Intracranial aneurysm risk factors

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Intracranial aneurysm risk factors

Observational evidence identified multiple clinical and anatomic risk factors for the formation of de novo IAs, including female sex, age <40 yr, family history, smoking history, multiple intracranial aneurysms at first diagnosis, and IC as the initial site. More aggressive long-term angiographic follow-up with digital subtraction angiography, computed tomography angiography, or magnetic resonance angiography is recommended for these patients 1).

Genetically determined HDL-C and LDL-C reduce the risk of intracranial aneurysm and ruptured intracranial aneurysm. The effects of different lipid-modifying drugs on IA need to be further investigated 2).

Although some previous reports have demonstrated an association between lipid accumulation and degenerative changes in aneurysm walls in humans, epidemiological studies have failed to identify dyslipidemia as a risk factor for intracranial aneurysm pathogenesis. Thus, Shimizu et al. examined whether an increase in serum cholesterol levels facilitates the progression of intracranial aneurysms in a rat model. Rats were given a high-fat diet (HFD) and subjected to an intracranial aneurysm model. The HFD elevated their serum cholesterol levels. The intracranial aneurysms induced at the anterior cerebral artery-olfactory artery bifurcation were significantly larger in the high-fat group than in the normal-chow group. Histological analysis demonstrated that the loss of medial smooth muscle layers was exacerbated in the high-fat group and indicated the presence of macrophage-derived foam cells in the lesions. In in vitro experiments, the expression levels of the pro-inflammatory genes induced by LPS in RAW264.7-derived foam cells were significantly higher than those in RAW264.7 cells. The combination of these results suggests that increased serum cholesterol levels facilitate degenerative changes in the media and the progression of intracranial aneurysms presumably through foam cell transformation 3).

Smoking

Although 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.

METHODS: Patients 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.

RESULTS: The 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).

CONCLUSIONS: Smoking 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 4).

Radiotherapy

Intracranial aneurysms after radiotherapy (RT) have previously been reported. However, the majority of studies were case reports. Therefore, we performed a nationwide study to explore the risk of radiation-induced intracranial aneurysms.

METHODS: This study included patients diagnosed with head and neck cancer (ICD9: 140-149, 161). Intracranial aneurysms formation was identified using the following ICD9 codes: nonruptured cerebral aneurysm (ICD9:4373), aneurysm clipping (ICD9:3951). Patients who did not receive curative treatment and those with intracranial aneurysms before the diagnosis of head and neck cancer were excluded.

RESULTS: In total, 70,691 patients were included in the final analysis; they were categorized into the following three groups: nasopharyngeal carcinoma (NPC) with RT, non-NPC with RT, and non-NPC without RT. Patients in the NPC with RT group had the highest risk of developing intracranial aneurysms (hazard ratio (HR) 2.57; P <  0.001). In addition, hypertension was also a risk factor of developing intracranial aneurysms (HR 2.14; P <  0.01). The mean time interval from cancer diagnosis to intracranial aneurysm formation in the NPC with RT group was 4.3 ± 3.1 years.

CONCLUSIONS: Compared with the non-NPC with RT and the non-NPC without RT groups, patients with NPC who received RT had a higher risk of developing intracranial aneurysms 5).

1)

Hu S, Yu N, Li Y, Hao Z, Liu Z, Li MH. A Meta-Analysis of Risk Factors for the Formation of de novo Intracranial Aneurysms. Neurosurgery. 2019 Oct 1;85(4):454-465. doi: 10.1093/neuros/nyy332. PubMed PMID: 30085204.
2)

Zhang B, Dong S, Miao Y, Song G, Yuan F, Liu L, Xia S, Qin Y, Huo X, Wu Z, Miao Z, Mo D, Liu A; International Stroke Genetics Consortium (ISGC) Intracranial Aneurysm Working Group. Effects of blood lipids and lipid-modifying drugs on intracranial aneurysms. Eur J Neurol. 2022 Jun 21. doi: 10.1111/ene.15471. Epub ahead of print. PMID: 35726534.
3)

Shimizu K, Miyata H, Abekura Y, Oka M, Kushamae M, Kawamata T, Mizutani T, Kataoka H, Nozaki K, Miyamoto S, Aoki T. High-Fat Diet Intake Promotes the Enlargement and Degenerative Changes in the Media of Intracranial Aneurysms in Rats. J Neuropathol Exp Neurol. 2019 Jul 24. pii: nlz057. doi: 10.1093/jnen/nlz057. [Epub ahead of print] PubMed PMID: 31340038.
4)

Schatlo B, Gautschi OP, Friedrich CM, Ebeling C, Jägersberg M, Kulscar Z, Pereira VM, Schaller K, Bijlenga P. Association of single and multiple aneurysms with tobacco abuse: an @neurIST risk analysis. Neurosurg Focus. 2019 Jul 1;47(1):E9. doi: 10.3171/2019.4.FOCUS19130. PubMed PMID: 31261132.
5)

Yang WH, Yang YH, Chen PC, Wang TC, Chen KJ, Cheng CY, Lai CH. Intracranial aneurysms formation after radiotherapy for head and neck cancer: a 10-year nationwide follow-up study. BMC Cancer. 2019 Jun 4;19(1):537. doi: 10.1186/s12885-019-5766-2. PubMed PMID: 31164088; PubMed Central PMCID: PMC6549276.

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