Assessing all-cause mortality and years of life lost associated with impaired biological health over time: the Tromsø study

Prior research has shown that high composite biological health scores (BHS, based on the allostatic load theory of multisystem physiological dysregulation) are associated with mortality. However, most of this work remains cross-sectional and does not explore the implications of long-term biological health changes, although this is an essential perspective for a better understanding of ageing and health span. To explore the relationship between BHS-at two time points and longitudinally-and mortality, we analysed waves six (2007-08) and seven (2015-16) of the Tromsø Study linked with all-cause mortality data from the Norwegian Population Registry up to 2022. Using 10 biomarkers from 8117 individuals, we created 2-category (low/high) Tromsø6-BHS, Tromsø7-BHS, and longitudinal BHS measures. Cox proportional hazard regression analysis adjusted for confounders revealed that both higher Tromsø6-BHS and Tromsø7-BHS were significant predictors of mortality 15 and 7 years later, respectively (Tromsø6-BHS: HR = 1.20 [0.99-1.45]; Tromsø7-BHS: HR = 1.26 [1.05-1.52]), and that the 7-year mortality risk was more pronounced for the longitudinal BHS (1.30 [1.09-1.56]). Corresponding sex- and age-adjusted median survival was lowered by 0.71, 1.69, and 1.84 years in participants with a high versus low Tromsø6-BHS, Tromsø7-BHS and longitudinal-BHS, respectively. These results indicate that both historical elevations of BHS and their cumulation over time play a role in determining mortality risk. Our findings underline the importance of monitoring biological health over the life course as a preventive measure and suggest that individuals with high BHS levels may benefit from dynamic monitoring from mid-adulthood to mitigate the risk of premature mortality.