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Systematic review and Meta-Analysis of Mendelian randomisation analyses of Abdominal aortic aneurysms
Muhammad Ibrahim1,2, Shivshankar Thanigaimani1,2, Tejas P Singh1,2,3
1The Queensland Research Centre for Peripheral Vascular Disease (QRC-PVD), College of Medicine and Dentistry, James Cook University, Queensland, Australia.
Introduction:
Mendelian randomisation (MR) has been suggested to be able to overcome biases of observational studies, but no meta-analysis is available on MR studies on abdominal aortic aneurysm (AAA). This systematic review and Meta-analysis examined the evidence of causal risk factors for AAA identified in MR studies.
Methods:
Publicly available databases were systematically searched for MR studies that reported any causal risk factors for AAA diagnosis. Meta-analyses were performed using random effect models and reported as odds ratio (OR) and 95% confidence intervals (CI). Study quality was assessed using a modified version of Strengthening the Reporting of Mendelian Randomisation Studies (STROBE-MR) guidelines.
Results:
Sixteen MR studies involving 34,050 patients with AAA and 2,205,894 controls were included. Meta-analyses suggested that one standard deviation increase in high density lipoprotein (HDL) significantly reduced (OR: 0.66, 95% CI: 0.61, 0.72) and one standard deviation increase in low density lipoprotein (LDL) significantly increased the risk (OR: 1.68, 95%, CI: 1.55, 1.82) of AAA. One standard deviation increase in triglycerides did not significantly increase the risk of AAA (OR: 1.21, 95% CI: 0.86, 1.71). Quality assessment suggested that ten and five studies were of low and moderate risk of bias respectively, with one study considered as high risk of bias.
Conclusion:
This meta-analysis suggests LDL and HDL are positive and negative casual risk factors for AAA.
Insights
This meta-analysis reveals that high-density lipoprotein (HDL) is a protective factor against abdominal aortic aneurysm (AAA), while low-density lipoprotein (LDL) increases AAA risk. These findings highlight key lipid factors in AAA development.
Area of Science:
- Genetics and Epidemiology
- Cardiovascular Research
- Biomarkers
Background:
- Abdominal aortic aneurysm (AAA) is a significant vascular disease with complex etiology.
- Observational studies on AAA risk factors are prone to biases.
- Mendelian randomisation (MR) offers a method to infer causality by leveraging genetic variants.
Purpose of the Study:
- To systematically review and meta-analyze existing MR studies on causal risk factors for AAA.
- To consolidate evidence on the causal relationship between lipid profiles and AAA risk.
Main Methods:
- Systematic search of public databases for MR studies on AAA.
- Meta-analysis using random effect models to calculate odds ratios (OR) and 95% confidence intervals (CI).
- Study quality assessment using modified STROBE-MR guidelines.
Main Results:
- Sixteen MR studies (34,050 AAA cases, 2,205,894 controls) were included.
- Increased high-density lipoprotein (HDL) significantly reduced AAA risk (OR: 0.66, 95% CI: 0.61–0.72).
- Increased low-density lipoprotein (LDL) significantly elevated AAA risk (OR: 1.68, 95% CI: 1.55–1.82).
- Triglycerides showed no significant association with AAA risk (OR: 1.21, 95% CI: 0.86–1.71).
Conclusions:
- LDL is a causal risk factor that increases AAA risk.
- HDL is a causal risk factor that decreases AAA risk.
- Lipid metabolism plays a significant role in the pathogenesis of AAA.
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