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Sex differences in aneurysmal subarachnoid haemorrhage

Rehman, S ORCID: 0000-0003-0056-719X 2021 , 'Sex differences in aneurysmal subarachnoid haemorrhage', PhD thesis, University of Tasmania.

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Abstract

Background:
Aneurysmal subarachnoid haemorrhage (aSAH) has a greater incidence in women compared to men. Few studies have explored if sex differences in risk factors for aSAH contribute to this disparity. Similarly, very few authors examined sex differences in long and short-term outcomes and there are inconsistent findings reported among the studies that have been conducted. Therefore, there is a need for high-quality studies to examine sex differences in the risk factors and the outcomes of aSAH. Such findings will be useful to devise sex-specific interventions to improve the prevention, management, and outcome of aSAH.
Aims:
(1) Examine sex differences in the risk factors for aSAH; (2) examine sex differences in the short and long-term outcomes after aSAH; and (3) identify factors that explain sex differences in poor outcomes after aSAH. Methods: This thesis contains four chapters presenting studies addressing these aims.
Chapter 3:
A systematic review and meta-analysis to examine sex differences in risk factors for aSAH. I included case-control and cohort studies based on sex differences in the risk factors for aSAH published up to 2017. Random-effects meta-analysis was used to pool estimates for a risk factor in men and women by approximating odds ratio (OR) and risk ratios (RR) when a risk factor was reported in ≥2 studies. Chapter 4 and chapter 5:
Data were from REDucing Delays In aneurysmal Subarachnoid Haemorrhage (REDDISH) study, comprising of a retrospective cohort of all patients diagnosed with aSAH across two large public healthcare networks in Australia between 2010-2016. Multiple overlapping sources were used to identify the potential cases of aSAH with data extracted from medical records by trained research assistants. Study factors include sex, demographics, social factors, aneurysm characteristics, neurological complications, and clinical management. Outcome after aSAH were (1) discharge destination (home vs rehabilitation and death) after acute hospital admission; and (2) survival up to 1 year or (3) causes of death up to 1 year obtained by data linkage to the National Death Index (NDI). The REDDISH study was used to examine sex differences in neurological complications, aneurysm characteristics, and outcomes. This data source was also used to examine sex differences in adherence to evidence-based processes of care after aSAH, 1-year mortality and causes of death, including if these differed by sex.
Chapter 6:
Data were from the International Stroke Outcomes Study (INSTRUCT). This study is a collaboration between investigators for 13 high quality population-based stroke incidence studies from Australasia, Asia, Europe, South America, and the Caribbean between 1993-2017. De-identified individual participant data was harmonised on sociodemographic factors, health behaviours, pre-stroke comorbidities, the severity of stroke and outcomes of (1) mortality at 30 days, 1 year, and 5 years and (2) poor functional outcome at 30 days, 1 year, and 5 years. This dataset was used to examine sex differences in the prevalence and predictors of short and long term outcomes after SAH, including mortality and functional outcomes at 30 days, 1 year and 5 years.
Results:
Chapter 3:
There were 31 studies (27 case-control and 4 cohort) identified. Female sex was associated with greater likelihood of aSAH. There was no detectable difference between the sexes for common risk factors like hypertension, smoking, aSAH family history, systolic blood pressure, age, and some genetic variations. Alcohol, high alanine aminotransferase (ALT) levels, and some gene variants increased the risk of aSAH in men. Reproductive factors, divorce and some genetic variations increased the risk in women. High aspartate aminotransferase (AST) levels in men and, diabetes and parity in women reduced the risk of aSAH.
Chapter 4:
There were a total of 577 patients with aSAH included and women were over-represented compared to men (69% vs 31%). Mean aneurysm size was greater in men than women. Delayed cerebral ischaemia (DCI) and hydrocephalus were more common neurological complications in women than men. Pre-stroke confounders including age, hypertension history, smoking status, and neurological complications (DCI and hydrocephalus) explained the slightly greater risk of poor outcomes in women after acute admission.
Chapter 5:
There were 549 patients with aSAH included in this study from the REDDISH dataset. Approximately 60% were managed according to the treatment guidelines, with no sex differences noted. Individual indicators of care were associated with improved survival up to 1 year. Optimal care reduced mortality at 1 year independent of age, sex, severity, comorbidities, and hospital network.
Chapter 6:
There were 657 patients with SAH (46% men) in the INSTRUCT study. There was limited evidence of sex differences in mortality and poor functional outcome at 30 days, 1 year and 5 years. Poor outcomes were associated with non-modifiable factors including age and severity of the stroke, but also risk factors that predict SAH incidence including smoking.
Conclusion:
Despite the over-representation of women in cohorts with aSAH, there were no striking differences between men and women in the risk factors and outcomes examined in this thesis. Most established risk factors (e.g. hypertension and smoking) are equally a risk for aSAH in men and women. However, the role of hormonal risk factors needs further exploration as these may assist in the prevention and management of aneurysmal rupture in both men and women. Men and women mostly had the same survival and functional outcomes in the short and long term after aSAH. Women more often suffered complications like DCI and hydrocephalus than men. Across analyses, outcomes after aSAH were mostly associated with modifiable risk factors for aSAH incidence (e.g. smoking or hypertension) but also non modifiable risk factors such as age and severity of stroke. Thus, devising better strategies for prevention and management of risk factors for aSAH, ensuring evidence-based care for aSAH is provided to all patients, and improving management of neurological complications could help improve the outcomes after aSAH for men and women.

Item Type: Thesis - PhD
Authors/Creators:Rehman, S
Keywords: Sex differences, aneurysmal subarachnoid haemorrhage, risk factors, outcomes
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Copyright 2021 the author

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