Calcification of abdominal aorta is an underappreciated cardiovascular disease risk factor

Background Calcification of the abdominal artery is an important contributor to cardiovascular disease in diabetic and chronic kidney disease (CKD) populations. However, prevalence of the pathology, risk factors, and long term disease outcomes in a general population have not been systematically analyzed. Method We developed machine learning models to quantify levels of abdominal aortic calcification (AAC) in 29,957 whole body dual-energy X-ray absorptiometry (DEXA) scans from the UK Biobank cohort. Using regression techniques we associated severity of calcification across a wide range of physiological parameters, clinical biomarkers, and environmental risk factors (406 in total). We performed a common variant genetic association study spanning 9,572,557 single-nucleotide polymorphisms to identify genetic loci relevant to AAC. We evaluated the prognostic value of AAC across 151 disease classes using Cox proportional hazard models. We further examined an epidemiological model of calcification on cardiovascular morbidity with and without LDL interactions. Findings We find evidence for AAC in >10.4% of the cohort despite low prevalence of diabetes (2.5%) and CKD (0.5%). Increased level of AAC is a strong prognostic indicator of cardiovascular outcomes for stenosis of precerebral arteries (HR~1.5), Myocardial Infarction (HR~1.5), & Ischemic Heart Disease (HR~1.33). We find that AAC is genetically correlated with cardiovascular-related traits and that the genetic signals are enriched in vascular and adipose tissue. We report three loci associated with AAC, with the strongest association occuring at the TWIST1/HDAC9 locus (beta=0.078, p-value=1.4e-11) in a region also associated with coronary artery disease. Surprisingly, we find that elevated but still within clinically normal levels of serum phosphate and glycated hemoglobin are linked to increased vascular calcification. Furthermore, we show AAC arises in the absence of hypercholesterolemia. By our estimate, AAC is an LDL-independent risk factor for cardiovascular outcomes, with risk similar to elevated LDL. Data This research has been conducted using the UK Biobank Resource.