Contribution of short-term changes in a composite health score on pathways linking social disadvantage and health: evidence from the UK biobank prospective cohort study.

Background: Chronic and repeated exposure to external stresses may be embodied and generate an adverse biological response, in-turn affecting health. We investigated the role of 4-year change in a Biological Health Score (BHS) in the pathway linking social exposures to all-cause mortality, atherosclerotic cardiovascular disease (AS-CVD), and cancer incidence. Methods: In this prospective cohort study, we analysed 20,048 participants (10,266 women and 9782 men, aged 37-73 years at baseline) from the UK Biobank prospective cohort with repeated biomarker assessments. The BHS was derived from 15 biomarkers covering cardiovascular, metabolic, inflammatory, liver, and renal systems. We examined associations between BHS change and six social exposures using sex-stratified linear models. Associations between BHS change and subsequent all-cause mortality, AS-CVD incidence, and cancer incidence (ascertained through registry linkage until December 2022) were estimated using sex-specific Cox proportional hazards models adjusted for baseline BHS and time between assessments, with sequential adjustment for additional exposures. Finally, we assessed whether BHS change mediated associations between social exposures and health outcomes using counterfactual mediation analysis. Findings: Total BHS increased over a mean interval of 4.3 years in both men and women, as did all sub-scores except the cardiovascular one. Lower education, low qualification, and financial difficulties were associated with greater increases in BHS. A 1-unit increase in BHS change was associated with: higher all-cause mortality in both men (hazard ratio [HR] 1.46, 95% CI 1.25-1.71) and women (1.26, 1.02-1.56); higher AS-CVD incidence in men (1.33, 1.13-1.57) and women (1.24, 1.03-1.48) and higher cancer incidence in men (1.16, 1.01-1.41) and women (1.29, 1.06-1.58). While no clear mediation by BHS change was observed for women, AS-CVD, or cancer, BHS change explained a small but statistically significant proportion of the association between low income and financial difficulties and mortality, in men. Interpretation: Whilst acknowledging the limitations of our dataset, we show that changes in a composite biological score over a few years, independent of age and baseline score, are socially-patterned and associated with subsequent mortality and cardiovascular disease, suggesting that repeated biological measurements may provide complementary information beyond single time-point assessments. Future research should extend these analyses to multiple repeated measurements, enabling the exploration of the dynamics of the embodiment of time-resolved external stresses and their effects on health. Funding: Research Council of Norway, European Commission.