Medical applications on cardiovascular disease (CVD) for hybrid computing models are an emerging research area. The CVD, including stroke, hypertension, and high cholesterol, is one of 10 leading causes of death in Taiwan in middle-aged and elderly; in particular, the CVD has become the top killer in advanced countries. Thus, this serious but interesting issue triggers the study to focus on patients of the CVD. The study explores variables, influencing cardiovascular functions for four risk factors of blood pressure, blood glucose, blood fat, and kidney diseases, in the middle-aged and elderly. By the data collection of regular physical examination system from a regional hospital, the original dataset contains 52 variables collected from October 2011 to February 2014. We model a hybrid knowledge-based classification system to organize expert experiences, integrated linear and nonlinear attribute selection methods, data discretization of smart expert method, rough set theory, the LEM2 algorithm, and rule-filtering technique to classify the CVD for the early warning purpose. After data cleaning, 20 attributes with 2027 records are remained. For effectively identifying the variables of CVD subjects, this study reclassifies the above four risk diseases into three classes: no disease, 1&2 diseases, and 3&4 diseases. To verify performance of the proposed procedure, we experience an empirical experiment to compare the full 20 used attributes, the used attributes of integrated linear and nonlinear attribute selections with rule-filtering technique, and various classifiers. Conclusively, the 13 used attributes obtained from optimal accuracy become the key determinants that affect the four risk factors of the CVD. The empirical results and findings benefit doctors’ and medical institutions’ early medical recommendations and treatments with the advantages of significantly reducing morbidity of CVD. © 2018, Springer-Verlag London Ltd., part of Springer Nature.