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Latent profiles of biological dysregulation and risk of mortality: time-to-event analysis using the Midlife in the US longitudinal study


Background There is a well-established relationship between high allostatic load (AL) and increased risk of mortality. This study expands on the literature by combined latent profile analysis (LPA) with survival data analysis techniques to assess the degree to which AL status is associated with time to death.

Methods LPA was employed to identify underlying classes of biological dysregulation among a sample of 815 participants from the Midlife in the US study. Sex-stratified Cox proportional hazards regression models were used to estimate the association between class of biological dysregulation and time to death while controlling for sociodemographic covariates.

Results The LPA resulted in three classes: low dysregulation, immunometabolic dysregulation and parasympathetic reactivity. Women in the immunometabolic dysregulation group had more than three times the risk of death as compared with women in the low dysregulation group (HR=3.25, 95% CI: 1.47 to 7.07), but that there was not a statistically significant difference between the parasympathetic reactivity group and the low dysregulation group (HR=1.80, 95% CI: 0.62 to 5.23). For men, the risk of death for those in the immunometabolic dysregulation (HR=1.79, 95% CI: 0.88 to 3.65) and parasympathetic reactivity (HR=0.90, 95% CI: 0.34 to 3.65) groups did not differ from the low dysregulation group.

Conclusion The findings are consistent with the previous research that demonstrates increased AL as a risk factor for mortality. Specifically, in women, that increased risk may be associated with immunometabolic dysregulation and not simply a generalised measure of cumulative risk as is typically employed in AL research.


Data availability statement

Data are available in a public, open access repository. Data from the MIdlife in the United States (MIDUS) study is freely available via

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