Accepted Manuscript Smoking associated with increased aneurysm size in patients with anterior communicating artery aneurysms Nengzhi Xia, MD, Yijun Liu, MD, Ming Zhong, MD, Qichuan Zhuge, MD, Lianghao Fan, MD, Weijian Chen, MD, Yunjun Yang, MD, Bing Zhao, MD PII:

S1878-8750(15)01717-9

DOI:

10.1016/j.wneu.2015.11.094

Reference:

WNEU 3510

To appear in:

World Neurosurgery

Received Date: 25 October 2015 Revised Date:

24 November 2015

Accepted Date: 26 November 2015

Please cite this article as: Xia N, Liu Y, Zhong M, Zhuge Q, Fan L, Chen W, Yang Y, Zhao B, Smoking associated with increased aneurysm size in patients with anterior communicating artery aneurysms, World Neurosurgery (2016), doi: 10.1016/j.wneu.2015.11.094. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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ACCEPTED MANUSCRIPT Smoking associated with increased aneurysm size in patients with anterior communicating artery aneurysms

MD,2 Weijian Chen MD,1 Yunjun Yang MD,1 Bing Zhao MD 2,3

Department of Radiology, the First Affiliated Hospital, Wenzhou Medical University,

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Wenzhou, China 2

Department of Neurosurgery, the First Affiliated Hospital, Wenzhou Medical University,

Wenzhou, China

Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota

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Nengzhi Xia MD,1 Yijun Liu MD,1 Ming Zhong MD,2 Qichuan Zhuge MD,2 Lianghao Fan

*

Correspondence to: Yunjun Yang or Bing Zhao

Yun-jun Yang

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Department of Radiology, the First Affiliated Hospital, Wenzhou Medical University;

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Nanbaixiang town, Wenzhou 325000, China Tel: 86-577-55579669

Email:[email protected]

Bing Zhao

Department of Neurosurgery, the First Affiliated Hospital, Wenzhou Medical University; Nanbaixiang town, Wenzhou 325000, China Tel: 0015072024656

Email:[email protected]

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ACCEPTED MANUSCRIPT Abstract

Background: Hypertension and smoking are risk factors for aneurysm formation or rupture. We aimed to identify differences in aneurysm morphologies associated with hypertension or

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smoking in patients with anterior communicating artery (AcoA) aneurysms. Methods: Between December 2007 and February 2015, 574 consecutive patients with AcoA aneurysms were identified from the Electronic Medical Record System. We extracted data on

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histories of hypertension alone, smoking alone, non-hypertension and non-smoking and both hypertension and smoking. The Morphological parameters of aneurysms were re-measured

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using CTA image reconstruction. Multivariate logistic regression analyses were used to determine the differences in morphologies in patients with hypertension or who smoked. Results: In the study 495 patients with single AcoA aneurysm were included. Age, gender, vessel size, aneurysm size and height, size ratio, A1 segment configuration, and aneurysm

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shape were significantly different among the groups. A larger aneurysm more often occurred in patients who only smoked compared with those without hypertension who did not smoke (adjusted OR, 1.19; 95% CI, 1.04–1.36; P=0.012). Patients with hypertension who also

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smoked more commonly had a larger aneurysm size than those with hypertension alone

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(adjusted OR, 0.89; 95% CI, 0.79–0.99; P=0.040). There were significant differences in age, sex, aneurysm morphology between the smoking patients and those with hypertension alone. Conclusion: Aneurysm size was an independent morphological parameter associated with smoking in patients with ACoA aneurysms compared with other aneurysm morphologies. Smoking may be independently associated with increased aneurysm size and should be quitted in patients with AcoA aneurysms. Keywords: Intracranial aneurysm; Anterior communicating artery; Hypertension; Smoking; Aneurysm morphology. 2

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ACCEPTED MANUSCRIPT Introduction

Intracranial aneurysms (IA) are the most common cause of non-traumatic subarachnoid hemorrhages, and are associated with high rates of morbidity and mortality [1]. Anterior

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communicating artery (AcoA) aneurysms account for approximately 25% of IAs [2], however, of all aneurysmal subarachnoid hemorrhage cases, about 40% are attributable to AcoA aneurysms [3]. The mechanisms for aneurysm formation and rupture are still unknown.

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Currently, hypertension has been shown to increase vascular wall tension, vascular

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inflammation and remodeling [4, 5], and smoking has been reported to increase wall shear stress and cause endothelial dysfunction and vascular inflammation [6]. A few studies have reported that hypertension and cigarette smoking are risk factors for both aneurysm formation and rupture [7-12]. In recent decades, several studies have shown that aneurysm

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morphologies, including aneurysm size [13, 14], aspect ratio [15, 16], size ratio [17, 18], flow angles [19, 20], aneurysm projection [21] and A1 segment configuration [22, 23] may affect aneurysm formation and rupture. Therefore, we hypothesized that these factors, including

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hypertension, smoking and aneurysm morphology, could interact to affect AcoA aneurysms

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formation and rupture.

In this report, we extracted the data on hypertension and smoking history from consecutive patients with AcoA aneurysms in our hospital. We re-measured aneurysm morphologies using CT angiography. We aimed to identify differences in aneurysm morphologies among patients with the following characteristics: hypertension alone, smoking alone, non-hypertension and non-smoking, and hypertension and smoking. Materials and methods 3

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ACCEPTED MANUSCRIPT Patients

This study was approved by the Institutional Review Board of the First Affiliated Hospital, Wenzhou Medical University. From December 2007 to February 2015, 574 consecutive

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patients with 584 AcoA aneurysms were identified from the Electronic Medical Record System using the search keywords “anterior communicating artery” and “aneurysm”. Clinical characteristics including sex, age, smoking, and hypertension history, family history and

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other previous history, admission, hospitalization and discharge record, and all the lab and

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radiological examination were prospectively recorded. All aneurysms were confirmed by both computed tomography angiography (CTA) and digital subtraction angiography (DSA). Patients with fusiform aneurysms, vascular malformation, Moyamoya disease, two AcoA aneurysms, and those whose CTA images were of poor quality and could not be used to

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measure the aneurysm morphology were excluded from the analysis. Data collection and definition

The data on hypertension history and smoking history were prospectively recorded by the

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treating physicians through the direct interview of patients or family members. In accordance

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with the Seventh Joint National Committee (JNC 7) report [24], hypertension was defined as a long-term history of hypertension with systolic blood pressures greater than 140 mmHg and/or diastolic blood pressures greater than 90 mmHg. Smoking status was defined as never smoker or current smoker. Ex-smokers at the diagnosis of aneurysm were included into patients with no smoking. Patients were grouped into four groups: hypertension alone, smoking alone, non-hypertension and non-smoking and hypertension and smoking groups.

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All image data on each patient were collected by the neuroradiologists. Aneurysm morphological characteristics were re-measured using CTA image reconstruction. 3D CTA image reconstruction

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Two neuroradiology fellows who are familiar with CTA image reconstruction and morphological measures, performed all measurements, and their average values were used for the analysis. If there was no consensus regarding the characteristics between both, they obtain

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the third opinion from the professor of neuroradiology. A 16-channel multi detector CT

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scanner (Lightspeed pro 16; General Electric Medical Systems, Milwaukee, WI, USA) with a section thickness of 1.25 mm and a reconstruction interval of 0.625 mm, a 64-channel multidetector CT scanner (Lightspeed VCT 64 General Electric Medical Systems, Milwaukee, WI, USA) with a section thickness of 0.625 mm and a reconstruction interval of 0.625 mm,

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and a 320-detector row CT scanner (Aquilion ONE, Toshiba Medical Systems, Japan) with a section thickness of 0.5 mm and a reconstruction interval of 0.5 mm were used to acquire the CTA images. A workstation (Version 4.6; GE Medical Systems) was used to reconstruct the

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3D images of the aneurysms and their surrounding vasculature and to measure the sizes,

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lengths and angles of the aneurysms or vasculatures. Aneurysm morphology and definition We measured the aneurysm morphologies, including the aneurysm size, aneurysm height, perpendicular height, neck size, size ratio, aspect ratio, flow angle, vessel angle, and aneurysm angle, which were defined previously [17]. The aneurysm size is the largest cross-sectional diameter of the aneurysm. Aneurysm height is measured between the center of the aneurysm neck and the greatest distance to the aneurysm dome. Vessel size was measured 5

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for all of the vessels involved with the aneurysm and was determined by averaging the cross sectional diameter of the vessel at the aneurysm neck (D1) with the diameter of the cross section at 1.5 × D1 distance from the aneurysm neck. The size ratio is the ratio between the

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aneurysm height and vessel size of all vessel branches associated with the aneurysm. The A1 segment configuration was divided into three patterns: dominant, complete, and symmetric configurations [22]. The direction of the dome around the AcoA was dichotomized as anterior

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through the ACoA and the anterior skull line[21].

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or posterior projection, according to the positional relation to the perpendicular line formed

Statistical Analysis

Continuous variables were presented as means ± standard deviation, and categorical variables were presented as frequencies (percentage). One-way ANOVA tests or Kruskal-Wallis H tests

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were used for the continuous variables, and chi-square tests were used for the categorical variables, as appropriate. We compared the value of each morphological parameter between hypertension alone and non-hypertension and non-smoking, between hypertension alone and

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hypertension and smoking, between smoking alone and non-hypertension and non-smoking,

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between smoking alone and hypertension and smoking, between hypertension alone and smoking alone, and between hypertension and smoking and non-hypertension and non-smoking. The variables with a P value