Aortic distensibility and aortic aneurysms
We identified common causal mechanisms relating cerebral small vessel disease and aortic structure and function that could explain the clinically observed relationships between late-life cognitive decline and aortic disease.
Diseases affecting the aorta are common and their complications are associated with high mortality even in young people. Quantitative aortic traits (aortic dimensions and functional measures) can predict progression of these aortopathies.
Here, we used convolutional neural networks for automated aortic segmentation25 to measure ascending and descending aortic areas and distensibilities on cardiac magnetic resonance (MRI) images from UK Biobank. We then performed a genome-wide association study (GWAS) of six cardiac magnetic resonance (CMR)-derived aortic traits and carried out functional analyses and a series of Mendelian randomisation (MR) studies to investigate possible causal associations of the aortic measures with aortic aneurysms.
We showed that aortic distensibility has a significant heritable component, with 11% of the variance in ascending aortic distensibility and 10% of the variance in descending aortic distensibility explained by the common genetic variants included in our study. The clinical significance of our findings is suggested by the potential causal associations between ascending aortic distensibility and aortic aneurysms defined by MR phenome-wide association studies (MR-PheWAS). We also presented new evidence for common causal mechanisms relating cerebral small vessel disease and aortic structure and function that could explain the clinically observed relationships between late-life cognitive decline and aortic disease.
A better understanding of the underlying mechanisms based on these genetic data could lead to the identification of new therapeutic targets for the reduction of both cardiovascular disease and dementia risks.