The U.S. Environmental Protection Agency (EPA) and National Institute of Environmental Health (NIEHS) held a workshop in 2012 to discuss principles and applications of cumulative risk assessment (CRA). The workshop organizers chose cardiovascular disease (CVD) as an example health outcome for which cumulative risk considerations could illuminate environmental and health management strategies. To guide discussions, we developed a series of conceptual models illustrating factors influencing CVD. The CVD conceptual model represents complex processes across varying space and time scales, different causal pathways, and multiple chemical and non-chemical stressors and factors. It includes causal influences of environmental exposures and lifestyle choices, in the context of genetics and medical factors. The representation of cumulative risk as a network of interrelated nodes and arrows helps define and organize the problem and available information, determine the scope and scale, and creates a platform for analysis. It provides an interface for discussing how different entities (e.g., environmental versus health-driven organizations) can work together on different parts of the problem, and facilitates relative risk ranking and management triage. Color coding is used to distinguish categories of stressors and possible oversight responsibility. This work informs guidelines for CRA planning and assessment of factor combinations affecting real-world risk.
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