Systems and methods are disclosed for using vessel reactivity to guide diagnosis or treatment for cardiovascular disease. One method includes receiving a patient-specific vascular model of a patients anatomy, including at least one vessel of the patient determining, by measurement or estimation, a first vessel size at one or more locations of a vessel of the patient-specific vascular model at a first physiological state determining a second vessel size at the one or more locations of the vessel of the patient-specific vascular model at a second physiological state using a simulation or learned information comparing the first vessel size to the corresponding second vessel size and estimating a characteristic of the vessel of the patient-specific vascular model based on the comparison.
