Risk Factors For Intracranial Aneurysms Research Articles

A predictive model for the recurrence of intracranial aneurysms following coil embolization.

This study aimed to identify risk factors for intracranial aneurysms (IAs) recurrence and establish a predictive model to aid evaluation. A total of 302 patients with 312 IAs undergoing coil embolization between September 2017 and October 2022 were divided into two groups based on digital subtraction angiography follow-up. Clinical characteristics, operation-related factors, and morphologies were measured. Cox proportional hazard regression was used to identify the risk factors. Hazard ratios (HRs) were used to score points, and a predictive model was established. The test cohorts consisted of 51 IAs. Receiver operating characteristic curves were generated to determine the cutoff values and area under the curves (AUCs). A Delong test was performed to compare the AUCs. Diameter maximum (D max) (p < 0.001, HR = 1.221), Raymond-Roy occlusion classification (RROC) II or III (p = 0.004, HR = 2.852), and ruptured status (p < 0.001, HR = 7.782) were independent risk factors for the recurrence of IAs. A predictive model was established: D max + 2 * RROC (II or III; yes = 1, no = 0) + 6 * ruptured status (yes = 1; no = 0). The AUC of the predictive model (0.818) was significantly higher than those of D max (0.704), RROC (II or III) (0.645), and rupture status (0.683), respectively (Delong test, p < 0.05). The cutoff values of the predictive model and D max were 9.75 points and 6.65 mm, respectively. The D max, RROC (II or III), and ruptured status could independently predict the recurrence of IAs after coil embolization. Our model could aid in practical evaluations.

Impact of blood pressure and antihypertensive drug classes on intracranial aneurysm: a Mendelian randomization study

BackgroundBlood pressure is a risk factor for intracranial aneurysms (IA). Nevertheless, whether various antihypertensive drug classes discriminate in reducing IA risk is unclear. MethodsGenome-wide association study summary statistics for systolic blood pressure (SBP), diastolic blood pressure (DBP), IA (non-ruptured), and IA [subarachnoid hemorrhage (SAH)] were downloaded. To proxy the effects of antihypertensive drugs, genetic variants associated with SBP adjacent to the coding regions of different antihypertensive drugs were selected. The inverse-variance-weighted (IVW) method was employed as the primary method for causal estimation. In addition, three additional MR methods and sensitivity tests were utilized to assess the reliability. ResultsElevated blood pressure significantly increases the risk of IA: (i) SBP-IA (non-ruptured): odds ratio (OR) = 1.046, 95 % confidence interval (CI): 1.032-1.061, P = 1.05E-10; (ii) SBP-IA (SAH): OR = 1.040, 95 % CI: 1.030-1.050, P = 2.56E-15; (iii) DBP-IA (non-ruptured): OR = 1.082, 95 % CI: 1.056-1.110, P = 3.15E-10; (iv) DBP-IA (SAH): OR = 1.066, 95 % CI: 1.047-1.085, P = 1.25E-12. In addition, among calcium channel blockers (CCBs), beta-blockers (BBs), and thiazide diuretics (TDs), only SBP mediated by TDs target genes significantly increased the risk of IA (non-rupture) (OR = 1.164, 95 % CI: 1.060-1.279, P = 0.001) and IA (SAH) (OR = 1.136, 95 % CI: 1.063-1.214, P = 1.58E-04), while SBP mediated by target genes of BBs or CCBs did not causally associate with IA. ConclusionElevated blood pressure significantly increases IA risk, while TDs may be a promising antihypertensive medication for reducing IA risk. Further research with larger cohorts is essential for validation.

Sox17 protects human brain microvascular endothelial cells from AngII-induced injury by regulating autophagy and apoptosis.

Intracranial aneurysm (IA), is a localized dilation of the intracranial arteries, the rupture of which is catastrophic. Hypertension is major IA risk factor that mediates endothelial cell damage. Sox17 is highly expressed in intracranial vascular endothelial cells, and GWAS studies indicate that its genetic alteration is one of the major genetic risk factors for IA. Vascular endothelial cell injury plays a vital role in the pathogenesis of IA. The genetic ablation of Sox17 plus hypertension induced by AngII can lead to an increased incidence of intracranial aneurysms had tested in the previous animal experiments. In order to study the underlying molecular mechanisms,we established stable Sox17-overexpressing and knockdown cell lines in human brain microvascular endothelial cells (HBMECs) first. Then flow cytometry, western blotting, and immunofluorescence were employed. We found that the knockdown of Sox17 could worsen the apoptosis and autophagy of HBMECs caused by AngII, while overexpression of Sox17 had the opposite effect. Transmission electron microscopy displayed increased autophagosomes after the knockdown of Sox17 in HBMECs.The RNA-sequencing analysis shown that dysregulation of the Sox17 gene was closely associated with the autophagy-related pathways. Our study suggests that Sox17 could protect HBMECs from AngII-induced injury by regulating autophagy and apoptosis.

Prevalence of Intracranial Aneurysms in Patients With Coarctation of the Aorta: A Systematic Review and Meta-Analysis

BackgroundCoarctation of the aorta (CoA) is associated with intracranial aneurysms (IAs); however, the prevalence and risk factors (RFs) are not well described. Current practice guidelines offer inconsistent recommendations on screening for IAs in this patient population ranging from “not recommended” (European Society of Cardiology 2020) to “recommended” (American Heart Association 2018). ObjectivesThe purpose of this study was to determine the prevalence and RFs for IAs in patients with CoA. MethodsWe completed a systematic review and meta-analysis of studies utilizing computed tomography or magnetic resonance angiographic screening for IAs in patients with CoA. ResultsFive cohort studies were included, representing 442 patients. The pooled prevalence of IAs in patients with CoA was 3.8% [95% CI: 0.1%-12.3%]. The results met our prespecified definition for high heterogeneity. Of 5 RFs evaluated, only hypertension was associated with the development of IAs with an odds ratio of 3.1 [95% CI: 1.1-8.2; P = 0.03]. There was an observed downward trend over time in the prevalence of IAs among the studies included. ConclusionsThe development of IAs is likely multifactorial in etiology and there may be modifiable RFs in their development. Considering the low prevalence of IAs in the pooled result, routine screening of patients with CoA for IAs is likely of low-value.

Identification of co-expressed central genes and transcription factors in atherosclerosis-related intracranial aneurysm.

Numerous clinical studies have shown that atherosclerosis is one of the risk factors for intracranial aneurysms. Calcifications in the intracranial aneurysm walls are frequently correlated with atherosclerosis. However, the pathogenesis of atherosclerosis-related intracranial aneurysms remains unclear. This study aims to investigate this mechanism. The Gene Expression Omnibus (GEO) database was used to download the gene expression profiles for atherosclerosis (GSE100927) and intracranial aneurysms (GSE75436). Following the identification of the common differentially expressed genes (DEGs) of atherosclerosis and intracranial aneurysm, the network creation of protein interactions, functional annotation, the identification of hub genes, and co-expression analysis were conducted. Thereafter, we predicted the transcription factors (TF) of hub genes and verified their expressions. A total of 270 common (62 downregulated and 208 upregulated) DEGs were identified for subsequent analysis. Functional analyses highlighted the significant role of phagocytosis, cytotoxicity, and T-cell receptor signaling pathways in this disease progression. Eight hub genes were identified and verified, namely, CCR5, FCGR3A, IL10RA, ITGAX, LCP2, PTPRC, TLR2, and TYROBP. Two TFs were also predicted and verified, which were IKZF1 and SPI1. Intracranial aneurysms are correlated with atherosclerosis. We identified several hub genes for atherosclerosis-related intracranial aneurysms and explored the underlying pathogenesis. These discoveries may provide new insights for future experiments and clinical practice.

Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity.

Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10-3 per year [95% CI, -6.49×10-3 to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH.

Regular medication as a risk factor for intracranial aneurysms: A comparative case-control study.

Previous medical history strongly contributes to the genesis of intracranial aneurysms (IA). A possible impact of regular medication on the occurrence of abdominal aortic aneurysms has been reported. To evaluate the value of regular medication on the risk of development and rupture of IA. Data on medication use and related comorbidities were obtained from the institutional IA registry. A 1:1 age- and sex-matched patient sample was collected from the population-based Heinz Nixdorf Recall Study with individuals from the same area. In the analysis comparing IA cohort (n = 1960) with the matched normal population (n = 1960), the use of statins (adjusted odds ratio, 1.34 [95% confidence interval 1.02-1.78]), antidiabetics (1.46 [1.08-1.99]), and calcium channel blockers (1.49 [1.11-2.00]) was independently associated with higher risk of IA, whereas uricostatics (0.23 [0.14-0.38]), aspirin (0.23 [0.13-0.43]), beta-blockers (0.51 [0.40-0.66]), and angiotensin-converting enzyme inhibitors (0.38 [0.27-0.53]) were related to lower risk of IA. In the multivariable analysis within the IA cohort (n = 2446), SAH patients showed higher drug exposure with thiazide diuretics (2.11 [1.59-2.80]), but lower prevalence of remaining antihypertensive medication-beta-blockers (0.38 [0.30-0.48]), calcium channel blockers (0.63 [0.48-0.83]), angiotensin-converting enzyme inhibitors (0.56 [0.44-0.72]), and angiotensin-1 receptor blockers (0.33 [0.24-0.45]). Patients with ruptured IA were less likely to be treated with statins (0.62 [0.47-0.81]), thyroid hormones (0.62 [0.48-0.79]), and aspirin (0.55 [0.41-0.75]). Regular medication might impact the risks related to the development and rupture of IA. Further clinical trials are required to clarify the effect of regular medication on IA genesis.

Genetically predicted tobacco consumption and risk of intracranial aneurysm: a Mendelian randomization study.

Several observational studies have suggested that tobacco consumption is a risk factor for intracranial aneurysms (IAs). We here genetically predict the causal association between specific smoking features and biomarkers for smokers and IA risk. The Mendelian randomization (MR) analysis considered summary statistics from the largest current genome-wide association studies of smoking and IA. The inverse-variance weighted (IVW) method, weighted median method, MR-RAPS, and multiple variants Mendelian randomization (MVMR) were performed to estimate the effect of different smoking features and drinking in IA. We observed significant causal effects of smoking on the risk of both aneurysmal subarachnoid hemorrhage (aSAH) and unruptured IA (uIA). The ORs of IAs based on the IVW method were 1.890 (95% CI 1.486-2.405) of ever smoking regularly. MVMR analysis afforded odds ratios of 1.685 (95% CI 1.136-2.501). In the further subgroup analysis, a similar causal relationship was observed in aSAH. Moreover, our analyses suggested that higher blood cotinine level and cadmium increases aSAH risk, and ORs were 1.235 (95%CI 1.009-1.186) and 1.235 (95%CI 1.046-1.458), respectively. Our study suggests that ever smoking regularly is associated with the IA risk, which includes both uIA and aSAH. Besides, higher blood cadmium and cotinine level may increases IA and aSAH risk. Thus, tobacco control should be promoted as primordial prevention for IAs, and screening for patients with a smoking history is emphasized.

Diagnostic yield of TOF-MRA for detecting incidental vascular lesions in patients with cognitive impairment: An observational cohort study.

ObjectivesThe role of three-dimensional (3D) TOF-MRA in patients with cognitive impairment is not well established. We evaluated the diagnostic yield of 3D TOF-MRA for detecting incidental extra- or intracranial artery stenosis and intracranial aneurysm in this patient group.MethodsThis retrospective study included patients with cognitive impairment undergoing our brain MRI protocol from January 2013 to February 2020. The diagnostic yield of TOF-MRA for detecting incidental vascular lesions was calculated. Patients with positive TOF-MRA results were reviewed to find whether additional treatment was performed. Logistic regression analysis was conducted to identify the clinical risk factors for positive TOF-MRA findings.ResultsIn total, 1,753 patients (mean age, 70.2 ± 10.6 years; 1,044 women) were included; 199 intracranial aneurysms were detected among 162 patients (9.2%, 162/1,753). A 3D TOF-MRA revealed significant artery stenoses (>50% stenosis) in 162 patients (9.2%, 162/1,753). The overall diagnostic yield of TOF-MRA was 16.8% (294/1,753). Among them, 92 patients (31.3%, 92/294) underwent either medical therapy, endovascular intervention, or surgery. In total, eighty-one patients with stenosis were prescribed with either antiplatelet medications or lipid-lowering agent. In total, fifteen patients (aneurysm: 11 patients, stenosis: 4 patients) were further treated with endovascular intervention or surgery. Thus, the “number needed to scan” was 19 for identifying one patient requiring treatment. Multivariate logistic regression analysis showed that being female (odds ratio [OR] 2.05) and old age (OR 1.04) were the independent risk factors for intracranial aneurysm; being male (OR 1.52), old age (OR 1.06), hypertension (OR 1.78), and ischemic heart disease history (OR 2.65) were the independent risk factors for significant artery stenosis.ConclusionsOur study demonstrated the potential benefit of 3D TOF-MRA, given that it showed high diagnostic yield for detecting vascular lesions in patients with cognitive impairment and the considerable number of these lesions required further treatment. A 3D TOF-MRA may be included in the routine MR protocol for the work-up of this patient population, especially in older patients and patients with vascular risk factors.

Multinational Genome-Wide Association Study and Functional Genomics Analysis Implicates Decreased SIRT3 Expression Underlying Intracranial Aneurysm Risk.

The genetic mechanisms regulating intracranial aneurysm (IA) formation and rupture are largely unknown. To identify germline-genetic risk factors for IA, we perform a multinational genome-wide association study (GWAS) of individuals from the United Kingdom, Finland, and Japan. To identify a shared, multinational genetic basis of IA. Using GWAS summary statistics from UK Biobank, FinnGen, and Biobank Japan, we perform a meta-analysis of IA, containing ruptured and unruptured IA cases. Logistic regression was used to identify IA-associated single-nucleotide polymorphisms. Effect size was calculated using the coefficient r , estimating the contribution of the single-nucleotide polymorphism to the genetic variance of the trait. Genome-wide significance was set at 5.0 × 10 -8 . Expression quantitative trait loci mapping and functional genomics approaches were used to infer mechanistic consequences of implicated variants. Our cohort contained 155 154 individuals (3132 IA cases and 152 022 controls). We identified 4 genetic loci reaching genome-wide: rs73392700 ( SIRT3 , effect size = 0.28, P = 4.3 × 10 -12 ), rs58721068 ( EDNRA , effect size = -0.20, P = 4.8 × 10 -12 ), rs4977574 ( AL359922.1 , effect size = 0.18, P = 7.9 × 10 -12 ), and rs11105337 ( ATP2B1 , effect size = -0.15, P = 3.4 × 10 -8 ). Expression quantitative trait loci mapping suggests that rs73392700 has a large effect size on SIRT3 gene expression in arterial and muscle, but not neurological, tissues. Functional genomics analysis suggests that rs73392700 causes decreased SIRT3 gene expression. We perform a multinational GWAS of IA and identify 4 genetic risk loci, including 2 novel IA risk loci ( SIRT3 and AL359922.1 ). Identification of high-risk genetic loci across ancestries will enable population-genetic screening approaches to identify patients with IA.

Differences Between Ruptured Aneurysms With and Without Blebs: Mechanistic Implications.

Blebs are known risk factors for intracranial aneurysm (IA) rupture. We analyzed differences between IAs that ruptured with blebs and those that ruptured without developing blebs to identify distinguishing characteristics among them and suggest possible mechanistic implications. Using image-based models, 25 hemodynamic and geometric parameters were compared between ruptured IAs with and without blebs (n = 673), stratified by location. Hemodynamic and geometric differences between bifurcation and sidewall aneurysms and for aneurysms at five locations were also analyzed. Ruptured aneurysms harboring blebs were exposed to higher flow conditions than aneurysms that ruptured without developing blebs, and this was consistent across locations. Bifurcation aneurysms were exposed to higher flow conditions than sidewall aneurysms. They had larger maximum wall shear stress (WSS), more concentrated WSS distribution, and larger numbers of critical points than sidewall aneurysms. Additionally, bifurcation aneurysms were larger, more elongated, and had more distorted shapes than sidewall aneurysms. Aneurysm morphology was associated with aneurysm location (p < 0.01). Flow conditions were different between aneurysm locations. Aneurysms at different locations are likely to develop into varying morphologies and thus be exposed to diverse flow conditions that may predispose them to follow distinct pathways towards rupture with or without bleb development. This could explain the diverse rupture rates and bleb presence in aneurysms at different locations.

Mutation Type and Intracranial Aneurysm Formation in Autosomal Dominant Polycystic Kidney Disease

Background Screening for intracranial aneurysms (IAs) in patients with risk factors of IA is recommended. However, genetic risk factors of IA in patients with autosomal dominant polycystic kidney disease (ADPKD) remain unclear, and genotype–phenotype relationships in IAs in patients with ADPKD have not been clarified. Therefore, we aimed to clarify the associations between germline mutations and IA formation in patients with ADPKD. Methods A total of 135 patients with ADPKD who were evaluated for ADPKD mutations were examined for IA formation in this single‐center observational study. Results The incidence of de novo IA formation was 1.3% per patient‐year. Age at IA diagnosis was younger in patients with frameshift (median, 36 years; P =0.003) and splicing mutations (median, 43 years; P =0.046) than in patients with substitutions (median, 63 years). Multivariable analyses showed that IA was associated with female sex (odds ratio [OR], 3.32 [95% CI, 1.10–10.01]; P =0.03), a family history of IA or subarachnoid hemorrhage (OR, 3.05 [95% CI, 1.07–8.71]; P =0.04), estimated glomerular filtration rate (OR, 0.69 [95% CI, 0.54–0.87]; P =0.002), and splicing mutations (OR, 9.30 [95% CI, 1.71–50.44]; P =0.01). Splicing mutations showed a significant association with IA formation even in subcohorts with minimal risk factors for IA, such as age &lt;50 years (OR, 19.52 [95% CI, 3.22–118.51]; P =0.001), nonhypertension (OR, 49.28 [95% CI, 3.60–673.98]; P =0.004), and nonsmoking behavior (OR, 27.79 [95% CI, 3.49–221.21]; P =0.002). Conversely, substitutions showed significant associations with IA formation in subcohorts such as age ≥50 years (OR, 8.66; 95% CI, 1.43–52.51; P =0.02) and chronic kidney disease stages 4 and 5 (OR, 10.70 [95% CI, 1.05–108.75]; P =0.045). Conclusions Genetic analyses in patients with ADPKD could contribute to IA screening and could be useful for evaluating the prognosis, including complications. IA screening should be recommended for patients with ADPKD who have splicing and frameshift mutations and for older patients or patients with advanced ADPKD who have substitutions.

Diagnosis and risk factors for intracranial aneurysms in autosomal polycystic kidney disease: a cross-sectional study from the Genkyst cohort.

Autosomal dominant polycystic kidney disease (ADPKD) is associated with an increased risk for developing intracranial aneurysms (IAs). We aimed to evaluate the frequency of diagnosis of IAs in the cross-sectional, population-based, Genkyst cohort, to describe ADPKD-associated IAs and to analyse the risk factors associated with the occurrence of IAs in ADPKD patients. A cross-sectional study was performed in 26 nephrology centres from the western part of France. All patients underwent genetic testing for PKD1/PKD2 and other cystogenes. Among the 2449 Genkyst participants, 114 (4.65%) had a previous diagnosis of ruptured or unruptured IAs at inclusion, and ∼47% of them had a positive familial history for IAs. Most aneurysms were small and saccular and located in the anterior circulation; 26.3% of the patients had multiple IAs. The cumulative probabilities of a previous diagnosis of IAs were 3.9%, 6.2% and 8.1% at 50, 60 and 70 years, respectively. While this risk appeared to be similar in male and female individuals &lt;50years, after that age, the risk continued to increase more markedly in female patients, reaching 10.8%versus 5.4% at 70 years. The diagnosis rate of IAs was &gt;2-fold higher in PKD1 compared with PKD2, with no influence of PKD1 mutation type or location. In multivariate analysis, female sex, hypertension &lt;35years, smoking and PKD1 genotype were associated with an increased risk for diagnosis of IAs. This study presents epidemiological data reflecting real-life clinical practice. The increased risk for IAs in postmenopausal women suggests a possible protective role of oestrogen.

Modifiable risk factors for intracranial aneurysms: Evidence from genetic studies.

Intracranial aneurysm (IA) is a crucial health concern with limited strategies for prevention and treatment. To identify potentially modifiable risk factors, such as socioeconomic, behaviors, dietary, and cardiometabolic factors, for IA and its subtypes. Summary statistics for IA were derived from a genome-wide association study with an overall 79,429 participants. Single nucleotide polymorphisms associated with modifiable risk factors at genome-wide significance (P = 5 × 10-8) were used as instrumental variables. The inverse-variance-weighted method, weighted-median method, Mendelian randomization (MR)-Egger regression, MR-Pleiotropy RESidual Sum and Outlier, and multivariable MR analyses were performed to evaluate the effect estimates. Genetically predicted educational attainment, insomnia, smoking, and systolic and diastolic blood pressure (SBP and DBP) were significantly associated with the risk of IA. The odds ratios (ORs) were 0.44 (95% confidence interval (CI): 0.37-0.52) for educational attainment, 1.15 (95% CI: 1.08-1.23) for insomnia, 1.56 (95% CI: 1.38-1.75) for smoking initiation, 2.69 (95% CI: 1.77-4.07) for cigarette per day, 2.65 (95% CI: 1.72-4.08) for lifetime smoking, 1.07 (95% CI: 1.06-1.09), and 1.06 (95% CI: 1.04-1.10) for SBP and DBP, respectively. Similar effect estimates were observed for unruptured IAs and aneurysmal subarachnoid hemorrhage. This study provided genetic evidence that several modifiable risk factors, including blood pressure, smoking, educational attainment, and insomnia were associated with the risk of IA.

Antisense Non-Coding Ribonucleic Acid in the INK4 Locus Long Noncoding Ribonucleic Acid Rs1333040 Polymorphism and Susceptibility to the Intracranial Aneurysm in Asian Population

Several researchers have suggested that the antisense non-coding ribonucleic acid in the INK4 locus long non-coding ribonucleic acid (cyclin-dependent kinase inhibitor 2B antisense ribonucleic acid 1) plays a key role in the pathogenesis of the intracranial aneurysm. However, because single studies are often underpowered due to inadequate sample sizes, the role of the antisense non-coding ribonucleic acid in the INK4 locus rs1333040 polymorphism in intracranial aneurysms has been inconclusive among Asian population. To obtain a comprehensive conclusion, we conducted a meta-analysis with 4260 cases and 14 536 controls to estimate the association between the rs1333040 polymorphism and intracranial aneurysms susceptibility. The electronic databases of PubMed and Embase were searched before May 2022, to identify the relevant literature. Cochran’s Q statistics and the I2 test were applied to assess heterogeneity among the included investigations. The summary pooled odds ratios and 95 % confidence intervals were evaluated for the strength of association using the random or fixed-effects model. A total of 6 eligible studies were enrolled in this meta-analysis, involving 4260 cases and 14 536 controls. The pooled results indicated a significant association between the rs1333040 polymorphism and the intracranial aneurysm in Asians under 3 genetic models (TT vs. CC: Odds ratio=1.48, 95 % confidence interval=1.30-1.70; TC vs. CC: Odds ratio=1.20, 95 % confidence interval=1.05-1.38; dominant model-TT+TC vs. CC: Odds ratio=1.34, 95 % confidence interval=1.18-1.53). The findings of this meta-analysis emphasize the rs1333040 polymorphism as a common risk factor for intracranial aneurysms in Asian people.

Effect of Aneurysm and Patient Characteristics on Intracranial Aneurysm Wall Thickness.

Background: The circle of Willis is a network of arteries allowing blood supply to the brain. Bulging of these arteries leads to formation of intracranial aneurysm (IA). Subarachnoid hemorrhage (SAH) due to IA rupture is among the leading causes of disability in the western world. The formation and rupture of IAs is a complex pathological process not completely understood. In the present study, we have precisely measured aneurysmal wall thickness and its uniformity on histological sections and investigated for associations between IA wall thickness/uniformity and commonly admitted risk factors for IA rupture.Methods: Fifty-five aneurysm domes were obtained at the Geneva University Hospitals during microsurgery after clipping of the IA neck. Samples were embedded in paraffin, sectioned and stained with hematoxylin-eosin to measure IA wall thickness. The mean, minimum, and maximum wall thickness as well as thickness uniformity was measured for each IA. Clinical data related to IA characteristics (ruptured or unruptured, vascular location, maximum dome diameter, neck size, bottleneck factor, aspect and morphology), and patient characteristics [age, smoking, hypertension, sex, ethnicity, previous SAH, positive family history for IA/SAH, presence of multiple IAs and diagnosis of polycystic kidney disease (PKD)] were collected.Results: We found positive correlations between maximum dome diameter or neck size and IA wall thickness and thickness uniformity. PKD patients had thinner IA walls. No associations were found between smoking, hypertension, sex, IA multiplicity, rupture status or vascular location, and IA wall thickness. No correlation was found between patient age and IA wall thickness. The group of IAs with non-uniform wall thickness contained more ruptured IAs, women and patients harboring multiple IAs. Finally, PHASES and ELAPSS scores were positively correlated with higher IA wall heterogeneity.Conclusion: Among our patient and aneurysm characteristics of interest, maximum dome diameter, neck size and PKD were the three factors having the most significant impact on IA wall thickness and thickness uniformity. Moreover, wall thickness heterogeneity was more observed in ruptured IAs, in women and in patients with multiple IAs. Advanced medical imaging allowing in vivo measurement of IA wall thickness would certainly improve personalized management of the disease and patient care.

Association of Versican Gene Polymorphisms with Intracranial Aneurysm Susceptibility in the Eastern Chinese Population

ObjectiveThe proteoglycan versican (VCAN) plays an important role in extracellular matrix (ECM) assembly, and diminished maintenance of the ECM has been increasingly regarded as an important factor in the development of intracranial aneurysms (IAs). Previous studies have revealed that single-nucleotide polymorphisms (SNPs) of the VCAN gene are associated with susceptibility to IAs in European or Japanese populations. However, the association between IA susceptibility and VCAN SNPs in the Eastern Chinese population remains unclear. This study aimed to investigate the associations of the SNPs rs251124, rs2287926, and rs173686 with IA susceptibility in the Eastern Chinese population.MethodsA total of 162 patients with IA and 182 controls were enrolled in this study. The study was conducted between January 2017 and December 2020. SNP genotyping for rs251124, rs2287926, and rs173686 was performed using Kompetitive Allele Specific PCR (KASP) after DNA extraction. The SNP data were analysed with CFX Manager Software version 3.1 (Bio-Rad).Resultsrs251124 and rs173686 were significantly associated with susceptibility to IA. The frequency of rs251124-TT in IA was higher than in controls (OR =1.26, 95% CI: 1.07–1.49; P<0.01), and its risk mainly came from the T allele. Furthermore, logistic regression analysis showed that the T/T genotype and T allele of rs251124 were independent risk factors for IA (OR=1.726, 95% CI: 1.136–2.263; P=0.011). Moreover, the G/G genotype and G allele of rs173686 were associated with increased IA susceptibility (OR=2.52, 95% CI: 1.261–5.037; P=0.009).ConclusionThe SNPs rs251124 and rs173686 were strongly associated with genetic susceptibility to IA in the Eastern Chinese population; however, no such association was found in the SNP rs2287926 of VCAN. Our findings suggest that the VCAN gene is an IA susceptible gene that should be further studied as a screening marker for IAs.

Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study.

BackgroundThe aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation and kidney function markers) with risks of any (ruptured or unruptured) intracranial aneurysm and aneurysmal subarachnoid hemorrhage using Mendelian randomization.Methods and ResultsSummary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta‐analyses of genome‐wide association studies. The inverse‐variance weighted method was used as the main Mendelian randomization analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy. Genetic predisposition to smoking, insomnia, and higher blood pressure was associated with an increased risk of both intracranial aneurysm and aneurysmal subarachnoid hemorrhage. For intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93–5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10–1.40) per unit increase in log‐odds of insomnia, and 2.92 (95% CI, 2.49–3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher triglyceride levels, higher body mass index, and lower low‐density lipoprotein cholesterol levels with higher risk of intracranial aneurysm and aneurysmal subarachnoid hemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses.ConclusionsThis Mendelian randomization study suggests that smoking, insomnia, and high blood pressure are major risk factors for intracranial aneurysm and aneurysmal subarachnoid hemorrhage.

Intracranial Aneurysms in Patients with Marfan Syndrome: A Multicenter Propensity-Matched Analysis

We sought to identify risk factors for intracranial aneurysms (IAs) in Marfan syndrome (MFS) patients and to describe their characteristics. Patients with confirmed MFS and vessel-dedicated brain imaging from January 1, 1980-December 1, 2020 were categorized according to the presence (IA) or absence (NIA) of IAs. Unmatched logistic regression analysis and propensity score matching were used for comparison. We included 159 patients, of whom 18 (11.3%) patients had radiographic diagnosis of IAs. Three patients (16.7%) had multiple lesions for a total of 24 IAs. One patient (5.5%) had de novo IA formation. Four patients (22.2%) underwent treatment: Two (11.1%) had open surgical clipping for ruptured aneurysms, and two (11.1%) patients had endovascular embolization for growth. In the unmatched analysis, current tobacco smoker status (odds ratio [OR]: 4.20; confidence interval [CI]: 1.11-15.6; P= 0.027) and history of coronary artery disease (CAD) (OR: 5.79; CI 1.76-20.2; P= 0.004) increased the odds for IA. Propensity score matching yielded 18 IA and 18 NIA patients matched for age, gender, race, priorstroke, and family history of aneurysms. History of CAD (IA= 11 [61.1%] vs. NIA= 4 (22.2%), P= 0.043) and current smoker status (IA= 6 [33.3%] vs. NIA= 0 (0%), P < 0.01) weresignificantly higher in the IA cohort. Body mass index (P= 0.622), diabetes (P= 0.180), hypertension (P= 0.732), prior stroke (P= 1.00), family history (P= 0.732), alcohol (P= 0.314), recreational drugs (P= 1.00), and other aneurysms (P= 0.585) were not statistically significant. Prevalence of IAs in our series of MFS patients was 11.3%, and de novo formation was 5.5%. MFS patients with a history of CAD and current smoker status had an increased risk of IA. Neurovascular radiographic screening should be considered in all patients with MFS, particularly in patients who smoke or have a history of heart disease.

The association of CDKN2BAS gene polymorphisms and intracranial aneurysm: A meta-analysis.

Intracranial aneurysm (IA) is one of the main causes of subarachnoid hemorrhage (SAH) leading to a high percentage of disability and mortality worldwide. In addition to environmental factors, the risk of rupture or prognosis of intracranial aneurysm is also closely related to gene. Thus, a lot of genetic studies have been used to explore associated risk genes as well as variant loci of intracranial aneurysm and found several chromosome variates including 9p21.3 (CDKN2BAS) related to Intracranial aneurysm. However, due to differences in population and the existence of SNP, it is still not determined that whether these genetic changes can be identified as independent risk factors for intracranial aneurysm. Therefore, we performed a meta-analysis of CDKN2BAS SNPs to explore its association with intracranial aneurysms and the results show a significance relation between rs10757272, rs1333040, and rs6475606 with intracranial aneurysm. This will open a new perspective for future intracranial aneurysm gene research and therapy.