In Reply In their Letter about my recent Editorial, Dr Yuan and colleagues rightly identify a central limitation in how the contribution of lead to CHD is estimated. We rely heavily on population-level models that fail to capture the cumulative, interactive effects of multiple risk factors—lead, air pollution, cadmium, arsenic, diet, tobacco smoke, and more recently identified exposures such as per- and polyfluoroalkyl substances and microplastics. Even this likely understates the true burden, as these exposures contribute to CHD and a range of conditions across the life course, including preterm birth, cognitive deficits, and kidney disease.