertensive agents (OR, 0.50; 95% confidence interval [95% CI], 0.33-0.74), statins (OR, 0.55; 95% CI, 0.35-0.85), biguanides (OR, 0.57; 95% CI, 0.34-0.96), and acetylsalicylic acid (ASA) (OR, 0.62; 95% CI, 0.41-0.94) were inversely associated with the risk of aSAH. Non-ASA non-steroidal anti-inflammatory drugs (OR, 1.73; 95% CI, 1.07-2.79), selective cyclooxygenase-2 inhibitors (OR, 2.04; 95% CI, 1.24-3.35), vitamin K antagonists (OR, 1.50; 95% CI, 1.18-1.91), and dipyridamole (OR, 1.77; 95% CI, 1.23-2.54) were positively associated with the incidence of aSAH. There was also a trend toward a positive association between glucocorticoids (OR, 1.38; 95% CI, 0.97-1.94) and aSAH. The present study suggests that anti-hypertensive agents, statins, biguanides, and ASA are candidate drugs for preventing aSAH. By contrast, several drugs (e.g., anti-thrombotic drugs) may increase the risk of aSAH. Thus, the indications of these drugs in patients with intracranial aneurysms should be carefully determined.

Lysyl oxidase family gene polymorphisms and risk of aneurysmal subarachnoid hemorrhage: a case-control study.

BackgroundAneurysmal subarachnoid hemorrhage (aSAH) is a devastating disease caused by intracranial aneurysm (IA) rupture. Lysyl oxidase (LOX) family genes (LOX-like [LOXL] 1-4) have roles in collagen cross-linking in the extracellular matrix (ECM) and may be associated with IA rupture. We aimed to explore the association between LOX polymorphisms and the risk of aSAH.MethodsThis case-control study included 2 cohorts: 133 single ruptured and 115 unruptured IA patients, and 65 multiple ruptured and 71 unruptured IA patients. Genotyping of 27 single nucleotide polymorphisms (SNPs) in LOX was performed. Logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of the SNPs of LOX and the risk of aSAH.Results LOX rs1800449 and LOXL4 rs3793692 were positively associated with the risk of single IA rupture in the recessive model (OR =5.66, 2.06; 95% CI =1.22–26.24, 1.11–3.82, respectively) and LOX rs10519694 demonstrated a protective effect on single IA rupture (dominant model: OR =0.42, 95% CI =0.21–0.83; recessive model: OR =0.16, 95% CI =0.04–0.65; additive model: OR =0.46, 95% CI =0.28–0.78). LOXL1 rs2165241, LOXL2 rs1063582, and LOXL3 rs17010021 showed risk effects on multiple IAs rupture. LOXL3 rs17010022 showed a protective effect on multiple IAs ruptures (dominant model: OR =0.41, 95% CI =0.21–0.82; additive model: OR =0.51, 95% CI =0.30–0.85).Conclusions LOX and LOXL4 may be susceptibility genes for single IA rupture, whereas LOXL1-3 may have a role in susceptibility to multiple IAs ruptures in the Chinese population, suggesting that LOX family genes may be associated with aSAH.

Liver Cirrhosis and Inpatient Mortality in Aneurysmal Subarachnoid Hemorrhage: A Propensity-Adjusted Analysis

Liver cirrhosis is associated with an increased risk of aneurysmal subarachnoid hemorrhage (aSAH). However, large studies analyzing the prognosis of cirrhotic patients after aSAH treatment are lacking. This study explores factors associated with inpatient mortality among aSAH patients with cirrhosis. All patients who underwent open or endovascular treatment for an aSAH at a large quaternary center between January 1, 2003, and July 31, 2019, were retrospectively reviewed. Patients were grouped into cirrhosis versus noncirrhosis groups. Univariate analysis determined variables associated with inpatient mortality. Variables with P < 0.20 were included in a propensity-adjusted multivariable logistic regression analysis to predict inpatient mortality. A total of 1419 patients were treated for aSAH; 17 (1.2%) had confirmed cirrhosis. Inpatient mortality was significantly higher among cirrhotic patients than noncirrhotic patients (35.3% vs. 6.8%; P < 0.001). In the univariate analysis for inpatient mortality, the variables cirrhosis, age >65years, Charlson Comorbidity Index >4, aneurysm size ≥10mm, Hunt and Hess grade >3, Fisher grade 4, delayed cerebral ischemia (DCI), and posterior circulation aneurysm had P < 0.20 and were included in the multivariable analysis. The propensity-adjusted stepwise multivariable logistic regression analysis showed that cirrhosis (odds ratio [OR]: 12.7, 95% confidence interval [CI]: 3.3-48.7), Hunt and Hess grade >3 (OR: 3.9, 95% CI: 2.3-6.4), Fisher grade 4 (OR: 3.7, 95% CI: 1.3-10.7), and DCI (OR: 2.4, 95% CI: 1.5-3.9) were associated with inpatient mortality (P ≤ 0.01). Cirrhosis was a predictor of inpatient mortality among aSAH patients and was a stronger predictor than DCI or a poor Hunt and Hess grade among patients in this study.

Treatment during cerebral vasospasm phase—complication association and outcome in aneurysmal subarachnoid haemorrhage

BackgroundAneurysm treatment during cerebral vasospasm (CVS) phase is frequently considered as particularly dangerous, mainly because of the risk of cerebral infarct.ObjectiveWe aimed to evaluate the risk of aneurysmal subarachnoid haemorrhage (aSAH)-specific complications and functional outcome in patients treated during CVS phase.MethodsWe retrospectively analysed a large, retro- and prospectively collected database of aSAH patients admitted to our department between March 2006 and March 2020. We conducted a uni- and multivariable logistic regression analysis to evaluate influencing factors on rebleeding, cerebral infarct, Glasgow Outcome Score (GOS) at discharge and mortality and assessed the rate of angiographic vasospasm on admission.ResultsWe included 853 patients. The majority of patients were female (66.6%), mean age was 57.3 years. Out of 853 included patients, 92 (10.8%) were treated during CVS phase, 312 (36.6%) underwent clipping and 541 (63.4%) endovascular treatment. Treatment during CVS phase was significantly associated with cerebral infarct in the multivariable logistic regression analysis, unrelated to the nature of intervention (OR 2.42, 1.29–4.54 95% CI p-value = 0.006). However, patients treated during CVS phase did not have increased risk of unfavourable outcome by GOS on discharge. In addition, they did not have a higher rate of rebleeding or mortality.ConclusionsTreatment during CVS phase was significantly associated with a higher rate of cerebral infarct as confirmed by imaging. This did not reflect on GOS on discharge, rebleeding, or mortality. Aneurysm treatment during CVS phase is relatively safe and should not be postponed due to the risk of rebleeding and subsequent devastating deterioration.

Sex Hormones and Risk of Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study.

Background:The risk of aneurysmal subarachnoid hemorrhage (aSAH) is increased in postmenopausal women compared with men of similar age, suggesting a role for sex hormones. We aimed to explore whether sex hormones, and age at menarche/menopause have a causal effect on aSAH risk by conducting a 2-sample MR study (Mendelian randomization).Methods:We obtained sex-specific genetic instruments for serum estradiol, bioavailable testosterone (BioT), SHBG (sex hormone-binding globulin), and age at menarche/menopause from genome-wide association studies. The associated sex-specific aSAH risk was estimated with inverse-variance weighted MR analyses with various statistical sensitivity analyses. Multivariable and cluster MR analyses were performed for BioT and SHBG to account for a genetic and phenotypic correlation between the 2 exposures. The clusters represented (1) single-nucleotide polymorphisms primarily increasing SHBG, with secondary decreasing effects on BioT, and (2) single-nucleotide polymorphisms affecting BioT without affecting SHBG.Results:Univariable MR analyses showed an 18% increased aSAH risk among women per 1-SD increase in genetically determined SHBG levels (odds ratio, 1.18 [95% CI, 1.05–1.34]; P=0.007). Suggestive evidence was identified for a 27% decreased risk of aSAH among women per 1-SD increase in BioT (odds ratio, 0.73 [95% CI, 0.55–0.95]; P=0.02). The latter association disappeared in cluster analysis when only using SHBG-independent variants. MR analyses with variants from the cluster with primary SHBG effects and secondary (opposite) BioT-effects yielded a statistically significant association (odds ratio, 1.21 [95% CI, 1.05–1.40]; P=0.008). No other causal associations were identified.Conclusions:Genetic predisposition to elevated serum levels of SHBG, with secondary lower serum BioT levels, is associated with an increased aSAH risk among women, suggesting that SHBG and BioT causally elevate aSAH risk. Further studies are required to elucidate the underlying mechanisms and their potential as an interventional target to lower aSAH incidence.

Cumulative Time of Cigarette Smoking Is Associated with a Greater Risk of Aneurysmal Subarachnoid Hemorrhage and Younger Age at Presentation: A Nationwide Observation Study

Smoking is known to be associated with an increased risk of intracranial aneurysm rupture; however, the risk in smokers stratified by age, sex, and aneurysm location is not clear. A retrospective study of all aneurysmal subarachnoid hemorrhage (aSAH) cases in Australia between 2008 and 2018 was conducted. The relative risk of aSAH in smokers compared with nonsmokers was calculated on the basis of nationwide smoking statistics and was stratified according to sex, age group, and aneurysm location. Out of 12,915 aSAH patients, 3249 (25.2%) were active smokers. Across both men and women, smoking increased the risk of aSAH by 2.4× in 30- to 39-year-olds (95% CI 2.1-2.7), 2.4× in 40- to 49-year-olds (95% CI 2.2-2.7), 2.3× in 50- to 59-year-olds (95% CI 2.1-2.4), and 1.8× in 60- to 69-year-olds (95% CI 1.7-2.0) with less of an effect in smokers younger than 30 years (RR: 1.2, 95% CI 1.0-1.5) and older than 70 years (RR: 1.0, 95% CI 0.9-1.2). Compared with a nonsmoker younger than 30 years old, the relative risk of aSAH increased by an average of 7.2 for every decade spent smoking in women and an average of 4.0 for every decade spent smoking in men. Additionally, smokers were 5.2× more likely to present before 50 years of age. Smoking increased the risk of aSAH by 2-fold between the ages of 30 and 60. Smokers experienced aSAH at younger ages.

Association of Reproductive Life Span and Age at Menopause With the Risk of Aneurysmal Subarachnoid Hemorrhage.

Subarachnoid hemorrhage from cerebral aneurysm remains a devastating disease with high mortality and morbidity. Cerebral aneurysm and its rupture are more prevalent in postmenopausal women and have been postulated to be hormonally influenced. The goal of this study was to investigate the associations of female-specific factors, including reproductive life span, age at menarche, and age at menopause, with the incidence of aneurysmal subarachnoid hemorrhage (aSAH) in women. Participants in the Nurses' Health Study were followed up from 1980 or the time of reaching menopause until 2018. Only women with natural menopause or surgical menopause due to bilateral oophorectomy were included. Reproductive life span was defined by subtracting the age at menarche from the age at menopause. Multivariable-stratified proportional hazards models were used to study reproductive life span, age at menarche, and age at menopause with the incidence of aSAH. Multivariable models were adjusted for age, race, smoking, hysterectomy, hypertension, hyperlipidemia, body mass index, hormone therapy use, oral contraceptive use, and parity. A total of 97,398 postmenopausal women with reproductive life span data were included; 138 participants developed aSAH, which was confirmed on medical record review by a physician. A shorter reproductive life span (≤35 years) was associated with a 2-fold higher incidence of aSAH after multivariable adjustment (hazard ratio [HR] 2.0 [95% CI 1.4-2.8]). Early age at menopause (age <45 years) was similarly associated with a higher risk of aSAH (HR 2.1 [95% CI 1.4-3.1]), but age at menarche was not. Use of oral contraceptives and postmenopausal hormone therapy was not associated with the incidence of aSAH. An earlier age at menopause and a shorter reproductive life span duration (≤35 years) were associated with a higher risk of incident aSAH in women. No associations were noted for age at menarche, parity, oral contraceptive use, or postmenopausal therapy use.

137 A Review of Current Criteria for Risk of Aneurysmal Subarachnoid Haemorrhage

Abstract Introduction There is a need to evaluate the existing guidelines regarding the size criteria for the risk of rupture of intracranial aneurysms. The current understanding is that small intracranial aneurysms (less than 7 mm) are not at significant risk for rupture according to the ISUIA 1 &amp; 2 trials. However, there have been several published series of rupture and subarachnoid haemorrhage from aneurysms less than 5 mm in both, anterior and posterior cerebral circulation. Methods We conducted a systematic review of aneurysmal subarachnoid haemorrhage, specifically to identify their size and the anatomical location at the time of rupture, using the healthcare databases advanced search. Results Our search yielded 1438 results matching our inclusion criteria. Our results demonstrated that 50.4 – 76.8% of aneurysms were under 7 mm in diameter at the time of rupture. Subarachnoid haemorrhage from smaller aneurysms (&amp;lt;5 mm) was also shown to present with poor prognoses (Hunt and Hess grades 4–5). There were no significant differences observed between the anterior and posterior circulation. Conclusions The existing criterion to determine the risk of rupture of intracranial aneurysms need to be updated, accounting for multiple clinical factors including, but not limited to, the size. With advances in endovascular treatments in recent years, the associated intra-procedural risks are greatly reduced compared to traditional neurosurgical approaches, making the argument for intervention at earlier presentations.

Number of Affected Relatives, Age, Smoking, and Hypertension Prediction Score for Intracranial Aneurysms in Persons With a Family History for Subarachnoid Hemorrhage.

Background:Persons with a positive family history of aneurysmal subarachnoid hemorrhage are at increased risk of aneurysmal subarachnoid hemorrhage. Preventive screening for intracranial aneurysms (IAs) in these persons is cost-effective but not very efficient. We aimed to develop and externally validate a model for predicting the probability of an IA at first screening in persons with a positive family history of aneurysmal subarachnoid hemorrhage.Methods:For model development, we studied results from initial screening for IA in 660 prospectively collected persons with ≥2 affected first-degree relatives screened at the University Medical Center Utrecht. For validation, we studied results from 258 prospectively collected persons screened in the University Hospital of Nantes. We assessed potential predictors of IA presence in multivariable logistic regression analysis. Predictive performance was assessed with the C statistic and a calibration plot and corrected for overfitting.Results:IA were present in 79 (12%) persons in the development cohort. Predictors were number of affected relatives, age, smoking, and hypertension (NASH). The NASH score had a C statistic of 0.68 (95% CI, 0.62–0.74) and showed good calibration in the development data. Predicted probabilities of an IA at first screening varied from 5% in persons aged 20 to 30 years with two affected relatives, without hypertension who never smoked, up to 36% in persons aged 60 to 70 years with ≥3 affected relatives, who have hypertension and smoke(d). In the external validation data IA were present in 67 (26%) persons, the model had a C statistic of 0.64 (95% CI, 0.57–0.71) and slightly underestimated IAs risk.Conclusions:For persons with ≥2 affected first-degree relatives, the NASH score improves current predictions and provides risk estimates for an IA at first screening between 5% and 36% based on 4 easily retrievable predictors. With the information such persons can now make a better informed decision about whether or not to undergo preventive screening.

Preventive screening for intracranial aneurysms.

BackgroundSubarachnoid hemorrhage from rupture of an intracranial aneurysm (aneurysmal subarachnoid hemorrhage) is a devastating subset of stroke. Since brain damage from the initial hemorrhage is a major cause for the poor outcome after aneurysmal subarachnoid hemorrhage, prevention of aneurysmal subarachnoid hemorrhage has the highest potential to prevent poor outcome from aneurysmal subarachnoid hemorrhage.AimIn this review, we describe the groups at high risk of aneurysmal subarachnoid hemorrhage who may benefit from preventive screening for unruptured intracranial aneurysms followed by preventive treatment of unruptured intracranial aneurysms found. Furthermore, we describe the advantages and disadvantages of screening and advise how to perform counseling on screening.Summary of reviewModeling studies show that persons with two or more affected first-degree relatives with aneurysmal subarachnoid hemorrhage and patients with autosomal dominant polycystic kidney disease (ADPKD) are candidates for screening for unruptured intracranial aneurysms. One modeling study also suggests that persons with only one affected first-degree relative with aneurysmal subarachnoid hemorrhage are also likely candidates for screening. Another group who may benefit from screening are persons ≥35 years who smoke(d) and are hypertensive, given their high lifetime risk of aneurysmal subarachnoid hemorrhage of up to 7%, but the prevalence of unruptured intracranial aneurysms in such persons and the efficiency and cost-effectiveness of screening in this group are not yet known. The ultimate goal of screening is to increase the number of quality years of life of the screening candidates, and therefore the benefits but also many downsides of screening –such as risk of incidental findings, very small unruptured intracranial aneurysms that require regular follow-up, preventive treatment with inherent risk of complications and anxiety – should be discussed with the candidate so that an informed decision can be made before intracranial vessels are imaged.ConclusionsSeveral groups of persons who may benefit from screening have been identified, but since these constitute only a minority of all aneurysmal subarachnoid hemorrhage patients, additional high-risk groups still need to be identified. Further research is also needed to identify persons at low or high risk of aneurysmal development and rupture within the groups identified thus far to improve the efficiency of screening. Moreover, if new medical treatment strategies that can reduce the risk of rupture of unruptured intracranial aneurysm become available, the groups of persons who may benefit from screening could increase considerably.

Trends of Ruptured and Unruptured Aneurysms Treatment in the United States in Post-ISAT Era: A National Inpatient Sample Analysis.

BackgroundThe ISAT (International Subarachnoid Aneurysm Trial) has generated a paradigm shift towards endovascular treatment for intracranial aneurysms but remains unclear if this has led to a true reduction in the risk for aneurysmal subarachnoid hemorrhage (aSAH). We sought to study the association between the treatment burden of unruptured and ruptured aneurysms in the post‐ISAT era.Methods and ResultsAdmissions data from the National Inpatient Sample (2004–2014) were extracted, including patients with a primary diagnosis of aSAH or unruptured intracranial aneurysms treated by clipping or coiling. Within each year, this combined group was randomly matched to non‐aneurysmal control group, based on age, sex, and Elixhauser comorbidity index. Multinomial regression was performed to calculate the relative risk ratio of undergoing treatment for either ruptured or unruptured aneurysms in comparison with the reference control group, adjusted for time. After adjusting for National Inpatient Sample sampling effects, 243 754 patients with aneurysm were identified, 174 580 (71.6%) were women; mean age, 55.4±13.2 years. A total of 121 882 (50.01%) patients were treated for unruptured aneurysms, 79 627 (65.3%) endovascularly and 42 256 (34.7%) surgically. A total of 121 872 (49.99%) patients underwent procedures for aSAH, 68 921 (56.6%) endovascular, and 52 951 (43.5%) surgically. Multinomial regression revealed a significant year‐to‐year decrease in aSAH procedures compared with the control group of non‐aneurysmal hospitalizations (relative risk ratio, 0.963 per year; P<0.001), while there was no statistical significance for unruptured aneurysms procedures (relative risk ratio, 1.012 per year; P=0.35).ConclusionsWith each passing year, there is a significant decrease in relative risk ratio of undergoing treatment for aSAH, concomitant with a stable annual risk of undergoing treatment for unruptured intracranial aneurysms.

Letter to the Editor Regarding “Association Between Aspirin Use and Risk of Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis”

Letter to the Editor Regarding “Association Between Aspirin Use and Risk of Aneurysmal Subarachnoid Hemorrhage: A Meta-Analysis”

Relationship between aspirin use and subarachnoid hemorrhage: A systematic Review and meta-analysis

BackgroundAspirin has been associated with a decreasing risk of subarachnoid hemorrhage due to its anti-inflammatory mechanism of action and potential protective properties against aneurysm growth. ObjectiveTo determine the association between aneurysmal subarachnoid hemorrhage and aspirin use. MethodsA systematic review of the literature and a meta-analysis were performed across the PubMed database. The following keywords were used: “aspirin, acetylsalicylic acid, 2-acetyloxy-benzoic acid, ruptured intracranial aneurysm, aneurysmal subarachnoid hemorrhage, spontaneous subarachnoid hemorrhage, intracerebral hemorrhage, spontaneous aneurysmal hemorrhage, spontaneous intracerebral bleeding”. Studies that were performed with animals or analyzed patients with traumatic brain injury were excluded. A total of five studies were included in our meta-analysis, with a total of 19,222 patients evaluated. Statistical analysis was performed to determine the association between the use of aspirin and the risk of subarachnoid hemorrhage. ResultsAspirin use reduce the risk of subarachnoid hemorrhage (odds ratio [OR] 0.51, 95 % confidence interval [CI] 0.34-0.76). ConclusionAlthough some previous studies suggested that aspirin may potentially reduce the risk of subarachnoid hemorrhage, our meta-analysis found an association between the reduction of risk of aneurysmal subarachnoid hemorrhage.

Predicting the Poor Recovery Risk of Aneurysmal Subarachnoid Hemorrhage: Clinical Evaluation and Management Based on a New Predictive Nomogram

PurposeTo develop and validate a model for identifying the risk factors of poor recovery in patients with aneurysmal subarachnoid hemorrhage (aSAH). MethodsA prediction model was developed using training data obtained from 1577 aSAH patients from multiple centers. The patients were followed for 6 months on average and assessed using the modified Rankin Scale; patient information was collected with a prospective case report form. The least absolute shrinkage and selection operator regression were applied to optimize factor selection for the poor recovery risk model. Multivariable logistic regression, incorporating the factors selected in the previous step, was used for model predictions. Predictive ability and clinical effectiveness of the model were evaluated using C-index, receiver operating characteristic curve, and decision curve analysis. Internal validation was performed using the C-index, taking advantage of bootstrapping validation. ResultsThe predictors included household income per capita, hypertension, smoking, migraine within a week before onset, Glasgow Coma Scale at admission, average blood pressure at admission, modified Fisher score at admission, treatment method, and complications. Our newly developed model made satisfactory predictions; it had a C-index of 0.796 and an area under the receiver operating characteristic curve of 0.784. The decision curve analysis showed that the poor recovery nomogram was of clinical benefit when an intervention was decided at a poor recovery threshold between 2% and 50%. Internal validation revealed a C-index of 0.760. ConclusionOur findings indicate that the novel poor recovery nomogram may be conveniently used for risk prediction in aSAH patients. For patients with intracranial aneurysms, migraine needs to be vigilant. Quitting smoking and blood pressure management are also beneficial.

Abstract 144: Roles of Aging and Cellular Senescence in Intracranial Aneurysm Rupture

Background: Aging is an independent risk factor for the rupture of intracranial aneurysm. One of the hallmarks of aging is chronic tissue inflammation. Sirtuin-1 keeps inflammation in check through the deacetylation of various proteins. It is well known that the levels of Sirtuin-1 in vascular tissues decrease with aging, resulting in chronic vascular inflammation. Age-dependent decrease in Sirtuin-1 may explain the link between aging and increased risk for aneurysmal rupture. Hypothesis: Reduction of Sirtuin-1 promotes aneurysmal rupture by inducing sustained aneurysmal wall inflammation. Methods: First, we assessed the levels of Sirtuin-1 expression in intracranial aneurysm tissues from patients older than 70 y.o. and compared with those from the younger patients (40 to 50 y.o.). Second, using a mouse model, we tested effects of Sirtuin-1 specific activator SRT1720 (15mg/kg/day) and specific inhibitor EX-527 (2.5mg/kg/day) on the development of aneurysmal rupture. In addition, we assessed the mRNA expression of inflammatory cytokines (IL-6, IL-1beta, MCP-1, and MMP-9) in cerebral arteries and aneurysms in mice treated with vehicle, SRT1720, or EX-527. Results: Sirtuin-1 expression levels in intracranial aneurysm tissues from the older patients were lower than those from the younger patients. The pharmacological inhibition of Sirtuin-1 increased rupture rate in mice (vehicle vs. EX-527: 58% vs. 88%, P &lt;0.05). Moreover, the pharmacological activation of Sirtuin-1 reduced rupture rate in mice (vehicle vs. SRT1720: 80% vs. 50%, P &lt;0.05). Levels of IL-6, MMP-9 mRNAs in cerebral arteries were significantly higher in the inhibitor group than in the vehicle group. On the other hand, both mRNA levels were lower in the activator group than in the vehicle group. Conclusions: Our findings suggest that the reduction of Sirtuin-1 promotes aneurysmal rupture via the induction of inflammation. This may explain the increased risk for aneurysmal subarachnoid hemorrhage in the older population. Our findings may become a basis for future studies to develop new therapies that target Sirtuin-1 for the prevention of aneurysmal rupture, especially in older patients.

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.