COMPETENCY IN MEDICAL KNOWLEDGE: Aortic distensibility is predictive of incident cardiovascular diseases and may be an intermediate phenotype for changes in aortic diameter.
TRANSLATIONAL OUTLOOK:
All population-level analyses were conducted in the UK Biobank, which is a richly phenotyped, prospective, population-based cohort that recruited 500,000 participants aged 40 to 69 years in the UK via mailer from 2006 to 2010.11 As part of an ongoing imaging substudy, cardiac magnetic resonance imaging (MRI) was performed for 42,342 participants with 1.5-T scanners (Magnetom Aera, Siemens Healthcare).12 Access was provided under UK Biobank application no. 7089 and approved by the Mass General
The deep learning model had high accuracy: In a held-out test set of 20 images not used for training, the average Dice scores (maximum 1.0) (Supplemental Methods) were 0.97 for the ascending aorta and 0.96 for the descending aorta (Supplemental Table 2). The model was applied to all available aortic distensibility images in 42,342 UK Biobank participants. This allowed measurement of aortic diameter and circumferential aortic strain (Central Illustration). Strain was divided by a previously
Multiple cardiovascular morbidities have been associated with abnormalities of aortic distensibility, most prominently atherosclerosis, aneurysms, hypertension, and aging. Unlike the static measurement of aortic diameter, distensibility accounts for the dynamic change in aortic cross-sectional area during the cardiac cycle and pulse pressure. Despite the importance of this function in the cardiovascular system, few biological determinants have been identified. In this study, using a deep
We measured ascending and descending thoracic aortic strain and distensibility in up to 42,342 UK Biobank participants, investigated their epidemiology, and identified 41 significantly associated loci, many of which have established connections to TGF-β signaling, elastogenesis, and atherosclerosis. COMPETENCY IN MEDICAL KNOWLEDGE: Aortic distensibility is predictive of incident cardiovascular diseases and may be an intermediate phenotype for changes in aortic diameter. TRANSLATIONAL OUTLOOK:
This work was funded by a collaboration between the Broad Institute and IBM Research. Support for title page creation and format was provided by AuthorArranger, a tool developed at the National Cancer Institute. Dr Pirruccello was supported by a Sarnoff Scholar Award and National Institutes of Health (NIH) grant K08HL159346. Dr Rämö was funded by a Fellowship from the Sigrid Jusélius Foundation. Dr Chou was funded by NIH grant T32HL007208. Dr Lindsay was supported by the Fredman Fellowship for
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Drs Lindsay and Ellinor contributed equally to this work.