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Background: Most cardiovascular (CV)/stroke risk calculators using the integration of carotid ultrasound image-based phenotypes (CUSIP) with conventional risk factors (CRF) have shown improved risk stratification compared with either method. However such approaches have not yet leveraged the potential of machine learning (ML). Most intelligent ML strategies use follow-ups for the endpoints but are costly and time-intensive. We introduce an integrated ML system using stenosis as an endpoint for training and determine whether such a system can lead to superior performance compared with the conventional ML system. Methods: The ML-based algorithm consists of an offline and online system. The offline system extracts 47 features which comprised of 13 CRF and 34 CUSIP. Principal component analysis (PCA) was used to select the most significant features. These offline features were then trained using the event-equivalent gold standard (consisting of percentage stenosis) using a random forest (RF) classifier framework to generate training coefficients. The online system then transforms the PCA-based test features using offline trained coefficients to predict the risk labels on test subjects. The above ML system determines the area under the curve (AUC) using a 10-fold cross-validation paradigm. The above system so-called "AtheroRisk-Integrated" was compared against "AtheroRisk-Conventional", where only 13 CRF were considered in a feature set. Results: Left and right common carotid arteries of 202 Japanese patients (Toho University, Japan) were retrospectively examined to obtain 395 ultrasound scans. AtheroRisk-Integrated system [AUC =0.80, P<0.0001, 95% confidence interval (CI): 0.77 to 0.84] showed an improvement of ~18% against AtheroRisk-Conventional ML (AUC =0.68, P<0.0001, 95% CI: 0.64 to 0.72). Conclusions: ML-based integrated model with the event-equivalent gold standard as percentage stenosis is powerful and offers low cost and high performance CV/stroke risk assessment.

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Motivation:This study presents a novel nonlinear model which can predict 10-year carotid ultrasound image-based phenotypes by fusing nine traditional cardiovascular risk factors (ethnicity, gender, age, artery type, body mass index, hemoglobin A1c, hypertension, low-density lipoprotein, and smoking) with five types of carotid automated image phenotypes (three types of carotid intima-media thickness (IMT), wall variability, and total plaque area).Methodology: Two-step process was adapted: First, five baseline carotid imagebased phenotypes were automatically measured using AtheroEdge™ (AtheroPoint™, CA, USA) system by two operators (novice and experienced) and an expert. Second, based on the annual progression rates of cIMT due to nine traditional cardiovascular risk factors, a novel nonlinear model was adapted for 10-year predictions of carotid phenotypes.