Allostatic load and subsequent all-cause mortality: which biological markers drive the relationship? Findings from a UK birth cohort

Abstract

The concept of allostatic load (AL) refers to the idea of a global physiological 'wear and tear' resulting from the adaptation to the environment through the stress response systems over the life span. The link between socioeconomic position (SEP) and mortality has now been established, and there is evidence that AL may capture the link between SEP and mortality. In order to quantitatively assess the role of AL on mortality, we use data from the 1958 British birth cohort including eleven year mortality in 8,113 adults. Specifically, we interrogate the hypothesis of a cumulative biological risk (allostatic load) reflecting 4 physiological systems potentially predicting future risk of death (N = 132). AL was defined using 14 biomarkers assayed in blood from a biosample collected at 44 years of age. Cox proportional hazard regression analysis revealed that higher allostatic load at 44 years old was a significant predictor of mortality 11 years later [HR = 3.56 (2.3 to 5.53)]. We found that this relationship was not solely related to early-life SEP, adverse childhood experiences and young adulthood health status, behaviours and SEP [HR = 2.57 (1.59 to 4.15)]. Regarding the ability of each physiological system and biomarkers to predict future death, our results suggest that the cumulative measure was advantageous compared to evaluating each physiological system sub-score and biomarker separately. Our findings add some evidence of a biological embodiment in response to stress which ultimately affects mortality.

Keywords: Allostatic load; Cohort study; Health behaviours; Mortality; Social environment.

Fig. 1

a Forest plot of hazard ratio for all-cause of mortality associated with the AL and b Kaplan–Meier curve of the Survival probability over the 11 years follow-up period according to category of the allostatic load (N = 8,113, 132 deaths). Allostatic load was classified as low, intermediate, or high as described in Table 2

Fig. 2

a Forest plot of hazard ratio for all-cause of mortality associated with AL and each physiological system and b corresponding log10 (P-values). The grey line represents a Bonferroni correct P value of 0.01. NEU: neuro-endocrine

Fig. 3

Kaplan-Meier probability of the cumulative probability of death according to each physiological system and the AL. Cumulative mortality is shown for the ‘high’ AL score and each ‘high’ physiological sub-score

Fig. 4

a Forest plot of hazard ratio for all-cause of mortality associated with AL and each physiological biomarkers grouped by system and b corresponding log10 (P-values). The grey line represents a Bonferroni correct P-value of 0.003. NEU: neuro-endocrine. AL: allostatic load

Fig. 5

Kaplan-Meier probability of the cumulative probability of death according to each individual biomarker and the AL. Cumulative mortality is shown for the ‘high’ AL score and each ‘high’ individual components: neuroendocrine (a), immune and inflammatory (b), metabolic system (c) and cardiovascular (d)