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Evidence of an association between psychosocial stress and mortality continues to accumulate. However, despite repeated calls in the literature for further examination into the physiological and behavioral pathways though which stress affects health and mortality, research on this topic remains limited. This study addresses this gap by employing a counterfactual-based mediation analysis of eight behavioral, biological, and psychological pathways often hypothesized to play a role in the association between stress and health. First, we calculated the survival rate of all-cause mortality associated with cumulative psychosocial stress (high vs. low/moderate) using random effects accelerated failure time models among a sample of 7108 adults from the Midlife in the United States panel study. Then, we conducted a multiple mediator mediation analysis utilizing a counterfactual regression framework to determine the relative contributions of each mediator and all mediators combined in the association between stress and mortality. Exposure to high psychosocial stress was associated with a 0.76 times reduced survival rate over the follow-up period 1995-2015, while adjusting for age, sex, race, income, education, baseline health, and study design effects. The mediators accounted for 49% of this association. In particular, smoking, sedentary behavior, obesity/BMI, and cardiovascular disease displayed significant indirect effects and accounted for the largest reductions in the total effect of stress on mortality, with natural indirect effects of 14%, 12%, 11%, and 4%, respectively. In conclusion, traditional behavioral and biological risk factors play a significant role in the association between psychosocial stress and mortality among middle and older adults in the US context. While eliminating stress and the socioeconomic disparities that so often deliver people into high-stress scenarios should be the ultimate goal, public health interventions addressing smoking cessation, physical activity promotion, and cardiovascular disease treatment may pay dividends for preventing premature mortality in the near-term.

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The relative contributions of behavioral, biological, and psychological risk factors in the association between psychosocial stress and all-cause mortality among middle- and older-aged adults in the USA