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Development of a Prediction Model for Ascending Aortic Diameter Among Asymptomatic Individuals

James P. Pirruccello,Honghuang Lin,Shaan Khurshid, Mahan Nekoui, Lu-Chen Weng, Ramachandran S. Vasan, Eric M. Isselbacher, Emelia J. Benjamin, Steven A. Lubitz, Mark E. Lindsay, Patrick T. Ellinor

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION(2022)

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Abstract
IMPORTANCE Ascending thoracic aortic disease is an important cause of sudden death in the US, yet most aortic aneurysms are identified incidentally. OBJECTIVE To develop and validate a clinical score to estimate ascending aortic diameter. DESIGN, SETTING, AND PARTICIPANTS Using an ongoingmagnetic resonance imaging substudy of the UK Biobank cohort study, which had enrolled participants from 2006 through 2010, score derivation was performed in 30 018 participants and internal validation in an additional 6681. External validation was performed in 1367 participants from the Framingham Heart Study (FHS) offspring cohort who had undergone computed tomography from 2002 through 2005, and in 50 768 individuals who had undergone transthoracic echocardiography in the Community Care Cohort Project, a retrospective hospital-based cohort of longitudinal primary care patients in the Mass General Brigham (MGB) network between 2001-2018. EXPOSURES Demographic and clinical variables (11 covariates that would not independently prompt thoracic imaging). MAIN OUTCOMES AND MEASURES Ascending aortic diameterwas modeled with hierarchical group least absolute shrinkage and selection operator (LASSO) regression. Correlation between estimated and measured diameter and performance for identifying diameter 4.0 cm or greater were assessed. RESULTS The 30 018-participant training cohort (52% women), were a median age of 65.1 years (IQR, 58.6-70.6 years). The mean (SD) ascending aortic diameter was 3.04 (0.31) cm for women and 3.32 (0.34) cm for men. A score to estimate ascending aortic diameter explained 28.2% of the variance in aortic diameter in the UK Biobank validation cohort (95% CI, 26.4%-30.0%), 30.8% in the FHS cohort (95% CI, 26.8%-34.9%), and 32.6% in the MGB cohort (95% CI, 31.9%-33.2%). For detecting individuals with an ascending aortic diameter of 4 cmor greater, the score had an area under the receiver operator characteristic curve of 0.770 (95% CI, 0.737-0.803) in the UK Biobank, 0.813 (95% CI, 0.772-0.854) in the FHS, and 0.766 (95% CI, 0.757-0.774) in the MGB cohorts, although the model significantly overestimated or underestimated aortic diameter in external validation. Using a fixed-score threshold of 3.537, 9.7 people in UK Biobank, 1.8 in the FHS, and 4.6 in the MGB cohorts would need imaging to confirm 1 individual with an ascending aortic diameter of 4 cmor greater. The sensitivity at that threshold was 8.9% in the UK Biobank, 11.3% in the FHS, and 18.8% in theMGB cohorts, with specificities of 98.1%, 99.2%, and 96.2%, respectively. CONCLUSIONS AND RELEVANCE A prediction model based on common clinically available data was derived and validated to predict ascending aortic diameter. Further research is needed to optimize the prediction model and to determine whether its use is associated with improved outcomes.
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