Predictors of Rupture Risk of Intracranial Aneurysms

Subarachnoid hemorrhage (SAH) is a condition mainly caused by the rupture of intracranial aneurysms. The estimated prevalence of intracranial aneurysms in the general population is 1-2%, with an annual incidence of aneurysm rupture causing subarachnoid hemorrhage estimated around 1% in Norway. The mortality rates for aneurysmal subarachnoid hemorrhage (aSAH) are as high as 35%, and for the survivors the condition represents a significant morbidity with long-term cognitive impairment and other challenges. With a mean age of 51-55 years at presentation, the burden, both for the patients themselves and on health care resources, is substantial.

Thus, the risk assessment and management of patients with unruptured intracranial aneurysms (UIA) represents a substantial challenge. The number of patients with incidentally discovered cerebral aneurysms is rapidly growing with the increasing use of non-invasive intracranial magnetic resonance imaging (MRI). Therapy options are endovascular coiling, neurosurgical clipping, or observation. To decide whether to perform a potentially harmful prophylactic procedure or not, better tools to predict the risk of rupture in the given individual are required.

Some risk factors, both for the development of an intracranial aneurysm and for the rupture leading to hemorrhage are identified, such as hypertension, age and smoking. Recent research has shown that obesity and hypercholesterolemia is surprisingly associated with an apparent lower risk of aSAH. However, underlying body composition and dyslipidemic patterns has not yet been explored. Increased knowledge of predictors for aneurysm rupture is required, both to improve the patient care and the decision-making concerning the neurosurgical prevention of aSAH.

In the RAPID project, the investigators aim to identify potential new risk factors for the rupture of intracranial aneurysms by comparing the lipid and lipoprotein profile and the body mass composition in patients with UIA and aSAH.

Direct-segmental multisegmental bioimpedance analysis (DSM-BIA) is a valid tool for the assessment of total body and segmental composition and has shown excellent agreements when compared with dual energy X-ray absorptiometry (DEXA). Body composition will be analysed within day 2 after intervention or surgery using a DSM-BIA scanner (InBody S10, BioSpace Ltd, Seoul, South Korea).

Lipids will be measured enzymatically in ethylenediaminetetraacetic acid (EDTA) plasma/serum on a Hitachi 917 system (Roche Diagnostics GmbH, Mannheim, Germany) using the triacylglycerol (GPO-PAP), cholesterol (CHOD-PAP), HDL-cholesterol plus and LDL-cholesterol plus kit from Roche Diagnostics, and the non-esterifies fatty acid (NEFA FD) kit and the phospholipids kit (Phospholipids FS) from "DiaSys Diagnostic Systems GmbH" (Holzheim, Germany). Glucose will be measured in EDTA-plasma using the Gluco-quant Glucose/HK (GLU) kit from Roche. The total fatty acid composition in EDTA-plasma will be analysed using gas chromatography/mass spectrometry (GC/MS).

Lipoprotein particle size analysis will be performed by proton nuclear magnetic resonance (NMR) spectroscopy. Particle concentrations of lipoproteins of different sizes will be calculated from the measured amplitudes of their spectroscopically lipid methyl group NMR signals. Lipoprotein particle size will be derived from the sum of diameter of each subclass multiplied by its relative mass percentage based on the amplitude of its methyl NMR signal. Particle size analysis will be performed by the Norwegian University of Science and Technology (NTNU).