Jennifer Beam Dowd

Seropositivity to Cytomegalovirus, Inflammation, All-Cause and Cardiovascular Disease-Related Mortality in the United States

Background Studies have suggested that CMV infection may influence cardiovascular disease (CVD) risk and mortality. However, there have been no large-scale examinations of these relationships among demographically diverse populations. The inflammatory marker C-reactive protein (CRP) is also linked with CVD outcomes and mortality and may play an important role in the pathway between CMV and mortality. We utilized a U.S. nationally representative study to examine whether CMV infection is associated with all-cause and CVD-related mortality. We also assessed whether CRP level mediated or modified these relationships. Methodology/Principal Findings Data come from subjects ≥25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31st, 2006 (N = 14153) in the National Health and Nutrition Examination Survey (NHANES) III (1988–1994). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and CVD-related mortality by CMV serostatus. After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41). The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment. CRP did not mediate these associations. However, CMV seropositive individuals with high CRP levels showed a 30.1% higher risk for all-cause mortality and 29.5% higher risk for CVD-related mortality compared to CMV seropositive individuals with low CRP levels. Conclusions/Significance CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality.

Socio-economic status, cortisol and allostatic load: a review of the literature

BACKGROUND The notion that chronic stress contributes to health inequalities by socio-economic status (SES) through physiological wear and tear has received widespread attention. This article reviews the literature testing associations between SES and cortisol, an important biomarker of stress, as well as the summary index of allostatic load (AL). METHODS A search of all published literature on the PubMed and ISI Web of Knowledge literature search engines was conducted using broad search terms. The authors reviewed abstracts and selected articles that met the inclusion criteria. A total of 26 published studies were included in the review. RESULTS Overall, SES was not consistently related to cortisol. Although several studies found an association between lower SES and higher levels of cortisol, many found no association, with some finding the opposite relationship. Lower SES was more consistently related to a blunted pattern of diurnal cortisol secretion, but whether this corresponded to higher or lower overall cortisol exposure varied by study. Approaches to collecting and analysing cortisol varied widely, likely contributing to inconsistent results. Lower SES was more consistently related to higher levels of AL, but primarily via the cardiovascular and metabolic components of AL rather than the neuroendocrine markers. CONCLUSIONS Current empirical evidence linking SES to cortisol and AL is weak. Future work should standardize approaches to measuring SES, chronic stress and cortisol to better understand these relationships.

The Impact of Bisphenol A and Triclosan on Immune Parameters in the U.S. Population, NHANES 2003–2006

Background Exposure to environmental toxicants is associated with numerous disease outcomes, many of which involve underlying immune and inflammatory dysfunction. Objectives To address the gap between environmental exposures and immune dysfunction, we investigated the association of two endocrine-disrupting compounds (EDCs) with markers of immune function. Methods Using data from the 2003–2006 National Health and Nutrition Examination Survey, we compared urinary bisphenol A (BPA) and triclosan levels with serum cytomegalovirus (CMV) antibody levels and diagnosis of allergies or hay fever in U.S. adults and children ≥ 6 years of age. We used multivariate ordinary least squares linear regression models to examine the association of BPA and triclosan with CMV antibody titers, and multivariate logistic regression models to investigate the association of these chemicals with allergy or hay fever diagnosis. Statistical models were stratified by age (< 18 years and ≥ 18 years). Results In analyses adjusted for age, sex, race, body mass index, creatinine levels, family income, and educational attainment, in the ≥ 18-year age group, higher urinary BPA levels were associated with higher CMV antibody titers (p < 0.001). In the < 18-year age group, lower levels of BPA were associated with higher CMV antibody titers (p < 0.05). However, triclosan, but not BPA, showed a positive association with allergy or hay fever diagnosis. In the < 18-year age group, higher levels of triclosan were associated with greater odds of having been diagnosed with allergies or hay fever (p < 0.01). Conclusions EDCs such as BPA and triclosan may negatively affect human immune function as measured by CMV antibody levels and allergy or hay fever diagnosis, respectively, with differential consequences based on age. Additional studies should be done to investigate these findings.

Cytomegalovirus Antibody Levels, Inflammation, and Mortality Among Elderly Latinos Over 9 Years of Follow-up

This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60-101 years) in California followed in 1998-2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.

Early origins of health disparities: burden of infection, health, and socioeconomic status in U.S. children.

Recent work in biodemography has suggested that lifetime exposure to infection and inflammation may be an important determinant of later-life morbidity and mortality. Early exposure to infections during critical periods can predispose individuals to chronic disease, in part through the reallocation of energy away from development needed for immune and inflammatory responses. Furthermore, markers of inflammation are known to vary by socioeconomic status in adults and may contribute to overall socioeconomic health inequalities, but little is known about how the sources of this inflammation differ over the life course. This paper uses novel biomarker data from the Third National Health and Nutrition Examination Survey (NHANES III) to test the association of the burden of common chronic infections (Helicobacter pylori (H. pylori), cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), hepatitis A and hepatitis B) with height-for-age and asthma/chronic respiratory conditions in U.S. children ages 6 and older, and the association of these chronic infections to childrens socioeconomic status. A higher burden of infection is found to be associated with lower height-for-age as well as an increased likelihood of asthma net of race/ethnicity, family income, and parental education. Children with lower family income, lower parental education, and non-white race/ethnicity have a higher likelihood of infection with several individual pathogens as well as the overall burden of infection. Differential exposure and/or susceptibility to infections may be one mechanism through which early social factors get embodied and shape later-life health outcomes.

Does Self-Rated Health Mean the Same Thing Across Socioeconomic Groups? Evidence From Biomarker Data

PURPOSE Self-rated health (SRH) is widely used to study health inequalities by socioeconomic status (SES), but concern has arisen that SRH may not correspond to objective health in the same way for different SES groups. We test whether levels of biological risk differ by SES for those with the same SRH. METHODS We analyzed a U.S. nationally representative sample of 13,877 adults aged 25 to 80 years. We tested whether education modifies the association between SRH and 14 biomarkers representing metabolic, cardiovascular, inflammatory, and organ function using both interaction models and models stratified by four levels of SRH. Estimated education coefficients in the stratified models indicated whether biomarker levels varied by educational attainment within a given self-rated health category. RESULTS Significant variation in biological risk by education within the same self-rated health category was found, especially at higher levels of SRH. In general, respondents with more education had healthier levels of biomarkers for the same level of SRH. CONCLUSIONS The results suggest that the relation of self-reported health to objective health, as measured by biological risk factors, differs by socioeconomic status. Caution should be exercised when using SRH to compare health risks across SES groups.

Does Self-reported Health Bias the Measurement of Health Inequalities in U.S. Adults? Evidence Using Anchoring Vignettes From the Health and Retirement Study

OBJECTIVES Measurement of health inequalities based on self-reports may be biased if individuals use response scales in systematically different ways. We use anchoring vignettes to test and adjust for reporting differences by education, race/ethnicity, and gender in self-reported health in 6 domains (pain, sleep, mobility, memory, shortness of breath, and depression). METHOD Using data from the 2006 U.S. Health and Retirement Study (HRS) and the 2007 Disability Vignette Survey, we estimated generalized ordered probit models of the respondents rating of each vignette characters health problem, allowing cut-points to vary by age, gender, education, and race/ethnicity. We then used one-step hierarchical ordered probit (HOPIT) models to jointly estimate the respondents cut-points from the vignettes and the severity of the respondents own health problems based on these vignette cut-points. RESULTS We found strong evidence of reporting differences by age, gender, education, and race/ethnicity, with the magnitude depending on the specific health domain. Overall, traditional models not accounting for reporting differences underestimated the magnitude of health inequalities by education and race/ethnicity. DISCUSSION These results suggest caution in relying on self-reported health measures to quantify and explain health disparities by socioeconomic status and race/ethnicity/ethnicity in the United States. The findings support expansion of the use of anchoring vignettes to properly account for reporting differences in self-reports of health.

Do biomarkers of stress mediate the relation between socioeconomic status and health

Objectives: To test the relation between socioeconomic status (SES) and biomarkers of chronic stress, including basal cortisol, and to test whether these biomarkers account for the relation between SES and health outcomes. Design: Cross sectional study using data from the 2000 social and environmental biomarkers of aging study (SEBAS). Setting: Taiwan. Participants: Nationally representative sample of 972 men and women aged 54 and older. Main outcome measures: Highest risk quartiles for 13 biomarkers representing functioning of the neuroendocrine system, immune/inflammatory systems, and the cardiovascular system: cortisol, adrenaline (epinephrine), noradrenaline (norepinephrine), serum dihydroepiandrosterone sulphate (DHEA-S), insulin-like growth factor 1 (IGF1), interleukin 6 (IL6), albumin, systolic blood pressure, diastolic blood pressure, waist-hip ratio, total cholesterol-HDL ratio, HDL cholesterol, and glycosylated haemoglobin; self reported health status (1–5) and self reported mobility difficulties (0–6). Results: Lower SES men have greater odds of falling into the highest risk quartile for only 2 of 13 biomarkers, and show a lower risk for 3 of the 13 biomarkers, with no association between SES and cortisol. Lower SES women have a higher risk for many of the cardiovascular risk factors, but a lower risk for increased basal readings of adrenaline, noradrenaline, and cortisol. Inclusion of all 13 biological markers does not explain the relation between SES and health outcomes in the sample. Conclusions: These data do not support the hypothesis that chronic stress, via sustained activation of stress related autonomic and neuroendocrine responses, is an important mediator in the relation between SES and health outcomes. Most notably, lower SES is not associated with higher basal levels of cortisol in either men or women. These results place an increased burden of proof on researchers who assert that psychosocial stress is an important pathway linking SES and health.

Predictors of inflammation in U.S. children aged 3-16 years.

BACKGROUND Little is known about the correlates of low-grade inflammation in U.S. children. PURPOSE This study describes the factors associated with increased levels of C-reactive protein (CRP) in U.S. children and tests whether differences in CRP emerge in childhood because of socioeconomic factors. METHODS Data were analyzed in 2009 from 6004 children aged 3-16 years from the National Health and Nutrition Examination Survey, 1999-2004, a representative sample of the U.S. non-institutionalized population. Tobit regression models are used to evaluate associations between predictors, including BMI-for-age, skinfold body fat measures, chronic infections, environmental tobacco exposure, low birth weight, and sociodemographics and continuous high-sensitivity CRP in milligrams per liter. RESULTS CRP levels were higher in U.S. children with lower family income, and these differences were largely accounted for by differences in adiposity and recent illness. Mexican-American children had higher levels of CRP compared to both whites and blacks, but these differences were not explained by measured physical risk factors. CONCLUSIONS Increased adiposity is associated with higher CRP concentrations in U.S children aged 3-16 years, and both socioeconomic and racial/ethnic differences exist in systemic inflammation in U.S. children. Increased childhood obesity and low-grade inflammation may contribute to later life chronic disease risk.

Socioeconomic and race/ethnic patterns in persistent infection burden among U.S. adults.

BACKGROUND The pathophysiological mechanisms that underlie health disparities by socioeconomic status and race/ethnicity are poorly understood. Promising new research suggests that the burden of persistent infection may influence adult disease risk and mortality. This article examines how multiple persistent infections cluster within individuals and how this clustering varies by socioeconomic position and race/ethnicity in U.S. adults. METHODS We analyze data from the National Health and Nutrition Examination Survey III (N = 19,275) for adults aged 17-90 years. The clustering of infections within individuals is studied using tetrachoric correlations. Multiple indicator multiple cause models are used to analyze the infection burden construct as measured by seropositivity to Helicobacter pylori, cytomegalovirus, herpes simplex virus-1, and hepatitis B, focusing on the burdens distribution by socioeconomic position and race/ethnicity. The results are corroborated using ordered logistic regression for a commonly used count index of individual infections. RESULTS Seroprevalence of individual persistent infections is positively correlated, suggesting common factors related to exposure or susceptibility. Education, income, and race/ethnicity are strong and significant independent predictors of infection burden in U.S. adults in all models. CONCLUSION The disproportionate burden of persistent infections among disadvantaged groups across all ages may be one biologic pathway by which low socioeconomic position is related to increased rates of morbidity and mortality in the United States.