In 1 large single-site study, the factors associated with an earlier increase in risk included diabetes mellitus, male sex, increased age (ie, $70 years), a history of previous MI or revascularization, and having undergone a pharmacological stress test rather than an exercise test327 (Figure 15). The relationships were, however, complex and covarying. Impor- tantly, among patients who were younger and female and did not have diabetes mellitus or a history of MI or revascular- ization, the annual risk of adverse cardiovascular events was predicted to remain ,1% for as long as 9 years, on the basis of hard events observed during the 2-year follow-up period. In contrast, in an 80-year-old man with a normal pharmaco- logical stress study, the risk of an adverse event rose to .1% in ,1 year after an index-negative perfusion evaluation. 6.3.6. Utility of Repeat Stress Testing in Patients With Known CAD The interpretation of repeat testing should be based on a threshold change value that exceeds the expected variability in test results, even in patients at high risk for recurrent events, and especially in those with no interval clinical change.1244 Although the variability of exercise and stress testing results is not well established,306,1251 factors such as differences in day-to-day operations in the same laboratory, interobserver variability, and differences between practices in different imaging laboratories are important contributory factors in observed differences in serial testing. A 5% change in the percent of ischemic myocardium (based on extent and severity) has been suggested by some investigators as a threshold that indicates clinically significant change for stress nuclear MPI.306,1251 The findings from different exercise or stress imaging modalities (echocardiography versus nuclear MPI) can be even more difficult to compare, such that clinicians should use the same imaging modality over time whenever possible. 