Biologic Correlates and Consequences of the Social Determinants of Health and Disease.

The consequences of experiences and exposures suffered by those living in poverty can last a lifetime and can even be passed on to the next generation. The challenges associated with poverty have been labeled the "social determinants of health" (SDoH), but this is something of a misnomer. A more appropriate label would be the "social determinants of disease." This essay is a broad overview of the processes, including allostatic load and epigenetic aging, that might contribute to prolonging the adverse effects of the social determinants of disease.

Comparison between grip strength and relative grip strength in their relationship with allostatic load among adolescents.

PURPOSE: To assess the associations of muscle strength, measure by grip strength and relative grip strength (grip strength divided by body weight), on the allostatic load (AL) index in adolescent boys and girls. METHODS: A total of 1,323 students were recruited (boys = 776, girls = 547). Data on general demographic characteristics, anthropometric indicators, grip strength, blood pressure, pulse rate, and biological samples were collected. A 20-indicator-based AL index (using the AL1, AL2, and AL3 calculation methods) was used as the dependent variable. Multiple linear regression models were used to evaluate the association between grip strength, relative grip strength, and AL. All analyses were stratified by sex. RESULTS: The mean age of the participants was 14.17 ± 1.45 years. Overall, the linear regression model adjusting for demografic characteristics showed that greater grip strength was associated with higher AL1 scores (R2 = 10.1%, ß = 0.096, P < 0.001). Then, we further adjusted for body weight, and negative associations were observed between grip strength and AL1 (R2 = 35.3%, ß = -0.027, P = 0.030). However, after sex stratification, this association was not statistically significant in girls. Moreover, relative grip strength was negatively associated with AL1 (R2 = 14.8%, ß = -8.529, P < 0.001) after adjusting for demographic characteristics in the total sample. Specifically, relative grip strength was more strongly associated with the AL1 burden in boys than in girls. Finally, sensitivity analyses of AL2 and AL3 yielded similar results. CONCLUSION: We observed that compared with grip strength, relative grip strength might be a useful indicator for the identification of AL burden in adolescents. The results suggest that strengthening relative handgrip strength in adolescents might help reduce the AL burden, especially in boys.

Allostatic load in rat model: An efficient tool for evaluating and understanding aging.

AIM: Aging and age-related diseases are an ever-increasing social and public health problem. Allostatic load (AL) shows great potential as an interdisciplinary tool for assessing the aging of human beings but as yet lacks investigation in animal models which is our study focus at. METHODS: Here a continuous study of AL was conducted on naturally aging rats. Blood samples were collected from the rats at ages of 5, 8, 14, 18, and 21 months. Dozens of blood biochemical indicators, including serum corticosterone, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, interleukin-6, 25-hydroxyvitamin D, free fatty acid, CD3+ T cell count, CD4+/CD3+ T cell ratio, CD8+/CD3+ T cell ratio, and CD3/4/8+ T cell apoptosis, were determined. RESULTS: AL was scored from those indicators, and we found that AL score gradually increased with age. CONCLUSIONS: AL can reliably reveal the cumulative and systemic changes in aging. Geriatr Gerontol Int 2024; 24: 1077-1084.

The Role of Online Well-Being Therapy in Overcoming Allostatic Overload in Medical Workers: A Pilot Randomized Controlled Study.

INTRODUCTION: Stress may lead to allostatic overload. Well-being therapy (WBT) might mitigate it by enhancing psychological well-being and protecting from psychological symptoms. Since no reports are available on the use of WBT in allostatic overload, we evaluated online WBT effects in reducing allostatic overload in medical workers during the coronavirus pandemic. METHODS: Sixty-six participants with allostatic overload were enrolled and randomly assigned to eight sessions of online WBT (n = 32) or eight sessions of an online psychoeducation program on healthy lifestyle (CON) (n = 34). The primary outcome was the prevalence rate of allostatic overload in the two groups at session 8 (T2). Secondary analyses were performed on changes in the PsychoSocial Index (PSI) and Psychological Well-Being (PWB) scales scores at the same time points. Generalized estimating equation models were employed. RESULTS: The WBT group showed a significantly lower rate of allostatic overload at T2 than the CON group (28.13% vs. 70.59%, p < 0.001); similar results were found at T1, T3, and T4 (p < 0.001). Compared to CON, WBT produced a significant decrease in psychological distress (p < 0.001) and abnormal illness behavior (p = 0.031), as well as a significant improvement in PWB autonomy, environmental mastery, personal growth, positive relations with others, purpose in life, and self-acceptance (p < 0.001). CONCLUSION: Online WBT may be an effective non-pharmacological therapeutic strategy for individuals with allostatic overload. These findings need to be further validated in different clinical populations.

What Explains the Link Between Hearing and Vision Impairment and Cognitive Function? Analysis of Mediating Effects in the USA, England and Ireland.

OBJECTIVES: Hearing and vision impairments are associated with cognitive decline and dementia risk. Explanations for this include age-related processes impacting on sensory and cognitive function (common cause), or sensory impairments having a direct or indirect impact on cognition via social engagement, depression and physical activity (cascade). We tested whether associations between hearing, vision and episodic memory were mediated by allostatic load, social engagement, depression and physical activity. METHODS: We used structural equation modelling with cross-sectional data from the USA (n = 4746, aged 50-101), England (n = 4907, aged 50-89) and Ireland (4292, aged 50-80) to model factors related to the common cause (indexed by allostatic load) and the cascade hypothesis with respect to cognitive ability (episodic memory). RESULTS: Poorer hearing/vision was associated with lower social engagement, depression and sedentary lifestyle. Poor vision was not related to allostatic load, and poor hearing was associated with allostatic load in only one data set, contributing to a common-cause hypothesis. Lower social engagement, depression and a sedentary lifestyle were associated with poorer episodic memory, contributing to the cascade hypothesis. Using effect estimates to calculate the proportion of the total effects mediated by the combined mediator variables, up to two fifths of the relationship between hearing and vision with episodic memory can be explained by the mediators. CONCLUSIONS: The association between hearing, vision and episodic memory is mediated by allostatic load, social engagement, depression, and physical activity. The finding that social engagement, depression, and physical activity mediate the association between sensory abilities and cognitive function supported the cascade hypotheses. Interventions to improve healthy lifestyle, reduce depression and foster social engagement of older people with sensory impairments are likely to be beneficial in preventing cognitive decline and dementia.

Elevated allostatic load is associated with poorer response to repetitive transcranial magnetic stimulation in treatment-resistant depression.

This cohort study investigated whether allostatic load (AL) is associated with treatment response to repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant depression (TRD). Pre-treatment blood samples measured AL across multiple systems. Pre- and post-treatment mood changes were assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Associations between AL and treatment outcomes were explored. Higher pre-treatment AL was significantly associated with poorer post-treatment response status but was not significantly associated with smaller reduction in MADRS score after 4 weeks of treatment. Identifying biomarker profiles informed by the AL model could enhance treatment decisions in TRD, reducing risks associated with prolonged, ineffective rTMS trials and emphasizing the need for reliable predictive biomarkers.

Chronic Work Discrimination, Allostatic Load, and HbA1c in Older Workers.

BACKGROUND AND OBJECTIVE: Work discrimination is an important public health problem with consequences for health. This study examined the effect of chronic work discrimination on 4-year changes in HbA1c, as a reflection of glucose control and type 2 diabetes risk in older workers and assessed whether allostatic load (AL) affected the strength of this association. RESEARCH DESIGN AND METHODS: We used Health and Retirement Study data (2010-2016, n = 3,246). Conditional change multinomial logistic regression examined the association between chronic work discrimination, high AL (4 or more out of 8 high-risk biomarkers), and HbA1c, while accounting for relevant covariates. RESULTS: Black participants had the highest rates of baseline (22.7%) and follow-up (28%) HbA1c levels, AL (38%), and chronic work discrimination (39%; p < .01). Severe chronic work discrimination was associated with elevated HbA1c (relative risk ratio [RRR] = 1.61, 95% confidence interval [CI] = 1.07, 2.43). AL was associated with elevated HbA1c (RRR = 1.49, 95% CI = 1.04, 2.14). Relative to White participants, Hispanic (RRR = 1.52, 95% CI = 1.07, 2.16, RRR = 1.81, 95% CI = 1.051, 3.12), and Black (RRR = 2.42, 95% CI = 1.82, 3.23; RRR = 3.00, 95% CI = 1.97, 4.56) participants had an increased risk of intermediate and elevated HbA1c, respectively. Among those with long job tenure (≥5 years), both moderate (RRR = 1.81, 95% CI = 1.11, 2.96) and severe (RRR = 1.90, 95% CI = 1.15, 3.12) chronic work discrimination was associated with elevated HbA1c. DISCUSSION AND IMPLICATIONS: Chronic work discrimination was associated with HbA1c; however, no moderating effects of AL were observed. Findings underscore a need for organizational and public health measures to establish strong anti-discrimination laws in the workplace to improve the work environment of older workers and reduce diabetes risk.

Examining emotion regulation and inflammation as predictors of maternal mental health after fetal anomaly diagnosis.

OBJECTIVE: Fetal anomalies occur in approximately 3% of pregnancies and receiving the diagnosis may be a potentially traumatic experience for families. The mental health of mothers receiving diagnoses and what predicts resilience or poor mental health is understudied. Emotion regulation is an important, modifiable, transdiagnostic factor of mental health, and may be protective post-diagnosis. Evaluating biomarkers of stress, including IL-6 and Allostatic Load (AL), can also serve as early indicators of risk, indicative of early intervention. This study assessed whether reappraisal, suppression, IL-6, and AL was associated with mental health outcomes and resilience in women after receiving a fetal anomaly diagnosis. METHODS: Pregnant women (N=108) presenting to a fetal concerns clinic for initial consultation completed measures of emotion regulation (i.e., reappraisal and suppression), depression, anxiety, posttraumatic stress symptoms, and resilience between 2019-2022. A blood draw was used to assess IL-6 and create composite allostatic load measure including: IL-6, blood pressure, heart rate, glucose, cortisol, and body mass index. RESULTS: Linear regressions controlling for age, gestational age, and perceived fetal diagnosis severity, demonstrated that IL-6 was negatively associated with resilience and positively associated with depression. Reappraisal was positively associated to resilience and negatively associated with depression, anxiety, and PTSD, whereas state insurance status was positively associated to anxiety and PTS symptoms. Suppression and allostatic load were not significant. CONCLUSIONS: Women experiencing fetal anomaly diagnosis represent an understudied population with unaddressed mental health needs. Reappraisal serves as not only a protective factor, but one that can be enhanced to promote maternal resilience and mental health. Furthermore, elevated IL-6 may be a critical early indicator of potential intervention needs among women who are pregnant, to mitigate negative psychological states and enhance resilience.

Affect regulation and allostatic load over time.

OBJECTIVE: Emerging work suggests that affect regulation strategies (e.g., active coping, anger expression) predict disease and mortality risk, with sometimes divergent estimates by sex or education levels. However, few studies have examined potential underlying biological mechanisms. This study assessed the longitudinal association of affect regulation with future allostatic load. METHOD: In 2004-2006, 574 participants from the Midlife in the United States study completed validated scales assessing use of nine general and emotion-specific regulatory strategies (e.g., denial, anger expression). As a proxy for how flexibly participants regulate their affect, variability in the use of regulatory strategies was operationalized using a standard deviation-based algorithm and considered categorically (i.e., lower, moderate, greater variability) to assess non-linear effects. Participants also provided data on relevant covariates and 24 allostatic load biomarkers (e.g., cortisol, blood pressure). In 2017-2021, these biomarkers were again collected. Linear regressions modeled betas (ß) and 95 % confidence intervals (CI) examining associations of affect regulatory constructs with future allostatic load. RESULTS: In fully-adjusted models including initial allostatic load, general regulatory strategies were unrelated to future allostatic load. Yet, greater versus moderate affect regulation variability levels predicted lower allostatic load (ß=-0.14; 95 %CI: -0.27, -0.01). Only among more educated participants, greater use of anger expression predicted lower allostatic load, while the reverse was noted with anger control (ßexpression=-0.12; 95 %CI: -0.20, -0.05; ßcontrol=0.14; 95 %CI: 0.05, 0.24). CONCLUSIONS: While general regulatory strategies appeared unrelated to allostatic load, greater variability in their use and anger-related strategies showed predictive value. Subsequent studies should examine these associations in larger, more diverse samples.

Disturbed glucose homeostasis and its increased allostatic load in response to individual, joint and fluctuating air pollutants exposure: Evidence from a longitudinal study in prediabetes.

We investigated the effect of individual, joint and fluctuating exposure to air pollution (PM2.5, BC, NO3-, NH4+, OM, SO42-, PM10, NO2, SO2, O3) on glucose metabolisms among prediabetes, and simultaneously explored the modifying effect of lifestyle. We conducted a longitudinal study among prediabetes during 2018-2022. Exposure windows within 60-days moving averages and their variabilities were calculated. FBG, insulin, HOMA-IR, HOMA-B, triglyceride glucose index (TyG), glucose insulin ratio (GI) and allostatic load of glucose homeostasis system (AL-GHS) was included. Linear mixed-effects model and BKMR were adopted to investigate the individual and overall effects, respectively. We also explored the preventive role of lifestyle. Individual air pollutant was associated with increased FBG, insulin, HOMA-IR, HOMA-B, TyG, and decreased GI. People with FBG ≥6.1 mmol/L were more susceptible. Air pollutants mixture were only associated with increased HOMA-B, and constituents have the highest group-PIP. Air pollutants variation also exert harmful effect. We observed similar diabetic effect on AL-GHS. Finally, the diabetic effect of air pollutants disappeared if participants adopt a favorable lifestyle. Our findings highlighted the importance of comprehensively assessing multiple air pollutants and their variations, focusing on metabolic health status in the early prevention of T2D, and adopting healthy lifestyle to mitigate such harmful effect.

Allostatic load increases the incidence and risk of adverse prognosis in inflammatory bowel disease.

BACKGROUND: Elevated allostatic load (AL) has been associated with the risk and poor prognosis of many chronic diseases. The association between AL and inflammatory bowel disease (IBD) is unknown. AIMS: The aim of this study is to investigate the associations between AL and the risk and prognosis of IBD. METHODS: We included 326,345 adults and 3767 patients with IBD from the UK Biobank. AL served as the exposure, estimated using the AL biomarker panel, with the primary outcomes including the risk and prognosis of IBD. We used Cox regression models to examine the associations. RESULTS: High AL biomarker panel was associated with a greater risk of IBD (hazard ratio: 1.19, 95% CI: 1.08-1.31), ulcerative colitis (1.17, 95%CI: 1.04-1.32), and Crohn's disease (1.25, 95%CI: 1.05-1.49). Risk of developing IBD increased by 12% in quartile 2, 20% in quartile 3, and 37% in quartile 4 as AL biomarker panel increased. The all-cause mortality risk in IBD compared with quartile 1 rose by 54% for quartile 2, 72% for quartile 3, and 82% for quartile 4, as AL biomarker panel increased. Similar effects were also observed for ulcerative colitis and Crohn's disease. An increase in AL biomarker panel count was associated with an elevated risk of intestinal resection and colorectal cancer in IBD. CONCLUSIONS: Increased AL is associated with IBD risk, as well as the risks of intestinal resection, colorectal cancer and mortality.

Homeostasis to Allostasis: Prefrontal Astrocyte Roles in Cognitive Flexibility and Stress Biology.

In the intricate landscape of neurophysiology, astrocytes have been traditionally cast as homeostatic cells; however, their mechanistic involvement in allostasis-particularly how they modulate the adaptive response to stress and its accumulative impact that disrupts cognitive functions and precipitates psychiatric disorders-is now starting to be unraveled. Here, we address the gap by positing astrocytes as crucial allostatic players whose molecular adaptations underlie cognitive flexibility in stress-related neuropsychiatric conditions. We review how astrocytes, responding to stress mediators such as glucocorticoid and epinephrine/norepinephrine, undergo morphological and functional transformations that parallel the maladaptive changes. Our synthesis of recent findings reveals that these glial changes, especially in the metabolically demanding prefrontal cortex, may underlie some of the neuropsychiatric mechanisms characterized by the disruption of energy metabolism and astrocytic networks, compromised glutamate clearance, and diminished synaptic support. We argue that astrocytes extend beyond their homeostatic role, actively participating in the brain's allostatic response, especially by modulating energy substrates critical for cognitive functions.

Assessing the Correlation between Allostatic Load and False-Positive Image-Guided Breast Biopsies.

Background: Allostatic load (AL) is the accumulation of physiological dysregulation attributed to repeated activation of the stress response over a lifetime. We assessed the utility of AL as a prognostic measure for high-risk benign breast biopsy pathology results. Method: Eligible patients were women 18 years or older, with a false-positive outpatient breast biopsy between January and December 2022 at a tertiary academic health center. AL was calculated using 12 variables representing four physiological systems: cardiovascular (pulse rate, systolic and diastolic blood pressures, total cholesterol, high-density lipoprotein, and low-density lipoprotein); metabolic (body mass index, albumin, and hemoglobin A1C); renal (creatinine and estimated glomerular filtration rate); and immune (white blood cell count). Multivariable logistic regression was used to assess the association between AL before biopsy and breast biopsy outcomes controlling for patients' sociodemographics. Results: In total, 170 women were included (mean age, 54.1 ± 12.9 years): 89.4% had benign and 10.6% had high-risk pathologies (radial scar/complex sclerosing lesion, atypical ductal or lobular hyperplasia, flat epithelial atypia, intraductal papilloma, or lobular carcinoma in-situ). A total of 56.5% were White, 24.7% Asian, and 17.1% other races. A total of 32.5% identified as Hispanic. The mean breast cancer risk score using the Tyrer-Cuzick model was 11.9 ± 7.0. In multivariable analysis, with every one unit increase in AL, the probability of high-risk pathology increased by 37% (odds ratio, 1.37; 95% confidence interval, 1.03, 1.81; p = 0.03). No significant association was seen between high-risk pathology and age, ethnicity, breast cancer risk, or area deprivation index. Conclusion: Our findings support that increased AL, a biological marker of stress, is associated with high-risk pathology among patients with false-positive breast biopsy results.

Energetic Costs of Stress in Developing Fishes: Quantifying Allostasis and Allostatic Load.

Stress exerts negative effects on fish health through stimulation of the hypothalamic-pituitary-interrenal axis and autonomic nervous system, resulting in heightened neural and neuroendocrine responses. Energetic investment and physiological adaptation are then required to re-establish homeostatic stability or reach a new allostatic state. The cost of the energetic investment is referred to as allostatic load (AL). While determining the sources of stress and assessing their consequences have resulted in estimates of AL, most of this work has been conducted in adult mammals and humans; no ALs exist for developing fish. From a series of experiments on a model species, zebrafish (Danio rerio), whose yolk-sac larvae were exposed to two chronic stressors (high-temperature and hypoxia), ALs were quantified based on biomarkers of ontogenetic changes in growth, morphometrics, and metabolic activities. Results showed that for zebrafish yolk-sac larvae, chronic stress imposed high AL and, thus, high total allostatic energetic costs, (Rt (AL)), because of prolonged energy demand in the face of limited resources (e.g., yolk). Under severe chronic stress, energetic costs were sufficiently large that energy-limited developing fish may not be able to fully compensate, resulting in maladaptive responses from allostatic overload, leading either to death or to novel allostatic states, possibly more resilient to environmental change.

Association Between Uveal Melanoma and Allostatic Load.

BACKGROUND/AIM: Allostatic load (AL) is a measure of chronic stress that is associated with worse cancer outcomes. The purpose of this retrospective cohort study was to investigate the relationship between AL and uveal melanoma (UM) clinical features. PATIENTS AND METHODS: AL score was calculated as a composite of ten biomarkers in 111 patients with UM from the University of Illinois Hospital. One point was assigned to an AL score for each biomarker based on predetermined cutoff values. Linear and logistic regression analyses evaluated the relationship between AL score and several tumor clinical characteristics. RESULTS: High AL score had a significant relationship with extraocular extension (p=0.015). There was also a significant difference in mean blood glucose levels between the different tumor size groups (p=0.029). Higher AL scores also had a trend of being associated with a smaller tumor size (p=0.069). CONCLUSION: AL score was significantly associated with the presence of extraocular extension for uveal melanoma, while the smallest tumor size group was associated with the highest blood glucose level. No other significant correlations were found between AL and other clinical features of UM. The relationship between AL score and extraocular extension warrants further investigation. Additional research is needed to evaluate socioeconomic factors and their effect on the relationship between chronic stress and the clinical features of UM.

Allostatic Load/Chronic Stress and Cardiovascular Outcomes in Patients Diagnosed With Breast, Lung, or Colorectal Cancer.

BACKGROUND: Cardiovascular disease and cancer share a common risk factor: chronic stress/allostatic load (AL). A 1-point increase in AL is linked to up to a 30% higher risk of major cardiac events (MACE) in patients with prostate cancer. However, AL's role in MACE in breast cancer, lung cancer, or colorectal cancer remains unknown. METHODS AND RESULTS: Patients ≥18 years of age diagnosed with the mentioned 3 cancers of interest (2010-2019) and followed up at a large, hybrid academic-community practice were included in this retrospective cohort study. AL was modeled as an ordinal measure (0-11). Adjusted Fine-Gray competing risks regressions estimated the impact of AL precancer diagnosis on 2-year MACE (a composite of heart failure, ischemic stroke, acute coronary syndrome, and atrial fibrillation). The effect of AL changes over time on MACE was calculated via piecewise Cox regression (before, and 2 months, 6 months, and 1 year after cancer diagnosis). Among 16 467 patients, 50.5% had breast cancer, 27.9% had lung cancer, and 21.4% had colorectal cancer. A 1-point elevation in AL before breast cancer diagnosis corresponded to a 10% heightened associated risk of MACE (adjusted hazard ratio, 1.10 [95% CI, 1.06-1.13]). Similar findings were noted in lung cancer (adjusted hazard ratio, 1.16 [95% CI, 1.12-1.20]) and colorectal cancer (adjusted hazard ratio, 1.13 [95% CI, 1.08-1.19]). When considering AL as a time-varying exposure, the peak associated MACE risk occurred with a 1-point AL rise between 6 and 12 months post- breast cancer, lung cancer, and colorectal cancer diagnosis. CONCLUSIONS: AL warrants investigation as a potential marker in these patients to identify those at elevated cardiovascular risk and intervene accordingly.

Defining the brain control of physiological stability.

The last few decades have seen major advances in neurobiology and uncovered novel genetic and cellular substrates involved in the control of physiological set points. In this Review, I discuss the limitations in the definition of homeostatic set points established by Walter B Canon and highlight evidence that two other physiological systems, namely rheostasis and allostasis provide distinct inputs to independently modify set-point levels. Using data collected over the past decade, the hypothalamic and genetic basis of regulated changes in set-point values by rheostatic mechanisms are described. Then, the role of higher-order brain regions, such as hippocampal circuits, for experience-dependent, allostatic induced changes in set-points are outlined. I propose that these systems provide a hierarchical organization of physiological stability that exists to maintain set-point values. The hierarchical organization of physiology has direct implications for basic and medical research, and clinical practice.

Associations between allostatic load and hepatic steatosis and liver fibrosis: evidence from NHANES 2017-2020.

BACKGROUND: Allostatic load, the cumulative strain resulting from chronic stress responses, has been linked to disease occurrence and progression, yet research quantifying this relationship is limited. This study aimed to explore the relationship between allostatic load score (ALS) levels and the degree of hepatic steatosis and fibrosis. METHODS: Data from the National Health and Nutrition Examination Survey 2017-2020 were analyzed. The ALS was based on the statistical distribution, assigning one point for each biomarker if it was in the highest risk quartile, and then summing them to generate the ALS score (range, 0-8). The multivariate linear regression was employed to analyze the association between the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) with ALS. Additionally, multinomial logistic regression was used to investigate the association between ALS and the degree of hepatic steatosis and fibrosis. RESULTS: Participants had a weighted mean age of 52.69 years and 56.14% were female. In the multivariate linear regression analysis, ALS showed a significant positive correlation with CAP (ß = 15.56, 95% CI: 14.50-16.62) and LSM (ß = 0.58, 95% CI: 0.48-0.67). Age, healthy dietary level, and PIR had significant interactions with this positive correlation. In the multinomial logistic regression analysis, ALS exhibited a significant positive correlation with different degrees of hepatic steatosis and fibrosis. Consistency of the results was observed in sensitivity analyses using clinical thresholds of ALS. CONCLUSIONS: Comprehensive clinical assessment targeting load adaptation may enhance the effectiveness of risk assessment in patients with hepatic steatosis and fibrosis.

Association of allostatic load with overall survival in epithelial ovarian cancer.

OBJECTIVE: Elevated allostatic load (AL), an integrated, cumulative marker of physiologic damage due to socioenvironmental stress, is associated with increased mortality in patients with breast, lung, and other cancers. The relationship between allostatic load and mortality in ovarian cancer patients remains unknown. We examined the relationship between allostatic load and overall survival in ovarian cancer patients. METHODS: This cross-sectional study used data from 201 patients enrolled in a prospective observational ovarian cancer cohort study at a National Cancer Institute-designated Comprehensive Cancer Center from October 2012 through June 2022. All patients underwent debulking surgery and completed a full course of standard-of-care platinum-based chemotherapy. Follow-up was completed through January 2024. Allostatic load was calculated as a summary score by assigning one point to the worst sample quartile for each of ten biomarkers measured within 45 days before the ovarian cancer diagnosis. High allostatic load was defined as having an allostatic load in the top quartile of the summary score. A Cox proportional hazard model with robust variance tested the association between allostatic load and overall survival. RESULTS: There were no associations between allostatic load and ovarian cancer clinical characteristics. After accounting for demographic, clinical, and treatment factors, high allostatic load was associated with a significant increase in mortality (hazard ratio 2.17 [95%CI, 1.13-4.15]; P = 0.02). CONCLUSION: Higher allostatic load is associated with worse survival among ovarian cancer patients. Allostatic load could help identify patients at risk for poorer outcomes who may benefit from greater socioenvironmental support during treatment.