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Insomnia a possible risk factor for fatal brain aneurysm rupture

Insomnia may be a potential risk factor for a brain bleed from a ruptured aneurysm along with more well known risk factors of smoking and high blood pressure, according to research published in the Journal of the American Heart Association.

More than 3% of adults worldwide have unruptured blood vessel malformations in the brain, called intracranial aneurysms, most of which will never rupture. But about 2.5% of intracranial aneurysms will rupture, resulting in a subarachnoid haemorrhage (SAH), also called a brain bleed.

SAH is a type of stroke that occurs when a blood vessel on the surface of the brain ruptures and bleeds into the space between the brain and the skull.

“Ruptured aneurysms are highly fatal. It is, therefore, extremely important to identify modifiable risk factors that can help prevent aneurysms from rupturing,” said study author Susanna Larsson, associate professor in the unit of cardiovascular and nutritional epidemiology at the Karolinska Institutet in Stockholm, Sweden, and the unit of medical epidemiology at Uppsala University in Uppsala, Sweden.

The researchers sought to determine whether various factors were associated with intracranial aneurysm and/or the aneurysm rupturing. They studied established risk factors such as smoking and high blood pressure and also assessed the link between aneurysms and coffee consumption, sleep, physical activity, body mass index (BMI), blood glucose levels, type 2 diabetes, blood pressure, cholesterol, chronic inflammation and kidney function.

Data from several genome-wide association studies were used to gauge genetic associations to lifestyle and cardiometabolic risk factors. Genetic information from a meta-analysis conducted by the International Stroke Genetics Consortium was used to identify nearly 6,300 cases of intracranial aneurysm and nearly 4,200 cases of aneurysmal subarachnoid haemorrhage. Cases of intracranial aneurysm and subarachnoid haemorrhage were compared with more than 59,500 controls to determine genetic predisposition for aneurysms.

According to the analysis:
A genetic predisposition for insomnia was associated with a 24% increased risk for intracranial aneurysm and aneurysmal subarachnoid haemorrhage.
The risk for intracranial aneurysm was about three times higher for smokers vs. non-smokers.
The risk for intracranial aneurysm was almost three times higher for each 10mm Hg increase in diastolic blood pressure (the bottom number in a blood pressure reading).
High triglyceride levels and high BMI did not demonstrate an increased risk for intracranial aneurysm and aneurysmal subarachnoid haemorrhage.

“The association between insomnia and intracranial aneurysm has not been reported previously, and these findings warrant confirmation in future studies,” Larsson said. “Our research supports the thinking that risk factors that people can change or manage may impact brain aneurysms and haemorrhage risk. Once confirmed, future studies should examine ways to incorporate this knowledge into prevention programmes and therapies.”

According to a 2016 American Heart Association scientific statement, Sleep Duration and Quality: Impact on Lifestyle Behaviours and Cardiometabolic Health, insufficient and poor-quality sleep and sleep disorders are linked to a higher risk of high blood pressure. The statement summary notes that treating people with sleep disorders may provide clinical benefits, particularly for blood pressure.

Study limitations included that there was not enough information to adequately analyse some of the risk factors. In addition, the analysis included only people of European ancestry; therefore, the findings may not be generalisable to people from diverse racial and ethnic groups.

Study details

Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study

Ville Karhunen, Mark K. Bakker, Ynte M. Ruigrok, Dipender Gill, Susanna C. Larsson.

Published in the Journal of the American Heart Association on 3 November 2021

Abstract

Background
The aim of this study was to assess the associations of modifiable lifestyle factors (smoking, coffee consumption, sleep, and physical activity) and cardiometabolic factors (body mass index, glycemic traits, type 2 diabetes, systolic and diastolic blood pressure, lipids, and inflammation and kidney function markers) with risks of any (ruptured or unruptured) intracranial aneurysm and aneurysmal subarachnoid haemorrhage using Mendelian randomisation.

Methods and Results
Summary statistical data for the genetic associations with the modifiable risk factors and the outcomes were obtained from meta‐analyses of genome‐wide association studies. The inverse‐variance weighted method was used as the main Mendelian randomisation analysis, with additional sensitivity analyses conducted using methods more robust to horizontal pleiotropy. Genetic predisposition to smoking, insomnia, and higher blood pressure was associated with an increased risk of both intracranial aneurysm and aneurysmal subarachnoid haemorrhage. For intracranial aneurysm, the odds ratios were 3.20 (95% CI, 1.93–5.29) per SD increase in smoking index, 1.24 (95% CI, 1.10–1.40) per unit increase in log‐odds of insomnia, and 2.92 (95% CI, 2.49–3.43) per 10 mm Hg increase in diastolic blood pressure. In addition, there was weak evidence for associations of genetically predicted decreased physical activity, higher triglyceride levels, higher body mass index, and lower low‐density lipoprotein cholesterol levels with higher risk of intracranial aneurysm and aneurysmal subarachnoid haemorrhage, with 95% CI overlapping the null for at least 1 of the outcomes. All results were consistent in sensitivity analyses.

Conclusions
This Mendelian randomisation study suggests that smoking, insomnia, and high blood pressure are major risk factors for intracranial aneurysm and aneurysmal subarachnoid haemorrhage.

 

AHA Journal article – Modifiable Risk Factors for Intracranial Aneurysm and Aneurysmal Subarachnoid Hemorrhage: A Mendelian Randomization Study (Open access)

 

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