Accurate Prediction of Coronary Heart Disease for Patients With Hypertension From Electronic Health Records With Big Data and Machine-Learning Methods: Model Development and Performance Evaluation
Authors: Du Zhenzhen , Yang Yujie , Zheng Jing , Li Qi , Lin Denan , Li Ye , Fan Jianping , Cheng Wen , Chen Xie-Hui , Cai Yunpeng 
Published: March 2020

Background
Predictions of cardiovascular disease risks based on health records have long attracted broad research interests. Despite extensive efforts, the prediction accuracy has remained unsatisfactory. This raises the question as to whether the data insufficiency, statistical and machine-learning methods, or intrinsic noise have hindered the performance of previous approaches, and how these issues can be alleviated.

Objective
Based on a large population of patients with hypertension in Shenzhen, China, we aimed to establish a high-precision coronary heart disease (CHD) prediction model through big data and machine-learning

Methods
Data from a large cohort of 42,676 patients with hypertension, including 20,156 patients with CHD onset, were investigated from electronic health records (EHRs) 1-3 years prior to CHD onset (for CHD-positive cases) or during a disease-free follow-up period of more than 3 years (for CHD-negative cases). The population was divided evenly into independent training and test datasets. Various machine-learning methods were adopted on the training set to achieve high-accuracy prediction models and the results were compared with traditional statistical methods and well-known risk scales. Comparison analyses were performed to investigate the effects of training sample size, factor sets, and modeling approaches on the prediction performance.

Results
An ensemble method, XGBoost, achieved high accuracy in predicting 3-year CHD onset for the independent test dataset with an area under the receiver operating characteristic curve (AUC) value of 0.943. Comparison analysis showed that nonlinear models (K-nearest neighbor AUC 0.908, random forest AUC 0.938) outperform linear models (logistic regression AUC 0.865) on the same datasets, and machine-learning methods significantly surpassed traditional risk scales or fixed models (eg, Framingham cardiovascular disease risk models). Further analyses revealed that using time-dependent features obtained from multiple records, including both statistical variables and changing-trend variables, helped to improve the performance compared to using only static features. Subpopulation analysis showed that the impact of feature design had a more significant effect on model accuracy than the population size. Marginal effect analysis showed that both traditional and EHR factors exhibited highly nonlinear characteristics with respect to the risk scores.

Conclusions
We demonstrated that accurate risk prediction of CHD from EHRs is possible given a sufficiently large population of training data. Sophisticated machine-learning methods played an important role in tackling the heterogeneity and nonlinear nature of disease prediction. Moreover, accumulated EHR data over multiple time points provided additional features that were valuable for risk prediction. Our study highlights the importance of accumulating big data from EHRs for accurate disease predictions.