Low exposure to positive social determinants of health increases cardiovascular mortality risk modified by allostatic load in cancer and non-cancer patients

Background Allostatic load (AL) is a measure of the biological “wear and tear” or cumulative physiological effects of chronic stress exposure. High AL is associated with an increased risk of cardiovascular death (CVD). Methods We conducted a retrospective cohort analysis of the National Health and Nutrition Examination Survey (1999 - 2010) linked with the National Death Index through 2019. AL was calculated using a nine-point score assessing a combination of physiologic measurements. Positive social determinants of health (PSDOH) was calculated using a seven-point score assessing a combination of socioeconomic exposures. We fit age, race, and sex-adjusted Fine & Gray models to calculate sub-distribution hazard ratios (SHR) of CVD among adults exposed to high versus low levels of PSDOH, stratified by high and low AL status. Results Among 22,775 participants, 1939 had a cancer history. In the full cohort, low PSDOH was associated with 38% increased risk of CVD among high AL adults (SHR: 1.38, 95% CI: 1.22 - 1.56) and 57% increased risk among low AL adults (SHR: 1.57, 95% CI: 1.32 - 1.87). Among adults without a cancer history, low PSDOH was associated with 36% increased risk of CVD among high AL adults (SHR: 1.36, 95% CI: 1.19 – 1.55) and 59% increased risk among low AL adults (SHR: 1.59, 95% CI: 1.32 – 1.92). Among adults with a cancer history, low PSDOH was associated with 77% increased risk of CVD among high AL adults (SHR: 1.77, 95% CI: 1.32 – 2.37) and 73% increased risk among low AL adults (SHR: 1.73, 95% CI: 1.02 – 2.94). Conclusions Low PSDOH exposure amplified the association between AL and CVD in all cohorts, with the highest risk increases seen among adults with a cancer history. This suggests that the impact of social determinants supersedes biological changes from chronic stress alone with respect to CVD.