The Genetic Determinants of Aortic Distention
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Why the study?
Aortic distensibility decreases with age and vascular disease, but its epidemiological correlates and genetic determinants are not fully established.
Key Points
- To identify epidemiological correlates and genetic determinants of aortic distensibility and strain across the cardiac cycle.
- Trained a semantic segmentation deep learning model to quantify thoracic aortic area from cardiac magnetic resonance images across 42,342 UK Biobank participants.
- Calculated circumferential strain and distensibility, followed by genome-wide association studies in 40,577 participants using BOLT-LMM and incident disease analyses.
- Greater descending aortic distensibility was inversely associated with incident stroke (HR 0.59 per SD, P = 3.1E-04) and incident hypertension (HR 0.59 per SD, P = 3.8E-13).
- SNP heritability was 22–25% for aortic distensibility and 30–33% for aortic strain.
Study Design
Type
Cohort (n=42,342)
Multicenter
Yes
PICO
P
Population
42,342 UK Biobank participants aged 40 to 69 years at recruitment who underwent cardiac magnetic resonance imaging to assess aortic distensibility and its genetic determinants.
E
Exposure / Comparator
Descending aortic distensibility vs Lower distensibility (per SD decrease)
O
Primary Outcome
Incident stroke — HR 0.59, p=0.00031
Main Result
Hazard Ratio: 0.59
p-value: p=0.00031
Limitations
- Deep learning models have not been tested outside of the specific devices and imaging protocols used by the UK Biobank
- Study population was largely composed of people of European ancestries, limiting generalizability to global populations
- Central pulse pressure was estimated by a validated device and not directly measured
- The effect of medication classes on aortic phenotypes was estimated based on a biased sample
- Did not conduct external replication of the genetic analysis
Ask about this paper
Answers are grounded in this paper and cite their sources.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Analysis of aortic distensibility from 40,000 UK Biobank MRIs now out in @JACCjournals reveals medication effects; links to coronary disease and stroke; and new genetic loci for strain and distensibility that aren't found when just looking at static aortic diameter.”
“The aorta is not a passive conduit, but is rather an active organ that plays multiple roles in cardiovascular physiology. The normal function of the aorta depends on its elasticity to buffer the pulsatile flow generated by ventricular contraction.”
Implication
Cohort study reveals genetic determinants of aortic distensibility in over 42,000 adults, suggesting aortic biomechanics directly influence stroke and heart disease risk.
Abstract
Background: As the largest conduit vessel, aorta is responsible for the conversion of phasic systolic inflow from ventricular ejection into more continuous peripheral blood delivery. Systolic distension and diastolic recoil conserve energy and are enabled by the specialized composition of the aortic extracellular matrix. Aortic distensibility decreases with age and vascular disease. Objectives: To discover epidemiological correlates and genetic determinants of aortic distensibility and strain. Methods: We trained a deep learning model to quantify thoracic aortic area throughout the cardiac cycle from cardiac magnetic resonance images, and calculated aortic distensibility and strain in 42,342 UK Biobank participants. Results: Descending aortic distensibility was inversely associated with future incidence of cardiovascular diseases such as stroke (HR 0.59 per SD, P = 3.1E-04). The heritability of aortic distensibility and strain was 22–25% and 30–33%, respectively. Common variant analyses identified 12 and 26 loci for ascending and 11 and 21 loci for descending aortic distensibility and strain, respectively. Of the newly identified loci, 22 were not significantly associated with thoracic aortic diameter. Nearby genes were involved in elastogenesis and atherosclerosis. Aortic strain and distensibility polygenic scores had modest effect sizes for predicting cardiovascular outcomes (delaying or accelerating disease onset by 2–18% per standard deviation change in scores) and remained statistically significant predictors after accounting for aortic diameter polygenic scores. Conclusions: Genetic determinants of aortic function influence risk for stroke and coronary artery disease, and may lead to novel targets for medical intervention.
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Cite This Study
Pirruccello et al. (2023) conducted a cohort in Cardiovascular disease (n=42,342). Descending aortic distensibility vs. Lower distensibility (per SD decrease) was evaluated on Incident stroke (HR 0.59, p=0.00031).
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