Differences in Breastfeeding Initiation and Duration by Migration History in the Hispanic Community Health Study/Study of Latinos.

Objective: To estimate differences in breastfeeding initiation and duration across dimensions of migration history (migration to the U.S. 50 states/District of Columbia [DC] in childhood, adulthood, or not at all) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: We used data from HCHS/SOL on 520 individuals with a post-baseline live birth and information on breastfeeding collected at Visit 2 (2014-2017). We fit log binomial models adjusted for parity, age at pregnancy, education, income, and immigration history and incorporating sampling weights. Results: Overall, 84% of participants reported initiating breastfeeding and 30% reported breastfeeding for 6 or more months. On average, individuals reported breastfeeding for a median of 88 days (interquartile range: 156). Compared with those born in the U.S. 50 states/DC, individuals born in another country or U.S. territory who arrived in the U.S. 50 states/DC as children (<18 years old) were 2.7 times more likely to initiate breastfeeding (adjusted prevalence ratio 2.7, 95% confidence interval [CI]: 1.4, 4.9) and those who arrived as adults were 2 times more likely to initiate breastfeeding (adjusted prevalence ratio 2.0, 95% CI: 1.1, 3.6). We observed similar patterns for breastfeeding continuation. Conclusions: The timing and duration of life course experiences such as migration are key determinants of breastfeeding behavior among Hispanic/Latina postpartum persons.

Differential prediction performance between Caribbean- and Mainland-subgroups using state-of-the-art polygenic risk scores for coronary heart disease: Findings from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

Background: Coronary heart disease (CHD) is a leading cause of death for Hispanic/Latino populations in the United States. We evaluated polygenic risk scores (PRS) with incident myocardial infarction (MI) in a Hispanic/Latino study sample. Methods: We leveraged data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) to assess four CHD-PRS from the PGS catalog, derived using multiple methods (LDpred, AnnoPred, stacked clumping and thresholding, and LDPred2). We evaluated associations between each standardized PRS and time to adjudicated incident MI, adjusted for age, sex, first 5 principal components, and weighted for survey design. Concordance statistics (c-index) compared predictive accuracy of each PRS with, and in addition to, traditional risk factors (TRF) for CHD (obesity, hypercholesterolemia, hypertension, diabetes, and smoking). Analyses were stratified by self-reported Caribbean- (Puerto Rican, Dominican or Cuban) and Mainland- (those of Mexican, Central American, or South American) heritage subgroups. Results: After 11 years follow-up, for 9055 participants (mean age (SD) 47.6(13.1), 62.2% female), the incidence of MI was 1.0% (n = 95). Each PRS was more strongly associated with MI among Mainland participants. LDPred2 + TRF performed best among the Mainland subgroup; HR=2.69, 95% CI [1.71, 4.20], c-index = 0.897, 95% CI [0.848, 0.946]; a modest increase over TRF alone, c-index = 0.880, 95% CI [0.827, 0.933]. AnnoPred + TRF performed best among the Caribbean sample; c-index = 0.721, 95% CI [0.647, 0.795]; however, was not significantly associated with rate of MI (HR=1.14, 95% CI [0.82, 1.60]). Conclusion: PRS performance for CHD is lacking for Hispanics/Latinos of Caribbean origin who have substantial proportions of African genetic ancestry, risking increased health disparities. AnnoPred, using functional annotations, outperformed other PRS in the Caribbean subgroup, suggesting a potential strategy for PRS construction in diverse populations. These results underscore the need to optimize cumulative genetic risk prediction of CHD in diverse Hispanic/Latino populations.

Steroid Hormone Biosynthesis and Dietary Related Metabolites Associated with Excessive Daytime Sleepiness.

Background: Excessive daytime sleepiness (EDS) is a complex sleep problem that affects approximately 33% of the United States population. Although EDS usually occurs in conjunction with insufficient sleep, and other sleep and circadian disorders, recent studies have shown unique genetic markers and metabolic pathways underlying EDS. Here, we aimed to further elucidate the biological profile of EDS using large scale single- and pathway-level metabolomics analyses. Methods: Metabolomics data were available for 877 metabolites in 6,071 individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and EDS was assessed using the Epworth Sleepiness Scale (ESS) questionnaire. We performed linear regression for each metabolite on continuous ESS, adjusting for demographic, lifestyle, and physiological confounders, and in sex specific groups. Subsequently, gaussian graphical modelling was performed coupled with pathway and enrichment analyses to generate a holistic interactive network of the metabolomic profile of EDS associations. Findings: We identified seven metabolites belonging to steroids, sphingomyelin, and long chain fatty acids sub-pathways in the primary model associated with EDS, and an additional three metabolites in the male-specific analysis. The identified metabolites particularly played a role in steroid hormone biosynthesis. Interpretation: Our findings indicate that an EDS metabolomic profile is characterized by endogenous and dietary metabolites within the steroid hormone biosynthesis pathway, with some pathways that differ by sex. Our findings identify potential pathways to target for addressing the causes or consequences of EDS and related sleep disorders. Funding: Details regarding funding supporting this work and all studies involved are provided in the acknowledgments section.

A sociodemographic index identifies sex-related effects on insomnia in the Hispanic Community Health Study/Study of Latinos.

Study Objectives: Sex differences are related to both biological factors and the gendered environment. We constructed measures to model sex-related differences beyond binary sex. Methods: Data came from the baseline visit of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We applied the least absolute shrinkage and selection operator penalized logistic regression of male versus female sex over sociodemographic, acculturation, and psychological factors jointly. Two "gendered indices," the gendered index of sociodemographic environment (GISE) and gendered index of psychological and sociodemographic environment, summarizing the sociodemographic environment (GISE) and psychosocial and sociodemographic environment (GIPSE) associated with sex, were calculated by summing these variables, weighted by their regression coefficients. We examined the association of these indices with insomnia, a phenotype with strong sex differences, in sex-adjusted and sex-stratified analyses. Results: The distribution of GISE and GIPSE differed by sex with higher values in male individuals. In an association model with insomnia, male sex was associated with a lower likelihood of insomnia (odds ratio [OR] = 0.60, 95% CI [0.53, 0.67]). Including GISE in the model, the association was slightly weaker (OR = 0.63, 95% CI [0.56, 0.70]), and weaker when including instead GIPSE in the association model (OR = 0.78, 95% CI [0.69, 0.88]). Higher values of GISE and of GIPSE, more common in the male sex, were associated with a lower likelihood of insomnia, in analyses adjusted for sex (per 1 standard deviation of the index, GISE OR = 0.92, 95% CI [0.87, 0.99], GIPSE OR = 0.65, 95% CI [0.61, 0.70]). Conclusions: New measures such as GISE and GIPSE capture sex-related differences beyond binary sex and have the potential to better model and inform research studies of sleep health.

Analysis of C-reactive protein omics-measures associates methylation risk score with sleep health and related health outcomes.

Introduction: DNA methylation (DNAm) predictors of high sensitivity C-reactive protein (CRP) offer a stable and accurate means of assessing chronic inflammation, bypassing the CRP protein fluctuations secondary to acute illness. Poor sleep health is associated with elevated inflammation (including elevated blood CRP levels) which may explain associations of sleep insufficiency with metabolic, cardiovascular and neurological diseases. Our study aims to characterize the relationships among sleep health phenotypes and CRP markers -blood, genetic, and epigenetic indicators-within the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Methods: In HCHS/SOL, methylation risk scores (MRS)-CRP and polygenetic risk score (PRS)-CRP were constructed separately as weighted sums of methylation beta values or allele counts, respectively, for each individual. Sleep health phenotypes were measured using self-reported questionnaires and objective measurements. Survey-weighted linear regression established the association between the multiple sleep phenotypes (obstructive sleep apnea (OSA), sleep duration, insomnia and excessive sleepiness symptom), cognitive assessments, diabetes and hypertension with CRP markers while adjusting for age, sex, BMI, study center, and the first five principal components of genetic ancestry in HCHS/SOL. Results: We included 2221 HCHS/SOL participants (age range 37-76 yrs, 65.7% female) in the analysis. Both the MRS-CRP (95% confidence interval (CI): 0.32-0.42, p = 3.3 × 10-38) and the PRS-CRP (95% CI: 0.15-0.25, p = 1 × 10-14) were associated with blood CRP level. Moreover, MRS-CRP was associated with sleep health phenotypes (OSA, long sleep duration) and related conditions (diabetes and hypertension), while PRS-CRP markers were not associated with these traits. Circulating CRP level was associated with sleep duration and diabetes. Associations between OSA traits and metabolic comorbidities weakened after adjusting for MRS-CRP, most strongly for diabetes, and least for hypertension. Conclusions: MRS-CRP is a promising estimate for systemic and chronic inflammation as reflected by circulating CRP levels, which either mediates or serves as a common cause of the association between sleep phenotypes and related comorbidities, especially in the presence of diabetes.

LifeCourse Socioeconomic Position and Ideal Cardiovascular Health in Hispanic/Latino Adults of the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: The Hispanic/Latino population experiences socioeconomic disadvantages across the lifespan. Yet, little is known about the role of these disadvantages in cardiovascular health (CVH). We assessed the association of lifecourse socioeconomic position (SEP) with ideal CVH and change in Hispanic/Latino adults. METHODS AND RESULTS: We used longitudinal data from the HCHS/SOL (Hispanic Community Health Study/Study of Latinos). Childhood SEP was determined using parental educational attainment. Adult SEP was determined through an index combining participants' education, occupation, income, and assets at baseline. We classified participants into 4 socioeconomic mobility categories (eg, stable low or high SEP, upward or downward mobility). Using the 4 health factors of the American Heart Association "Life's Essential 8," we built a score of ideal CVH at baseline and the 6-year follow-up. Linear mixed-effects models using inverse probability weighting were fitted to assess the main associations. Higher childhood SEP was associated with higher ideal CVH at baseline (ß for high school versus high school versus

Intracranial Volume Is Driven by Both Genetics and Early Life Exposures: The SOL-INCA-MRI Study.

Intracranial volume (ICV) reflects maximal brain development and is associated with later-life cognitive abilities. We quantified ICV among first- and second-generation Hispanic and Latino adults from the Study of Latinos-Investigation of Cognitive Aging - MRI (SOL-INCA-MRI), estimated ICV heritability, and tested its associations with previously reported genetic variants, both individually and as a genetic risk score (GRS). We also estimated the association of ICV with early life environmental measures: nativity or age of immigration and parental education. The estimated heritability of ICV was 19% (95% CI, 0.1%-56%) in n=1781 unrelated SOL-INCA-MRI individuals. Four of 10 tested genetic variants were associated with ICV and an increase of 1 SD of the ICV-GRS was associated with an increase of 10.37 cm3 in the ICV (95% CI, 5.29-15.45). Compared to being born in the continental United States, immigrating to the United States at age 11 years or older was associated with 24 cm3 smaller ICV (95% CI, -39.97 to -8.06). Compared to both parents having less than high-school education, at least 1 parent completing high-school education was associated with 15.4 cm3 greater ICV (95% CI, 4.46-26.39). These data confirm the importance of early life health on brain development.

Blood metabolomic shift links diet and gut microbiota to multiple health outcomes among Hispanic/Latino immigrants in the U.S.

Immigrants from less industrialized countries who are living in the U.S. often bear an elevated risk of multiple disease due to the adoption of a U.S. lifestyle. Blood metabolome holds valuable information on environmental exposure and the pathogenesis of chronic diseases, offering insights into the link between environmental factors and disease burden. Analyzing 634 serum metabolites from 7,114 Hispanics (1,141 U.S.-born, 5,973 foreign-born) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we identified profound blood metabolic shift during acculturation. Machine learning highlighted the prominent role of non-genetic factors, especially food and gut microbiota, in these changes. Immigration-related metabolites correlated with plant-based foods and beneficial gut bacteria for foreign-born Hispanics, and with meat-based or processed food and unfavorable gut bacteria for U.S.-born Hispanics. Cardiometabolic traits, liver, and kidney function exhibited a link with immigration-related metabolic changes, which were also linked to increased risk of diabetes, severe obesity, chronic kidney disease, and asthma. Highlights: A substantial proportion of identified blood metabolites differ between U.S.-born and foreign-born Hispanics/Latinos in the U.S.Food and gut microbiota are the major modifiable contributors to blood metabolomic difference between U.S.-born and foreign-born Hispanics/Latinos.U.S. nativity related metabolites collectively correlate with a spectrum of clinical traits and chronic diseases.

Neurocognitive profiles are associated with subsequent brain integrity in a sample of Hispanics/Latinos: Findings from the SOL-INCA-MRI study (HCHS/SOL).

The Hispanic/Latino population is one of the largest and most diverse ethnoracial groups in the United States at high risk for dementia. We examined cognitive constructs and associations with subsequent hippocampal volume (HV) and white matter hyperintensity volume (WMHV). Participants were from the Hispanic Community Health Study/Study of Latinos-Magnetic Resonance Imaging Study (n = 2029). We examined confirmatory factor analysis and longitudinal invariance using neurocognitive scores at Visits 1 (2008-2011) and 2 (2014-2018) and path analyses. We obtained a longitudinally invariant two-factor episodic memory (EM) and working memory (WM) construct. Lower EM profile at both visits was associated with greater WMHV and smaller HV at Visit 2. Lower WM profile at both visits was associated with larger WMHV and smaller HV at Visit 2. Neurocognitive profiles were associated with subsequent neurodegeneration in a sample of Hispanics/Latinos. Identifying neurocognitive risk profiles may lead to early detection and intervention, and significantly impact the course of neurodegeneration. Highlights: Cognitive profiles predict brain integrity up to 10 years later.We observed two-factor latent memory constructs and longitudinal invariance.These findings were observed in a Hispanic/Latino cohort.

Dietary Acculturation Is Associated With Altered Gut Microbiome, Circulating Metabolites, and Cardiovascular Disease Risk in US Hispanics and Latinos: Results From HCHS/SOL.

BACKGROUND: Dietary acculturation, or adoption of dominant culture diet by migrant groups, influences human health. We aimed to examine dietary acculturation and its relationships with cardiovascular disease (CVD), gut microbiota, and blood metabolites among US Hispanic and Latino adults. METHODS: In the HCHS/SOL (Hispanic Community Health Study/Study of Latinos), US exposure was defined by years in the United States (50 states and Washington, DC) and US nativity. A dietary acculturation pattern was derived from 14 172 participants with two 24-hour dietary recalls at baseline (2008-2011) using least absolute shrinkage and selection operator regression, with food groups as predictors of US exposure. We evaluated associations of dietary acculturation with incident CVD across ≈7 years of follow-up (n=211/14 172 cases/total) and gut microbiota (n=2349; visit 2, 2014 to 2017). Serum metabolites associated with both dietary acculturation-related gut microbiota (n=694) and incident CVD (n=108/5256 cases/total) were used as proxy measures to assess the association of diet-related gut microbiome with incident CVD. RESULTS: We identified an empirical US-oriented dietary acculturation score that increased with US exposure. Higher dietary acculturation score was associated with higher risk of incident CVD (hazard ratio per SD, 1.33 [95% CI, 1.13-1.57]), adjusted for sociodemographic, lifestyle, and clinical factors. Sixty-nine microbial species (17 enriched from diverse species, 52 depleted mainly from fiber-utilizing Clostridia and Prevotella species) were associated with dietary acculturation, driven by lower intakes of whole grains, beans, and fruits and higher intakes of refined grains. Twenty-five metabolites, involved predominantly in fatty acid and glycerophospholipid metabolism (eg, branched-chain 14:0 dicarboxylic acid** and glycerophosphoethanolamine), were associated with both diet acculturation-related gut microbiota and incident CVD. Proxy association analysis based on these metabolites suggested a positive relationship between diet acculturation-related microbiome and risk of CVD (r=0.70, P<0.001). CONCLUSIONS: Among US Hispanic and Latino adults, greater dietary acculturation was associated with elevated CVD risk, possibly through alterations in gut microbiota and related metabolites. Diet and microbiota-targeted interventions may offer opportunities to mitigate CVD burdens of dietary acculturation.

Adverse childhood experiences and adult disease: Examining mediating pathways in the Hispanic Community Health Study/Study of Latinos Sociocultural Ancillary Study.

OBJECTIVES: Adverse childhood experiences (ACEs) have been linked to adulthood chronic diseases, but there is little research examining the mechanisms underlying this association. We tested pathways from ACEs to adult disease mediated via risk factors of depression, smoking, and body mass index. METHOD: Prospective data from adults 18 to 74 years old from the Hispanic Community Health Study/Study of Latinos and Sociocultural Ancillary Study were used. Retrospectively reported ACEs and hypothesized mediators were measured at Visit 1 (2008-2011). Outcomes of disease prevalence were assessed at Visit 2, approximately 6 years later. The analytic sample includes 5,230 Hispanic/Latino participants with ACE data. Statistical mediation was examined using structural equation modeling on cardiometabolic and pulmonary disease prevalence and reported probit regression coefficients with 95% confidence intervals (CIs). RESULTS: We found a significant association between ACEs and the prevalence of asthma/chronic obstructive pulmonary disorder (standardized ß = .07, 95% CI [0.02, 0.12]). In the mediational model, the direct association was nonsignificant (ß = .02, 95% CI [-0.04, 0.07]) but was mediated by depressive symptoms (ß = .03, 95% CI [0.02, 0.04]). There were no associations between ACEs and the prevalence of diabetes and self-reported coronary heart disease or cerebrovascular disease. However, a small indirect effect was identified via depressive symptoms and coronary heart disease (ß = .02, 95% CI [0.01, 0.03]). CONCLUSION: In this diverse Hispanic/Latino sample, depressive symptoms were found to be a pathway linking ACEs to self-reported cardiopulmonary diseases, although the effects were of small magnitude. Future work should replicate pathways, confirm the magnitude of effects, and examine cultural moderators that may dampen expected associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden. Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days. Design, Setting, and Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971. This report includes data collected through February 28, 2023, on adults aged 18 years or older with self-reported SARS-CoV-2 infection. Exposure: Preinfection health conditions and lifestyle factors assessed before and during the pandemic via prepandemic examinations and pandemic-era questionnaires. Main Outcomes and Measures: Probability of nonrecovery by 90 days and restricted mean recovery times were estimated using Kaplan-Meier curves, and Cox proportional hazards regression was performed to assess multivariable-adjusted associations with recovery by 90 days. Results: Of 4708 participants with self-reported SARS-CoV-2 infection (mean [SD] age, 61.3 [13.8] years; 2952 women [62.7%]), an estimated 22.5% (95% CI, 21.2%-23.7%) did not recover by 90 days post infection. Median (IQR) time to recovery was 20 (8-75) days. By 90 days post infection, there were significant differences in restricted mean recovery time according to sociodemographic, clinical, and lifestyle characteristics, particularly by acute infection severity (outpatient vs critical hospitalization, 32.9 days [95% CI, 31.9-33.9 days] vs 57.6 days [95% CI, 51.9-63.3 days]; log-rank P < .001). Recovery by 90 days post infection was associated with vaccination prior to infection (hazard ratio [HR], 1.30; 95% CI, 1.11-1.51) and infection during the sixth (Omicron variant) vs first wave (HR, 1.25; 95% CI, 1.06-1.49). These associations were mediated by reduced severity of acute infection (33.4% and 17.6%, respectively). Recovery was unfavorably associated with female sex (HR, 0.85; 95% CI, 0.79-0.92) and prepandemic clinical cardiovascular disease (HR, 0.84; 95% CI, 0.71-0.99). No significant multivariable-adjusted associations were observed for age, educational attainment, smoking history, obesity, diabetes, chronic kidney disease, asthma, chronic obstructive pulmonary disease, or elevated depressive symptoms. Results were similar for reinfections. Conclusions and Relevance: In this cohort study, more than 1 in 5 adults did not recover within 3 months of SARS-CoV-2 infection. Recovery within 3 months was less likely in women and those with preexisting cardiovascular disease and more likely in those with COVID-19 vaccination or infection during the Omicron variant wave.

Associations of Allostatic Load with Level of and Change in Cognitive Function Among Middle-Aged and Older Hispanic/Latino Adults: The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Background: Higher allostatic load (AL), a multi-system measure of physiological dysregulation considered a proxy for chronic stress exposure, is associated with poorer global cognition (GC) in older non-Hispanic white adults. However, evidence of these associations in middle-aged and older US-based Hispanic/Latino adults is limited. Objective: To examine associations of AL with level of cognition, performance in cognition 7 years later, and change in cognition over 7 years among middle-aged and older US-based Hispanic/Latino adults. Methods: We used data (n = 5,799, 45-74 years at baseline) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation of Neurocognitive Aging (SOL-INCA). The AL score comprised 16 biomarkers representing cardiometabolic, glucose, cardiopulmonary, parasympathetic, and inflammatory systems (higher scores = greater dysregulation). Cognitive outcomes included GC and individual tests of verbal learning and memory, world fluency (WF), Digit Symbol Substitution (DSS), and Trail Making (Parts A & B). Survey-linear regressions assessed associations of AL with performance in cognition at baseline, 7 years later, and via 7-year cognitive change scores adjusting for sociodemographic characteristics, lifestyle factors, and depressive symptoms. Results: Higher AL was associated with lower baseline performance in GC and WF; and lower 7-year follow-up performance in these same measures plus DSS and Trail Making Parts A & B. Higher AL was associated with more pronounced 7-year change (reduction) in GC and on WF and DSS tests. Conclusions: Findings extend previous evidence in predominantly older non-Hispanic white cohorts to show that AL is related to level of and change in GC (as well as WF and DSS) among middle-aged and older US-based Hispanic/Latino adults.

Cardiovascular disease risk exacerbates brain aging among Hispanic/Latino adults in the SOL-INCA-MRI Study.

Background: Cardiovascular disease (CVD) risk factors are highly prevalent among Hispanic/Latino adults, while the prevalence of MRI infarcts is not well-documented. We, therefore, sought to examine the relationships between CVD risk factors and infarcts with brain structure among Hispanic/Latino individuals. Methods: Participants included 1,886 Hispanic/Latino adults (50-85 years) who underwent magnetic resonance imaging (MRI) as part of the Study of Latinos-Investigation of Neurocognitive Aging-MRI (SOL-INCA-MRI) study. CVD risk was measured approximately 10.5 years before MRI using the Framingham cardiovascular risk score, a measure of 10-year CVD risk (low (<10%), medium (10- < 20%), and high (≥20%)). MR infarcts were determined as present or absent. Outcomes included total brain, cerebral and lobar cortical gray matter, hippocampal, lateral ventricle, and total white matter hyperintensity (WMH) volumes. Linear regression models tested associations between CVD risk and infarct with MRI outcomes and for modifications by age and sex. Results: Sixty percent of participants were at medium or high CVD risk. Medium and high CVD risk were associated with lower total brain and frontal gray matter and higher WMH volumes compared to those with low CVD risk. High CVD risk was additionally associated with lower total cortical gray matter and parietal volumes and larger lateral ventricle volumes. Men tended to have greater CVDRF-related differences in total brain volumes than women. The association of CVD risk factors on total brain volumes increased with age, equal to an approximate 7-year increase in total brain aging among the high-CVD-risk group compared to the low-risk group. The presence of infarct(s) was associated with lower total brain volumes, which was equal to an approximate 5-year increase in brain aging compared to individuals without infarcts. Infarcts were also associated with smaller total cortical gray matter, frontal and parietal volumes, and larger lateral ventricle and WMH volumes. Conclusion: The high prevalence of CVD risk among Hispanic/Latino adults may be associated with accelerated brain aging.

Thyroid-related Hormones and Hypertension Incidence in Middle-Aged and Older Hispanic/Latino Adults: The HCHS/SOL Study.

Background: Thyroid-related hormones act to regulate metabolic pathways and blood pressure (BP). However, the relationship of TSH and peripheral thyroid hormones and the role of the hypothalamic-pituitary-thyroid axis on hypertension development is not fully understood. We assessed sex-specific associations of thyroid-related hormones with BP and hypertension in Hispanic/Latino adults followed for 6 years. Methods: We studied 1789 adults, ages 45 to 74, free of diabetes at baseline from a subcohort of the Hispanic Community Health Study/Study of Latinos. We assessed TSH, free T4 (FT4), T3, and various indicators of thyroid axis. Using multivariable linear and Poisson regression adjusted for survey design and confounding variables, we estimated a priori sex-specific associations of thyroid-related hormones with changes in BP and hypertension development. Results: In men and women, TSH and TSH/FT4 ratios were associated with changes in diastolic BP and T3 with changes in pulse pressure and the development of hypertension from prehypertension. In men, a 1-SD increase in TSH [incident rate ratio (IRR) = 1.42; 95% confidence interval (CI): 1.15, 1.75] and TSH/FT4 ratio (IRR = 1.20; 95% CI: 1.07, 1.35) were positively associated with the development of hypertension from prehypertension while the TSH/FT4 ratio (IRR = 0.85; 95% CI: .72, 1.00) was protective in women. We observed sex-specific differences in associations of the T3/FT4 ratio and indices of pituitary sensitivity to thyroid hormones with changes in pulse pressure and hypertension development. Conclusion: Thyroid-related hormones are associated with sex-specific changes in BP and hypertension among Hispanic/Latino adults consistent with selected studies conducted in other populations. Mechanisms underlying associations of pituitary sensitivity to thyroid hormones with BP and hypertension development warrant further study.

Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes.

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.

Strategies to promote language inclusion at 17 CTSA hubs.

The prioritization of English language in clinical research is a barrier to translational science. We explored promising practices to advance the inclusion of people who speak languages other than English in research conducted within and supported by NIH Clinical Translational Science Award (CTSA) hubs. Key informant interviews were conducted with representatives (n = 24) from CTSA hubs (n = 17). Purposive sampling was used to identify CTSA hubs focused on language inclusion. Hubs electing to participate were interviewed via Zoom. Thematic analysis was performed to analyze interview transcripts. We report on strategies employed by hubs to advance linguistic inclusion and influence institutional change that were identified. Strategies ranged from translations, development of culturally relevant materials and consultations to policies and procedural changes and workforce initiatives. An existing framework was adapted to conceptualize hub strategies. Language justice is paramount to bringing more effective treatments to all people more quickly. Inclusion will require institutional transformation and CTSA hubs are well positioned to catalyze change.

Sleep Apnea and Hypertension Control among Hispanic/Latino Adults in the United States: Results from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL).

Objectives: Hispanic/Latino adults have a high prevalence of uncontrolled hypertension predisposing them to CVD. We hypothesize that sleep apnea severity is associated with uncontrolled blood pressure (BP) and resistant hypertension in Hispanic/Latino adults. Methods: This was a cross-sectional study of 2,849 Hispanic Community Health Study/Study of Latinos participants with hypertension (i.e., systolic BP ≥130 mm Hg, or diastolic BP ≥80 mm Hg or self-reported antihypertensive medication use) who were taking at least one class of antihypertensive medication. Participants were categorized as having controlled (BP < 130/80 mmHg among those on hypertension treatment) , uncontrolled (BP ≥ 130/80 mmHg using one or two classes of antihypertensive medications), or resistant hypertension (BP ≥ 130/80 mmHg while on ≥ 3 classes of antihypertensive medications or the use of ≥ 4 classes of antihypertensive medications regardless of BP control). Sleep apnea was classified based on the respiratory event index (REI; events/h) as mild (REI ≥ 5 and < 15), moderate-to-severe (REI ≥ 15), or no sleep apnea (REI < 5). Results: In multinomial logistic regression, moderate-to-severe sleep apnea (vs. no sleep apnea) was associated with higher odds of resistant hypertension (Odds Ratio [OR], 2.15; 95% CI, 1.36-3.39 at 4% desaturation and OR 1.68; 95% CI, 1.05-2.67 at 3% desaturation). Neither mild nor moderate-to-severe sleep apnea was associated with uncontrolled hypertension. Conclusion: Among diverse Hispanic/Latino persons, moderate-to-severe but not mild sleep apnea was associated with resistant hypertension. Identification and management of sleep apnea in this population may improve BP control and subsequently prevent adverse cardiovascular outcomes.

A sociodemographic index identifies non-biological sex-related effects on insomnia in the Hispanic Community Health Study/Study of Latinos.

Background: Sex differences are related to both biological factors and the gendered environment. To untangle sex-related effects on health and disease it is important to model sex-related differences better. Methods: Data came from the baseline visit of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a longitudinal cohort study following 16,415 individuals recruited at baseline from four study sites: Bronx NY, Miami FL, San Diego CA, and Chicago IL. We applied LASSO penalized logistic regression of male versus female sex over sociodemographic, acculturation, and psychological factors jointly. Two "gendered indices", GISE and GIPSE, summarizing the sociodemographic environment (GISE, primary) and psychosocial and sociodemographic environment (GIPSE, secondary) associated with sex, were calculated by summing these variables, weighted by their regression coefficients. We examined the association of these indices with insomnia derived from self-reported symptoms assessed via the Women Health Initiative Insomnia Rating Scale (WHIIRS), a phenotype with strong sex differences, in sex-adjusted and sex-stratified analyses. All analyses were adjusted for age, Hispanic/Latino background, and study center. Results: The distribution of GISE and GIPSE differed by sex with higher values in male individuals, even when constructing and validating them on separate, independent, subsets of HCHS/SOL individuals. In an association model with insomnia, male sex was associated with lower likelihood of insomnia (odds ratio (OR)=0.60, 95% CI (0.53, 0.67)). Including GISE in the model, the association was slightly weaker (OR=0.63, 95% CI (0.56, 0.70)), and weaker when including instead GIPSE in the association model (OR=0.78, 95% CI (0.69, 0.88)). Higher values of GISE and of GIPSE, more common in male sex, were associated with lower likelihood of insomnia, in analyses adjusted for sex (per 1 standard deviation of the index, GISE OR= 0.92, 95% CI (0.87, 0.99), GIPSE OR=0.65, 95% CI (0.61, 0.70)). Conclusions: New measures such as GISE and GIPSE capture sex-related differences beyond binary sex and have the potential to better model and inform research studies of health. However, such indices do not account for gender identity and may not well capture the environment experienced by intersex and non-binary persons.

Association Between Hypertensive Disorders of Pregnancy and Interval Neurocognitive Decline: An Analysis of the Hispanic Community Health Study/Study of Latinos.

OBJECTIVE: To evaluate whether hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia, are associated with cognitive decline later in life among U.S. Hispanic/Latina individuals. METHODS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a prospective population-based study of Hispanic/Latino individuals aged 18-74 years from four U.S. communities. This analysis included parous individuals aged 45 years or older who participated in the HCHS/SOL clinic study visit 1 (2008-2011) neurocognitive assessment and subsequently completed a repeat neurocognitive assessment as part of the Study of Latinos-Investigation of Neurocognitive Aging ancillary study visit 2 (2015-2018). Hypertensive disorders of pregnancy were assessed retrospectively by self-report of any gestational hypertension, preeclampsia, or eclampsia. Cognitive functioning was measured at both study visits with the Brief Spanish-English Verbal Learning Test, Digit Symbol Substitution, and Word Fluency. A regression-based approach was used to define cognitive decline at visit 2 as a function of cognition at visit 1 after adjustment for age, education, and follow-up time. Linear regression models were used to determine whether hypertensive disorders of pregnancy or their component diagnoses were associated with standardized cognitive decline after adjustment for sociodemographic characteristics, clinical and behavioral risk factors, and follow-up time. RESULTS: Among 3,554 individuals included in analysis, the mean age was 56.2 years, and 467 of individuals (13.4%) reported at least one hypertensive disorder of pregnancy. Individuals with hypertensive disorders of pregnancy compared with those without were more likely to have higher mean systolic blood pressure, fasting glucose, and body mass index. After an average of 7 years of follow-up, in fully adjusted models, gestational hypertension was associated with a 0.17-SD relative decline in Digit Symbol Substitution scores (95% CI, -0.31 to -0.04) but not other cognitive domains (Brief Spanish-English Verbal Learning Test or Word Fluency). Neither preeclampsia nor eclampsia was associated with neurocognitive differences. CONCLUSION: The presence of preeclampsia or eclampsia was not associated with interval neurocognitive decline. In this cohort of U.S. Hispanic/Latina individuals, gestational hypertension alone was associated with decreased processing speed and executive functioning later in life.