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

Can, Anil; Castro, Víctor M.; Ozdemir, Yildirim H.; Dagen, Sarajune; Yu, Sheng; Dligach, Dmitriy; Finan, Sean; Gainer, Vivian S.; Shadick, Nancy A.; Murphy, Shawn N.; Cai, Tianxi; Savova, Guergana; Dammers, Rúben; Weiss, Scott T.; Du, Rose

doi:10.1212/wnl.0000000000004419

Cited by 102 publications

(73 citation statements)

References 43 publications

(87 reference statements)

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“…For example, an already weakened wall caused by ageing, smoking, hypertension and inherited diseases would have a lower tolerance to hemodynamic disturbances. Meta‐analysis in patients correlating hemodynamic forces and IA development support the fact that IAs are triggered by SWSS and positive WSSG …”

Section: Wss and Ia Developmentmentioning

confidence: 75%

“…Meta-analysis in patients correlating hemodynamic forces and IA development support the fact that IAs are triggered by SWSS and positive WSSG. 53,54…”

Section: Ia Initiationmentioning

confidence: 99%

“…55 There are conflicting results concerning the impact of high or low WSS in aneurysm growth and rupture. CFD analysis comparing ruptured and unruptured IAs showed in some studies that LWSS promotes IA growth and rupture, 13,[16][17][18][19]54 while others have shown that SWSS was related to these events. 14,15,56,57 The discrepancy of results regarding WSS demonstrates the challenge of understanding IA pathology.…”

Section: Ia Growth and Rupturementioning

confidence: 99%

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Role of hemodynamics in initiation/growth of intracranial aneurysms

Diagbouga

Morel

Bijlenga

et al. 2018

Eur J Clin Investigation

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Background: Intracranial aneurysm (IA) is a disease of the vascular wall resulting in abnormal enlargement of the vessel lumen. It is a common pathology with a prevalence of 2%-3% in the adult population. IAs are mostly small, quiescent and asymptomatic; yet, upon rupture, severe brain damage or even death is frequently encountered. In addition to clinical factors, hemodynamic forces, mainly wall shear stress (WSS), have been associated with the initiation of IAs and possibly with their risk of rupture. However, the mechanism by which WSS contributes to aneurysm growth and rupture is not completely understood. Design: PubMed and Ovid MEDLINE databases were searched. In addition, key review articles were screened for relevant original publications. Results: Current knowledge about the relation between WSS and IA has been obtained from both computational fluid dynamic studies in patients and experimental models of IA formation and growth. It is increasingly recognized that a high wall shear stress (gradient) participates to IA formation and that both low and high WSS can drive IA growth. Primary cilia (PC) play an important role as mechanosensors as patients with polycystic kidney disease, which is characterized by the absence or dysfunction of PC, have increased risk to develop IAs as well as increased risk of rupture. Conclusion: Wall shear stress is a key player in IA initiation and progression. It is involved in vascular wall remodelling and inflammation, processes underlying aneurysm pathophysiology. K E Y W O R D Sendothelium, intracranial aneurysms, primary cilium, wall shear stress

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Section: Wss and Ia Developmentmentioning

confidence: 75%

“…Meta-analysis in patients correlating hemodynamic forces and IA development support the fact that IAs are triggered by SWSS and positive WSSG. 53,54…”

Section: Ia Initiationmentioning

confidence: 99%

Section: Ia Growth and Rupturementioning

confidence: 99%

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Role of hemodynamics in initiation/growth of intracranial aneurysms

Diagbouga

Morel

Bijlenga

et al. 2018

Eur J Clin Investigation

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“…Former smoking was also significantly associated with rupture, and duration of cessation had no effect on IA rupture (OR 1.6 [95% CI 1.3-1.9]). 4 A similar study observed a strong dose-response relationship for intensity and duration of smoking with risk of IA rupture, but in contrast found no association of former smoking with IA rupture. 10 Overall, it seems that IAs diagnosed in smokers are more frequently located at the middle cere- bral artery bifurcation and the anterior communicating artery complex than IAs diagnosed in nonsmokers.…”

Section: Current Knowledge On Smoking and Aneurysm Formationmentioning

confidence: 90%

Association of single and multiple aneurysms with tobacco abuse: an @neurIST risk analysis

Schatlo

Gautschi²,

Friedrich

et al. 2019

Neurosurgical Focus

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OBJECTIVEAlthough several studies have suggested that the incidence of intracranial aneurysms (IAs) is higher in smokers, the higher prevalence of subarachnoid hemorrhage (SAH) in smokers remains uncertain. It is unclear whether smoking additionally contributes to the formation of multiple aneurysms and the risk of rupture. The aim of this study was to determine whether smoking is associated with IA formation, multiplicity, or rupture.METHODSPatients from the prospective multicenter @neurIST database (n = 1410; 985 females [69.9%]) were reviewed for the presence of SAH, multiple aneurysms, and smoking status. The prevalence of smokers in the population of patients diagnosed with at least one IA was compared with that of smokers in the general population.RESULTSThe proportion of smokers was higher in patients with IAs (56.2%) than in the reference population (51.4%; p < 0.001). A significant association of smoking with the presence of an IA was found throughout group comparisons (p = 0.01). The presence of multiple IAs was also significantly associated with smoking (p = 0.003). A trend was found between duration of smoking and the presence of multiple IAs (p = 0.057). However, the proportion of smokers among patients suffering SAH was similar to that of smokers among patients diagnosed with unruptured IAs (p = 0.48).CONCLUSIONSSmoking is strongly associated with IA formation. Once an IA is present, however, smoking does not appear to increase the risk of rupture compared with IAs in the nonsmoking population. The trend toward an association between duration of smoking and the presence of multiple IAs stresses the need for counseling patients with IAs regarding lifestyle modification.

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“…[57][58][59] Indeed two genes in our model, LRRN3 and GPR15, are among the top differentially expressed genes in blood between current and never smokers according to a meta-analysis by Huan et al 60 Their presence in our predictive model may be because of the higher proportion of smokers in IA group or because these genes are capturing biological mechanisms related to smoking that are important in IA pathogenesis, such as endothelial dysfunction. [61][62][63] Still, when we performed covariate analysis using MatchIt to create subgroups with similar distributions of covariates between IA and control groups, we found that no one subgroup had signi cantly higher misclassi cation rates. For instance, 61% of all subjects in "Subclass 5" were smokers, and this subgroup had a misclassi cation rate of 13%.…”

Section: Discussionmentioning

confidence: 91%

Classification Models using Circulating Neutrophil Transcripts Can Detect Unruptured Intracranial Aneurysm

Poppenberg

Tutino

Li³

et al. 2020

Preprint

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Background: Intracranial aneurysms (IAs) are dangerous because of their potential to rupture. We previously found significant RNA expression differences in circulating neutrophils between patients with and without unruptured IAs and trained machine learning models to predict presence of IA using 40 neutrophil transcriptomes. Here, we aim to develop a predictive model for unruptured IA using neutrophil transcriptomes from a larger population and more robust machine learning methods. Methods: Neutrophil RNA extracted from the blood of 134 patients (55 with IA, 79 IA-free controls) was subjected to next-generation RNA sequencing. In a randomly-selected training cohort (n=94), the Least Absolute Shrinkage and Selection Operator (LASSO) selected transcripts, from which we constructed prediction models via 4 well-established supervised machine-learning algorithms (K-Nearest Neighbors, Random Forest, and Support Vector Machines with Gaussian and cubic kernels). We tested the models in the remaining samples (n=40) and assessed model performance by receiver-operating-characteristic (ROC) curves. Real-time quantitative polymerase chain reaction (RT-qPCR) of 9 IA-associated genes was used to verify gene expression in a subset of 49 neutrophil RNA samples. We also examined the potential influence of demographics and comorbidities on model prediction. Results: Feature selection using LASSO in the training cohort identified 37 IA-associated transcripts. Models trained using these transcripts had a maximum accuracy of 90% in the testing cohort. The testing performance across all methods had an average area under ROC curve (AUC)=0.97, an improvement over our previous models. The Random Forest model performed best across both training and testing cohorts. RT-qPCR confirmed expression differences in 7 of 9 genes tested. Gene ontology and IPA network analyses performed on the 37 model genes reflected dysregulated inflammation, cell signaling, and apoptosis processes. In our data, demographics and comorbidities did not affect model performance. Conclusions: We improved upon our previous IA prediction models based on circulating neutrophil transcriptomes by increasing sample size and by implementing LASSO and more robust machine learning methods. Future studies are needed to validate these models in larger cohorts and further investigate effect of covariates.

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

Cited by 102 publications

References 43 publications

Role of hemodynamics in initiation/growth of intracranial aneurysms

Role of hemodynamics in initiation/growth of intracranial aneurysms

Association of single and multiple aneurysms with tobacco abuse: an @neurIST risk analysis

Classification Models using Circulating Neutrophil Transcripts Can Detect Unruptured Intracranial Aneurysm

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