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OBJECTIVE: Chronic inflammation is a key biological risk factor for many widespread adult health conditions. This study examines racial/ethnic differences in inflammation across several inflammatory markers, including selected cytokines that are identified as important for aging and age-related health outcomes. METHODS: Data came from the 2016 Venous Blood Collection Subsample of the Health and Retirement Study. Using logistic regression models, we compared high-risk categories of C-reactive protein and cytokine markers (IL-6, IL-10, IL-1RA, TNFR1, and TGF-Beta), across race/ethnicity and whether these differences persisted among men and women. RESULTS: The findings provided evidence of significant race/ethnic differences in inflammatory measures, but the patterns differed across marker types. CONCLUSIONS: These findings emphasize that race/ethnic differences are not consistently captured across markers of inflammation and that researchers should proceed with caution when using individual markers of inflammation in an effort to not overlook potential racial/ethnic differences in biological risk.
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Biomarcadores , Etnicidad , Inflamación , Humanos , Masculino , Femenino , Inflamación/sangre , Inflamación/etnología , Anciano , Persona de Mediana Edad , Biomarcadores/sangre , Biomarcadores/análisis , Etnicidad/estadística & datos numéricos , Proteína C-Reactiva/análisis , Anciano de 80 o más Años , Citocinas/sangre , Factores de Riesgo , Grupos Raciales/estadística & datos numéricos , Modelos Logísticos , Población Blanca/estadística & datos numéricos , Estados Unidos/epidemiología , Factores SociodemográficosRESUMEN
RATIONALE: Discrimination is a risk factor and potential pathway through which social determinants such as race and sex contribute to chronic inflammation in Black Americans in middle and later adulthood. Questions remain regarding which forms of discrimination are most salient for inflammatory dysregulation, and whether there are sex-based differences in these pathways. OBJECTIVE: This exploratory study investigates sex differences in the relationships between four forms of discrimination and inflammatory dysregulation among middle aged and older Black Americans. METHODS: Using cross-sectionally linked data from participants in the Midlife in the United States (MIDUS II) Survey (2004-2006) and Biomarker Project (2004-2009) (N = 225, ages 37-84, 67% female), this study conducted a series of multivariable regression analyses. Inflammatory burden was measured using a composite indicator comprised of five biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, E-selectin, and intercellular adhesion molecule (ICAM). Discrimination measures were lifetime, daily, and chronic job discrimination and perceived inequality at work. RESULTS: Black men generally reported higher levels of discrimination than Black women (3 out of 4 forms), though only sex differences in job discrimination achieved statistical significance (p < .001). In contrast, Black women exhibited more overall inflammatory burden than Black men (2.09 vs. 1.66, p = .024), particularly elevated levels of fibrinogen (p = .003). Lifetime discrimination and inequality at work were associated with higher levels of inflammatory burden, after adjusting for demographic and health factors (p = .057 and p = .029, respectively). The discrimination-inflammation relationships further varied by sex, such that more lifetime and job discrimination predicted greater inflammatory burden in Black women, but not in Black men. CONCLUSION: These findings highlight the potentially detrimental impact of discrimination and emphasize the importance of sex-specific research on biological mechanisms of health and health disparities in Black Americans.
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Negro o Afroamericano , Inflamación , Discriminación Social , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores , Proteína C-Reactiva/análisis , Fibrinógeno/análisis , Inflamación/etnología , Estados Unidos/epidemiología , Blanco , Factores SexualesRESUMEN
The genetic background of Brazilians encompasses Amerindian, African, and European components as a result of the colonization of an already Amerindian inhabited region by Europeans, associated to a massive influx of Africans. Other migratory flows introduced into the Brazilian population genetic components from Asia and the Middle East. Currently, Brazil has a highly admixed population and, therefore, the study of genetic factors in the context of health or disease in Brazil is a challenging and remarkably interesting subject. This phenomenon is exemplified by the genetic variant CCR5Δ32, a 32 base-pair deletion in the CCR5 gene. CCR5Δ32 originated in Europe, but the time of origin as well as the selective pressures that allowed the maintenance of this variant and the establishment of its current frequencies in the different human populations is still a field of debates. Due to its origin, the CCR5Δ32 allele frequency is high in European-derived populations (~10%) and low in Asian and African native human populations. In Brazil, the CCR5Δ32 allele frequency is intermediate (4-6%) and varies on the Brazilian States, depending on the migratory history of each region. CCR5 is a protein that regulates the activity of several immune cells, also acting as the main HIV-1 co-receptor. The CCR5 expression is influenced by CCR5Δ32 genotypes. No CCR5 expression is observed in CCR5Δ32 homozygous individuals. Thus, the CCR5Δ32 has particular effects on different diseases. At the population level, the effect that CCR5Δ32 has on European populations may be different than that observed in highly admixed populations. Besides less evident due to its low frequency in admixed groups, the effect of the CCR5Δ32 variant may be affected by other genetic traits. Understanding the effects of CCR5Δ32 on Brazilians is essential to predict the potential use of pharmacological CCR5 modulators in Brazil. Therefore, this study reviews the impacts of the CCR5Δ32 on the Brazilian population, considering infectious diseases, inflammatory conditions, and cancer. Finally, this article provides a general discussion concerning the impacts of a European-derived variant, the CCR5Δ32, on a highly admixed population.
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Receptores CCR5/genética , África/etnología , Brasil , Quimiotaxis de Leucocito , Resistencia a la Enfermedad , Europa (Continente)/etnología , Femenino , Efecto Fundador , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Infecciones por VIH/etnología , Infecciones por VIH/genética , Humanos , Indígenas Sudamericanos/etnología , Infecciones/etnología , Infecciones/genética , Inflamación/etnología , Inflamación/genética , Masculino , Matrimonio , Neoplasias/etnología , Neoplasias/genética , Preeclampsia/etnología , Preeclampsia/genética , Embarazo , Eliminación de SecuenciaAsunto(s)
Pueblo Asiatico/etnología , Pueblo Asiatico/estadística & datos numéricos , Inflamación/diagnóstico , Inflamación/etnología , Estado Nutricional/etnología , Pruebas de Función Respiratoria/estadística & datos numéricos , Espirometría/estadística & datos numéricos , Adolescente , Femenino , Humanos , India/etnología , Masculino , Adulto JovenRESUMEN
Black Americans have vastly increased odds and earlier onsets of stress- and age-related disease compared to White Americans. However, what contributes to these racial health disparities remains poorly understood. Using a sample of 1577 older adults (32.7% Black; ages 55-65 at baseline), we examined whether stress, health behaviors, social isolation, and inflammation are associated with racial disparities in self-reported physical health. A latent cumulative stress factor and unique stress-domain specific factors were modeled by applying bifactor confirmatory analysis to assessments across the lifespan (i.e., childhood maltreatment, trauma exposure, discrimination, stressful life events, and indices of socioeconomic status). Physical health, health behavior, and social isolation were assessed using self-report. Interleukin-6 (IL-6) and C-reactive protein (CRP) were assayed from morning fasting serum samples; a z-scored inflammation index was formed across these 2 cytokines. A parallel serial mediational model tested whether race (i.e., Black/White) is indirectly associated with health through the following 3 independent pathways: (1) cumulative stress to preventative health behaviors (e.g., healthy eating) to inflammation, (2) cumulative stress to risky health behaviors (e.g., substance use) to inflammation; and (3) cumulative stress to social isolation to inflammation. There were significant indirect effects between race and self-reported physical health through cumulative stress, preventative health behaviors, and inflammation (B = -0.02, 95% CI: -0.05, -0.01). Specifically, Black Americans were exposed to greater cumulative stress, which was associated with reduced engagement in preventative health behaviors, which was, in turn, associated with greater inflammation and reduced physical health. A unique SES factor also indirectly linked race to physical health through preventative health behaviors. Cumulative stress exposure and unique aspects of socioeconomic status are indirectly associated with Black-White racial health disparities through behavioral (i.e., preventative health behavior) and biological (i.e., inflammation) factors. Culturally responsive evidence-based interventions that enhance engagement in preventative health behaviors are needed to directly confront health disparities. Ultimately, large scale anti-racist public policies that reduce cumulative stress burden (e.g., a living wage, universal healthcare) may best attenuate racial health disparities.
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Negro o Afroamericano , Disparidades en el Estado de Salud , Inflamación , Población Blanca , Negro o Afroamericano/psicología , Negro o Afroamericano/estadística & datos numéricos , Anciano , Conductas Relacionadas con la Salud/etnología , Humanos , Inflamación/etnología , Persona de Mediana Edad , Aislamiento Social , Estrés Psicológico/etnología , Población Blanca/psicología , Población Blanca/estadística & datos numéricosRESUMEN
BACKGROUND: Among Black Americans, interpersonal racial discrimination is common. Stress, including following discrimination, contributes to pregnancy complications. In this secondary analysis, we provide data on associations among discrimination, stress, and their interaction across the life course and inflammation, perceived stress, and depressive symptoms during pregnancy. METHODS: During the early third trimester, Black American women (n = 93) completed the Experiences of Discrimination Scale, the Stress and Adversity Inventory, the Perceived Stress Scale, and the Center for Epidemiological Studies Depression Inventory. Plasma interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and IL-ß levels were quantified. Associations were examined by linear regression, controlling for demographic, behavioral, and clinical covariates. RESULTS: Associations among racial discrimination and plasma IL-8, TNF-α, and IL-ß levels depended upon average ratings of life course stress. When stress was low, discrimination in the mid tertile was associated with the highest levels of IL-8, TNF-α, and IL-ß. Subscale analyses suggested that findings related to IL-8 were driven by chronic stress whereas findings related to TNF-α and IL-ß were driven by acute stress. When examined together, greater discrimination but not greater life course stress was associated with higher prenatal perceived stress. In subscale analyses, the association between discrimination and prenatal perceived stress depended upon average ratings of life course acute stress. When acute stress was low, discrimination in the midtertile was associated with the highest levels of prenatal perceived stress. When acute stress was high, discrimination in the high tertile was associated with the highest levels of prenatal perceived stress. There were also direct associations among greater life course chronic stress, prenatal perceived stress, and prenatal depressive symptoms. Associations were attenuated when discrimination was included as a covariate. CONCLUSIONS: The current analyses suggest that, among Black Americans, prenatal inflammation, perceived stress, and depressive symptoms may be shaped by racial discrimination and stress across the life course. In many cases, associations among discrimination and prenatal parameters depended upon how stressful exposures to life course stressors had been rated. The data suggest the potential for adaptive plasticity under some stress and highlight the deleterious nature of compounding stress.
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Depresión/psicología , Racismo/psicología , Estrés Psicológico/etiología , Adolescente , Adulto , Negro o Afroamericano , Depresión/etnología , Depresión/etiología , Femenino , Humanos , Inflamación/clasificación , Inflamación/etnología , Inflamación/etiología , Modelos Lineales , Masculino , Embarazo , Complicaciones del Embarazo/etnología , Complicaciones del Embarazo/etiología , Atención Prenatal/métodos , Atención Prenatal/psicología , Atención Prenatal/estadística & datos numéricos , Racismo/etnología , Racismo/estadística & datos numéricos , Factores Socioeconómicos , Estrés Psicológico/psicologíaRESUMEN
Brain atrophy is correlated with risk of cognitive impairment, functional decline, and dementia. Despite a high infectious disease burden, Tsimane forager-horticulturists of Bolivia have the lowest prevalence of coronary atherosclerosis of any studied population and present few cardiovascular disease (CVD) risk factors despite a high burden of infections and therefore inflammation. This study (a) examines the statistical association between brain volume (BV) and age for Tsimane and (b) compares this association to that of 3 industrialized populations in the United States and Europe. This cohort-based panel study enrolled 746 participants aged 40-94 (396 males), from whom computed tomography (CT) head scans were acquired. BV and intracranial volume (ICV) were calculated from automatic head CT segmentations. The linear regression coefficient estimate ß^T of the Tsimane (T), describing the relationship between age (predictor) and BV (response, as a percentage of ICV), was calculated for the pooled sample (including both sexes) and for each sex. ß^T was compared to the corresponding regression coefficient estimate ß^R of samples from the industrialized reference (R) countries. For all comparisons, the null hypothesis ßâT = ßâR was rejected both for the combined samples of males and females, as well as separately for each sex. Our results indicate that the Tsimane exhibit a significantly slower decrease in BV with age than populations in the United States and Europe. Such reduced rates of BV decrease, together with a subsistence lifestyle and low CVD risk, may protect brain health despite considerable chronic inflammation related to infectious burden.
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Encéfalo , Enfermedad de la Arteria Coronaria , Inflamación/etnología , Estilo de Vida , Adulto , Anciano , Anciano de 80 o más Años , Bolivia/epidemiología , Encéfalo/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/etnología , Femenino , Humanos , Pueblos Indígenas , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , América del Sur/epidemiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Flourensia fiebrigii is a plant used in traditional medicine in the Argentine Calchaquí Valley as purgative, expectorant, anti-rheumatic and anti-inflammatory. AIM OF THE STUDY: The aim of this study was to analyze the macroscopic and microscopic characteristics of F. fiebrigii leaf and stem, the phytochemical composition of leaves ethanolic extracts and to validate its traditional use as anti-rheumatic and anti-inflammatory. MATERIALS AND METHODS: The macroscopic and microscopic description of F. fiebrigii leaf and stem was carried out. Two extracts (immersions and tinctures) from leaves were obtained. The phytochemical analysis and UHPLC-OT-MS metabolome fingerprinting of both extracts were performed. The anti-rheumatic and anti-inflammatory activities of both extracts were determined using enzymatic inhibition assays of xanthine-oxidase (XOD), secretory phospholipase A2 (sPLA2) and lipoxygenase (LOX). RESULTS: The macroscopic and micrographic characters of F. fiebrigii were described to allow the botanical characterization of the plant species. The leaves extracts showed a high level of phenolic compounds with similar chromatographic patterns. Forty-five compounds were identified based on UHPLC-OT-MS including several sesquiterpenes, chalcones, flavonoids, isoflavonoids, a lignan and phenylpropanoids phenolic acids that have been identified for the first time in this plant species. F. fiebrigii extracts were able to inhibit the XOD activity and, consequently, the formation of uric acid and reactive oxygen species, primary cause of diseases, such as gouty arthritis (IC50 values of 1.10-2.12 µg/mL). Pro-inflammatory enzymes like sPLA2 and LOX were also inhibited by F. fiebrigii extracts (IC50 values of 22.00-2.20 µg/mL) decreasing the production of inflammation mediators. CONCLUSIONS: The present work validates the traditional medicinal use of F. fiebrigii as anti-rheumatic and anti-inflammatory through the use of enzymatic assays. The presence of several chemical compounds with demonstrated anti-rheumatic and anti-inflammatory properties also supports the bioactivity of the F. fiebrigii.
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Antiinflamatorios/uso terapéutico , Asteraceae , Inhibidores Enzimáticos/uso terapéutico , Componentes Aéreos de las Plantas , Extractos Vegetales/uso terapéutico , Plantas Medicinales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Argentina/etnología , Inhibidores Enzimáticos/aislamiento & purificación , Inhibidores Enzimáticos/farmacología , Inflamación/tratamiento farmacológico , Inflamación/enzimología , Inflamación/etnología , Componentes Aéreos de las Plantas/citología , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacologíaRESUMEN
OBJECTIVES: There are few papers concerning ethnic differences in disease expression in PsA, which may be influenced by a number of genetic, lifestyle and cultural factors. This article aims to compare clinical and radiographic phenotypes in people of South Asian (SA) and North European (NE) origin with a diagnosis of PsA. METHODS: This was a cross-sectional observational study recruiting patients of SA and NE origin from two hospitals in a well-defined area in the North of England. RESULTS: A total of 58 SA and 48 NE patients were recruited. SA patients had a more severe clinical phenotype with more tender (median 5 vs 2) and swollen (median 1 vs 0) joints, more severe enthesitis (median 3 vs 1.5), more patients with dactylitis (24% vs 8%), more severe skin disease (median PASI 2.2 vs 1) and worse disease activity as measured by the composite Psoriatic Arthritis Disease Activity Score (mean 4.5 vs 3.6). With regards to patient-completed measures, SA patients had worse impact with poorer quality of life and function (mean HAQ 0.9 vs 0.6; mean PsAQoL 10.8 vs 6.2; mean 36-item short form physical component score 33.5 vs 38.9). No significant differences in current MTX and biologics use were found. CONCLUSIONS: SA patients had a worse clinical phenotype and worse impact of disease than NE patients. Further studies are needed to confirm and explore the reasons behind these differences.
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Artritis Psoriásica/diagnóstico , Entesopatía/diagnóstico , Inflamación/diagnóstico , Calidad de Vida , Adulto , Artritis Psoriásica/diagnóstico por imagen , Artritis Psoriásica/etnología , Estudios Transversales , Progresión de la Enfermedad , Inglaterra , Entesopatía/diagnóstico por imagen , Entesopatía/etnología , Femenino , Humanos , Inflamación/diagnóstico por imagen , Inflamación/etnología , Masculino , Persona de Mediana Edad , Radiografía , Índice de Severidad de la EnfermedadRESUMEN
It is widely accepted that socioeconomic status (SES) is a fundamental cause of health inequality. There is evidence, however, that race is also a fundamental cause of disparities in health. Based on this idea, the weathering hypothesis developed by Geronimus and her colleagues views the elevated rates of illness and disability seen among Black Americans as a physiological response to the structural barriers, daily slights, and other threats to identity that comprise the Black experience. The current study tests the weathering hypothesis using chronic inflammation as an indicator of biological weathering. Specifically, we examine the extent to which persistent exposure to racial discrimination predicts elevated inflammation and, in turn, diagnosed chronic illness, after taking into account SES and several control variables. This mediation model was tested using zero-inflated Poisson path modeling with five waves of data collected from 391 African American women participating in the Family and Community Health Study (FACHS). A 13-item index was used to assess exposure to racial discrimination across 8 years. ELISA blood assays of seven cytokines central to the inflammatory response were used to construct an inflammatory index. Respondents reported their diagnosed chronic diseases. Consonant with the weathering hypothesis, persistent exposure to discrimination predicted inflammation which, in turn, predicted number of chronic diseases. This indirect effect was statistically significant. SES predicted having a chronic disease and the various controls showed no effect. The findings support the idea that race, like SES, is a fundamental cause of health inequalities.
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Negro o Afroamericano/estadística & datos numéricos , Enfermedad Crónica/etnología , Disparidades en el Estado de Salud , Inflamación/etnología , Racismo/estadística & datos numéricos , Femenino , Humanos , Persona de Mediana Edad , Clase SocialRESUMEN
Cardiovascular diseases are patterned by race and socioeconomic status, and chronic low-grade inflammation is proposed as a key underlying mechanism. Theories for how racial and socioeconomic disadvantages foster inflammation emphasize a lifecourse approach: social disadvantages enable chronic or repeated exposure to stressors, unhealthy behaviors, and environmental risks that accumulate across the lifecourse to increase low-grade inflammation. However, single samples rarely include multiple racial and socioeconomic groups that each span a wide age range, precluding examination of this proposition. To address this issue, the current study combined seven studies that measured C-reactive protein and interleukin-6, producing a pooled sample of 1650 individuals aged 11-60 years. We examined (a) whether race and socioeconomic disparities in inflammatory biomarkers vary across the lifecourse, (b) whether adiposity operates as a pathway leading to these disparities, and (c) whether any indirect pathways through adiposity also vary across the lifecourse. Relative to White individuals, Black individuals exhibited higher, whereas Asian individuals exhibited lower, levels of inflammatory biomarkers, and adiposity accounted for these racial differences. Similarly, lower socioeconomic status was associated with higher inflammatory biomarkers via elevated adiposity. Importantly, both racial and socioeconomic disparities, as well as their pathways via adiposity, widened across the lifecourse. This pattern suggests that the impact of social disadvantages compound with age, leading to progressively larger disparities in low-grade inflammation. More broadly, these findings highlight the importance of considering age when examining health disparities and formulating conceptual models that specify how and why disparities may vary across the lifecourse.
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Inflamación , Grupos Raciales , Clase Social , Adolescente , Adulto , Biomarcadores/sangre , Niño , Disparidades en el Estado de Salud , Humanos , Inflamación/sangre , Inflamación/etnología , Acontecimientos que Cambian la Vida , Persona de Mediana Edad , Obesidad/sangre , Obesidad/etnología , Factores Raciales , Grupos Raciales/estadística & datos numéricos , Adulto JovenRESUMEN
In the United States, causes of racial differences in stroke and its risk factors remain only partly understood, and there is a long-standing disparity in stroke incidence and mortality impacting Black Americans. Only half of the excess risk of stroke in the United States Black population is explained by traditional risk factors, suggesting potential effects of other factors including genetic and biological characteristics. Here, we nonsystematically reviewed candidate laboratory biomarkers for stroke and their relationships to racial disparities in stroke. Current evidence indicates that IL-6 (interleukin-6), a proinflammatory cytokine, mediates racial disparities in stroke through its association with traditional risk factors. Only one reviewed biomarker, Lp(a) (lipoprotein[a]), is a race-specific risk factor for stroke. Lp(a) is highly genetically determined and levels are substantially higher in Black than White people; clinical and pharmaceutical ramifications for stroke prevention remain uncertain. Other studied stroke risk biomarkers did not explain racial differences in stroke. More research on Lp(a) and other biological and genetic risk factors is needed to understand and mitigate racial disparities in stroke.
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Negro o Afroamericano/genética , Coagulación Sanguínea/genética , Disparidades en el Estado de Salud , Inflamación/etnología , Interleucina-6/genética , Lipoproteína(a)/genética , Accidente Cerebrovascular/etnología , Biomarcadores , Factor VIII/genética , Factor VIII/metabolismo , Productos de Degradación de Fibrina-Fibrinógeno/genética , Productos de Degradación de Fibrina-Fibrinógeno/metabolismo , Fibrinógeno/genética , Fibrinógeno/metabolismo , Predisposición Genética a la Enfermedad , Humanos , Incidencia , Inflamación/genética , Proteína C/genética , Proteína C/metabolismo , Factores de Riesgo , Rasgo Drepanocítico/etnología , Rasgo Drepanocítico/genética , Accidente Cerebrovascular/genética , Estados UnidosRESUMEN
OBJECTIVE: We aimed to characterize circulating HMGB1 (high-mobility group box-1) levels, one of the better-characterized damage-associated molecular patterns, with respect to age, sex, and race in the general population, and investigate the longitudinal associations of HMGB1 with inflammatory markers, obesity, and preclinical markers of cardiovascular disease. Approach and Results: The analyses included 489 participants (50% Blacks, aged 24.6±3.3 years at the first visit) with up to 4 follow-up visits (1149 samples) over a maximum of 8.5 years. Systolic blood pressure, diastolic blood pressure, carotid-femoral pulse wave velocity, and carotid intima-media thickness together with plasma HMGB1, hs-CRP (high-sensitivity C-reactive protein), IFN-γ (interferon-γ), IL-6 (interleukin-6), IL-10 (interleukin-10), and TNF-α (tumor necrosis factor-α) were measured at each visit. At baseline, plasma HMGB1 concentrations were higher in Blacks compared with Whites (3.86 versus 3.20 ng/mL, P<0.001), and in females compared with males (3.75 versus 3.30 ng/mL, P=0.005). HMGB1 concentrations increased with age (P=0.007), and higher levels of obesity measures (P<0.001). Without adjustment for age, sex, race, and body mass index, HMGB1 concentrations were positively associated with hs-CRP, IL-6, TNF-α, systolic blood pressure, diastolic blood pressure, and carotid-femoral pulse wave velocity (P<0.05) but not IL-10, IFN-γ or carotid intima-media thickness. After covariate adjustments, the associations of HMGB1 with hs-CRP, and carotid-femoral pulse wave velocity remained statistically significant (P<0.05). CONCLUSIONS: This study demonstrates the age, sex, and race differences in circulating HMGB1. The increasing circulating concentrations of HMGB1 with age suggest a potential role of HMGB1 in the pathogenesis of chronic low-grade inflammation, obesity, and subclinical cardiovascular disease risk.
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Enfermedades Cardiovasculares/sangre , Proteína HMGB1/sangre , Inflamación/sangre , Obesidad/sangre , Adulto , Negro o Afroamericano , Factores de Edad , Biomarcadores/sangre , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etnología , Femenino , Georgia/epidemiología , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Inflamación/diagnóstico , Inflamación/etnología , Estudios Longitudinales , Masculino , Obesidad/diagnóstico , Obesidad/etnología , Pronóstico , Factores Raciales , Medición de Riesgo , Factores Sexuales , Factores de Tiempo , Regulación hacia Arriba , Población Blanca , Adulto JovenRESUMEN
BACKGROUND: GlycA, a nuclear magnetic resonance composite marker of systemic inflammation, reflects serum concentration and glycosylation state of main acute phase reactants. Prior studies have shown plasma GlycA levels were associated with cardiovascular disease even after adjusting for other inflammatory markers. However, little is known about the association of GlycA with the heart failure (HF) subtypes: heart failure with preserved ejection fraction (HFpEF) or heart failure with reduced ejection fraction. We examined the association of GlycA with incident HF and its subtypes in a multiethnic cohort. METHODS: We studied 6507 Multi-Ethnic Study of Atherosclerosis participants aged 45 to 84 without baseline cardiovascular disease or HF who had data on GlycA and incident hospitalized HF. We used multivariable-adjusted Cox hazards models to evaluate the association of GlycA with incident total HF, HFpEF, and heart failure with reduced ejection fraction. Models were adjusted for sociodemographics, cardiovascular disease risk factors, and inflammatory biomarkers. RESULTS: The mean (SD) for age was 62 (10) years and for GlycA was 375 (82) µmol/L; 53% women. Over a median follow-up of 14.0 years, participants in the highest quartile of GlycA, compared with the lowest, experienced increased risk of developing any HF (hazard ratio, 1.48 [95% CI, 1.01-2.18]) in fully adjusted models. However, this increased risk was only seen for HFpEF (2.18 [1.15-4.13]) and not heart failure with reduced ejection fraction [1.06 (0.63-1.79)]. There was no significant interaction by sex, age, or race/ethnicity. CONCLUSIONS: GlycA was associated with an increased risk of any HF, and in particular, HFpEF. Future studies should examine mechanisms that might explain differential association of GlycA with HF subtypes, and whether therapeutic lowering of GlycA can prevent HFpEF development. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005487.
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Proteínas de Fase Aguda/metabolismo , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/etnología , Inflamación/sangre , Anciano , Anciano de 80 o más Años , Aterosclerosis/sangre , Aterosclerosis/etnología , Biomarcadores/sangre , Etnicidad , Femenino , Glicosilación , Humanos , Incidencia , Inflamación/etnología , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Volumen SistólicoRESUMEN
Chronic neuroinflammation is strongly associated with AD and altered peripheral and central levels of chemokines and cytokines have been frequently described in those with AD. Given the increasing evidence of ethnicity-related differences in AD, it was of interest to determine if those altered chemokine and cytokine levels are ethnicity-related. Because African Americans exhibit a higher incidence of AD and increased symptom severity, we explored chemokine and cytokine concentrations in post-mortem brain tissue from the BA21 region of African Americans and Caucasians with AD using multiplex assays. IL-1ß, MIG, TRAIL, and FADD levels were significantly increased in African Americans while levels of IL-3 and IL-8 were significantly decreased. Those effects did not interact with gender; however, overall levels of CCL25, CCL26 and CX3CL1 were significantly decreased in women. The NLRP3 inflammasome is thought to be critically involved in AD. Increased activation of this inflammasome in African Americans is consistent with the current results.
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Enfermedad de Alzheimer/etnología , Enfermedad de Alzheimer/metabolismo , Negro o Afroamericano/etnología , Mediadores de Inflamación/metabolismo , Lóbulo Temporal/metabolismo , Negro o Afroamericano/genética , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/genética , Femenino , Humanos , Inflamación/etnología , Inflamación/genética , Inflamación/metabolismo , Masculino , Población Blanca/etnología , Población Blanca/genéticaRESUMEN
BACKGROUND: Previous research documents an association between adverse childhood experiences (ACEs) and immune system inflammation. High chronic inflammation is believed to be one biological pathway through which childhood adversity may affect health into adulthood. The Blackfeet tribal community has high rates of childhood trauma and community members are disproportionately affected by inflammatory diseases. PURPOSE: To investigate whether belonging to the tribal community may moderate the relationship between childhood trauma and immune system inflammation in the Blackfeet tribal community. METHODS: In a sample of 90 adults residing on the Blackfeet reservation, we measured ACEs belonging to the tribal community and two markers of immune system inflammation, interleukin-6 (IL-6) and C-reactive protein (CRP). RESULTS: We found that independent of age, gender, annual income, body mass index, and depressive symptoms, belonging to the tribal community and ACEs interacted to predict levels of both IL-6 and CRP (B= -.37, t[81] = -3.82, p < .001, R2 change = .07 and B = -.29, t[81] = -2.75, p = .01, R2 change = .08, respectively). The association between ACEs and markers of immune system inflammation was statistically significant for community members who reported low levels of belonging to the community. CONCLUSIONS: The findings of this study have important implications for intervention research seeking to reduce risk for inflammatory diseases for at-risk populations. Fostering stronger connections to the larger tribal community may positively affect risk for inflammatory diseases. Future work should examine the behavioral and psychosocial pathways through which stronger connections to community may confer health benefits.
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Experiencias Adversas de la Infancia/etnología , Indígenas Norteamericanos/etnología , Inflamación/etnología , Trauma Psicológico/etnología , Medio Social , Adulto , Proteína C-Reactiva/metabolismo , Enfermedad Crónica/etnología , Femenino , Humanos , Inflamación/sangre , Inflamación/inmunología , Interleucina-6/sangre , Masculino , Montana/etnología , Factores Protectores , Factores de RiesgoRESUMEN
BACKGROUND: This study examines the relationship between self-reported instances of major discrimination and inflammation among older adults, and explores whether this relationship varies in accordance with race/ethnicity. We hypothesized that self-reported instances of major discrimination would be associated with higher levels of high-risk inflammation and that this relationship would be stronger for racial/ethnic minorities than whites. METHODS: Data from the 2006/2008 Health and Retirement Study, an ongoing biennial nationally representative sample of older adults in the United States, were used to collect measures of self-reported instances of major discrimination and high-risk C-reactive protein (CRP), which was assayed from blood samples. Modified Poisson regression with robust standard errors was applied to estimate the prevalence ratios of self-reported instances of major discrimination, as it relates to high-risk CRP (CRP ≥ 22 kg/m2), and test whether this relationship varies by race/ethnicity. RESULTS: Respondents who experienced any instances of major discrimination had a higher likelihood of high-risk CRP (prevalence ratio [PR]: 1.14, 95% confidence interval [CI] = 1.07-1.22) than those who did not report experiencing any instances of major discrimination. This association was independent of differences in newly diagnosed health conditions and socioeconomic status. The relationship between any self-reported instance of major discrimination and high-risk CRP was weaker for blacks than whites (PR: 0.81, 95% CI = 0.69-0.95). CONCLUSIONS: Our study confirms that self-reported instances of major lifetime discrimination is a psychosocial factor that is adversely associated with high-risk CRP among older adults; this association is especially pronounced among older whites. Future studies among this population are required to examine whether the relationship between self-reported instances of major discrimination and high-risk CRP changes over time.
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Proteína C-Reactiva/análisis , Inflamación/etnología , Racismo , Autoinforme , Anciano , Anciano de 80 o más Años , Biomarcadores/análisis , Etnicidad , Femenino , Encuestas Epidemiológicas , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estados UnidosRESUMEN
AIMS: Endothelial dysfunction is a major contributor to the pathogenesis of atherosclerosis. CD40-CD40 ligand interactions confer a pro-inflammatory phenotype to endothelial cells (ECs). Recently, a thymine to cytosine transition (-1T>C) in the Kozak sequence of the CD40 gene (rs1883832) has been associated with coronary heart disease (CHD) in an Asian population. As there are no reports yet regarding its role in other ethnic groups, this study determines if the -1T>C single-nucleotide polymorphism (SNP) could be a risk factor for CHD in Caucasians by performing an association study and elucidates its functional consequence in cultured ECs. METHODS AND RESULTS: Molecular and biochemical techniques, cell adhesion assays were used for genotype-stratified human EC characterization. SNP distribution in Caucasians was examined in a hospital-based case-control CHD study and serum levels of soluble CD40 (sCD40) were quantified by ELISA. The SNP in the CD40 gene affected baseline CD40 protein abundance on ECs. There was a genotype-dependent difference in CD40-mediated expression of pro-inflammatory genes. Monocyte adhesion was highest on the surface of cells homozygous for the C allele. Homozygosity for the C allele was associated with significant 2.32-fold higher odds of developing CHD as compared to TT genotype carriers. sCD40 plasma levels were genotype-dependently elevated in CHD patients, indicating a possible prognostic value. CONCLUSION: The C allele of the CD40 SNP provokes a pro-inflammatory EC phenotype, compensated by an enhanced CD40 shedding to neutralize excess CD40 ligand. Homozygosity for the C allele is the cause for a genetic susceptibility to atherosclerosis and its sequelae.
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Antígenos CD40/genética , Enfermedad Coronaria/genética , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Inflamación/genética , Polimorfismo de Nucleótido Simple , Anciano , Estudios de Casos y Controles , Adhesión Celular , Técnicas de Cocultivo , Enfermedad Coronaria/etnología , Enfermedad Coronaria/inmunología , Enfermedad Coronaria/metabolismo , Citocinas/metabolismo , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Homocigoto , Células Endoteliales de la Vena Umbilical Humana/inmunología , Humanos , Inflamación/etnología , Inflamación/inmunología , Inflamación/metabolismo , Masculino , Persona de Mediana Edad , Fenotipo , Transducción de Señal , Células THP-1 , Población Blanca/genéticaRESUMEN
Individuals of African descent are disproportionately affected by specific complex diseases, such as breast and prostate cancer, which are driven by both biological and nonbiological factors. In the case of breast cancer, there is clear evidence that psychosocial factors (environment, socioeconomic status, health behaviors, etc.) have a strong influence on racial disparities. However, even after controlling for these factors, overall phenotypic differences in breast cancer pathology remain among groups of individuals who vary by geographic ancestry. There is a growing appreciation that chronic/reoccurring inflammation, primarily driven by mechanisms of innate immunity, contributes to core functions associated with cancer progression. Germline mutations in innate immune genes that have been retained in the human genome offer enhanced protection against environmental pathogens, and protective innate immune variants against specific pathogens are enriched among populations whose ancestors were heavily exposed to those pathogens. Consequently, it is predicted that racial/ethnic differences in innate immune programs will translate into ethnic differences in both pro- and antitumor immunity, tumor progression, and prognosis, leading to the current phenomenon of racial/ethnic disparities in cancer. This review explores examples of protective innate immune genetic variants that are (i) distributed disproportionately among racial populations and (ii) associated with racial/ethnic disparities of breast and prostate cancer.
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Neoplasias de la Mama/etnología , Neoplasias de la Mama/inmunología , Disparidades en el Estado de Salud , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/inmunología , Neoplasias de la Mama/genética , Etnicidad , Femenino , Variación Genética , Humanos , Inmunidad Innata/genética , Inflamación/etnología , Masculino , Neoplasias de la Próstata/genética , Estados Unidos/epidemiologíaRESUMEN
OBJECTIVE: Bariatric surgery has a significant impact on levels of thyroid hormones and various inflammatory markers in obesity. The relationship between changes in thyroid hormones and inflammatory markers after bariatric surgery is unknown. We aimed to investigate the changes in thyroid hormones and their relations to inflammatory changes after laparoscopic sleeve gastrectomy (LSG) in Chinese patients with morbid obesity. METHODS: Eighty-eight patients with morbid obesity (56.8% female; age 30.9 ± 9.5 years; BMI 39.9 ± 5.7 kg/m2) submitted to LSG were selected. Patients were subdivided into euthyroid group and subclinical hypothyroidism (SH) group. Thyroid-stimulating hormone (TSH), free thyroxine (FT4), inflammatory markers, and related metabolic indexes were analyzed pre- and 12 months post-LSG. RESULTS: SH patients presented significantly higher interleukin (IL)-6, tumor necrosis factor (TNF)-α, and C-reactive protein (CRP) than euthyroid patients. Twelve-month post-surgery, the SH incidence decreased from 31.8 to 2.3% (P < 0.001). TSH levels were declined significantly in both groups but were more pronounced in SH group (P < 0.001), whereas no change in FT4 in either group. Additionally, we observed marked reduction of IL-6, TNF-α, and CRP in SH group, as well as TNF-α and CRP in euthyroid group. After adjusting for age, baseline BMI, and changes in BMI, decrease in TSH correlated significantly with decreased HOMA-IR and TNF-α in euthyroid group and decreased fasting insulin (FINS), IL-6, TNF-α, and CRP in SH group. CONCLUSION: LSG promotes TSH reduction in patients with morbid obesity that is more pronounced in patients with SH and correlated with improved inflammatory state after surgery.