Sex differences in risk factor relationships with subarachnoid haemorrhage and intracranial aneurysms: A Mendelian Randomisation study.


Journal

European journal of preventive cardiology
ISSN: 2047-4881
Titre abrégé: Eur J Prev Cardiol
Pays: England
ID NLM: 101564430

Informations de publication

Date de publication:
13 Jun 2024
Historique:
medline: 11 7 2024
pubmed: 11 7 2024
entrez: 11 7 2024
Statut: epublish

Résumé

The prevalence of intracranial aneurysms (IAs) and incidence of aneurysmal subarachnoid haemorrhage (aSAH) is higher in women than in men. Although several cardiometabolic and lifestyle factors have been related to the risk of IAs or aSAH, it is unclear whether there are sex differences in causal relationships of these risk factors. The aim of this study was to determine sex differences in causal relationships between cardiometabolic and lifestyle factors and risk of aSAH and IA. We conducted a sex-specific two-sample Mendelian randomisation study using summary-level data from genome-wide association studies. We analysed low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, total cholesterol, fasting glucose, systolic and diastolic blood pressure, smoking initiation, and alcohol use as exposures, and aSAH and IA (i.e., aSAH and unruptured IA combined) as outcomes. We found statistically significant sex differences in the relationship between genetically proxied non-HDL-C and aSAH risk, with odds ratios (ORs) of 0.72 (95% confidence interval 0.58, 0.88) in women and 1.01 (0.77, 1.31) in men (P-value for sex difference 0.044). Moreover, genetic liability to smoking initiation was related to a statistically significantly higher risk of aSAH in men compared to women (P-value for sex difference 0.007) with ORs of 3.81 (1.93, 7.52) and 1.12 (0.63, 1.99), respectively, and to a statistically significantly higher IA risk in men compared to women (P-value for sex difference 0.036) with ORs of 3.58 (2.04, 6.27) and 1.61 (0.98, 2.64), respectively. In addition, higher genetically proxied systolic and diastolic blood pressure were related to a higher risk of aSAH and IA in both women and men. Higher genetically proxied non-HDL-C was related to a lower risk of aSAH in women compared to men. Moreover, genetic liability to smoking initiation was associated with a higher risk for aSAH and IA in men compared to women. These findings may help improve understanding of sex differences in the development of aSAH and IA.

Sections du résumé

Background UNASSIGNED
The prevalence of intracranial aneurysms (IAs) and incidence of aneurysmal subarachnoid haemorrhage (aSAH) is higher in women than in men. Although several cardiometabolic and lifestyle factors have been related to the risk of IAs or aSAH, it is unclear whether there are sex differences in causal relationships of these risk factors.
Aims UNASSIGNED
The aim of this study was to determine sex differences in causal relationships between cardiometabolic and lifestyle factors and risk of aSAH and IA.
Methods UNASSIGNED
We conducted a sex-specific two-sample Mendelian randomisation study using summary-level data from genome-wide association studies. We analysed low-density lipoprotein cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, total cholesterol, fasting glucose, systolic and diastolic blood pressure, smoking initiation, and alcohol use as exposures, and aSAH and IA (i.e., aSAH and unruptured IA combined) as outcomes.
Results UNASSIGNED
We found statistically significant sex differences in the relationship between genetically proxied non-HDL-C and aSAH risk, with odds ratios (ORs) of 0.72 (95% confidence interval 0.58, 0.88) in women and 1.01 (0.77, 1.31) in men (P-value for sex difference 0.044). Moreover, genetic liability to smoking initiation was related to a statistically significantly higher risk of aSAH in men compared to women (P-value for sex difference 0.007) with ORs of 3.81 (1.93, 7.52) and 1.12 (0.63, 1.99), respectively, and to a statistically significantly higher IA risk in men compared to women (P-value for sex difference 0.036) with ORs of 3.58 (2.04, 6.27) and 1.61 (0.98, 2.64), respectively. In addition, higher genetically proxied systolic and diastolic blood pressure were related to a higher risk of aSAH and IA in both women and men.
Conclusions UNASSIGNED
Higher genetically proxied non-HDL-C was related to a lower risk of aSAH in women compared to men. Moreover, genetic liability to smoking initiation was associated with a higher risk for aSAH and IA in men compared to women. These findings may help improve understanding of sex differences in the development of aSAH and IA.

Identifiants

pubmed: 38989054
doi: 10.1093/eurjpc/zwae175.095
pmc: PMC7616166
pii:
doi:

Types de publication

Journal Article Comparative Study

Langues

eng

Sous-ensembles de citation

IM

Déclaration de conflit d'intérêts

Declaration of conflicting interests The authors declare that there is no conflict of interest.

Auteurs

Lena Tschiderer (L)

Institute of Health Economics; Medical University of Innsbruck, Innsbruck, Austria.

Mark K Bakker (MK)

Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht University, the Netherlands.

Dipender Gill (D)

Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.

Stephen Burgess (S)

Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
Heart and Lung Research Institute, University of Cambridge, Cambridge, United Kingdom.
MRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom.

Peter Willeit (P)

Institute of Health Economics; Medical University of Innsbruck, Innsbruck, Austria.
Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

Ynte M Ruigrok (YM)

Department of Neurology and Neurosurgery, University Medical Center Utrecht Brain Center, Utrecht University, the Netherlands.

Sanne Ae Peters (SA)

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
The George Institute for Global Health, School of Public Health, Imperial College London, London, United Kingdom.
The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.

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