Risk Factors For Aneurysm Growth Research Articles

A prospective observational study on hemodynamic risk in cerebral aneurysm growth

Introduction: Hemodynamic factors are thought to play a major role in the development, growth, and rupture of cerebral aneurysms, but the hemodynamics related to enlargement remain unclear. We prospectively enrolled patients with unruptured cerebral aneurysms and performed Computational Fluid Dynamics (CFD) analysis using 3D CT images to investigate differences in hemodynamic environments between aneurysms that grew and those that did not grow over a 3-year period. Methods: This prospective observational study was approved by the National Hospital Organization Central Ethics Review Board. Hemodynamic distributions were examined using ANSYS-CFX software. Patient-specific arterial geometries and inflow velocities were obtained from 3D-CTA and carotid ultrasound Doppler examinations. The distributions of hemodynamic metrics of 17 enlarged and 70 unenlarged aneurysms was compared. In addition, the distributions of hemodynamic metrics of the neck, body, and dome of the aneurysm was also examined in 9 enlarged and 41 non-enlarged cases. A multivariate logistic analysis was performed to investigate the influence of the six hemodynamic metrics, i.e., the time-averaged wall shear stress (TAWSS), time-averaged WSS gradient (TAWSSG), oscillatory shear index (OSI), gradient oscillatory number (GON), transverse WSS (transWSS), and normalized transWSS (NtransWSS) after adjustment forknown risk factors for aneurysm growth, i.e., age, sex, hypertension, smoking history, and aneurysm location, size, and history of subarachnoid hemorrhage. Results: Regarding the distributions of hemodynamic metrics throughout the aneurysm, NtransWSS was significantly higher in the cases with growth than in the cases without growth (odds ratio 2.09, 95% CI 1.02-4.29). the distributions of hemodynamic metrics at each cerebral aneurysm growth site showed that NtransWSS at the dome was significantly higher in the growth cases than in the non-enlargement cases (odds ratio 4.14, 95% CI 1.02-16.80). Conclusion: The data suggest that multidirectional disturbance of wall shear stress is involved in cerebral aneurysm growth, and the disturbance at the dome of the aneurysm may be particularly strongly related. This study was supported by a Grant-in-Aid from the Japanese National Hospital Organization Multi-Center Clinical Research, AMED under grant no. JP15gm0810006h0301 and a JSPS KAKENHI Grant, no. 15K10323. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Surveillance of Unruptured Intracranial Aneurysms: Cost-Effectiveness Analysis for 3 Countries.

No consensus exists on adequate surveillance of conservatively managed unruptured intracranial aneurysms (UIAs). We aimed to determine optimal MRI surveillance strategies for the growth of UIAs using cost-effectiveness analysis. A secondary aim was to develop a clinical tool for personalizing UIA surveillance. We designed a microsimulation model from a health care perspective simulating 100,000 55-year-old women to estimate costs and quality-adjusted life years (QALYs) over a lifetime horizon in the United States, the United Kingdom, and the Netherlands, using literature-derived model parameters. Country-specific costs and willingness-to-pay thresholds ($100,000/QALY for the United States, £30,000/QALY for the United Kingdom, and €80,000/QALY for the Netherlands) were used. Lifetime costs and QALYs were annually discounted at 3% for the United States, 3.5% for the United Kingdom, or 4% (costs) and 1.5% (QALYs) for the Netherlands. Strategies were no follow-up surveillance, follow-up with MRI in the first and fifth year after UIA discovery, every 5 years, every 2 years, or annually, or immediate intervention (i.e., clipping or coiling). Using the microsimulation model, we developed a tool for personalizing UIA surveillance for men and women, with different ages and varying aneurysm characteristics. Uncertainty in the input parameters was modeled with probabilistic sensitivity analysis. Among 55-year-old women, 2,222 individuals in the United States, 1,910 in the United Kingdom, and 2,040 in the Netherlands needed to undergo an annual MRI scan to prevent 1 case of subarachnoid hemorrhage per year. No surveillance MRI was most cost-effective in the United States (in 47% of the simulations) and United Kingdom (in 54% of simulations), whereas annual MRI was most cost-effective in the Netherlands (in 53% of simulations). In the United States and United Kingdom, annual surveillance or surveillance in the first and fifth year after discovery was cost-effective in patients <60 years and at increased risk of aneurysm growth. The optimal, personalized, surveillance strategies were summarized in a look-up table for use in clinical practice. Generally, the US and UK physicians should refrain from assigning patients, particularly older patients and those with few risk factors for aneurysm growth or rupture, to frequent MRI surveillance. In the Netherlands, annual follow-up is generally most cost-effective.

Four-Dimensional Magnetic Resonance Imaging Assessment of Intracranial Aneurysms: A State-of-the-Art Review.

Treatment of unruptured intracranial aneurysms can reduce the risk of subarachnoid hemorrhage and its associated morbidity and mortality. However, current methods to predict the risk of rupture and optimize treatment strategies for intracranial aneurysms are limited. Assessment of intra-aneurysmal flow using 4-dimensional magnetic resonance imaging (4D MRI) is a novel tool that could be used to guide therapy. A systematic search of the literature was performed to provide a state-of-the-art review on 4D MRI assessment of unruptured intracranial aneurysms. A total of 18 studies were available for review. Eccentric flow on 4D MRI is associated with a greater aspect ratio and peak wall shear stress (WSS). WSS, vorticity, and peak velocity are greater in saccular than fusiform aneurysms. Unstable aneurysms are associated with greater WSS, peak wall stress, and flow jet angle and may exhibit wall enhancement. In comparison to computational fluid dynamics (CFD), 4D MRI has a lower spatial resolution and reports lower WSS and velocity magnitudes, but these parameters equalize when spatial resolution is matched. 4D MRI demonstrates the intra-aneurysmal hemodynamic changes associated with flow diversion, including significantly decreased flow velocity. Thus, 4D MRI is a novel, noninvasive imaging tool used for the evaluation of hemodynamics within intracranial aneurysms. Hemodynamic indices derived from 4D MRI appear to correlate well with the simulated (CFD) values and may be used to measure the success of endovascular therapies and risk factors for aneurysm growth and rupture.

Correlation Between Laminar Wall Shear Stress and Growth of Unruptured Cerebral Aneurysms: In Vivo Assessment

Cerebral aneurysm growth is significantly associated with aneurysm rupture, but risk factors for aneurysm growth are not well characterized. It is believed that altered intracranial hemodynamics may contribute to the pathophysiology of aneurysm growth, but these mechanisms are not fully understood. Here, we assess the correlation between growth of unruptured cerebral aneurysms over time and average laminar shear stress on the wall of the parent vessel proximal to the aneurysm. Patients with unruptured, untreated cerebral aneurysms followed over time at our institution between 2005 and 2017 were retrospectively reviewed. Patients were included if at least 1 quantitative magnetic resonance angiography study was performed at baseline and follow-up. The nonparametric Wilcoxon-Mann-Whitney test was used to compare mean parent vessel-laminar wall shear stress (PV-LWSS) proximal to the aneurysm in growing versus stable aneurysms. Change in PV-LWSS over time was evaluated using the 1-way repeated measures analysis of variance test. Thirty-three patients with 45 total aneurysms were included (63% female, mean age 60 years). Four patients presented with aneurysm growth over time. Unstable aneurysms had significantly higher PV-LWSS compared with stable aneurysms at the time of first diagnosis (29.3 vs. 13.1 dynes/cm2, P= 0.02) and at 1-year follow-up (25.8 vs. 12.3 dynes/cm2, P= 0.05). The subset of unruptured cerebral aneurysms that demonstrate growth over time has a significantly higher mean PV-LWSS than stable aneurysms, as measured by quantitative magnetic resonance angiography. This information at the time of diagnosis may help predict future aneurysm growth, stratify rupture risk, and identify those aneurysms that should undergo prophylactic treatment.

A systematic review and meta-analysis of risk factors for unruptured intracranial aneurysm growth.

Many risk factors are associated with the growth of unruptured intracranial aneurysm; however, the effects of these risk factors on intracranial aneurysm growth remain poorly understood. Here, we performed a meta-analysis to evaluate the effects of these risk factors on intracranial aneurysm growth, incorporating different data types to provide comprehensive estimates of individual effects. We searched the Cochrane Library, PubMed, Embase, and Web of Science for cohort studies analyzing risk factors for aneurysm growth prior to January 10, 2019. The hazard ratio (HR) and odds ratio (OR) with its 95% confidence interval (CI) were calculated to assess the effect of individual risk factors on intracranial aneurysm growth. Both univariate analysis (UVA) and multivariate analysis (MVA) were performed. Two reviewers independently assessed the quality of the trials and the associated data. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. We included 23 studies (N = 7208 participants) in this meta-analysis. A total of 944 patients (13.1%) experienced intracranial aneurysm growth during their follow-up times. Aneurysm size and smoking may have significant effects on the growth of intracranial aneurysm, with pooled ORs of 2.73 (95% CI 2.21-3.36; P < 0.00001) and 1.45 (95% CI 1.07-1.98; P = 0.02) respectively. However, our results indicated that subarachnoid hemorrhage (SAH) had a negative effect on the growth of intracranial aneurysm (OR 0.64; 95% CI 0.48-0.86; P = 0.003). Other risk factors such as irregular shape of intracranial aneurysm, female sex, and multiple aneurysms were inconsistent across studies due to differences in data types and effect estimates. Our meta-analysis identified aneurysm size and smoking as independent risk factors for the growth of intracranial aneurysm, while prior SAH had a negative effect on the growth of intracranial aneurysm. The roles of other risk factors for intracranial aneurysm growth were inconsistent, with further research necessary to assess fully the roles of these factors in disease outcomes.

Aneurysm Size is the Strongest Risk Factor for Intracranial Aneurysm Growth in the Eastern Finnish Population.

Saccular intracranial aneurysm (sIA) growth during follow-up is associated with high risk for subsequent rupture. Finnish patients have been suggested to have higher risk for subarachnoid hemorrhage, but follow-up studies of sIA growth in the Finnish population are scarce. To identify the strongest risk factors for sIA growth in Eastern Finnish population by studying 205 patients with 350 unruptured sIAs with angiographic follow-up imaging. In this population-based cohort study, we included unruptured sIA patients from the Kuopio University Hospital Intracranial Aneurysm Patient and Family database with at least 6 mo of angiographic follow-up after the diagnosis of sIAs. Angiograms were re-evaluated to detect aneurysms with growth of at least 1.0 mm. Cox regression analysis with patient- and aneurysm-related risk factors was used to calculate hazard ratios with 95% confidence intervals for growth. In addition, we tested the diagnostic value of previously introduced PHASES score for the prediction of sIA growth in Eastern Finnish population. Of the 350 unruptured aneurysms, 36 (10.3%) showed growth during median follow-up of 1.7 yr and total follow-up of 790 yr. In the multivariate Cox regression analysis, sIA size and location in the middle cerebral artery were significant risk factors for sIA growth. In receiver operator characteristic curves, both PHASES score and sIA size had relatively low areas under the curve. Our study indicates that aneurysm size is the strongest risk factor for aneurysm growth in Eastern Finnish population. Further studies are required to identify new risk factors for aneurysm growth.

Patient- and Aneurysm-Specific Risk Factors for Intracranial Aneurysm Growth: A Systematic Review and Meta-Analysis.

Follow-up imaging is often performed in intracranial aneurysms that are not treated. We performed a systematic review and meta-analysis on patient- and aneurysm-specific risk factors for aneurysm growth. We searched EMBASE and MEDLINE for cohort studies describing risk factors for aneurysm growth. Two authors independently assessed study eligibility and rated quality with the Newcastle Ottawa Scale. With univariable Poisson regression analysis, we calculated risk ratios (RRs) with corresponding 95% confidence intervals (95% CI) of risk factors for aneurysm growth. Heterogeneity was assessed with I(2). Eighteen studies on 15 patient-populations described 3990 patients with 4972 unruptured aneurysms. A total of 437 aneurysms (9%) enlarged during 13 987 aneurysm-years of follow-up. Compared with aneurysms ≤4 mm, RRs were 2.56 (95% CI, 1.93-3.39; I(2)=98%) for ≥5 mm, 2.80 (95% CI, 2.01-3.90; I(2)=96%) for ≥7 mm, and 5.38 (95% CI, 3.76-7.70; I(2)=97%) for ≥10 mm. Compared with aneurysms on the middle cerebral artery, the RR for basilar artery was 1.94 (95% CI, 1.32-2.83; I(2)=57%). RRs were 2.03 (95% CI, 1.52-2.71; I(2)=59%) for smoking at baseline, 2.04 (95% CI, 1.56-2.66; I(2)=90%) for multiple unruptured aneurysms, 1.26 (95% CI, 0.97-1.62; I(2)=59%) for women, 1.24 (95% CI, 0.98-1.58; I(2)=40%) for hypertension, and 2.32 (95% CI, 1.46-3.68; I(2)=91%) for irregular aneurysm shape. Compared with other regions, RR was 0.75 (95% CI, 0.58-0.96) for Japan and 0.64 (95% CI, 0.45-0.90) for Finland. Most risk factors for aneurysm growth are consistent with risk factors for rupture. In contrast with rupture, the risk of growth was smaller in Japanese and Finnish cohorts compared with other regions. Pooling of individual patient data from low- and high-risk geographical regions is needed to assess independent predictors of aneurysm growth.

Risk Factors for Growth of Intracranial Aneurysms: A Systematic Review and Meta-Analysis.

Understanding risk factors for intracranial aneurysm growth is important for patient management. We performed a meta-analysis examining risk factors for intracranial aneurysm growth in longitudinal studies and examined the association between aneurysm growth and rupture. We searched the literature for longitudinal studies of patients with unruptured aneurysms. We examined the associations of demographics, multiple aneurysms, prior subarachnoid hemorrhage, family history of aneurysm or subarachnoid hemorrhage, smoking, and hypertension; and aneurysm shape, size, and location with aneurysm growth. We studied the association between aneurysm growth and rupture. A meta-analysis was performed by using a random-effects model by using summary statistics from included studies. Twenty-one studies including 3954 patients with 4990 aneurysms with 13,294 aneurysm-years of follow-up were included. The overall proportion of growing aneurysms was 3.0% per aneurysm-year (95% CI, 2.0%-4.0%). Patient risk factors for growth included age older than 50 years (3.8% per year versus 0.9% per year, P < .01), female sex (3.2% per year versus 1.3% per year, P < .01), and smoking history (5.5% per year versus 3.5% per year, P < .01). Characteristics associated with higher growth rates included cavernous carotid artery location (14.4% per year), nonsaccular shape (14.7% per year versus 5.2% per year for saccular, P < .01), and aneurysm size (P < .01). Aneurysm growth was associated with a rupture rate of 3.1% per year compared with 0.1% per year for stable aneurysms (P < .01). Observational evidence provided multiple clinical and anatomic risk factors for aneurysm growth, including age older than 50 years, female sex, smoking history, and nonsaccular shape. These findings should be considered when counseling patients regarding the natural history of unruptured intracranial aneurysms.

Clinical, radiological, and flow-related risk factors for growth of untreated, unruptured intracranial aneurysms.

Unruptured intracranial aneurysms are frequently followed to monitor aneurysm growth. We studied the yield of follow-up imaging and analyzed risk factors for aneurysm growth. We included patients with untreated, unruptured intracranial aneurysms and ≥6 months of follow-up imaging from 2 large prospectively collected databases. We assessed the proportion of patients with aneurysm growth and performed univariable and multivariable Cox regression analyses to calculate hazard ratios with corresponding 95% confidence intervals (CI) for clinical and radiological risk factors for aneurysm growth. We repeated these analyses for the subset of small (<7 mm) aneurysms. Fifty-seven (12%) of 468 aneurysms in 363 patients grew during a median follow-up of 2.1 years (total follow-up, 1372 patient-years). In multivariable analysis, hazard ratios for aneurysm growth were as follows: 1.1 (95% CI, 1.0-1.2) per each additional mm of initial aneurysm size; 2.7 (95% CI, 1.2-6.4) for dome > neck ratio; 2.1 (95% CI, 0.9-4.9) for location in the posterior circulation; and 2.0 (95% CI, 0.8-4.8) for multilobarity. In the subset of aneurysms <7 mm, 37 of 403 (9%) enlarged. In multivariable analysis, hazard ratios for aneurysm growth were 1.1 (95% CI, 0.8-1.5) per each additional mm of initial aneurysm size, 2.2 (95% CI, 1.0-4.8) for smoking, 2.9 (95% CI, 1.0-8.5) for multilobarity, 2.4 (95% CI, 1.0-5.8) for dome/neck ratio, and 2.0 (95% CI, 0.6-7.0) for location in the posterior circulation. Initial aneurysm size, dome/neck ratio, and multilobarity are risk factors for aneurysm growth. Cessation of smoking is pivotal because smoking is a modifiable risk factor for growth of small aneurysms.

外科的適応から外れ経過観察中に増大しくも膜下出血をきたした未破裂脳動脈瘤の3例

The UCAS Japan, the SUAVe Study, and the ISUIA have shown that the indications for surgical or endovascular treatment of unruptured small aneurysms and asymptomatic aneurysms in elderly patients require careful consideration. We describe three cases of intracranial aneurysms not indicated for surgical or endovascular treatment: a 3-mm middle cerebral artery aneurysm in a 36-year-old woman, a 4-mm pericallosal artery aneurysm in a 74-year-old woman, and an 8-mm posterior communicating artery aneurysm in an 83-year-old woman, which had all enlarged in the observation period and finally ruptured. All three patients had two or more risk factors for aneurysm growth or rupture identified by the UCAS Japan or SUAVe Study, indicating that careful follow-up monitoring for morphological changes in the aneurysm is mandatory, even for a small aneurysm, and especially in young patients with such multiple risk factors. However, surgical indications are limited for elderly patients, even after aneurysm enlargement, so the appropriate treatment for elderly patients requires careful consideration of the clinical condition of the individual patient.

Risk Factors for Growth of Unruptured Intracranial Aneurysms: Follow-up Study by Serial 0.5–T Magnetic Resonance Angiography

The independent risk factors for aneurysm growth were retrospectively investigated in 130 patients with unruptured aneurysms who were followed up by 0.5-T serial magnetic resonance angiography with stereoscopic images. Age, sex, site of aneurysm, size of aneurysm, multiplicity of aneurysms, type of circle of Willis, length of follow-up period, cerebrovascular event, hypertension, diabetes, hyperlipidemia, smoking habit, and family history of subarachnoid hemorrhage were investigated using multiple logistic analysis. Fourteen patients (16 aneurysms) among the 130 patients (159 aneurysms) showed aneurysm growth (10.8%) during follow-up of 10 to 69 months (mean 29.3 +/- 10.5 mo). Multiple logistic analysis disclosed that location on the middle cerebral artery (odds ratio [OR] 0.08, P < 0.01), multiplicity of aneurysms (OR 68.5, P < 0.01), aneurysm size of 5 mm or larger (OR 1.17, P = 0.05), and family history of subarachnoid hemorrhage (OR 10.9, P < 0.01) were independent risk factors. Location on the middle cerebral artery, multiplicity, aneurysm size of 5 mm or larger, and family history of subarachnoid hemorrhage are independent risk factors for aneurysm growth. These results may help to determine the treatment choice for unruptured aneurysms.

Incidence and risk factors for the growth of unruptured cerebral aneurysms: observation using serial computerized tomography angiography

The goal of this study was to examine the growth of unruptured intracranial aneurysms with the focus on the risk factors and incidence of these lesions. One hundred sixty-six untreated cerebral saccular aneurysms were analyzed in 140 patients. The age of the patients ranged from 29 to 82 years (mean 62.8 years), the female/male ratio was 94:46, and the mean follow-up period was 17.7 months. Aneurysms were located at the internal carotid artery (ICA) in 68 patients, the middle cerebral artery (MCA) in 43, the anterior cerebral artery in 38, the basilar artery (BA) in 13, and the vertebral artery in four patients. The maximum diameter of the lesions ranged from 2 to 20 mm (mean 4.1 mm). All patients were examined using serial computerized tomography angiography to evaluate signs of aneurysm growth. Although growth was identified in 10 aneurysms (nine patients 16.4%]), no bleeding occurred. Growth-related changes were significantly associated with the size of the aneurysm and occurred in three (2.4%) of 125 aneurysms measuring 2 to 4 mm, three (9.1%) of 33 lesions measuring 5 to 9 mm, and four (50%) of eight lesions measuring 10 to 20 mm. These changes were more frequently found in aneurysms located at the BA bifurcation (two [40%] of five lesions) and the ICA (six [8.8%] of 68 lesions) than in those located at the MCA (zero of 43 lesions, p < 0.05). The 1-, 2-, and 3-year cumulative growth rates calculated using the Kaplan-Meier method were 2.5, 8, and 17.6%, respectively. A diameter of at least 10 mm and a location at the BA bifurcation or the ICA were significant risk factors for aneurysm growth. The incidence of growth was 2.5% in the 1st year and this risk increased yearly. Computerized tomography angiography is useful for follow up of patients with aneurysms because it allows the detection of even subtle morphological changes.

Natural history of unruptured intracranial aneurysms: risks for aneurysm formation, growth, and rupture.

Several studies concerning risk factors for SAH and for subsequent rupture of an unruptured aneurysm have been published, but not risk factor studies for formation and growth rate of aneurysms. Because less than half of all aneurysms ever rupture, it is essential to know risk factors separately both for aneurysm formation and for its growth. Before 1979, unruptured aneurysms were not operated on in Helsinki. Recently, the results of risk factors for rupture of unruptured aneurysms of 142 patients (131 with a prior SAH) have been published. 89 were followed with conventional and/or 3D CT angiography, or at autopsy to define risk factors for aneurysm formation and growth. During 2575 person-years, 33 of the 142 patients (23%) suffered SAH, resulting in an annual incidence of 1.3% (95% CI, 0.9-1.7%). The cumulative rate of bleeding was 10.5% (95% CI, 5.3-15.8%) at 10 years, and 30.3% (21.1-39.6%) at 30 years. Independent risk factors for rupture were cigarette smoking (time-dependent relative risk, 3.04; 95% CI, 1.21-7.66), and size of aneurysm (1.14 per mm; 1.01-1.30) after adjustment for age, aneurysm group, and hypertension. In addition, current cigarette smoking at end of follow-up (age-adjusted odds ratio, 3.92; 95% CI, 1.29-11.93) and female gender 3.36 (1.11-10.22) were the only independent risk factors for aneurysm growth of > or = 1 mm but only current smoking (3.48, 1.14-10.64) was a risk factor for growth of > or = 3 mm. Probability of de novo aneurysm formation was 0.84% per year (95% CI, 0.47-1.37%). Female gender (adjusted odds ratio, 4.73; 95% CI, 1.16-19.38) and current smoking (4.07, 1.09-15.15) were the only significant (p < 0.05) independent risk factors for de novo aneurysm formation. Cessation of smoking is very important for these patients. It is recommended that unruptured aneurysms be operated on irrespective of their size and of patients' smoking status, in people aged < 50 to 60 years.