A Protocol to Exposure Path Analysis for Multiple Stressors Associated with Cardiovascular Disease Risk: A Novel Approach Using NHANES Data

Background: Multiple medical and non-medical stressors, along with the complicity of their exposure pathways, have posted significant challenges to the epidemiological interpretation of the non-communicable diseases, including cardiovascular disease (CVD). Objective: To develop a protocol for deconstructing the complex exposure pathways linking various stressors to adverse outcomes and to elucidate the sequential determinants contributing to CVD risk in depth. Methods: In this study, we developed a Path-Lasso approach, rooted in Adaptive Lasso regression, to construct the network and paths to interpret the determinants of CVD in an in-depth way by using data from the National Health and Nutrition Examination Survey (NHANES). Univariate logistic regression was initially employed to screen out all potential factors of influencing CVD. Then a programmed approach, using Path-Lasso technique, stratified covariates and established a causal network to predict CVD risk. Results: Age, smoking and waist circumference were identified as the most significant predictors of CVD risk. Other factors, such as race, marital status, physical activity, cadmium exposure and diabetes acted as the intermediary or proximal variables. All these stressors (or nodes) formed the network with paths (or edges to link the CVD), in which the latent layer variables that causally associate to the outcome are linearly formed by the stressors in each layer. Discussion: The Path-Lasso approach revealed the epidemiological pathways, linking covariates to CVD risk, which is instrumental in elucidating the inter-covariate transitions of their predication to the outcome, and providing the hierarchal network for foundation of the assessment of CVD risk and the beyond.