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.

Risk of Adverse Cardiovascular Outcomes in Postmenopausal Women with Inflammatory Bowel Disease.

BACKGROUND: Individuals with inflammatory bowel disease (IBD) who lack traditional cardiovascular disease (CVD) risk factors, such as young females, are observed to experience adverse CVD outcomes. Whether women with IBD have increased CVD risk after the menopause transition is unclear. METHODS: We conducted a survival analysis of Women's Health Initiative (WHI) participants and excluded those with missing IBD diagnosis, model covariate data, follow-up data, or a baseline history of the following CVD outcomes: coronary heart disease (CHD), ischemic stroke, venous thromboembolism (VTE), peripheral arterial disease (PAD). Risk of outcomes between IBD and non-IBD women was performed using Cox proportional hazard models, stratified by WHI trial and follow-up. Models were adjusted for age, socio-demographics, comorbidities (e.g., hypertension, diabetes, hypercholesterolemia, etc.), family history, and lifestyle factors (e.g., smoking, alcohol, physical activity, body mass index, etc.). RESULTS: Of 134,022 WHI participants meeting inclusion criteria, 1367 (1.0%) reported IBD at baseline. Mean baseline age was 63.4 years. After adjusting for age and other confounders, no significant difference was observed between IBD and non-IBD women for the risk of CHD (HR 0.96, 95% CI 0.73-1.24), VTE (HR 1.11, 95% CI 0.81-1.52) or PAD (HR 0.64, 95% CI 0.28-1.42). After adjusting for age, risk of ischemic stroke was significantly higher (HR 1.41, 95% CI 1.06-1.88) in IBD than non-IBD women. With further adjustment, the excess risk of ischemic stroke among IBD women was attenuated and no longer statistically significant (HR 1.31, 95% CI 0.98-1.76). CONCLUSIONS: Among postmenopausal women with IBD, risk of ischemic stroke may be higher than in non-IBD women.

Genetic subtypes of prediabetes, healthy lifestyle, and risk of type 2 diabetes.

Prediabetes is a heterogenous metabolic state with various risk for development of type 2 diabetes (T2D). In this study, we used genetic data on 7,227 US Hispanic/Latinos without diabetes from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and 400,149 non-Hispanic whites without diabetes from the UK Biobank (UKBB) to calculate five partitioned polygenetic risk scores (pPRSs) representing various pathways related to T2D. Consensus clustering was performed in participants with prediabetes in HCHS/SOL (n=3,677) and UKBB (n=16,284) separately, based on these pPRSs. Six clusters of individuals with prediabetes with distinctive patterns of pPRSs and corresponding metabolic traits were identified in the HCHS/SOL, five of which were confirmed in the UKBB. Although baseline glycemic traits were similar across clusters, individuals in Cluster 5 and Cluster 6 showed elevated risk of T2D during follow-up compared to Cluster 1 (RR=1.29 [95% CI 1.08-1.53] and1.34 [1.13-1.60], respectively). Inverse associations between a healthy lifestyle score and risk of T2D were observed across different clusters, with a suggestively stronger association observed in Cluster 5 compared to Cluster 1. Among individuals with healthy lifestyle, those in Cluster 5 had a similar risk of T2D compared to those in Cluster 1 (RR=1.03 [0.91-1.18]). This study identified genetic subtypes of prediabetes which differed in risk of progression to T2D and in benefits from healthy lifestyle.

Systolic Blood Pressure and Survival to Very Old Age: Results From the Women's Health Initiative.

BACKGROUND: The relationship between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine which SBP levels in women ≥65 years of age with or without blood pressure medication were associated with the highest probability of surviving to 90 years of age. METHODS: The study population consisted of 16 570 participants enrolled in the Women's Health Initiative who were eligible to survive to 90 years of age by February 28, 2020, without a history of cardiovascular disease, diabetes, or cancer. Blood pressure was measured at baseline (1993 through 1998) and then annually through 2005. The outcome was defined as survival to 90 years of age with follow-up. Absolute probabilities of surviving to 90 years of age were estimated for all combinations of SBP and age using generalized additive logistic regression modeling. The SBP that maximized survival was estimated for each age, and a 95% CI was generated. RESULTS: During a median follow-up of 19.8 years, 9723 of 16 570 women (59%) survived to 90 years of age. Women with an SBP between 110 and 130 mm Hg at attained ages of 65, 70, 75, and 80 years had a 38% (95% CI, 34%-48%), 54% (52%-56%), 66% (64%-67%), or 75% (73%-78%) absolute probability to survive to 90 years of age, respectively. The probability of surviving to 90 years of age was lower for greater SBP levels. Women at the attained age of 80 years with 0%, 20%, 40%, 60%, 80%, or 100% time in therapeutic range (defined as an SBP between 110 and 130 mm Hg) had a 66% (64%-69%), 68% (67%-70%), 71% (69%-72%), 73% (71%-74%), 75% (72%-77%), or 77% (74%-79%) absolute survival probability to 90 years of age. CONCLUSIONS: For women >65 years of age with low cardiovascular disease and other chronic disease risk, an SBP level <130 mm Hg was found to be associated with longevity. These findings reinforce current guidelines targeting an SBP target <130 mm Hg in older women.

Cumulative All-Cause Mortality in Diverse Hispanic/Latino Adults : A Prospective, Multicenter Cohort Study.

BACKGROUND: All-cause mortality among diverse Hispanic/Latino groups in the United States and factors underlying mortality differences have not been examined prospectively. OBJECTIVE: To describe cumulative all-cause mortality (and factors underlying differences) by Hispanic/Latino background, before and during the COVID-19 pandemic. DESIGN: Prospective, multicenter cohort study. SETTING: Hispanic Community Health Study/Study of Latinos. PARTICIPANTS: 15 568 adults aged 18 to 74 years at baseline (2008 to 2011) of Central American, Cuban, Dominican, Mexican, Puerto Rican, South American, and other backgrounds from the Bronx, New York; Chicago, Illinois; Miami, Florida; and San Diego, California. MEASUREMENTS: Sociodemographic, acculturation-related, lifestyle, and clinical factors were assessed at baseline, and vital status was ascertained through December 2021 (969 deaths; 173 444 person-years of follow-up). Marginally adjusted cumulative all-cause mortality risks (11-year before the pandemic and 2-year during the pandemic) were examined using progressively adjusted Cox regression. RESULTS: Before the pandemic, 11-year cumulative mortality risks adjusted for age and sex were higher in the Puerto Rican and Cuban groups (6.3% [95% CI, 5.2% to 7.6%] and 5.7% [CI, 5.0% to 6.6%], respectively) and lowest in the South American group (2.4% [CI, 1.7% to 3.5%]). Differences were attenuated with adjustment for lifestyle and clinical factors. During the pandemic, 2-year cumulative mortality risks adjusted for age and sex ranged from 1.1% (CI, 0.6% to 2.0%; South American) to 2.0% (CI, 1.4% to 3.0%; Central American); CIs overlapped across groups. With adjustment for lifestyle factors, 2-year cumulative mortality risks were highest in persons of Central American and Mexican backgrounds and lowest among those of Puerto Rican and Cuban backgrounds. LIMITATION: Lack of data on race and baseline citizenship status; correlation between Hispanic/Latino background and site. CONCLUSION: Differences in prepandemic mortality risks across Hispanic/Latino groups were explained by lifestyle and clinical factors. Mortality patterns changed during the pandemic, with higher risks in persons of Central American and Mexican backgrounds than in those of Puerto Rican and Cuban backgrounds. PRIMARY FUNDING SOURCE: National Institutes of Health.

Depressive symptoms and antidepressant use in relation to white blood cell count among postmenopausal women from the Women's Health Initiative.

Inflammation can play a role in the pathophysiology of depression, and specific types of antidepressants may have inflammatory or anti-inflammatory properties. Furthermore, depression and antidepressant use has been linked to white blood cell (WBC) count, a routinely measured inflammatory marker. We examined the cross-sectional and longitudinal relationships of depressive symptoms and/or antidepressant use with WBC count among postmenopausal women. Analyses of cross-sectional data at enrollment were performed on 125,307 participants, 50-79 years of age, from the Women's Health Initiative Clinical Trials and Observational Studies who met eligibility criteria, and a subset of those with 3-year follow-up data were examined for longitudinal relationships. Depressive symptoms were defined using the Burnam Algorithm whereas antidepressant use was defined using therapeutic class codes. WBC count (Kcell/ml) was obtained through laboratory evaluations of fasting blood samples. Multivariable regression modeling was performed taking sociodemographic, lifestyle and health characteristics into consideration. At enrollment, nearly 85% were non-users of antidepressants with no depressive symptoms, 5% were antidepressant users with no depressive symptoms, 9% were non-users of antidepressants with depressive symptoms, and 2% were users of antidepressants with depressive symptoms. In fully-adjusted models, cross-sectional relationships were observed whereby women in the 2nd (OR = 1.06, 95% CI: 1.01, 1.13), 3rd (OR = 1.06, 95% CI: 1.00, 1.12) or 4th (OR = 1.10, 95% CI: 1.05, 1.17) quartiles of WBC count were more likely to exhibit depressive symptoms, and women in the 4th quartile were more likely to be users of antidepressants (OR = 1.07, 95% CI: 1.00, 1.15), compared to women in the 1st quartile. Compared to women who exhibited no depressive symptoms at either visit, those with consistent depressive symptoms at enrollment and at 3-year follow-up had faster decline in WBC count (ß = -0.73, 95% CI: -1.33, -0.14) over time. No significant bidirectional relationships were observed between changes in depressive symptoms score and WBC count over time. In conclusion, depressive symptoms and/or antidepressant use were cross-sectionally related to higher WBC counts among postmenopausal women. Further evaluation of observed relationships is needed in the context of prospective cohort studies involving older adult men and women, with repeated measures of depression, antidepressant use, and WBC count.

Associations between sodium, potassium, and blood pressure: results from the Hispanic Community Health Study/Study of Latinos, a prospective cohort study.

BACKGROUND: Although the subject of numerous studies, the associations between dietary sodium, potassium, and the ratio of dietary sodium to potassium with blood pressure are not clear-cut. In addition, there is a paucity of research on these relationships in prospective cohort studies with representation from diverse Hispanic/Latino adults. OBJECTIVES: To evaluate the associations between dietary intake of sodium, potassium, and the ratio of dietary sodium to potassium and blood pressure in a diverse sample of Hispanics living in the United States. METHODS: This analysis included 11,429 Hispanic/Latino participants of the prospective cohort Hispanic Community Health Study/Study of Latinos recruited between 2008 and 2011 in visit 1 who participated in a follow-up visit in 2014-2017. Dietary sodium and potassium intakes were averaged from 2 interviewer-administered 24-h diet recalls collected at visit 1. At both visits, blood pressure was measured 3 times in a seated position and averaged. We assessed the relationship between dietary sodium, potassium, and the sodium-to-potassium ratio with changes in systolic and diastolic blood pressure using survey-weighted multivariable-adjusted regression models. RESULTS: At visit 1, the mean age was 41 y, and the mean sodium intake was 3203 mg/d. Each 500 mg/d sodium increment in intake was associated with an increase in systolic blood pressure (ß: 0.35 [mmHg]; 95% confidence interval: 0.06, 0.63) and diastolic blood pressure (ß: 0.45 [mmHg]; 95% confidence interval: 0.08, 0.82). Dietary potassium and the molar ratio of dietary sodium to potassium were not associated with changes in systolic or diastolic blood pressure. CONCLUSIONS: Among a large sample of diverse United States Hispanic/Latino adults, higher sodium intake was associated with small increases in systolic blood pressure over 6 y. This research underscores the importance of dietary sodium reduction in maintaining lower blood pressure.

Hypertension, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (SOL-INCA).

BACKGROUND: Hypertension can have deleterious effects on cognitive function; however, few studies have examined its effects on cognition among Hispanics/Latinos. OBJECTIVE: To assess associations between hypertension status with 1) change in cognitive performance, and 2) having mild cognitive impairment (MCI) among diverse Hispanics/Latinos. METHODS: This population-based, prospective cohort, multisite study included Hispanic/Latino adults aged 45 to 72 years in enrolled in the Hispanic Community Health Study/Study of Latinos at Visit 1 (2008-2011; mean age of 63.40±8.24 years), and the Study of Latinos-Investigation of Neurocognitive Aging at Visit 2 (2016-2018), with a mean follow-up duration of 7 years (n = 6,173). Hypertension status was assessed at both visits: normotension (no hypertension), incident hypertension (only at Visit 2), and persistent hypertension (at both visits). We examined change in cognitive performance and having MCI (only assessed at Visit 2) relative to hypertension status and adjusted for demographics and cardiovascular disease risk factors. RESULTS: Compared to normotension, persistent hypertension was associated with significantly increased decline in verbal fluency (ß= -0.08; CI = [-0.16;-0.01]; p < 0.05), and processing speed (ß= -0.11; CI = [-0.20;-0.02]; p < 0.05). Incident hypertension was not associated with significant change in cognitive performance. Both incident (OR = 1.70; CI = [1.16;2.50]; p < 0.01) and persistent hypertension (OR = 2.13; CI = [1.57;2.88]; p < 0.001) were associated with significantly higher odds ratios of having MCI. CONCLUSIONS: These findings indicate that persistent hypertension is associated with clinical impairment and domain-specific cognitive decline in middle-aged and older Hispanics/Latinos. It underscores the importance of monitoring blood pressure in routine healthcare visits beginning at midlife in this population to reduce the burden of cognitive decline.

Life's Essential 8 and Incident Hypertension Among US Hispanic/Latino Adults: Results From the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Life's Essential 8 (LE8) is a new metric to define cardiovascular health. We aimed to describe LE8 among Hispanics/Latinos and its association with incident hypertension. METHODS AND RESULTS: The HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is a study of Hispanic/Latino adults aged 18 to 74 years from 4 US communities. At visit 1 (2008-2011), information on behavioral and clinical factors (diet, smoking status, physical activity, sleep duration, body mass index, blood pressure, cholesterol, fasting glucose, and medication use) were measured and used to estimate an LE8 score (range, 0-100) for 14 772 participants. Hypertension was defined as systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg, or self-reported use of antihypertensive medications. Among the 5667 participants free from hypertension at visit 1, we used Poisson regression models to determine the multivariable adjusted association between LE8 and incident hypertension in 2014 to 2017. All analyses accounted for the complex survey design of the study. Mean population age was 41 years, and 21.6% (SE, 0.7) had high cardiovascular health (LE8 ≥80). Mean LE8 score (68.2; SE, 0.3) varied by Hispanic/Latino background (P<0.05), ranging from 72.6 (SE, 0.3) among Mexican Americans to 62.2 (SE, 0.4) among Puerto Ricans. Each 10-unit decrement in LE8 score was associated with a 22% increased risk of hypertension over ≈6 years (incident density ratio, 1.22 [95% CI, 1.16-1.29]). CONCLUSIONS: Only 1 in 5 Hispanic/Latino adults had high cardiovascular health, and LE8 varied substantially across Hispanic/Latino background groups. Improvements in other components of cardiovascular health may result in a lower risk of developing hypertension.

Risk Factors for Cardiovascular Disease: Knowledge Gained from the Hispanic Community Health Study/Study of Latinos.

PURPOSE OF REVIEW: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL) has made important contributions on the prevalence of and factors associated with cardiovascular disease (CVD) risk factors among diverse Hispanic/Latino adults in the US. This article summarizes the knowledge gained thus far on major CVD risk factors from this landmark study. RECENT FINDINGS: HCHS/SOL demonstrated the sizeable burdens of CVD risk in all major Hispanic/Latino groups in the US, as well as the marked variations in prevalence of hypertension, hypercholesterolemia, diabetes, obesity, and smoking by sex and background. It also identified sociodemographic, lifestyle, and sociocultural characteristics associated with risk factors. HCHS/SOL has yielded an expanding body of literature on characteristics associated with adverse CVD risk factors in this population. Long-term follow-up of this cohort will shed further light on the observed heterogeneity in CVD risk across Hispanic/Latino groups and identify specific risk/protective factors driving these variations.

Association of anxiety and depressive symptoms with C-reactive protein in diverse Latinos: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND: High sensitivity C-reactive protein (hsCRP) is a marker of systemic inflammation that has been associated with persistent depressive symptoms. Depression and anxiety are frequently associated with a chronic inflammatory state, yet the nature of this relationship has not been rigorously examined in diverse Hispanic/Latino populations. We aimed to study the association of anxiety and depressive symptoms as well as comorbid presentations, with circulating high sensitivity C-reactive protein (hsCRP) levels in a large Latino cohort of diverse heritages. We hypothesized a significant positive associations of both anxiety and depressive symptoms and hsCRP levels and potential variations among the heritage groups. METHODS: Depressive symptoms and anxiety were measured by the Center for Epidemiological Studies Depression Scale (CES-D) and State-Trait Anxiety Inventory (STAI), respectively. Serum hsCRP (hsCRP) levels of 15,448 participants (age 18 to 75 years; 52.3% women) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were measured and categorized based on the established cardiovascular disease (CVD) risk reference values (< 1mg/L, low; 1-<3 mg/L, intermediate; ≥ 3mg/L, high). RESULTS: Mean CES-D, STAI scores, and hsCRP levels were 7.0 (SD = 5.9), 17.0 (SD = 5.7), and 3.84 (SD = 7.85), respectively. Generalized linear modeling, adjusted for sociodemographic characteristics revealed significant associations between depression (exp(ß) = 1.12; p<0.01) and anxiety symptoms (exp(ß) = 1.10; p<0.05) with continuous hsCRP levels. For categorical values of hsCRP, one SD increase in CES-D and STAI scores was associated with a 10% and 8% increase in the RRRs of high vs. low hsCRP, respectively. However, these relationships between CES-D or STAI and hsCRP were no longer statistically significant after adjustment for CVD risk factors and medications. CONCLUSION: We found modest associations between anxiety and depressive symptoms and systemic inflammation measured by hsCRP among diverse Hispanics/Latinos that did not appreciably differ between heritage groups.

A polygenic risk score for Alzheimer's disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.

INTRODUCTION: Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome. METHODS: We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region. We also assessed PRS associations with MCI in an independent dataset from the Mass General Brigham Biobank. RESULTS: A simple sum of 5 PRSs ("PRSsum"), each constructed based on a different AD GWAS, was associated with MCI (OR = 1.28, 95% CI [1.14, 1.41]) in a model adjusted for counts of the APOE-[Formula: see text] and APOE-[Formula: see text] alleles. Associations of single-GWAS PRSs were weaker. When removing SNPs from the APOE region from the PRSs, the association of PRSsum with MCI was weaker (OR = 1.17, 95% CI [1.04,1.31] with adjustment for APOE alleles). In all association analyses, APOE-[Formula: see text] and APOE-[Formula: see text] alleles were not associated with MCI. DISCUSSION: A sum of AD PRSs is associated with MCI in Hispanic/Latino older adults. Despite no association of APOE-[Formula: see text] and APOE-[Formula: see text] alleles with MCI, the association of the AD PRS with MCI is stronger when including the APOE region. Thus, APOE variants different than the classic APOE alleles may be important predictors of MCI in Hispanic/Latino adults.

Association of Later-Life Weight Changes With Survival to Ages 90, 95, and 100: The Women's Health Initiative.

BACKGROUND: Associations of weight changes and intentionality of weight loss with longevity are not well described. METHODS: Using longitudinal data from the Women's Health Initiative (N = 54 437; 61-81 years), we examined associations of weight changes and intentionality of weight loss with survival to ages 90, 95, and 100. Weight was measured at baseline, year 3, and year 10, and participants were classified as having weight loss (≥5% decrease from baseline), weight gain (≥5% increase from baseline), or stable weight (<5% change from baseline). Participants reported intentionality of weight loss at year 3. RESULTS: A total of 30 647 (56.3%) women survived to ≥90 years. After adjustment for relevant covariates, 3-year weight loss of ≥5% vs stable weight was associated with lower odds of survival to ages 90 (OR, 0.67; 95% CI, 0.64-0.71), 95 (OR, 0.65; 95% CI, 0.60-0.71), and 100 (OR, 0.62; 95% CI, 0.49-0.78). Compared to intentional weight loss, unintentional weight loss was more strongly associated with lower odds of survival to age 90 (OR, 0.83; 95% CI, 0.74-0.94 and OR, 0.49; 95% CI, 0.44-0.55, respectively). Three-year weight gain of ≥5% vs stable weight was not associated with survival to age 90, 95, or 100. The pattern of results was similar among normal weight, overweight, and obese women in body mass index (BMI)-stratified analyses. CONCLUSIONS: Weight loss of ≥5% vs stable weight was associated with lower odds of longevity, more strongly for unintentional weight loss than for intentional weight loss. Potential inaccuracy of self-reported intentionality of weight loss and residual confounding were limitations.

Systolic Blood Pressure and Survival to Very Old Age. Results from the Women's Health Initiative.

Background: The association between systolic blood pressure (SBP) and longevity is not fully understood. We aimed to determine survival probabilities to age 90 for various SBP levels among women aged ≥ 65 years with or without BP medication. Methods: We analyzed blood pressure data from participants in the Women's Health Initiative (n=16,570) who were aged 65 or older and without history of cardiovascular disease, diabetes or cancer. Blood pressure was measured at baseline (1993-1998) and then annually through 2005. The outcome was defined as survival to age 90 with follow-up until February 28, 2020. Results: During a follow-up of 18 years, 9,723 (59%) of 16,570 women survived to age 90. The SBP associated with the highest probability of survival was about 120mmHg regardless of age. Compared to an SBP between 110 and 130 mmHg, women with uncontrolled SBP had a lower survival probability across all age groups and with or without BP medication. A 65-year-old women on BP medication with an interpolated SBP between 110 and 130 mmHg in 80% of the first 5 years of follow-up had a 31% (95% confidence interval, 24%, 38%) absolute survival probability. For those with 20% time in range, the probability was 21% (95% confidence interval, 16%, 26%). Conclusions: An SBP level below 130 mmHg was found to be associated with longevity among older women. The longer SBP was controlled at a level between 110 and 130 mmHg, the higher the survival probability to age 90. Preventing age-related rises in SBP and increasing the time with controlled BP levels constitute important measures for achieving longevity.

Evaluating the use of blood pressure polygenic risk scores across race/ethnic background groups.

We assess performance and limitations of polygenic risk scores (PRSs) for multiple blood pressure (BP) phenotypes in diverse population groups. We compare "clumping-and-thresholding" (PRSice2) and LD-based (LDPred2) methods to construct PRSs from each of multiple GWAS, as well as multi-PRS approaches that sum PRSs with and without weights, including PRS-CSx. We use datasets from the MGB Biobank, TOPMed study, UK biobank, and from All of Us to train, assess, and validate PRSs in groups defined by self-reported race/ethnic background (Asian, Black, Hispanic/Latino, and White). For both SBP and DBP, the PRS-CSx based PRS, constructed as a weighted sum of PRSs developed from multiple independent GWAS, perform best across all race/ethnic backgrounds. Stratified analysis in All of Us shows that PRSs are better predictive of BP in females compared to males, individuals without obesity, and middle-aged (40-60 years) compared to older and younger individuals.

Economic and Psychosocial Impact of COVID-19 in the Hispanic Community Health Study/Study of Latinos.

Objectives: To examine the prevalence and correlates of economic hardship and psychosocial distress experienced during the initial phase of the coronavirus disease 2019 (COVID-19) pandemic in a large cohort of Hispanic/Latino adults. Methods: The Hispanic Community Health Study/Study of Latinos (HCHS/SOL), an ongoing multicenter study of Hispanic/Latino adults, collected information about COVID-19 illness and psychosocial and economic distress that occurred during the pandemic (N=11,283). We estimated the prevalence of these experiences during the initial phase of the pandemic (May 2020 to May 2021) and examined the prepandemic factors associated with pandemic-related economic hardship and emotional distress using multivariable log linear models with binomial distributions to estimate prevalence ratios. Results: Almost half of the households reported job losses and a third reported economic hardship during the first year of the pandemic. Pandemic-related household job losses and economic hardship were more pronounced among noncitizens who are likely to be undocumented. Pandemic-related economic hardship and psychosocial distress varied by age group and sex. Contrary to the economic hardship findings, noncitizens were less likely to report pandemic-related psychosocial distress. Prepandemic social resources were inversely related to psychosocial distress. Conclusions: The study findings underscore the economic vulnerability that the pandemic has brought to ethnic minoritized and immigrant populations in the United States, in particular noncitizens. The study also highlights the need to incorporate documentation status as a social determinant of health. Characterizing the initial economic and mental health impact of the pandemic is important for understanding the pandemic consequences on future health. Clinical Trial Registration Number: NCT02060344.

Evolving Science on Cardiovascular Disease Among Hispanic/Latino Adults: JACC International.

The landmark, multicenter HCHS/SOL (Hispanic Community Health Study/Study of Latinos) is the largest, most comprehensive, longitudinal community-based cohort study to date of diverse Hispanic/Latino persons in the United States. The HCHS/SOL aimed to address the dearth of comprehensive data on risk factors for cardiovascular disease (CVD) and other chronic diseases in this population and has expanded considerably in scope since its inception. This paper describes the aims/objectives and data collection of the HCHS/SOL and its ancillary studies to date and highlights the critical and sizable contributions made by the study to understanding the prevalence of and changes in CVD risk/protective factors and the burden of CVD and related chronic conditions among adults of diverse Hispanic/Latino backgrounds. The continued follow-up of this cohort will allow in-depth investigations on cardiovascular and pulmonary outcomes in this population, and data from the ongoing ancillary studies will facilitate generation of new hypotheses and study questions.

Cardiovascular Disease and Mortality in Black Women Carrying the Amyloidogenic V122I Transthyretin Gene Variant.

BACKGROUND: Long-term data on cardiovascular disease (CVD) and mortality in female carriers of the transthyretin (TTR) V122I (pV142I) variant, one of the most common variants of hereditary transthyretin cardiac amyloidosis, are sparse and the effects of blood pressure, heart rate, body mass index, and physical activity on CVD outcomes remain largely unknown. OBJECTIVES: The aim was to first examine the relationship of TTR V122I (pV142I) carrier status with CVD and mortality and second to investigate the effects of blood pressure, heart rate, body mass index, and physical activity in a large cohort of postmenopausal women. METHODS: The study population consisted of 9,862 non-Hispanic Black/African American women, 9,529 noncarriers and 333 TTR V122I carriers, enrolled in the Women's Health Initiative at 40 centers in the United States. Women were generally healthy and postmenopausal at the time of enrollment (1993-1998). CVD was defined as a composite endpoint consisting of coronary heart disease, stroke, acute heart failure or CVD death, and all-cause mortality. CVD cases were based on self-reported annual mailed health updates. All information was centrally adjudicated by trained physicians. HRs and 95% CIs were obtained from adjusted Cox proportional hazards models. RESULTS: Among 9,862 Black female participants (mean age: 62 years [IQR: 56-67 years]), the population frequency of the TTR V122I variant was 3.4% (333 variant carriers and 9,529 noncarriers). During a mean follow-up of 16.1 years (IQR: 9.7-22.2 years), incident CVD occurred in 2,229 noncarriers and 96 carriers, whereas 2,689 noncarriers and 108 carriers died. In adjusted models including demographic, lifestyle, and medical history covariates, TTR V122I carriers were at higher risk of the composite endpoint CVD (HR: 1.52; 95% CI: 1.22-1.88), acute heart failure (HR: 2.21; 95% CI: 1.53-3.18), coronary heart disease (HR: 1.80; 95% CI: 1.30-2.47), CVD death (HR: 1.70; 95% CI: 1.26-2.30), and all-cause mortality (HR: 1.28; 95% CI: 1.04-1.56). The authors found a significant interaction by age but not by blood pressure, heart rate, body mass index, or physical activity. CONCLUSIONS: Black female TTR V122I (pV142I) carriers have a higher CVD and all-cause mortality risk compared to noncarriers. In case of clinical suspicion of amyloidosis, they should be screened for TTR V122I (pV142I) carrier status to ensure early treatment onset.

Collectrin (Tmem27) deficiency in proximal tubules causes hypertension in mice and a TMEM27 variant associates with blood pressure in males in a Latino cohort.

Collectrin (Tmem27), an angiotensin-converting enzyme 2 homologue, is a chaperone of amino acid transporters in the kidney and endothelium. Global collectrin knockout (KO) mice have hypertension, endothelial dysfunction, exaggerated salt sensitivity, and diminished renal blood flow. This phenotype is associated with altered nitric oxide and superoxide balance and increased proximal tubule (PT) Na+/H+ exchanger isoform 3 (NHE3) expression. Collectrin is located on the X chromosome where genome-wide association population studies have largely been excluded. In the present study, we generated PT-specific collectrin KO (PT KO) mice to determine the precise contribution of PT collectrin in blood pressure homeostasis. We also examined the association of human TMEM27 single-nucleotide polymorphisms with blood pressure traits in 11,926 Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Hispanic/Latino participants. PT KO mice exhibited hypertension, and this was associated with increased baseline NHE3 expression and diminished lithium excretion. However, PT KO mice did not display exaggerated salt sensitivity or a reduction in renal blood flow compared with control mice. Furthermore, PT KO mice exhibited enhanced endothelium-mediated dilation, suggesting a compensatory response to systemic hypertension induced by deficiency of collectrin in the PT. In HCHS/SOL participants, we observed sex-specific single-nucleotide polymorphism associations with diastolic blood pressure. In conclusion, loss of collectrin in the PT is sufficient to induce hypertension, at least in part, through activation of NHE3. Importantly, our model supports the notion that altered renal blood flow may be a determining factor for salt sensitivity. Further studies are needed to investigate the role of the TMEM27 locus on blood pressure and salt sensitivity in humans.NEW & NOTEWORTHY The findings of our study are significant in several ways: 1) loss of an amino acid chaperone in the proximal tubule is sufficient to cause hypertension, 2) the results in global and proximal tubule-specific collectrin knockout mice support the notion that vascular dysfunction is required for salt sensitivity or that impaired renal tubule function causes hypertension but is not sufficient to cause salt sensitivity, and 3) our study is the first to implicate a role of collectrin in human hypertension.

Genetic associations between sleep traits and cognitive ageing outcomes in the Hispanic Community Health Study/Study of Latinos.

BACKGROUND: Sleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults. METHODS: We used summary statistics from published genome-wide association studies to construct PRSs representing the genetic basis of each sleep trait, then we studied the association of the PRSs of the sleep phenotypes with cognitive outcomes in the Hispanic Community Healthy Study/Study of Latinos. The primary model adjusted for age, sex, study centre, and measures of genetic ancestry. Associations are highlighted if their p-value <0.05. FINDINGS: Higher PRS for insomnia was associated with lower global cognitive function and higher risk of mild cognitive impairment (MCI) (OR = 1.20, 95% CI [1.06, 1.36]). Higher PRS for daytime sleepiness was also associated with increased MCI risk (OR = 1.14, 95% CI [1.02, 1.28]). Sleep duration PRS was associated with reduced MCI risk among short and normal sleepers, while among long sleepers it was associated with reduced global cognitive function and with increased MCI risk (OR = 1.40, 95% CI [1.10, 1.78]). Furthermore, adjustment of analyses for the measured sleep phenotypes and APOE-ε4 allele had minor effects on the PRS associations with the cognitive outcomes. INTERPRETATION: Genetic measures underlying insomnia, daytime sleepiness, and sleep duration are associated with MCI risk. Genetic and self-reported sleep duration interact in their effect on MCI. FUNDING: Described in Acknowledgments.