Broad strategies for reducing the burden of heart disease and stroke in the United States are identified in A Public Health Action Plan for Heart Disease and Stroke Prevention (1), the American Heart Association’s Community Guidance (2), and other policy documents (3). These guides call for a spectrum of interventions extending from primordial prevention to end-of-life care, but they do not specify how best to allocate limited resources. Not only are data on effect sizes lacking for certain intervention pathways, but the contributing risk factors and social determinants interact in dynamically complex ways that defy simple calculation.