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.

Machine learning (ML)-based stroke risk stratification systems have typically focused on conventional risk factors (CRF) (AtheroRisk-conventional). Besides CRF, carotid ultrasound image phenotypes (CUSIP) have shown to be powerful phenotypes risk stratification. This is the first ML study of its kind that integrates CUSIP and CRF for risk stratification (AtheroRisk-integrated) and compares against AtheroRisk-conventional. Two types of ML-based setups called (i) AtheroRisk-integrated and (ii) AtheroRisk-conventional were developed using random forest (RF) classifiers. AtheroRisk-conventional uses a feature set of 13 CRF such as age, gender, hemoglobin A1c, fasting blood sugar, low-density lipoprotein, and high-density lipoprotein (HDL) cholesterol, total cholesterol (TC), a ratio of TC and HDL, hypertension, smoking, family history, triglyceride, and ultrasound-based carotid plaque score. AtheroRisk-integrated system uses the feature set of 38 features with a combination of 13 CRF and 25 CUSIP features (6 types of current CUSIP, 6 types of 10-year CUSIP, 12 types of quadratic CUSIP (harmonics), and age-adjusted grayscale median). Logistic regression approach was used to select the significant features on which the RF classifier was trained. The performance of both ML systems was evaluated by area-under-the-curve (AUC) statistics computed using a leave-one-out cross-validation protocol. Left and right common carotid arteries of 202 Japanese patients were retrospectively examined to obtain 404 ultrasound scans. RF classifier showed higher improvement in AUC (~57%) for leave-one-out cross-validation protocol. Using RF classifier, AUC statistics for AtheroRisk-integrated system was higher (AUC = 0.99,p-value<0.001) compared to AtheroRisk-conventional (AUC = 0.63,p-value<0.001). The AtheroRisk-integrated ML system outperforms the AtheroRisk-conventional ML system using RF classifier.