racial disparities, stress and mortality

 a recent study found (again) that racial disparities are associated with stress, chronic inflammation and increased mortality (see racial disparities stress and mortality JAMA2026 in dropbox, or doi:10.1001/jamanetworkopen.2025.54701)

Details:

-- The St Louis Personality and Aging Network recruited 1554 participants who lived in the metropolitan area of St Louis, Missouri. Participants were required to have a mailing address to permit longitudinal follow-up and sixth grade reading to facilitate understanding the consent form. this was a longitudinal cohort study from 2007 to 2011; data were analyzed from April to September 2025.

-- A lifespan cumulative stress factor was used to assess childhood maltreatment, lifetime trauma exposure, research assistant-verified stressful life events, major experiences of discrimination, and indices of socioeconomic status

-- 505 Black participants (32.5% of the group) and 1049 White participants (67.5%) were recruited

-- age 58; 55% female; annual income: 74% of Black participants had <$60K, 61% of White participants had income of $20-$80K and 17% had >$140K; highest level of education: 86% of Black participants had high school or from GED up to 4 years of college, 65% of White participants had the same, but 35% had a master's or doctoral degree

-- C-reactive protein (CRP) and interleukin-6 (IL-6) inflammatory markers were measured from serum collected from 2014-2019

    -- the researchers developed a CRP-IL-6 composite to reflect the level of systemic inflammation

-- the latent lifetime cumulative stress, collected up to 2014 to 2016, was assessed by:

    -- the Childhood Trauma Questionnaire to assess childhood maltreatment

    -- the Traumatic Life Events Questionnaire to assess adult lifetime trauma exposure

    -- List of Threatening Experiences as researcher-verified stressful life events

    -- Major Experiences of Discrimination to assess the level of discrimination

    --  participant annual household income and highest level of education of the participant and their parent were indices of socioeconomic status

-- major outcome: 

    -- the effects of cumulative lifespan stress and chronic inflammation on mortality, comparing Black vs White individuals 

Results:

-- see the end of the results section to understand the "b" statistic below (all of these are statistically significant)

-- of 1554 participants (505 Black [32.5%], 1049 White [67.5%]):

    -- deaths: Black participants 128 (25.3%) died vs 125 White participants (11.9%)

    -- Black participants experienced:

        -- significantly shorter survival times (128 [25.3%] died; time ratio = 0.937 [0.918  to 0.957]; P < .001) 

        -- greater cumulative stress (b = 0.567 [0.493 to 0.641])

        -- higher CRP–IL-6 (b = 0.173 [0.110 to 0.238])

-- cumulative stress and CRP–IL-6 partially mediated racial disparities in mortality between Black and White individuals: 

    -- total association (race, stress, CRP–IL-6, mortality), b = −0.065 (−0.086 to −0.044); time ratio = 0.937 (0.918 to 0.957)

    -- direct association (race, mortality independent of stress and CRP–IL-6), b = −0.033 (−0.055 to −0.01); time ratio = 0.968 (0.947 to 0.990)

    -- significant serial (race, stress, CRP–IL-6, mortality), b = −0.006 [−0.008 to −0.044)

    -- independent cumulative stress (race, stress, mortality), b = −0.009 [−0.017 to −0.002)

    -- inflammation (race, CRP–IL-6, mortality, b = −0.016 (−0.025 to −0.009)

-- the associations between cumulative lifetime stress plus the CRP-IL-6 composite inflammation marker among Black vs White individuals collectively accounted for 49.3% of the decreased survival time among Black compared with White individuals  ("E" in above figure)

    -- for more specific findings/figures, see the appendix Supplement 1

-- i personally had never seen a "b" statistic before, but this is what i found:

    -- per the extent of what i was able to find on the "b" statistic by my own search: the "b" statistic refers to unstandardized regression coefficient in a linear regression model with the change in the dependent variable for a one-unit change in the independent variable

    -- b=0 reflects there is no influence on the independent variable

-- given the continued lack of clarity after my search findings, i emailed one of the authors of the study article and found the following about "b":

    -- it reflects a statistically significant finding when the 95% confidence intervals (the numbers in parentheses after the b number) does not include zero

    -- in the chart above, race (0=White, 1=Black) of cumulative stress (higher = higher): Black individuals have higher reported stress (see panel C in the figure).

    -- higher stress is associated with significant greater inflammation

    -- higher inflammation is associated with significantly accelerated mortality (i.e., death at a younger age).

    -- then figure E above demonstrates:

        -- stress alone mediates the link between race and accelerated mortality

        -- inflammation alone mediates the link between race and accelerated mortality

        -- stress and inflammation in combination mediate the link between race and mortality

            -- ie, what the combination of cumulative lifetime stress and inflammation explains a significant portion of accelerated mortality in Black individuals (49.3% of it)

Commentary:

-- between 1999 and 2000 the Black US population experienced more than 1.63 million excess deaths vs the White population

    -- this increase starts early (in perinatal period) but then increases at a higher rate in later life , when chronic conditions such as heart disease predominate (the graph B above documents the increasing Black-White longevity discrepancy beginning around age 65)

-- there is lots of evidence in the medical literature that high exposures to chronic stress, including from systemic and explicit discrimination across generations, is associated with increased mortality

    -- https://gmodestmedblogs.blogspot.com/2021/11/mental-stress-and-heart-disease.html : a study finding that in patients with documented coronary artery disease, mental stress-induced ischemia was even more associated with adverse cardiovascular events than conventional-induced ischemia (treadmill etc)

    -- and chronic inflammation increases cancer risk, along with the attendant increase in tumor's growth, survivability, and potential migration. Also, angiogenesis and general immunologic dysregulation are associated with the development of liver cancer, head and neck cancer, cervical cancer, colorectal cancer and lung cancer: https://www.sciencedirect.com/science/article/pii/S0753332223008053

-- one older pivotal study based on data from NHANES IV data (National Health and Nutrition Examination Survey IV) addressed the role of racial/ethnic differences in chronic morbidity and mortality, which they refer to as the "weathering  effects", whereby Black individuals experience early health deterioration as a consequence of the cumulative impact of repeated experience with social or economic adversity and political marginalization over time. the attendant stress led to disproportionate physiological deterioration that was pronounced by middle age, noting that the many adverse health effects are related to disruption of the cardiovascular, metabolic and immune systems. this dysfunction and increased mortality are not explained by racial differences in poverty levels (https://ajph.aphapublications.org/doi/full/10.2105/AJPH.2004.060749 ).

-- more current studies, including the present one, have broadened the definition of important social differences to include neighborhood deprivation, inflammation, availability of accessible health care that the individuals trust, toxic exposures, intergenerational epigenetic signatures, and the general social determinants of health

    -- over many decades, there have been tens of thousands studies on the effects of both acute and (of particular importance) chronic stress on health. one particularly poignant article assessed the "brain-body communication" associated with chronic stress, in particular noting the effects of "stress through the activation of the sympathetic-adrenal-medullary and HPA networks", leading to the later effects on the cardiovascular system,  hematopoietic stem and progenitor cells, etc mediated through these changes in the nervous system (https://pmc.ncbi.nlm.nih.gov/articles/PMC5137920/)

    -- this current study found that half the risk of increased early mortality of Black vs White individuals could be explained by assessing the cumulative lifespan stress and the level of measured systemic inflammation

        -- it is important mechanistically to assess the individual's response to stress, in this case by measuring physiological markers of stress (inflammation in this case), since individuals experiencing similar stresses may have very different responses. the stress response can be moderated by the degree of social support people have, their level of exercise, the individual's sense of their control over the stressors, adequate sleep, etc: https://www.apa.org/topics/stress/body

-- and, elevated cortisol levels, as found frequently in those individuals with chronic stress, is associated with a myriad of effects in the body, including changes in most of the other hormones: https://www.ncbi.nlm.nih.gov/books/NBK538239/

    -- this all represents the fact that the evolutionary fight-or-flight response to the approaching saber-toothed tiger is fundamentally transformed as an acute and potentially life-saving response to a threatening situation to a chronic condition

Limitations:

-- there are many markers of chronic inflammation beyond the CRP and IL-2. are other inflammatory markers more predictive of mortality risk? what are the diseases promoted by the different constellations of inflammatory markers, and which markers are associated with which diseases (important to know if we are to have medical interventions to decrease the associated bad diseases)

    -- is the finding that only about 50% of the Black/White mortality difference is related to an issue of not having a more inclusive measurement of inflammation than their combo of CRP and IL-2? or that there is insufficient assessment and inclusion of other known stress risk factors, such as the level of pollution, housing crowding, numbers of people living in a single house,  noise pollution/sleep interference, job satisfaction, etc, etc

        -- ie, there are clearly other known issues associated with racial/ethnic differences not included above but that could add significantly improve our understanding of the reasons for the profound health effects associated with the racial/ethnic differences that we know. For example, generational wealth (the ability to pass wealth to the next generation, a huge step-up in allowing the next generation to succeed socially, politically, and health-wise). or including assessments of microplastics that are associated with chronic inflammation (https://gmodestmedblogs.blogspot.com/2024/03/plastics-too-many-and-too-bad-for-our.html), or air pollution (https://gmodestmedblogs.blogspot.com/2016/06/air-pollution-and-heart-disease.html), and undoubtedly stress related to occupations (environmental exposures, stresses at work), chemicals/toxins in air/water/earth that make it into our food chain, lack of exercise, and undoubtedly many more....)

-- another important issue with this study is that it assesses mortality (though this is certainly an important finding about the racial divide). Mortality is a late finding. the health effects of chronic stress and inflammation begin much earlier as a differential morbidity between the racial groups associated with the life-long stressors from discrimination, with more type 2 diabetes, hypertension, heart disease, cancer, etc. These diseases have profound effects on peoples' lives as well as those of families and communities, leading to much increased mortality much later (ie, the conclusion in this study on mortality is really just the tip of the iceberg) 

so, this article is particularly noteworthy in our current political atmosphere in the US:

-- there are obvious and very substantial adverse effects of inequalities in our society in terms of pretty much all aspects of life

-- it is pretty astounding that we have morphed from the pretty recent "Black Lives Matter" and "Me, too" movements that directly confronted major issues of inequality, to the current erasure of the concept of "Diversity, Equity, and Inclusion". And having this being acceptable to so many people and institutions so quickly in our society....

-- this study, as so many before, have added to the current literature that race is a social construct and not an inherent/genetic one. and the social issues that lead to discrimination have a plethora of affects on the human body, leading to increased inflammation and the array of associated diseases and premature mortality

    -- life expectancy in the US declined 2.7 years between 2019 to 2021, from 78.8 to 76.1 years (the largest 2-year decrease since the 1920s), with Covid being a driver for this, but there were continued differences:

        -- life expectancy for white individuals in 2021 was 76.4 years, for Black individuals (second lowest) 70.8 years, and lowest for AIAN individuals (American Indian or Alaska Native) at 65.2 years: https://www.kff.org/racial-equity-and-health-policy/what-is-driving-widening-racial-disparities-in-life-expectancy/#Appendix )

-- and, unfortunately in the US we are also having a systematic demolition of our public health system, with pretty clear orders-from-above to stop accumulating/promulgating information that would normally lead to public health intervention

geoff

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