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Objectives: In non-industrialized and low-income populations, adipose stores can serve as a valuable buffer against harsh conditions such as seasonal food scarcity. However, these reserves may incur costs due to adipocytes' production of pro-inflammatory cytokines; inflammation is associated with increased risk for cardiometabolic diseases later in life. Life history theory posits that, especially in populations with high juvenile mortality, higher adiposity may nonetheless be advantageous if its benefits in early life outweigh its later costs. Relatively little is known about adolescents' C-reactive protein concentration (CRP; an inflammation biomarker) in such environments. We investigated CRP and its associations with several hypothesized predictors in adolescents in an economically diverse peri-urban Andean community., Methods: We measured CRP in dried blood spots and collected data on anthropometrics, illnesses, socioeconomic status (SES), and menarcheal status in 59 female and 40 male adolescents ("Alteños", 11.0-14.9 years old) with normal vital signs in El Alto, Bolivia (~4150 m amsl). We used Cole's LMS method to standardize all anthropometrics for sex and age, and principal components analysis to construct a "fat-factor" variable loading on these standardized z-scores. We used multiple linear regression to assess the influence of fat-factor and other likely predictors on CRP rank., Results: Compared to a national Bolivian growth reference, Alteños were, on average, shorter and leaner; only 6% were classified as overweight and none were obese. Pre-menarche females were on average leaner than post-menarche females. The best-fitting model explained 24% of the variance in CRP rank. Significant predictors were fat-factor, SES, current illness for males and pre-menarche females, and z-height for females., Conclusions: Our results are consistent with a tradeoff between investments in growth versus immune functioning, as might be expected in an environment with limited resources and high pathogen exposure (e.g., soil-transmitted helminths, poor sanitation). Thinner Alteños appear to maintain a minimum CRP concentration independent of fat-factor, while fatter (or less-thin) Alteños' CRP rises with fat-factor. Female Alteños appear to be trading off investment in immune response for investment in growth and maturation. Alteños' high rate of stunting and absence of obesity suggests chronic, presumably multifactorial, stress. Adipose stores likely buffer against some of these stressors and, in an environment such as this-in which many lack sufficient nutritious foods, potable water, adequate sewage, and health care-may confer a net lifetime benefit., (© 2024 The Author(s). American Journal of Human Biology published by Wiley Periodicals LLC.)

Objectives: Recent discussions in human biology have highlighted how local ecological contexts shape the relationship between social stressors and health across populations. Chronic low-grade inflammation has been proposed as a pathway linking social stressors to health, with evidence concentrated in high-income Western contexts. However, it remains unclear whether this is an important pathway in populations where prevalence is lower due to lower adiposity and greater infectious exposures. To investigate this further, we tested associations between multiple types of intimate partner violence (IPV), a highly prevalent stressor and health crisis globally, and C-reactive protein (CRP), a commonly used measure of chronic low-grade inflammation, in Cebu, Philippines. For reference, we compared results for CRP to depression, a well-established and consistently observed health outcome of IPV., Methods: Data came from 1601 currently partnered women (ages 35-69 years) as part of the Cebu Longitudinal Health and Nutrition Survey. IPV exposures included physical, emotional, and controlling behavior. Depression scores were measured using a modified version of the Center for Epidemiologic Studies-Depression Scale for this population, whereas plasma CRP was measured from overnight-fasted morning blood samples., Results: All three types of IPV were associated with a higher depression score. However, none of the IPV measures were associated with CRP. In a post hoc interaction test, emotional IPV became positively associated with CRP as waist circumference increased above the mean., Conclusions: Our results suggest a complex relationship between social stressors and chronic low-grade inflammation, which is likely dependent on the population-specific context of lifestyle and environmental factors., (© 2024 The Authors. American Journal of Human Biology published by Wiley Periodicals LLC.)

Inflammation is associated with increased risk for chronic degenerative diseases, as well as age-related functional declines across many systems and tissues. Current understandings of inflammation, aging, and human health are based on studies conducted almost exclusively in high-income nations that rely primarily on baseline measures of chronic inflammation. This analysis investigates the inflammatory response to vaccination as a predictor of cardiovascular disease (CVD) among older women in the Philippines, a lower-middle income nation with rising rates of overweight/obesity and relatively high burdens of infectious disease. Concentrations of C-reactive protein (CRP) were measured at baseline and 72 h following influenza vaccination in 530 women (mean age = 55.2 years). Ankle-brachial index (ABI) - an indicator of peripheral arterial disease and broader CVD risk - was measured approximately three years later. The magnitude of CRP response to vaccination was positively associated with ABI, indicating that a larger inflammatory response predicts lower CVD risk. Baseline CRP was negatively associated with CRP response to vaccination, and was not associated with ABI independently of CRP response. These results suggest that research across ecological settings, and with more dynamic measures of inflammatory response and regulation, may yield important insights into the associations among inflammation, aging, and disease.

Objective: Children exposed to institutional rearing often exhibit problems across a broad array of developmental domains. We compared the consequences of long-term, high-quality foster care versus standard institution-based care, which began in early childhood on cardiometabolic and immune markers assessed at the time of adolescence., Methods: The Bucharest Early Intervention Project is a longitudinal investigation of children institutionalized during early childhood (ages 6 to 30 months at baseline) who were subsequently randomized to either high-quality foster care or continued institutional care. At the age of 16 years, 127 respondents participated in a biomarker collection protocol, including 44 institutionalized children randomly assigned to receive care as usual, 41 institutionalized children randomized to be removed from institutional care and placed in high-quality foster care in infancy, and a control group of 42 demographically matched children raised in biological families. Outcomes included body mass index (BMI), systolic and diastolic blood pressure, C-reactive protein, interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor α, glycosylated hemoglobin A1c, and Epstein-Barr virus antibody titers., Results: Early institutional rearing was not associated with differences in cardiometabolic or immune markers. Randomization to foster care and age of placement into foster care were also unrelated to these markers, with the exception of BMI z-score, where children assigned to care as usual had lower BMI z-scores relative to children assigned to foster care (-0.23 versus 0.08, p = .06), and older age at placement was associated with lower BMI (β = -0.07, p = .03)., Conclusions: The impact of institutional rearing on measures of cardiometabolic health and immune system functioning is either absent or not evident until later in development. These findings provide new insights into the biological embedding of adversity and how it varies developmentally and across regulatory systems and adversity type., Clinical Trial Registration: NCT00747396.

Social experiences can affect the relationship between depression and physical health. The current study examined how social support from parents and friends may moderate the association of depressive symptoms with hypothalamic-pituitary-adrenal (HPA) axis activity and C-reactive protein among adolescents (N=316, Mage=16.40, SD=.74; 57% female) from diverse ethnic backgrounds (23.1% Asian, 29.1% European, 41.8% Latino, and 6.0% other backgrounds). Results indicated that parent support, but not friend support, moderated the link between depressive symptoms and both total daily cortisol output (a measure HPA activity) and C-reactive protein (a marker of inflammation). These patterns did not differ by ethnicity. Overall, the study highlights the continued, and perhaps accumulated, importance of parents during adolescence despite increasing needs for autonomy from and exploration outside of the family unit., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Rates of overweight and obesity are on the rise globally, and excess adipose tissue may contribute to elevations in inflammation during pregnancy, leading to pregnancy complications and adverse birth outcomes., Objective: The purpose of this study was to evaluate adiposity and inflammation in young women as predictors of inflammation in the third trimester of pregnancy in a community-based sample of healthy women., Methods: Female participants (24-30 y) in a prospective observational cohort study (Cebu Longitudinal Health and Nutrition Survey) were contacted between 2009 and 2014 to identify new pregnancies. A total of 309 women provided data from 409 pregnancies. An in-home interview was scheduled for the third trimester to collect pregnancy information, anthropometric measurements, and a blood sample. Circulating C-reactive protein (CRP) was measured with a high-sensitivity immunoassay. Data collected from assessments in 2005 and 2009 were used to assess body mass index (BMI) and CRP in young adulthood, before pregnancy. Robust regression models were implemented to evaluate BMI and CRP in young adulthood as predictors of pregnancy CRP., Results: Pre-pregnancy BMI was a stronger predictor of third-trimester circulating CRP than BMI in the third trimester. No association was found between pregnancy weight gain and CRP. Pre-pregnancy CRP was a significant predictor of CRP in pregnancy, independent of BMI., Conclusions: Levels of overweight/obesity and inflammation in young adulthood, before pregnancy, are important predictors of inflammation in the third trimester of pregnancy. These results may have implications for addressing the growing concern about the contribution of obesity to adverse birth outcomes, and they suggest that factors that influence the regulation of inflammation, before pregnancy and independent of adiposity, may be important in shaping the inflammatory response to pregnancy., (© 2016 American Society for Nutrition.)

Background: C-reactive protein (CRP) is increasingly measured as a marker of systemic inflammation that predicts elevated risk for cardiovascular disease. Influenza vaccination is a mild pro-inflammatory stimulus, and the CRP response to vaccination may provide additional information on individual differences in inflammatory response and risk for disease., Aim: To document the pattern of CRP response to influenza vaccination among a large sample of older women in the Philippines. The Philippines exemplifies current global trends toward increasing rates of overweight/obesity, but also maintains relatively high rates of infectious disease. The secondary aim of the study is to investigate the impact of infectious symptoms on the pattern of response to vaccination., Methods: A community-based sample of 934 women (mean age=55.4 years) received the influenza vaccine. CRP was assessed at baseline and 72h post-vaccination. Descriptive, non-parametric, and parametric analyses were implemented to assess the magnitude of CRP response, and to investigate whether responses were associated with baseline CRP or the presence of infectious symptoms prior to vaccination., Results: Influenza vaccination resulted in a statistically significant CRP response of 0.35mg/L (p<0.001), representing a 30.2% increase from baseline. For individuals with symptoms of infectious disease at baseline, the CRP response was smaller (12.9%) and not statistically significant (p=0.77). Lower CRP at baseline was associated with larger CRP response to vaccination in the entire sample, and among participants without recent symptoms of infection., Conclusions: Influenza vaccination produces a mild CRP response in the Philippines. This study extends prior research in US and European populations validating influenza vaccination as an in vivo model for investigating the dynamics of inflammation, but also raises potential complications in settings where rates of infectious disease are elevated., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Dried blood spot (DBS) methodology offers significant advantages over venipuncture in studies of vulnerable populations or large-scale studies, including reduced participant burden and higher response rates. Uncertainty about the validity of cardiovascular disease (CVD) risk biomarkers remains a barrier to wide-scale use. We determined the validity of DBS-derived biomarkers of CVD risk versus gold-standard assessments, and study-specific, serum-equivalency values for clinical relevance of DBS-derived values. Concurrent venipuncture serum and DBS samples (n = 150 adults) were assayed in Clinical Laboratory Improvement Amendments-certified and DBS laboratories, respectively. Time controls of DBS standard samples were assayed single-blind along with test samples. Linear regression analyses evaluated DBS-to-serum equivalency values; agreement and bias were assessed via Bland-Altman plots. Linear regressions of venipuncture values on DBS-to-serum equivalencies provided R(2) values for total cholesterol, high-density lipoprotein cholesterol (HDL-C), and C-reactive protein (CRP) of 0.484, 0.118, and 0.666, respectively. Bland-Altman plots revealed minimal systematic bias between DBS-to-serum and venipuncture values; precision worsened at higher mean values of CRP. Time controls revealed little degradation or change in analyte values for HDL-C and CRP over 30 weeks. We concluded that DBS-assessed biomarkers represent a valid alternative to venipuncture assessments. Large studies using DBS should include study-specific serum-equivalency determinations to optimize individual-level sensitivity, the viability of detecting intervention effects, and generalizability in community-level primary prevention interventions.

Chronic inflammation is a potentially important physiological mechanism linking early life environments and health in adulthood. Elevated concentrations of C-reactive protein (CRP)--a key biomarker of inflammation--predict increased cardiovascular and metabolic disease risk in adulthood, but the developmental factors that shape the regulation of inflammation are not known. We investigated birth weight and breastfeeding duration in infancy as predictors of CRP in young adulthood in a large representative cohort study (n = 6951). Birth weight was significantly associated with CRP in young adulthood, with a negative association for birth weights 2.8 kg and higher. Compared with individuals not breastfed, CRP concentrations were 20.1%, 26.7%, 29.6% and 29.8% lower among individuals breastfed for less than three months, three to six months, 6-12 months and greater than 12 months, respectively. In sibling comparison models, higher birth weight was associated with lower CRP for birth weights above 2.5 kg, and breastfeeding greater than or equal to three months was significantly associated with lower CRP. Efforts to promote breastfeeding and improve birth outcomes may have clinically relevant effects on reducing chronic inflammation and lowering risk for cardiovascular and metabolic diseases in adulthood.

Chronic inflammation is a potentially important pathway through which psychosocial stressors increase risk for cardiovascular disease. However, prior research on stress and inflammation has been conducted almost exclusively in high income, industrialized populations with low levels of infectious disease. In this study we test the hypothesis that psychosocial stressors are associated with elevated concentrations of C-reactive protein (CRP) among young adults in the Philippines (n=1622), who have grown up in an ecological and epidemiological setting that differs substantially from that of the US. In addition, we apply a developmental, ecological perspective to consider whether microbial and nutritional environments in infancy alter patterns of association between stressors and CRP. Data come from the Cebu Longitudinal Health and Nutrition Survey, a prospective cohort study that began collecting data in 1983-1984 when participants were in utero. A series of regression models indicate trends toward significant interactions between perceived stress and environmental factors in infancy, including exposure to animal feces, season of birth, and birth weight. Parental absence in childhood was a significant predictor of CRP in adulthood in interaction with exposure to animal feces in infancy. Positive associations between stressors and CRP were only evident for individuals with lower levels of microbial exposure in infancy, or lower birth weight. These results suggest that early environments influence the development of inflammatory phenotypes in ways that moderate sensitivity to psychosocial stressors in adulthood, and they underscore the value of a comparative, developmental approach to research on social environments, inflammation, and disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: Pregnancy and lactation involve adaptations in immune regulation, but little is known about cross-cultural variation in inflammatory changes during pregnancy or lactation. Here we report concentrations of C-reactive protein (CRP) in a large cross-sectional sample of healthy Filipino women who vary in parity, gestational, and lactational status, and who come from a population previously described as having low CRP., Methods: Fasting plasma CRP was measured among female participants (ages 20.8-22.4 years) in the Cebu Longitudinal Health and Nutrition Survey (n = 822)., Results: Median CRP was 0.2 mg/l in nulliparous women and peaked at 2.0 mg/l in women in their 3rd trimester of pregnancy. Parous but post-partum women had higher CRP compared to nulliparous women, which was largely explained by body composition differences as reflected in waist circumference and skinfold measures. Among post-partum women with infants, CRP was similar in women who were currently breastfeeding compared to those who were not., Conclusions: At Cebu, women late in gestation have 10-fold higher C-reactive protein compared to nulliparous women, with no evidence that lactation is inflammatory. These population-based findings are similar with findings from prior clinic-based studies and are consistent with the maternal immunological adaptations initiated during pregnancy. The tendency of human females to spend more time than females of other great apes in gestation rather than lactation suggests that the human life history strategy involved increased time spent by reproductively aged females in a pro-inflammatory state., (Copyright © 2012 Wiley Periodicals, Inc.)

Objectives: The aim of this study was to examine whether health-related self-protection (e.g., using positive reappraisals or avoiding self-blame) prevents lonely older adults from exhibiting increases in diurnal cortisol secretion and higher levels of C-reactive protein (CRP)., Methods: This longitudinal study (n = 122) examined diurnal cortisol levels (area under the curve) at baseline and 2-year follow-up. Levels of CRP were measured at 6-year follow-up. The main predictors included baseline levels of loneliness and health-related self-protection., Results: Among lonely participants, baseline self-protection predicted an amelioration of 2-year increases in diurnal cortisol volume (β = -.34, p = .03) and lower levels of CRP at 6-year follow-up (β = -.42, p = .006). These significant associations were not found among nonlonely participants (β < .14, p = .33). In addition, mediation analyses demonstrated that the buffering effect of self-protection on lonely older adults' levels of CRP at 6-year follow-up was statistically mediated by 2-year changes in cortisol volume (β = -.16, p = .06)., Conclusions: These findings suggest that lonely older adults may ameliorate biologic disturbances if they engage in self-protection to cope with their health threats.

Objectives: C-reactive protein (CRP) is a central component of innate immune defenses, and high sensitivity CRP has emerged as an important biomarker of chronic inflammation and cardiovascular disease risk. Prior analyses of CRP variability have reported stable between-individual differences in CRP over time, but a limitation of current knowledge is that it is based on research conducted in post-epidemiologic transition populations., Methods: This study evaluated CRP variability among adults in the southeastern region of the Ecuadorian Amazon where rates of infectious diseases remain high. Blood samples were collected from 52 adults at four weekly sampling intervals and were quantified using a high-sensitivity immunoassay., Results: Median CRP concentration was 0.52 mg/l. About 34.6% of participants had CRP >3 mg/l at one time point, but no individuals had CRP >3 mg/l across two or more sampling intervals, and within-individual correlations revealed low levels of stable, between-individual differences in CRP. The application of current guidelines for the assessment of chronic inflammation failed to detect a single case of "high risk" CRP., Conclusions: This study is the first to investigate CRP variability in a nonindustrialized, high infectious disease environment. It documents a pattern of variation over time that is distinct from prior research, with no evidence for chronic low-grade inflammation. These results may have substantial implications for research on inflammation and diseases of aging globally, as well as for scientific understandings of the regulation of inflammation., (Copyright © 2012 Wiley Periodicals, Inc.)

Recent genome-wide association studies have related several genetic loci, including C-reactive protein (CRP), hepatocyte nuclear factor 1 homeobox (HNF1A), and genetic variations in the leptin receptor (LEPR), to circulating CRP levels in populations of European ancestry. The genetic effects in other populations and across varying levels of exposure to a pathogenic environment, an important environmental factor associated with CRP, remain to be determined. We tested 2,073,674 single-nucleotide polymorphisms (SNPs) for association with plasma CRP (limited to ≤10 mg/L) in 1,709 unrelated Filipino women from the Cebu Longitudinal Health and Nutrition Survey. The strongest evidence of association was observed with variants at CRP (rs876537, P = 1.4 × 10(-9)) and HNF1A (rs7305618, P = 1.0 × 10(-8)). Among other previously reported CRP-associated loci, the apolipoprotein E ε4 haplotype was associated with decreased CRP level (P = 7.1 × 10(-4)), and modest association was observed with LEPR (rs1892534, P = 0.076), with direction of effects consistent with previous studies. The strongest signal at a locus not previously reported mapped to a gene desert region on chromosome 6q16.1 (rs1408282, P = 2.9 × 10(-6)). Finally, we observed nominal evidence of interaction with exposure to a pathogenic environment for top main effect SNPs at HNF1A (rs7305618, P = 0.031), LEPR (rs1892535, P = 0.030) and 6q16.1 (rs1408282, P = 0.046). Our findings demonstrate convincing evidence that genetic variants in CRP and HNF1A contribute to plasma CRP in Filipino women and provide the first evidence that exposure to a pathogenic environment may modify the genetic influence at the HNF1A, LEPR, and 6q16.1 loci on plasma CRP level.

C-reactive protein (CRP) is a component of nonspecific immune defense and is a reliable marker of low-grade inflammation involved in obesity, type 2 diabetes and cardiovascular disease. Genome-wide association studies in middle-aged and elderly populations, predominantly of European descent, demonstrated associations of CRP levels with single-nucleotide polymorphisms (SNPs) at several loci. To examine whether the variants identified are replicated in Filipino young adults, we applied Tobit regression models to study the association of plasma CRP with 12 SNPs at seven loci in a cohort of 1691 Filipino young adults (aged 21.5±0.3 years) from the Cebu Longitudinal Health and Nutrition Survey. SNPs in or near CRP (P=3.2 × 10(-11)), HNF1A, IL6R, APOE-APOC1 and LEPR showed significant associations (P<0.05) and together explained 4.8% of the total variation in CRP. Modest interactions were observed between LEPR-rs1892534 and waist circumference (uncorrected P(interaction)=0.020) and between APOE-rs769449 and pathogen exposure (uncorrected P(interaction)=0.0073) in models predicting CRP. Our results demonstrated that variants in several loci are significantly associated with plasma CRP in Filipino young adults, suggesting shared genetic influences on circulating CRP across populations and age groups.

Objectives: Inflammation has been associated with a wide range of chronic degenerative diseases, but the developmental factors contributing to the regulation of inflammation are poorly understood. This study investigates the within-individual association between antibody response to vaccination in adolescence and C-reactive protein (CRP) concentration in young adulthood., Methods: In 1998-99, at age 14-15 years, a subset of participants (N = 96) in the Cebu Longitudinal Health and Nutrition Survey were administered a typhoid vaccine, and baseline and follow-up blood samples were drawn to assess the strength of the antibody response to vaccination. In 2005, at age 20-21 years, blood samples were drawn from the full cohort for measurement of CRP. N = 74 individuals had complete data at both time points. Bivariate associations and multivariate logistic regression models were evaluated to test the hypothesis that vaccine responsiveness in adolescence was significantly associated with CRP level in young adulthood., Results: There was a strong and statistically significant association between antibody response to vaccination in adolescence and CRP in young adulthood. Median CRP was more than four times higher among nonresponders than responders, and nonresponders were 2.3 to 3.6 times more likely to have CRP in the top tertile of the sample distribution., Conclusions: This study provides evidence for a prospective, within-individual link between more effective antibody-mediated immune defenses and lower levels of inflammation. In the context of prior research in this population, these results suggest that early environments are important determinants of multiple aspects of an individual's immuno-phenotype., (Copyright © 2010 Wiley-Liss, Inc.)

Objective: Inflammation plays an important role in many chronic degenerative diseases associated with aging, and social, economic, and behavioral factors that contribute to inflammation may lead to differential burdens of morbidity and mortality in later life. This study examines socioeconomic status and race/ethnicity as predictors of C-reactive protein (CRP) among older adults in the United States and considers the degree to which health behaviors, medical conditions and medication use, and psychosocial factors account for these associations., Methods: Multiple linear regression analysis of survey data for 1,580 participants, 57-85 years of age, in a population-based nationally representative sample of community-residing older adults in the United States., Results: Educational attainment, household wealth, and race/ethnicity were independently associated with CRP, with limited evidence for interactions with age. Health-related behaviors and usage of medications related to inflammation accounted for substantial proportions of these associations., Discussion: These results highlight the fundamental causes of inflammation among older adults and suggest pathways through which social disparities in inflammation may be reduced.

Objective: The purpose of this study was to determine whether there is an association between self-reported and biologic measures of stress in low-income, reproductive-age women., Study Design: Between 1999 and 2005, randomly selected reproductive-age women from the 1998 welfare rolls in Chicago, IL, were interviewed yearly to assess psychosocial, socioeconomic, and health characteristics. The association of 2 stress-sensitive biomarkers (Epstein-Barr virus antibody titer (EBV) and C-reactive protein level) with self-reported stress was assessed., Results: Of the 206 women who were interviewed, 205 women (99%) agreed to provide a blood sample. There was no difference in mean EBV or C-reactive protein levels based on age, race, parity, employment, marital status, or education. Women who reported a higher degree of perceived stress or reported experiences of discrimination had significantly higher levels of EBV (P < .05)., Conclusion: Measures of self-reported psychosocial stress are associated with elevated levels EBV antibody in a low-income population of reproductive-age women., (Copyright © 2010 Mosby, Inc. All rights reserved.)

C-reactive protein, a marker of chronic, low-grade inflammation, is strongly associated with current central adiposity, and has been linked to elevated risk of cardiovascular disease. Less is known about the contribution of longitudinal change in waist circumference to current inflammation. We evaluated the extent to which current waist circumference and change over an 11-year interval contribute independently to low-grade systemic inflammation measured in a group of 1,294 women, 35-69 years, participating in the Cebu Longitudinal Nutrition and Health Survey in the Philippines. Waist circumference was measured at the time of blood draw for CRP analysis in 2005 and during an earlier survey in 1994. A waist circumference delta variable was constructed by subtracting current circumference from past circumference. We used logistic regression models to predict having an elevated plasma CRP concentration (3 mg L(-1) < CRP < 10 mg L(-1)). Waist circumference in 2005 was a strong predictor of elevated CRP (OR 1.10, 95% CI = 1.08, 1.12, P < 0.001). In combined models, increase in circumference over 11 years was a significant and independent predictor of elevated CRP risk (OR = 1.023, 95% CI = 1.00, 1.05, P < 0.05). Considering the average increase over time, the cumulative risk of elevated CRP due to increased central adiposity was 25.7%. However, women who reduced their waist circumference between 1994 and 2005 had greatly reduced risk (6.2%), suggesting that even long-term inflammatory burden can be reversed by weight loss. Although current waist circumference is an important contributor to risk of elevated systemic inflammation in this as in other populations, history of central adiposity may be an independent phenomenon.

Ecological factors are important determinants of the development and function of anti-pathogen defences. Inflammation is a central part of innate immunity, but the developmental factors that shape the regulation of inflammation are not known. We test the hypothesis that microbial exposures in infancy are associated with high sensitivity C-reactive protein (CRP) in adulthood using prospective data from a birth cohort in the Philippines (n = 1461). Lower birth weight was associated with increased CRP, consistent with a role for inflammation in the widely documented inverse relationship between birth weight and adult cardiovascular diseases. In addition, higher levels of microbial exposure in infancy were associated with lower CRP. These associations were independent of socioeconomic status, measures of current body fat and other health behaviours. We conclude that measures of microbial exposure and nutrition during the pre-natal and early post-natal periods are important predictors of CRP concentration in young adulthood. We speculate that the development of anti-inflammatory regulatory networks in response to early microbial exposure represents plasticity in the development of anti-pathogen defences, and that this process may help explain the low CRP concentrations in this population.

Objectives: To examine the cross-sectional and longitudinal relationships between cardiac autonomic tone and serum CRP and to investigate potential causal links between these measures., Methods: A population-based sample of 188 home-dwelling, middle-aged and older adults (104 women, mean age 59 years) from Cook County, IL, participated in this prospective cohort study. High-frequency heart rate variability (HF) and pre-ejection period (PEP) served as markers of cardiac parasympathetic and sympathetic tone, respectively. Cardiac autonomic balance (CAB) was defined as the arithmetic difference between normalized values of HF and PEP. Multivariate regression and autoregressive cross-lagged panel analyses were used to investigate cross-sectional and longitudinal relationships, respectively. High-sensitivity enzyme immunoassay measured serum CRP., Results: After removing three cases with CRP values suggesting acute inflammation, the mean CRP value was 1.43 mg/L (range 0.02-7.96 mg/L, SD = 1.55). In models that adjusted for gender, age, race/ethnicity, education, body mass index, smoking, exercise, systolic blood pressure and health conditions including diabetes and hypertension, HF (B = -0.15, SE = 0.04, P < 0.01) and CAB (B = -0.14, SE = 0.04, P < 0.01) were significantly associated with natural log (ln) CRP. In longitudinal analysis, higher CRP levels in any one year predicted greater increases in HF in the subsequent year., Interpretation: The inverse relationship between HF and CRP in cross-sectional analysis is consistent with previous studies, while the longitudinal results suggest that cardiac parasympathetic tone may increase over time as a result of higher circulating CRP.

Background: Inflammation may be an important mediator of the association between nutrition and cardiovascular diseases, but most studies have been conducted in Western populations with high rates of overweight and obesity and low levels of infectious disease., Objectives: This study sought to investigate the predictors of C-reactive protein (CRP) in young adults living in the Philippines and to examine patterns of association with adiposity compared with young adults in the United States., Design: Maximum likelihood logistic regression models were used to predict elevated high-sensitivity CRP (>3 mg/L) in relation to anthropometric measures of adiposity, symptoms of infectious disease, and proxy measures of pathogen exposure in men and women from the Philippines (n = 1648; age: 20-22 y). Comparative data were drawn from a nationally representative sample in the United States (National Health and Nutrition Examination Survey; n = 616; age: 19-24 y)., Results: Median concentrations of CRP were substantially lower in the Philippines (0.2 mg/L) than in the United States (0.9 mg/L), and the likelihood of elevated CRP was lower in the Philippines than in the United States at the same level of waist circumference or skinfold thickness. In the Philippines, infectious symptoms and pathogen exposure predicted elevated CRP, independent of adiposity., Conclusions: Adiposity and infectious exposures are associated with elevated CRP in the Philippines; other populations undergoing comparable lifestyle and dietary changes associated with increasing rates of overweight and obesity are likely experiencing similar double burdens of inflammatory stimuli. Low concentrations of CRP in this Philippine sample raise the question of whether CRP cutoffs based on European or European-American reference populations are appropriate for predicting disease risk in populations undergoing the nutrition transition.

Obesity and infectious agents are both sources of inflammatory stimuli that result in increased production of C-reactive protein (CRP). Rates of overweight and obesity are increasing globally, but for many populations, gains in body fat are set against a backdrop of high levels of pathogen exposure. Our primary objective was to evaluate the extent to which adiposity and pathogenicity contribute to a double burden of inflammation in a population currently undergoing the nutrition transition. Measures of adiposity, pathogen exposure, and infectious disease symptoms were evaluated as predictors of high-sensitivity CRP concentration in plasma samples from 1875 women participating in the Cebu Longitudinal Health and Nutrition Survey in the Philippines. Proxy measures of pathogen exposure included household crowding and cleanliness, quality of water source, mode of waste disposal, and fecal exposure. A series of maximum likelihood logistic regression models were used to predict a plasma CRP concentration > 3 mg/L. Waist circumference was the strongest anthropometric predictor of elevated CRP [odds ratio (OR) = 2.29; 95% CI = 2.00, 2.62; P < 0.001]. Presence of infectious disease symptoms (OR = 2.51; 95% CI = 1.84, 3.44; P < 0.001) and level of pathogen exposure (OR = 1.56; 95% CI = 1.15, 2.12; P < 0.01) were also associated with elevated CRP. These associations were independent of socioeconomic status and other health behaviors. Overweight/obesity and infectious exposures are associated with elevated CRP in the Philippines; it is likely that other populations undergoing the nutrition transition are experiencing comparable double burdens of inflammatory stimuli. These results underscore the need for additional research on the contributions of pathogenicity, adiposity, and inflammation to global epidemics of cardiovascular and metabolic diseases.

C-reactive protein (CRP) is an inflammatory marker, which at low-level elevations is associated with increased cardiovascular risk. Although CRP has been extensively investigated in North American and European settings, few studies have measured CRP among non-Western groups. The present study used dried whole blood spot samples to examine high-sensitivity CRP concentrations among the Yakut (Sakha) of Siberia (85 females, 56 males; 18-58 years old). Our goals were: (1) to compare Yakut CRP concentrations with other populations; (2) to investigate sex differences; and (3) to explore anthropometric correlates of CRP. Results indicate that serum equivalent CRP concentrations are similar to those from industrializing nations, lower than US and European values, and greater than Japanese concentrations. Yakut men and women display similar CRP concentrations; however, CRP was significantly higher among men after adjustment for body fat, age, and smoking. Positive associations were documented between CRP and BMI, body fat, and central adiposity.

Objective: C-reactive protein (CRP) is emerging as an important predictor of cardiovascular disease (CVD), and chronic inflammation may be a mechanism through which stress affects disease risk. We investigated the contribution of behavioral and psychosocial factors to variation in CRP concentrations in a population-based sample of middle-aged and older adults., Methods: A high sensitivity enzyme-linked immunosorbent assay (ELISA) validated for use with dried blood spot samples was used to determine CRP concentrations in a representative sample of 188 52- to 70-year-olds. Demographic (gender, ethnicity, socioeconomic status), anthropometric (height, weight, waist circumference, percent body fat), behavioral (alcohol consumption, smoking, sleep quality, dietary quality), and psychosocial data (perceived stress, chronic stress, depressive symptoms, loneliness, perceived social support) were collected on the same day as blood samples. Psychosocial variables collected the year before were also used to investigate the impact of changing psychosocial environments. Log-transformed CRP concentrations were examined in a series of nested multivariate regression models., Results: African American and female participants were found to have higher CRP concentrations, as did individuals with lower levels of education. However, ethnic differences disappeared after the addition of behavioral and psychosocial variables. Waist circumference, latency to sleep, smoking, and perceived stress were independently associated with increased concentrations of CRP., Conclusions: Psychosocial stress, as well as health behaviors, are important predictors of inflammatory activity in a population-based sample and should be considered in future research on inflammation and CVD.

Community-based surveys of iron deficiency (ID) require simple, accurate methods that can be used in remote areas. The objective of this study was to assess iron status in rural Kenya using "field-friendly" methods for capillary blood, including an improved dried blood spot assay for transferrin receptor (TfR). A single finger stick was used to obtain capillary blood from 275 school-age children. Whole blood was applied directly to filter paper, dried, and later analyzed for TfR, as well as C-reactive protein (CRP), an acute-phase protein that serves as a general marker of inflammation. Capillary blood was also used to measure hemoglobin (Hb) concentration and the ratio of zinc protoporphyrin to heme (ZPP:H). The Hb concentration alone provides the lowest estimate of the prevalence of ID (8.0%). Because ZPP:H is reported to be elevated in the presence of inflammation, we constructed a preliminary diagnostic model based on elevated ZPP:H and normal CRP level, estimating the prevalence of ID at 25.9%. When TfR is added to a multiple criteria model (elevated ZPP:H in the absence of elevated CRP and/or elevated TfR level) the prevalence of ID is estimated to be 31.2%. This study demonstrates the diagnostic utility of combining TfR with other indexes of iron status, enabling the detection of ID in both the presence and absence of infection. Furthermore, this study is the first field application of TfR blood-spot methods, and it demonstrates their feasibility in remote field settings.

Social experiences can affect the relationship between depression and physical health. The current study examined how social support from parents and friends may moderate the association of depressive symptoms with hypothalamic-pituitary-adrenal (HPA) axis activity and C-reactive protein among adolescents (N=316, Mage=16.40, SD=.74; 57% female) from diverse ethnic backgrounds (23.1% Asian, 29.1% European, 41.8% Latino, and 6.0% other backgrounds). Results indicated that parent support, but not friend support, moderated the link between depressive symptoms and both total daily cortisol output (a measure HPA activity) and C-reactive protein (a marker of inflammation). These patterns did not differ by ethnicity. Overall, the study highlights the continued, and perhaps accumulated, importance of parents during adolescence despite increasing needs for autonomy from and exploration outside of the family unit.

Chronic inflammation is a potentially important physiological mechanism linking early life environments and health in adulthood. Elevated concentrations of C-reactive protein (CRP)--a key biomarker of inflammation--predict increased cardiovascular and metabolic disease risk in adulthood, but the developmental factors that shape the regulation of inflammation are not known. We investigated birth weight and breastfeeding duration in infancy as predictors of CRP in young adulthood in a large representative cohort study (n = 6951). Birth weight was significantly associated with CRP in young adulthood, with a negative association for birth weights 2.8 kg and higher. Compared with individuals not breastfed, CRP concentrations were 20.1%, 26.7%, 29.6% and 29.8% lower among individuals breastfed for less than three months, three to six months, 6-12 months and greater than 12 months, respectively. In sibling comparison models, higher birth weight was associated with lower CRP for birth weights above 2.5 kg, and breastfeeding greater than or equal to three months was significantly associated with lower CRP. Efforts to promote breastfeeding and improve birth outcomes may have clinically relevant effects on reducing chronic inflammation and lowering risk for cardiovascular and metabolic diseases in adulthood.

Methamphetamine use and HIV disproportionately affect sexual and gender minority (SGM) people assigned male at birth. Identifying risk factors for methamphetamine use is crucial to inform preventive interventions. In this cohort study with 1,296 SGM people assigned male at birth, ages 16 to 29, and who resided in Chicago, Poisson regression analyses indicated the prevalence of methamphetamine use increased from 2015 to 2023 [Incidence Rate Ratio (IRR) = 1.07; 95% CI = 1.01 to 1.13; P = 0.02]. This increase was most pronounced among those ages 25 or older at baseline (IRR = 2.20; 95% CI = 1.33 to 3.63; P = 0.002), and 23.9 [Interquartile Range (IQR) = 22.1 to 26.9] was the median age of first-time methamphetamine use. In 826 participants with a prior HIV diagnosis or previous inflammatory measurements, Cox proportional-hazards models examined risk factors for incident, first-time methamphetamine use. Adjusting for other substance use, the rate of incident, first-time methamphetamine use was two-fold greater after HIV diagnosis [adjusted hazard ratio (aHR) = 2.02; 95% CI = 1.27 to 3.23; P = 0.003]. For each SD higher C-reactive protein, the rate of incident, first-time methamphetamine use was 18% greater (aHR = 1.18; 95% CI, 1.05 to 1.34; P = 0.008). HIV seroconversion and inflammation could increase the risk of initiating methamphetamine use in SGM people assigned male at birth. [ABSTRACT FROM AUTHOR]

• Socioeconomic status (SES) predicts numerous health outcomes. • Chronic inflammation and immunosenescence are implicated pathways. • Studies on SES and immune function outside high income countries are limited. • In Cebu, Philippines, SES was negatively associated with measures of immunosenescence. • SES was positively associated with inflammation and mediated by adiposity. Socioeconomic status (SES) gradients in health are well-documented, and while biological pathways are incompletely understood, chronic inflammation and accelerated immune aging (immunosenescence) among lower SES individuals have been implicated. However, previous findings have come from samples in higher income countries, and it is unclear how generalizable they are to lower- and middle-income countries (LMIC) with different infectious exposures and where adiposity—an important contributor to chronic inflammation—might show different SES patterning. To address this gap, we explored associations between SES and inflammation and immunosenescence in a sample of women in Cebu, Philippines. Data came from the mothers of the Cebu Longitudinal Health and Nutrition Survey birth cohort (mean age: 47.7, range: 35–69 years). SES was measured as a combination of annual household income, education level, and assets. Chronic inflammation was measured using C-reactive protein (CRP) in plasma samples from 1,834 women. Immunosenescence was measured by the abundance of exhausted CD8T (CD8 + CD28-CD45RA-) and naïve CD8T and CD4T cells, estimated from DNA methylation in whole blood in a random subsample of 1,028. Possible mediators included waist circumference and a collection of proxy measures of pathogen exposure. SES was negatively associated with the measures of immunosenescence, with slight evidence for mediation by a proxy measure for pathogen exposure from the household's drinking water source. In contrast, SES was positively associated with CRP, which was explained by the positive association with waist circumference. Similar to higher income populations, in Cebu there is an SES-gradient in pathogen exposures and immunosenescence. However, lifestyle changes occurring more rapidly among higher SES individuals is contributing to a positive association between SES and adiposity and inflammation. Our results suggest more studies are needed to clarify the relationship between SES and inflammation and immunosenescence across LMIC. [ABSTRACT FROM AUTHOR]

Background: This was a secondary analysis of a pilot randomized controlled trial (RCT) of mindfulness-based stress reduction (MBSR) among young adult (YA) survivors of cancer, which showed preliminary evidence for improving psychosocial outcomes. Secondary outcomes assessed were the feasibility of collecting biological data from YAs and preliminary effects of MBSR on markers of inflammation and cardiovascular function. Method: Participants were randomized to 8-week MBSR or a waitlist control condition. Participants provided whole blood spot samples for analysis of C-reactive protein (CRP) and interleukin (IL)-6 as well as blood pressure data in-person at baseline and 16-week follow-up. Feasibility was assessed with rates of providing biological data. Linear mixed effects modeling was used to evaluate preliminary effects of MBSR on inflammatory markers and blood pressure over time. Results: Of 126 total participants enrolled, 77% provided biological data at baseline (n = 48/67 MBSR, n = 49/59 control). At 16 weeks, 97% of the 76 retained participants provided follow-up biological data (n = 34/35 MBSR, n = 40/41 control). Relative to the control group, MBSR was associated with decreased systolic blood pressure (p = 0.042, effect sizes (ES) = 0.45) and decreased diastolic blood pressure (p = 0.017, ES = 0.64). There were no changes in CRP or IL-6. Conclusion: This was the first study to explore the feasibility of collecting biological data from YA survivors of cancer and assess preliminary effects of MBSR on inflammatory and cardiovascular markers in an RCT. Minimally invasive biological data collection methods were feasible. Results provide preliminary evidence for the role of MBSR in improving cardiovascular outcomes in this population, and results should be replicated. [ABSTRACT FROM AUTHOR]

Objective: A growing body of evidence suggests inflammatory markers can help predict poor outcomes in pregnancy. We evaluated C‐reactive protein (CRP)—a key biomarker of inflammation—before and after a safe immune provocation (the seasonal influenza vaccine) during pregnancy. We evaluated predictors of the magnitude of response, as well as the association between CRP response and birth outcomes. Methods: Nonrandomized prospective cohort trial measuring CRP before and 3 days after administering seasonal flu vaccine to low‐risk obstetrical patients in Calgary, Alberta. Results: We analyzed 27 prevaccination/postvaccination samples. Body mass index (BMI) was positively associated with CRP at Day 0, and women with higher prepregnancy BMI had a less robust response to vaccination than did leaner women. There was a strong positive association between CRP response and infant birth weight; women who had the greatest response to vaccination (by tertile) gave birth to babies that weighed, on average, 256.2 g more than babies born to women with the lowest response. Conclusions: Higher BMI in pregnant women was associated with higher baseline CRP and less pronounced CRP response to vaccination. Stronger CRP response was associated with higher birth weight. These findings underscore the potential value of a more dynamic approach to studying the regulation of inflammation during pregnancy and its implications for birth outcomes. This study was registered as a clinical trial in clinicaltrials.gov (ID: REB15/1418). [ABSTRACT FROM AUTHOR]

Cumulative exposure to chronic stressors has been shown to contribute to immigrants' deteriorating health with more time in US residence. Few studies, however, have examined links among common psychosocial stressors for immigrants (e.g., acculturation-related) and contexts of immigrant settlement for physical health. The study investigated relationships among social stressors, stress buffers (e.g., family support), and allostatic load (AL)-a summary measure of physiological 'wear and tear'-among 126 adult Mexican immigrant farm workers. Analyses examined social contributors to AL in two locales: (1) White, English-speaking majority sites, and (2) a Mexican immigrant enclave. Our six-point AL scale incorporated immune, cardiovascular, and metabolic measures. Among men and women, older age predicted higher AL. Among women, lower family support related to higher AL in White majority communities only. Findings suggest that Latino immigrants' cumulative experiences in the US significantly compromise their health, with important differences by community context. [ABSTRACT FROM AUTHOR]

Objective To estimate the association between biomarkers of chronic stress during pregnancy and chronic placental inflammation. Study Design African-American and Caucasian pregnant women were recruited between May 2008 and July 2009. Blood samples were collected between 14 and 226/7 weeks and between 28 and 326/7 weeks of gestation. Samples were analyzed for serum C-reactive protein (CRP), Epstein-Barr virus (EBV) antibody, corticotropin-releasing hormone (CRH), and adrenocorticotropic hormone (ACTH). Placentas were collected at delivery and evaluated for chronic inflammation. Results Placentas were available from 88 of the 112 women enrolled in the study. EBV antibody levels were significantly higher during both the second and third trimester in women whose placentas demonstrated chronic villitis. CRP values also were significantly higher during the third trimester when chronic villitis was present. No association between placental chronic inflammation and CRH or ACTH was found. Conclusion Chronic placental inflammation is associated with elevated serum EBV antibody and CRP levels during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Although maternal infection and inflammation during pregnancy can adversely affect offspring birth weight (BW), whether low grade inflammation in the non-pregnant state predicts BW is unknown. Aim: To evaluate relationships between offspring BW and pro- and anti-inflammatory factors measured in parous but non-pregnant women. Subjects and methods: Data come from 234 parous Filipino females (21.5 ± 0.3 years) in the Cebu Longitudinal Health and Nutrition Survey, a population-based birth cohort in Metropolitan Cebu, Philippines. Pro-inflammatory [Interleukin-6 (IL-6), Interleukin-1 beta (IL-1β), tumour necrosis factor alpha (TNFα), C-reactive protein (CRP)] and anti-inflammatory [Interleukin-10 (IL-10)] factors were measured in fasting plasma when the women were not pregnant, and related to recalled offspring BW. Results: BW in female offspring was lower only among women with high IL-1β. Although pro-inflammatory cytokines did not predict BW in male offspring, women with higher anti-inflammatory IL-10 gave birth to larger males. Women with a combination of low inflammatory (IL-6) and high anti-inflammatory (IL-10) factors (interaction p < 0.104) gave birth to the largest males. Conclusion: Immune factors measured outside of pregnancy predict offspring BW in these young women. Stable variation in inflammatory phenotype could impact the gestational environment of offspring, thus pointing to potential inter-generational effects of chronic low-grade inflammation. [ABSTRACT FROM AUTHOR]

Background: Cannabis use has been linked to lower systemic inflammation, but the pathways connecting cannabis use and systemic inflammation are unclear. Here we investigate whether body mass index (BMI) accounts for the association between cannabis use and systemic inflammation in a cohort of sexual and gender minority youth assigned male at birth (n = 712).Methods: Substance use was assessed across six biannual visits. Cannabis use was measured using the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) and urine screening for tetrahydrocannabinol (THC). At the final visit, BMI was measured, and a plasma sample was collected to measure biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6, interleukin-1β, and tumor necrosis factor-α. Inflammatory markers were log2-transformed. Age, gender, race/ethnicity, education, HIV status, cigarette use, alcohol use, and polydrug use were included as covariates.Results: In models including all covariates except BMI, greater cumulative CUDIT-R score was associated with lower CRP (β = -0.14; 95% CI: -0.22,-0.05) and lower interleukin-6 (β = -0.12; 95% CI: -0.21,-0.04). These associations were attenuated when BMI was added to the model. Mediation analyses revealed an indirect effect of cumulative CUDIT-R score on CRP (β = -0.08; 95% CI: -0.12,-0.05) and interleukin-6 (β = -0.08; 95% CI: -0.12,-0.05), mediated by BMI. Models using urine THC or self-reported frequency to operationalize cannabis use produced similar results. We found no clear evidence that HIV status moderates these associations.Conclusions: These results suggest that BMI may partially account for the apparent anti-inflammatory effects of cannabis use. Research on the mechanisms linking cannabis use, adiposity, and inflammation may uncover promising intervention targets. [ABSTRACT FROM AUTHOR]

Chronic inflammation is a potentially important mechanism through which social inequalities may contribute to health inequalities over the life course. Excess body fat contributes to chronic inflammation, and younger adults in the US have come of age during a pronounced secular increase in body mass index (BMI). We aim to document levels of chronic inflammation in a nationally representative sample of 33-to-44 year-old adults in the US, and to describe associations with BMI, race/ethnicity, and education. High sensitivity C-reactive protein (CRP) was measured in Wave V (2016–18) of the National Longitudinal Study of Adolescent to Adult Health, with complete data available for 4349 participants. Sex-stratified weighted regression models were implemented to investigate CRP in association with education, race/ethnicity, and BMI. Geometric mean CRP was 1.9 mg/L, and 35.4% of the sample had CRP >3 mg/L. Females had significantly higher CRP than males. Body mass index was a strong positive predictor of CRP, and education level was negatively associated with CRP. Associations between education and CRP were substantially attenuated after adjusting for BMI. High risk CRP increased linearly with BMI even among the obese: 87.0 percent of females and 74.1 percent of males with class 3 obesity (BMI ≥40) were predicted to have high risk CRP > 3 mg/L. The obesity epidemic is producing an epidemic of chronic inflammation in early mid-adulthood in the US. Strong associations between BMI and chronic inflammation portend high risk for future disease—and inequitable distribution of disease—as the cohort ages. • Levels of chronic inflammation are high among young and middle-age US adults. • Body mass predicts chronic inflammation and largely explains differences by education. • The obesity epidemic is producing an epidemic of chronic inflammation in the US. • High levels of chronic inflammation portend increased risk for future disease. [ABSTRACT FROM AUTHOR]

Objective: Interleukin-6 (IL-6) is a pro-inflammatory cytokine that is associated with the production of C-reactive protein, the acute phase response, and chronic low-grade inflammation. In this report, we describe and validate a highly sensitive enzyme-linked immunosorbent assay (ELISA) for quantifying IL-6 at low concentrations in samples of capillary whole blood collected from a simple finger stick and dried on filter paper (dried blood spots, DBS). Methods: A commercially available ELISA for IL-6 was modified to develop a protocol for the quantification of IL-6 in DBS samples. Procedures for sample elution and incubation were optimized for precision, reliability, accuracy, and lower limit of detection using small volumes of DBS. A set of 46 matched serum/DBS samples were used to evaluate agreement between serum and DBS results. Results: The protocol demonstrated acceptable levels of precision, reliability, accuracy, and agreement with serum-based results. The lower limit of detection was sufficiently low to measure levels of IL-6 associated with both chronic, low-grade inflammation, and acute increases in inflammatory activity. Conclusions: This protocol adds to the growing panel of analytes validated for quantification in DBS samples and should facilitate future research on the causes and consequences of inflammation in diverse non-clinical settings. Am. J. Hum. Biol., 2012. © 2012 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The United States is characterized by persistent and widening social inequities in a wide range of adult health outcomes. A life course approach challenges us to consider if, and how, these inequities trace back to early life conditions, and chronic inflammation represents a potentially important mechanism through which early environments may have lasting effects on health in adulthood. Low birth weight (LBW) and shorter durations of breastfeeding both predict increased inflammation in adulthood, which is associated with increased risk for cardiovascular disease, metabolic syndrome, and all-cause mortality. Using data from a large representative sample of young adults in the US (National Longitudinal Study of Adolescent to Adult Health (Add Health)), we document the socioeconomic status (SES) gradient in chronic inflammation, as indicated by concentrations of C-reactive protein (CRP). Using a nested set of structural equation models and marginal standardization techniques, we investigate the extent to which this gradient is explained by patterns of LBW and breastfeeding in infancy. Findings reveal a particularly important role for breastfeeding duration: Based on model predictive margins, increasing breastfeeding duration to three or more months corresponds to a flattening of the SES gradient by 80%, and 83% when LBW is eliminated. This study expands current understandings of the consequential role of developmental environments for population health and for addressing health inequities in future generations. • Lower socioeconomic status is associated with higher chronic inflammation. • Breastfed individuals have lower levels of chronic inflammation in young adulthood. • Breastfeeding accounts for 80 percent of the socioeconomic gradient in inflammation. • Body mass partly mediates the association between breastfeeding and inflammation. [ABSTRACT FROM AUTHOR]

• Threats to social safety and inflammation is connected with risk of depression. • Inflammation has a mechanistic role in linking social threats to future depression. • Sexual minorities were more likely to display chronically elevated inflammation. • Increased coupling of inflammation and depression is more common in sexual minorities. Sexual minority individuals have a markedly elevated risk of depression compared to heterosexuals. We examined early threats to social safety and chronically elevated inflammation as mechanisms contributing to this disparity in depression symptoms, and compared the relative strength of the co-occurrence between chronic inflammation and depression symptoms for sexual minorities versus heterosexuals. To do so, we analyzed data from a prospective cohort of sexual minority and heterosexual young adults (n = 595), recruited from a nationally representative sample, that included assessments of early threats to social safety in the form of adverse childhood interpersonal events, three biomarkers of inflammation (i.e., CRP, IL-6, TNF-α) measured at two time points, and depression symptoms over four years. In pre-registered analyses, we found that sexual minorities experienced more adverse childhood interpersonal events, were more likely to display chronically elevated inflammation, and reported more severe depression symptoms than heterosexuals. Adverse childhood interpersonal events and chronically elevated inflammation explained approximately 23 % of the total effect of the association between sexual orientation and depression symptom severity. Further, there was an increased coupling of chronically elevated inflammation and depression symptoms among sexual minorities compared to heterosexuals. These results provide novel longitudinal, population-based evidence for the role of chronically elevated inflammation in linking threats to social safety during childhood with depression symptom severity in young adulthood, consistent with the primary tenets of the social signal transduction theory of depression. Our study extends this theory to the population level by finding that members of a stigmatized population (i.e., sexual minorities) experience a greater risk of depression because of their greater exposure to adverse childhood interpersonal events and the subsequent link to chronic inflammation, highlighting potential biopsychosocial intervention targets. [ABSTRACT FROM AUTHOR]

This paper examines how body size changes over the early life course to predict high sensitivity Creactive protein in a U.S. based sample. Using three waves of the National Longitudinal Study of Adolescent Health (Add Health), we test the chronic disease epidemiological models of fetal origins, sensitive periods, and chains of risk from birth into adulthood. Few studies link birth weight and changes in obesity status over adolescence and early adulthood to adult obesity and inflammation. Consistent with fetal origins and sensitive periods hypotheses, body size and obesity status at each developmental period, along with increasing body size between periods, are highly correlated with adult CRP. However, the predictive power of earlier life course periods is mediated by body size and body size change at later periods in a pattern consistent with the chains of risk model. Adult increases in obesity had effect sizes of nearly 0.3 sd, and effect sizes from overweight to the largest obesity categories were between 0.3 and 1 sd. There was also evidence that risk can be offset by weight loss, which suggests that interventions can reduce inflammation and cardiovascular risk, that females are more sensitive to body size changes, and that body size trajectories over the early life course account for African American- and Hispanic-white disparities in adult inflammation. [ABSTRACT FROM AUTHOR]