Many indices have been proposed for cardiovascular risk stratification from electrocardiogram signal processing, still with limited use in clinical practice. We created a system integrating the clinical definition of cardiac risk subdomains from ECGs and the use of diverse signal processing techniques. Three subdomains were defined from the joint analysis of the technical and clinical viewpoints. One subdomain was devoted to demographic and clinical data. The other two subdomains were intended to obtain widely defined risk indices from ECG monitoring: a simple-domain (heart rate turbulence (HRT)), and a complex-domain (heart rate variability (HRV)). Data provided by the three subdomains allowed for the generation of alerts with different intensity and nature, as well as for the grouping and scrutinization of patients according to the established processing and risk-thresholding criteria. The implemented system was tested by connecting data from real-world in-hospital electronic health records and ECG monitoring by considering standards for syntactic (HL7 messages) and semantic interoperability (archetypes based on CEN/ISO EN13606 and SNOMED-CT). The system was able to provide risk indices and to generate alerts in the health records to support decision-making. Overall, the system allows for the agile interaction of research and clinical practice in the Holter-ECG-based cardiac risk domain.