Abstract P541: High Allostatic Load is Associated With Increased Risk of All-cause Mortality - A Systematic Review and Meta-analysis

Introduction: Allostatic load (AL) is a measure of physiological damage from chronic stress, quantified using a variety of neuroendocrine, metabolic, cardiovascular, and immune biomarkers. While AL has been associated with several mortality risk factors (e.g., metabolic disorders, inflammation, cardiovascular disease (CVD), frailty), to date, no meta-analyses have examined the relationship between AL and mortality. This systematic review and meta-analysis examines the relationship between AL and mortality (CVD and all-cause). Hypothesis: Higher AL (i.e., increased dysregulation) will be associated with an increased risk of all-cause and CVD mortality. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement guided this review. Two databases (PubMed and EMBASE) were searched in Feb 2019 with the terms: ((mortality) OR survival) AND ((allostatic load) OR allostasis); references of included studies were also screened. Included studies met the a priori inclusion criteria (i.e. compared mortality (all-cause and/or CVD) in high vs. low AL (defined by study) in adults). Study quality was assessed with the Newcastle Ottawa Criteria. Findings were qualitatively synthesized then the meta-analysis was completed in Review Manager 5.3. Subgroups were examined by design and sample age. Results: Database searches and references identified 400 studies; after removing duplicates, 266 abstracts were screened and 32 full texts were reviewed. The systematic review included 12 observational studies (2001-18) examining all-cause mortality; half were also included in meta-analyses. Of the 12 included studies, most examined CVD mortality (n=7), were longitudinal (n=7), from the US (n=7), and had a balanced sex distribution. In the qualitative review, high AL was consistently associated with increased risk of all-cause mortality (n=11 of 12 studies, hazard ratio (HR) range=1.13-2.98), however, the association was less consistent for CVD mortality (n=4 of 7 studies, HR=1.12-3.06). In meta-analyses, high AL was associated with increased risk of all-cause (HR= 1.46 [1.24, 1.72], n=6) and CVD mortality (HR= 1.18 [1.02, 1.38], n=4). High AL was associated with all-cause mortality in subgroup analyses stratified by design (cross-sectional HR=1.44 [1.14, 1.81], n=3; longitudinal HR=1.61 [1.11, 2.33], n=3) and sample age (older adults HR=1.17 [1.10, 1.24], n=3; all adults HR=1.94 [1.45, 2.60], n=3). Heterogeneity was high (I 2 =85-96%) in analyses except for the older adults subgroup (I 2 =18%). Study quality was good in 7 studies (including all studies in the meta-analysis), fair in 3 studies, and poor in 2 studies. Conclusions: In this review of relatively high-quality studies, high AL was associated with a 46% increased risk of all-cause mortality and may also be associated with CVD mortality. Thus, AL shows promise as a prognostic indicator for mortality.