Computer-implemented methods are disclosed for assessing the effect of musculoskeletal activities on disease and/or clinical events, the method comprising: receiving a patient-specific vascular and musculoskeletal model of a patient's anatomy, including at least one vessel of the patient; receiving at least one characteristic of the patient's musculoskeletal activity; generating or updating a computational anatomic vascular and musculoskeletal model of the patient's anatomy based on the received at least one characteristic of musculoskeletal activity; performing at least one of a computational fluid dynamics analysis or a structural mechanics simulation on the computational anatomic vascular and musculoskeletal model; and estimating at least one of the patient's risk of disease or clinical events based on the performed computational fluid dynamics analysis and/or structural mechanics simulation. Systems and computer readable media for executing these methods are also disclosed.