Among asymptomatic middle-aged to older adults, one of the most sensitive, reliable, and reproducible ways of noninvasively identifying subclinical atherosclerosis is coronary artery calcium (CAC) testing. Numerous studies have demonstrated the robust association between presence and severity of CAC and future risk of cardiovascular disease (CVD).1,2 Conversely, the absence of CAC has been associated with low rates of CVD.3,4 Based on the available evidence of the role of CAC in improving the estimation of CVD risk, multisociety practice guidelines from the United States, Europe, and others endorse the selective use of CAC in adults aged 40 to 75 years with borderline or intermediate estimated 10-year atherosclerotic CVD risk to guide the intensification of preventive strategies (eg, lipid-lowering therapy).5,6 When CAC is absent, current American Heart Association/American College of Cardiology guidelines recommend that clinicians consider providing no statin to some patients who are not at an elevated risk on the basis of smoking status, family history, and diabetes. Beyond this recommendation, however, some investigators have called for even more aggressive de-risking of patients with a CAC score of 0, suggesting that even those with familial hypercholesterolemia and a CAC score of 0 may not need statins.7 The article by Mortensen et al8 in this issue of JAMA Cardiology should give pause to efforts to broaden the use of a CAC score of 0 to de-escalate or defer statin therapy in all individuals.