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Summary: In women with HIV, higher activation and exhaustion of CD4+ T cells were associated with risk of non-HIV-related mortality during a median of 13.3 years of follow-up, independent of baseline demographic, behavioral, HIV-related, and cardiometabolic factors and longitudinal HIV disease progression.Background: Dysregulation of adaptive immunity is a hallmark of human immunodeficiency virus (HIV) infection that persists on antiretroviral therapy (ART). Few long-term prospective studies have related adaptive immunity impairments to mortality in HIV, particularly in women.Methods: Among 606 women with HIV in the Women's Interagency HIV Study, peripheral blood mononuclear cells collected from 2002 to 2005 underwent multiparameter flow cytometry. Underlying cause of death was ascertained from the National Death Index up to 2018. We examined associations of CD4+ and CD8+ T-cell activation (%CD38+HLA-DR+), senescence (%CD57+CD28-), exhaustion (%PD-1+), and nonactivation/normal function (%CD57-CD28+) with natural-cause, HIV-related, and non-HIV-related mortality.Results: At baseline, median participant age was 41, and 67% were on ART. Among 100 deaths during a median of 13.3 years follow-up, 90 were natural-cause (53 non-HIV-related, 37 HIV-related). Higher activation and exhaustion of CD4+ T cells were associated with risk of natural-cause and non-HIV-related mortality, adjusting for age, demographic, behavioral, HIV-related, and cardiometabolic factors at baseline. Additional adjustment for time-varying viral load and CD4+ T-cell count did not attenuate these associations. CD8+ T-cell markers were not associated with any outcomes adjusting for baseline factors.Conclusions: Persistent CD4+ T-cell activation and exhaustion may contribute to excess long-term mortality risk in women with HIV, independent of HIV disease progression. [ABSTRACT FROM AUTHOR]

Background: Associations of adult height with cardiometabolic and pulmonary traits have been studied in majority European ancestry populations using Mendelian randomization and polygenic risk score (PRS) analysis. The standard PRS approach entails creating a PRS for height using variants identified in prior genome-wide association studies (GWAS). It is unclear how well the standard PRS approach performs in non-European populations and whether height-trait associations observed in Europeans are also observed in other populations.Methods: In the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we used: (i) the standard approach to create a PRS for height (PRS1) and (ii) a novel approach to optimize the selection of variants from previously established height association loci to better explain height in HCHS/SOL (PRS2). We also estimated the extent to which PRS-trait associations were independent or mediated by the PRS effect on height.Results: In 7539 women and 5245 men, PRS1 and PRS2 explained 9 and 29% of the variance in measured height, respectively. Both PRS1 and PRS2 were associated with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), FEV1/ FVC ratio, total cholesterol and 2-hour oral glucose-tolerance test insulin levels. Additionally, PRS2 was associated with estimated glomerular filtration rate and ankle brachial index. Both PRS1 and PRS2 had pleiotropic associations with FEV1/ FVC ratio in mediation analyses.Conclusions: Associations of polygenic scores of height with measures of lung function and cholesterol were consistent with those observed in prior studies of majority European ancestry populations. Mediation analysis may augment standard PRS approaches to disentangle pleiotropic and mediated effects. [ABSTRACT FROM AUTHOR]

Background: Hispanics/Latinos are at increased risk for cardiovascular disease and cognitive decline and dementias. High blood pressure (BP) has been implicated in both stroke and dementias. Associations between BP and cognition among diverse Latinos are still unpublished.Objective: We examined associations between cognition and four BP based measures among diverse Hispanics/Latinos. We hypothesized that higher BP, particularly systolic pressure, and increased arterial stiffness (i.e., pulse pressure), would be associated with lower cognitive function.Methods: We used baseline (2008-2011) Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 9,019; ages 45-74 years) data to examine cognition in relation to BP measures.Results: In age, sex, and education adjusted models, systolic, pulse, and mean arterial pressure were consistently negatively associated with executive function, psychomotor speed and sustained attention, verbal episodic learning and memory, speech fluency, and mental status measures. These associations were attenuated but remained statistically significant in fully adjusted models.Conclusion: Among middle-aged and older diverse Hispanics/Latinos, we found modest but consistent associations between indicators of arterial stiffness, and compromised blood flow and lower cognitive function. Clinical management and public health interventions to raise awareness and enhance BP management beginning in midlife could reduce disparities and improve population health by reducing cognitive decline burdens. [ABSTRACT FROM AUTHOR]

Background: Healthful diet quality has been associated with a lower risk of metabolic syndrome (MetS) in several populations, but reports on Hispanic and Latino cohorts, grouped or by ethnic background, have been limited and inconsistent.Objective: We aimed to examine diet quality by using the 2010 Alternate Healthy Eating Index [(AHEI) range: 0-110, lowest to highest quality] and its cross-sectional association with MetS and its cardiometabolic components across 6 Hispanic and Latino backgrounds.Methods: We studied 12,406 US Hispanics and Latinos, aged 18-74 y and free of diabetes, from the multicenter, population-based Hispanic Community Health Study/Study of Latinos cohort. Food and nutrients were assessed from two 24-h recalls. MetS was defined by using the 2009 harmonized guidelines. Complex survey procedures were used in multivariable-adjusted linear regression models to test the association of the AHEI with continuous markers and in logistic regression models with MetS as an outcome.Results: The prevalence of MetS was 24.2%. Overall, Hispanics and Latinos had low scores for intakes of sugar-sweetened beverages and fruit juices, whole grains, and fruit and favorable scores for trans fats and nuts and legumes, according to AHEI criteria. Adjusted mean AHEI and its individual components differed by ethnic background (P < 0.001), ranging from 43.0 for Puerto Ricans to 52.6 for Mexicans. Overall, adjusted odds (95% CIs) of having MetS were 22% (9%, 33%) lower for each 10-unit increase in AHEI. This association was modified by ethnic background (P-interaction = 0.03), with significantly lower odds observed only for Mexicans (30%; 95% CIs: 13%, 44%) and Central Americans (42%; 95% CIs: 9%, 64%) for each 10-unit increase in AHEI. AHEI was inversely associated with waist circumference, blood pressure, and glucose among Mexicans and Puerto Ricans and with triglycerides among Mexicans only, and positively associated with HDL cholesterol among Puerto Ricans and Central Americans (all P < 0.05).Conclusions: Diet quality differed by Hispanic or Latino background. Although healthier diet quality was associated with lower odds of MetS in the overall Hispanic and Latino cohort, the association of AHEI and cardiometabolic factors varied by ethnic background. Nutrition-related research and interventions among ethnically diverse groups should consider individual ethnic backgrounds to optimally address diet quality and cardiometabolic health. This trial was registered at clinicaltrials.gov as NCT02060344. [ABSTRACT FROM AUTHOR]

Objectives To ascertain whether older adults with extensive disease but relative vigor (adapters) shorten the period at the end of life in which they live with morbidity (compress morbidity). Design Prospective, community-based cohort study in four U.S. cities. Setting Cardiovascular Health Study. Participants Individuals aged 65 and older. Measurements Participants were categorized into three groups according to extent of disease (assessed noninvasively), vigor, and frailty (expected agers (n = 3,528, extent of disease similar to vigor and frailty-reference group), adapters (n = 882, higher disease but vigorous), and prematurely frail (n = 855, lower disease but frail)) and compared according to years of able life ( YAL), years of self-reported healthy life ( YHL), and mortality using multivariable regression and survival analysis. Results After adjustment, adapters had 0.97 (95% confidence interval ( CI) = 0.60-1.33) more YAL and 0.54 (95% CI = 0.19-0.90) more YHL than expected agers, and those who were prematurely frail had −0.99 (95% CI = −1.36 to −0.62) fewer YAL and −0.53 (95% CI = −0.89 to −0.17) fewer YHL than expected agers. Adapters had 0.9 more and prematurely frail had 1.5 fewer years of total life than expected agers ( P < .001). Adapters spent 55% of their remaining life able and healthy, those who were prematurely frail spent 37%, and of expected agers spent 47% ( P < .001). Conclusion Despite similar levels of disease burden, older adults who were more vigorous appeared to compress morbidity and live longer. Older adults with higher frailty lengthened morbidity and had greater mortality. Adaptive factors may compress morbidity and decrease mortality. [ABSTRACT FROM AUTHOR]

Background: Older adults have a high prevalence of postload hyperglycemia. Postload glucose has shown more robust associations with cardiovascular disease (CVD) and death than fasting glucose, but data in the oldest old are sparse.Methods: Fasting and 2-hour postload glucose were measured in community-dwelling older adults, mean age 78, at the 1996-1997 follow-up visit of the Cardiovascular Health Study. We evaluated their associations with atherosclerotic CVD (ASCVD) and mortality using standard Cox regression and competing-risks analyses and assessed improvement in prediction-model discrimination with the c-statistic.Results: Among 2,394 participants without treated diabetes and available data on glycemic measures, there were 579 ASCVD events and 1,698 deaths during median follow-up of 11.2 years. In fully adjusted models, both fasting and 2-hour glucose were associated with ASCVD (HR per SD, 1.13 [1.03-1.25] and 1.17 [1.07-1.28], respectively) and all-cause mortality (HR 1.12 [1.07-1.18] and 1.14 [1.08-1.20]). After mutual adjustment, however, the associations for fasting glucose with both outcomes were abolished, but those for postload glucose were largely unchanged. Consistent findings were observed for ASCVD in competing-risks models.Conclusion: In adults surviving to advanced old age, postload glucose was associated with ASCVD and mortality independently of fasting glucose, but fasting glucose was not associated with these outcomes independently of postload glucose. These findings affirm the robust association of postload glucose with ASCVD and death late in life. [ABSTRACT FROM AUTHOR]

Background: Sedentary behavior is recognized as a distinct construct from lack of moderate-vigorous physical activity and is associated with deleterious health outcomes. Previous studies have primarily relied on self-reported data, whereas data on the relationship between objectively measured sedentary time and cardiometabolic biomarkers are sparse, especially among US Hispanics/Latinos.Methods and Results: We examined associations of objectively measured sedentary time (via Actical accelerometers for 7 days) and multiple cardiometabolic biomarkers among 12 083 participants, aged 18 to 74 years, from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Hispanics/Latinos of diverse backgrounds (Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American) were recruited from 4 US cities between 2008 and 2011. Sedentary time (<100 counts/min) was standardized to 16 hours/d of wear time. The mean sedentary time was 11.9 hours/d (74% of accelerometer wear time). After adjustment for moderate-vigorous physical activity and confounding variables, prolonged sedentary time was associated with decreased high-density lipoprotein cholesterol (P=0.04), and increased triglycerides, 2-hour glucose, fasting insulin, and homeostatic model assessment of insulin resistance (all P<0.0001). These associations were generally consistent across age, sex, Hispanic/Latino backgrounds, and physical activity levels. Even among individuals meeting physical activity guidelines, sedentary time was detrimentally associated with several cardiometabolic biomarkers (diastolic blood pressure, high-density lipoprotein cholesterol, fasting and 2-hour glucose, fasting insulin and homeostatic model assessment of insulin resistance; all P<0.05).Conclusions: Our large population-based, objectively derived data showed deleterious associations between sedentary time and cardiometabolic biomarkers, independent of physical activity, in US Hispanics/Latinos. Our findings emphasize the importance of reducing sedentary behavior for the prevention of cardiometabolic diseases, even in those who meet physical activity recommendations. [ABSTRACT FROM AUTHOR]