Causal Inference Challenges in the Relationship Between Social Determinants and Cardiovascular Outcomes.

The effects of social determinants on cardiovascular outcomes are frequently estimated in epidemiologic analyses, but the profound causal and statistical challenges of this research program are not widely discussed. Here, we carefully review definitions and measures for social determinants of cardiovascular health and then examine the various assumptions required for valid causal inference in multivariable analyses of observational data, such as what one would typically encounter in cohorts, population surveys, health care databases, and vital statistics databases. We explain the necessity of the "well-defined exposure" and show how this goal relates to the "consistency assumption" that is necessary for valid causal inference. Well-defined exposure is especially challenging for social determinants of health because they are seldom simple atomistic interventions that are easily conceptualized and measured. We then review threats to valid inference that arise from confounding, selection bias, information bias, and positivity violations. Other causal considerations are reviewed and explained, such as correct model specification, absence of immortal time, and avoidance of the "Table 2 Fallacy," and their application to social determinants of cardiovascular outcomes are discussed. Fruitful approaches, including focusing on policy interventions and the "target trial" frameworks are proposed and provide a pathway for a more efficacious research program that can more reliably improve population health. Valid causal inference in this setting is quite challenging, but-with clever design and thoughtful analysis-the important role of social factors in patterning cardiovascular outcomes can be quantified and reported.