{"doi":"10.3389/fcvm.2022.1003246","title":"Calcification of the abdominal aorta is an under-appreciated cardiovascular disease risk factor in the general population","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.","journal":"Frontiers in Cardiovascular Medicine","year":2022,"id":239125,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":51,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9585,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":439257,"name":"D. Leland Taylor","orcid":"0000-0001-6498-6970","position":1,"is_corresponding":false},{"id":87705,"name":"J. Graham Ruby","orcid":"0000-0002-4798-5420","position":2,"is_corresponding":false},{"id":865231,"name":"Jagadish Venkataraman","orcid":null,"position":3,"is_corresponding":false},{"id":318186,"name":"Elena P. Sorokin","orcid":"0000-0001-8957-8869","position":4,"is_corresponding":false},{"id":439258,"name":"Madeleine Cule","orcid":"0000-0002-7400-5643","position":5,"is_corresponding":false},{"id":439256,"name":"Eugene Melamud","orcid":"0000-0002-5943-6189","position":6,"is_corresponding":false},{"id":43155,"name":"Anurag Sethi","orcid":"0000-0003-3295-3116","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T00:22:36.865157Z","pmid":"36277789","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}