Allostatic Load and Mortality: A Systematic Review and Meta-Analysis

Allostatic load, a measure of stress-related physiologic dysregulation, is associated with numerous mortality risk factors. This systematic review and meta-analysis examines the relationship between high allostatic load (i.e., increased dysregulation versus low dysregulation) and mortality (cardiovascular disease and all-cause mortality).Systematic searches of 2 databases conducted in May 2021 yielded 336 unique records; 17 eligible studies (2001-2020) were included.High allostatic load was associated with increased risk of all-cause mortality across all the 17 individual studies (hazard ratio=1.08-2.75) and in 6 of 8 studies examining cardiovascular disease mortality (hazard ratio=1.19-3.06). Meta-analyses indicated that high allostatic load was associated with increased risk of all-cause mortality, overall (hazard ratio=1.22, 95% CI=1.14, 1.30, n=10) and across subgroups (hazard ratio=1.11-1.41), and similarly for cardiovascular disease mortality (hazard ratio=1.31, 95% CI=1.10, 1.57, n=6). Although studies were generally of good quality (n=13), heterogeneity was high in most pooled estimates (I2>90%).In this review of relatively good-quality studies, high allostatic load was associated with an increased mortality risk of 22% for all-cause mortality and 31% for cardiovascular disease mortality. Thus, allostatic load is an emerging and potent modifiable risk factor for all-cause and cardiovascular disease mortality that shows promise as a prognostic indicator for mortality. The heterogeneity in allostatic load assessment across studies highlights the need for standardized measurement. The findings underscore the importance of allostatic load's dynamic nature, which may be especially relevant for mitigating mortality risk in younger adults. Because older adults are oversampled, future allostatic load research should prioritize younger adults and longitudinal monitoring and specific cardiovascular disease mortality risk associations and individualize behavioral and lifestyle targets for reducing allostatic load.