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Differentially conserved transcriptomic response to adversity related to self-rated health in the multi-ethnic study of atherosclerosis.

ABSTRACT: Self-rated health (SRH) is considered a strong indicator of well-being and clinical health status and has been linked to inflammatory markers. The objective of this work was to examine how self-rated physical health (SRPH) and mental health (SRMH) influence the immune system through the regulation of a stress-related gene expression profile known as the 'conserved transcriptional response to adversity' (CTRA), which involves the up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I interferon (IFN) response and antibody synthesis. CTRA expression data were derived from genome-wide transcriptional data on purified monocytes in 1264 adult participants from the multi-ethnic study of atherosclerosis. SRPH and SRMH were assessed through the SF-12 questionnaire. Multiple linear regression models were used to determine the association between the composite score of the CTRA subsets and SRPH and SRMH. Higher scores of SRPH and SRMH were associated with an increased expression of the overall CTRA profile. The individual gene subsets analysis did not reveal an increased expression of pro-inflammatory genes in persons with lower scores of SRH. However, we observed that higher scores of SRPH positively modulate the immune response through the up-regulation of both type I interferon response and antibody synthesis-related genes, while better scores of SRMH were associated with a down-regulation of genes involved in antibody synthesis. The significant association between SRH and a gene expression profile related to type I IFN response and antibody synthesis suggests that SRH may be linked to the immunocompetence status. Impact statement In this work, we evaluated for the first time how self-rated mental (SRMH) and physical health (SRPH) influence the immune response at the molecular level in a large multi-ethnic cohort. We observed that both SRMH and SRPH are related to immunocompetence status. These findings indicated that the link between how we perceive our health and poorer health outcomes could be explained by alterations in the immune response by shifting the expression of genes related to the type I IFN response and antibody synthesis.

SUBMITTER: Riestra P

PROVIDER: S-EPMC5714146 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Differentially conserved transcriptomic response to adversity related to self-rated health in the multi-ethnic study of atherosclerosis.

Riestra Pia P Gebreab Samson Y SY Liu Yongmei Y Diez Roux Ana V AV Khan Rumana R RR Gaye Amadou A Xu Ruihua R Davis S K SK

Experimental biology and medicine (Maywood, N.J.) 20170919 18

Self-rated health (SRH) is considered a strong indicator of well-being and clinical health status and has been linked to inflammatory markers. The objective of this work was to examine how self-rated physical health (SRPH) and mental health (SRMH) influence the immune system through the regulation of a stress-related gene expression profile known as the 'conserved transcriptional response to adversity' (CTRA), which involves the up-regulation of pro-inflammatory genes and down-regulation of gene ...[more]

PMID: 28927291

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Project description:ImportanceThe interplay of self-rated health (SRH), coronary artery calcium (CAC) scores, and cardiovascular risk is poorly described.ObjectivesTo assess the degree of correlation between SRH and CAC, to determine whether these measures are complementary for risk prediction, and to assess the incremental value of the addition of SRH to established risk tools.Design, setting, and participantsThe Multi-Ethnic Study of Atherosclerosis (MESA) is a large population-based prospective cohort study of adults aged 45 to 84 years who were recruited from 6 US communities. A total of 6764 participants without baseline cardiovascular disease (CVD) were included in the analysis. Data were collected from July 2000 through August 2002. Follow-up was completed by December 2013, and data were analyzed from October 2018 to December 2018.ExposuresThe EVGGFP (excellent, very good, good, fair, and poor) self-assessment of overall health (assessed before the baseline study examination) and CAC score. The EVGGFP rating was categorized as poor/fair, good, very good, or excellent.Main outcomes and measuresHard coronary heart disease (CHD) events, hard CVD events, and all-cause mortality during a median follow-up of 13.2 years (interquartile range, 12.7-13.7 years).ResultsAmong the study population of 6764 participants, the mean (SD) age was 62.1 (10.2) years, and 52.9% were women. The EVGGFP rating was strongly associated with age, sex, race/ethnicity, educational and income levels, healthy diet and physical activity, and cardiovascular risk factors. Despite encapsulating many risk variables, no correlation (r = -0.007; P = .57) or association between EVGGFP and the presence (χ2 = 0.84; P = .84) or severity (χ2 = 4.64; P = .86) of CAC was found. During follow-up, 1161 deaths, 637 hard CVD events, and 405 hard CHD events were recorded. In models adjusted for age, sex, race/ethnicity, and CAC, participants who reported excellent health had a 45% lower risk of CVD (hazard ratio [HR], 0.55; 95% CI, 0.39-0.77) and a 42% lower risk of CHD (HR, 0.58; 95% CI, 0.37-0.90) compared with those who reported poor/fair health. Participants in the excellent SRH category who had any CAC had markedly elevated risk of hard CHD (HR, 6.19; 95% CI, 2.1-18.3) and CVD (HR, 6.50; 95% CI, 2.7-15.6) events compared with those with a CAC score of 0. The addition of the EVGGFP rating to CAC improved the area under the curve (C statistic) for CHD events (0.725 vs 0.734; P = .007), CVD events (0.693 vs 0.706; P < .001), and all-cause mortality (0.685 vs 0.707; P < .001). However, the addition of the EVGGFP rating to the combination of CAC and atherosclerotic CVD risk score did not significantly improve C statistics for CHD events (0.751 vs 0.753; P = .39), CVD events (0.739 vs 0.741; P = .18), or all-cause mortality (0.779 vs 0.781; P = .13).Conclusions and relevanceAlthough SRH and CAC integrate many risk variables, this study suggests that they are poorly correlated and have complementary predictive utility. A perception of excellent health does not obviate the need for definitive assessment of CVD risk, whereas fair/poor perceived health may serve as a risk enhancer, arguing for advanced risk assessment in selected clinical scenarios.

Project description:PURPOSE:To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. DESIGN:Prospective cohort study. PARTICIPANTS:A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. METHODS:Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. MAIN OUTCOME MEASURES:Incident early and late AMD. RESULTS:The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. CONCLUSIONS:Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study.

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Differentially conserved transcriptomic response to adversity related to self-rated health in the multi-ethnic study of atherosclerosis.

Publications

Differentially conserved transcriptomic response to adversity related to self-rated health in the multi-ethnic study of atherosclerosis.

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