The following is a summary of “Genetic Determinants of Aortic Distention,” published in the April 2023 issue of Cardiology by Pirruccello, et al.

As the largest conduit vessel, the aorta played a crucial role in converting phasic systolic inflow into continuous peripheral blood delivery. The function is enabled by the specialized composition of the aortic extracellular matrix, which allows for systolic distention and diastolic recoil. However, aortic distensibility decreases with age and vascular disease. For a study, researchers sought to investigate the epidemiologic correlates and genetic determinants of aortic distensibility and strain.

Using cardiac magnetic resonance images, a deep learning model was trained to quantify the thoracic aortic area throughout the cardiac cycle. Aortic distensibility and strain were calculated in a cohort of 42,342 participants from the UK Biobank.

Descending aortic distensibility showed an inverse association with the future incidence of cardiovascular diseases, including stroke (HR: 0.59 per SD; P = 0.00031). The heritabilities of aortic distensibility and strain ranged from 22% to 25% and 30% to 33%, respectively. By conducting common variant analyses, researchers identified 12 and 26 loci associated with ascending aortic distensibility and strain and 11 and 21 loci associated with descending aortic distensibility and strain, respectively. Among these newly discovered loci, 22 showed no significant association with thoracic aortic diameter. The genes located near these loci were found to be involved in elastogenesis and atherosclerosis. Through common variant analyses, several loci were identified as associated with aortic distensibility and strain, both in the ascending and descending aorta. Importantly, many of these loci were not significantly associated with thoracic aortic diameter. 

The nearby genes implicated in elastogenesis and atherosclerosis suggest potential mechanisms underlying these associations. Furthermore, polygenic scores for aortic strain and distensibility showed modest effect sizes in predicting cardiovascular outcomes, independent of aortic diameter polygenic scores.

Genetic determinants of aortic function play a role in the risk of stroke and coronary artery disease, highlighting potential novel targets for medical interventions. The study shed light on the complex interplay between genetics, aortic function, and cardiovascular health.

Source: jacc.org/doi/10.1016/j.jacc.2023.01.044