Abstract
Background Cardiovascular diseases are the leading cause of morbidity and mortality in the United States. Despite the complexity of cardiovascular disease etiology, we do not fully comprehend the interactions between non-modifiable factors (e.g., age, sex, and race) and modifiable risk factors (e.g., health behaviors and occupational exposures).Objective We examined proximal and distal drivers of cardiovascular disease and elucidated the interactions between modifiable and non-modifiable risk factors.Methods We used a machine learning approach on four cohorts (2005-2012) of the National Health and Nutrition Examination Survey data to examine the effects of risk factors on cardiovascular risk quantified by the Framingham Risk Score (FRS) and the Pooled Cohort Equations (PCE). We estimated a network of risk factors, computed their strength centrality, closeness, and betweenness centrality, and computed a Bayesian network embodied in a directed acyclic graph.Results In addition to traditional factors such as body mass index and physical activity, race and ethnicity and exposure to heavy metals are the most adjacent drivers of PCE. In addition to the factors directly affecting PCE, sleep complaints had an immediate adverse effect on FRS. Exposure to heavy metals is the link between race and ethnicity and FRS.Conclusion Heavy metal exposures and race/ethnicity have similar proximal effects on cardiovascular disease risk as traditional clinical and lifestyle risk factors, such as physical activity and body mass. Our findings support the inclusion of diverse racial and ethnic groups in all cardiovascular research and the consideration of the social environment in clinical decision-making.