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Updated: Aug 24, 2025
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general
Anurag Sethi1, D Leland Taylor1, J Graham Ruby1
1Calico Life Sciences LLC, South San Francisco, CA, United States.
Insights
Large artery calcification, like abdominal aortic calcification (AAC), is a common and dangerous condition, often under-diagnosed. Increased monitoring is crucial for cardiovascular disease prevention.
Area of Science:
- Cardiovascular Medicine
- Medical Imaging
- Genetics
Background:
- Arterial calcification is a significant risk factor for cardiovascular diseases but is often under-diagnosed due to lack of routine monitoring.
- The prevalence and associated risk factors of abdominal aortic calcification (AAC) in the general population are not well understood.
Purpose of the Study:
- To develop machine learning methods for quantifying abdominal aortic calcification (AAC) using UK Biobank imaging data.
- To conduct the largest analysis to date of genetic, biochemical, and epidemiological risk factors associated with AAC.
- To assess the predictive value of AAC for future cardiovascular events and other diseases.
Main Methods:
- Utilized machine learning algorithms to quantify AAC levels from UK Biobank imaging data.
- Performed a genetic association study to identify novel loci linked to AAC.
- Analyzed epidemiological and biochemical data to identify risk factors and disease associations.
Main Results:
- Identified three novel genetic loci (FGF9, NAV9, APOE) and replicated one (TWIST1/HDAC9) associated with AAC.
- Found AAC to be highly prevalent (~1 in 10 adults over 40) with significant hydroxyapatite build-up.
- AAC presentation strongly predicted cardiovascular events (e.g., myocardial infarction, ischemic heart disease) and COPD.
- Risk of myocardial infarction from AAC was comparable to hypercholesterolemia, often occurring without known risk factors like CKD or diabetes.
Conclusions:
- Abdominal aortic calcification (AAC) is a prevalent, high-risk cardiovascular condition that is significantly under-diagnosed.
- AAC poses a substantial risk for cardiovascular events, independent of traditional risk factors like hypercholesterolemia, CKD, and diabetes.
- There is an urgent need for increased awareness and routine monitoring of AAC in the general population to mitigate its lethal consequences.
Abstract:
Calcification of large arteries is a high-risk factor in the development of cardiovascular diseases, however, due to the lack of routine monitoring, the pathology remains severely under-diagnosed and prevalence in the general population is not known. We have developed a set of machine learning methods to quantitate levels of abdominal aortic calcification (AAC) in the UK Biobank imaging cohort and carried out the largest to-date analysis of genetic, biochemical, and epidemiological risk factors associated with the pathology. In a genetic association study, we identified three novel loci associated with AAC (FGF9, NAV9, and APOE), and replicated a previously reported association at the TWIST1/HDAC9 locus. We find that AAC is a highly prevalent pathology, with ~ 1 in 10 adults above the age of 40 showing significant levels of hydroxyapatite build-up (Kauppila score > 3). Presentation of AAC was strongly predictive of future cardiovascular events including stenosis of precerebral arteries (HR~1.5), myocardial infarction (HR~1.3), ischemic heart disease (HR~1.3), as well as other diseases such as chronic obstructive pulmonary disease (HR~1.3). Significantly, we find that the risk for myocardial infarction from elevated AAC (HR ~1.4) was comparable to the risk of hypercholesterolemia (HR~1.4), yet most people who develop AAC are not hypercholesterolemic. Furthermore, the overwhelming majority (98%) of individuals who develop pathology do so in the absence of known pre-existing risk conditions such as chronic kidney disease and diabetes (0.6% and 2.7% respectively). Our findings indicate that despite the high cardiovascular risk, calcification of large arteries remains a largely under-diagnosed lethal condition, and there is a clear need for increased awareness and monitoring of the pathology in the general population.
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