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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.

BackgroundThe availability of whole-genome sequencing data in large studies has enabled the assessment of coding and noncoding variants across the allele frequency spectrum for their associations with blood pressure.MethodsWe conducted a multiancestry whole-genome sequencing analysis of blood pressure among 51 456 Trans-Omics for Precision Medicine and Centers for Common Disease Genomics program participants (stage-1). Stage-2 analyses leveraged array data from UK Biobank (N=383 145), Million Veteran Program (N=318 891), and Reasons for Geographic and Racial Differences in Stroke (N=10 643) participants, along with whole-exome sequencing data from UK Biobank (N=199 631) participants.ResultsTwo blood pressure signals achieved genome-wide significance in meta-analyses of stage-1 and stage-2 single variant findings (P

Racial residential segregation is associated with multiple adverse health outcomes in Black individuals. Yet, the influence of structural racism and racial residential segregation on brain aging is less understood. In this study, we investigated the association between cumulative exposure to racial residential segregation over 25 years (1985-2010) in young adulthood, as measured by the Getis-Ord Gi* statistic, and year 25 measures of brain volume (cerebral, gray matter, white matter, and hippocampal volumes) in midlife. We studied 290 Black participants with available brain imaging data who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a prospective cohort study. CARDIA investigators originally recruited 2,637 Black participants aged 18-30 years from 4 field centers across the United States. We conducted analyses using marginal structural models, incorporating inverse probability of treatment weighting and inverse probability of censoring weighting. We found that compared with low/medium segregation, greater cumulative exposure to a high level of racial residential segregation throughout young adulthood was associated with smaller brain volumes in general (e.g., for cerebral volume, β = -0.08, 95% confidence interval: -0.15, -0.02) and with a more pronounced reduction in hippocampal volume, though results were not statistically significant. Our findings suggest that exposure to segregated neighborhoods may be associated with worse brain aging.

BackgroundLittle is known about long-term lipid variability in young adulthood in relation to cognitive function and brain integrity in midlife.MethodWe studied 3 328 adults from the Coronary Artery Risk Development in Young Adults. We defined low- and high-density lipoprotein (LDL and HDL) variability as the intraindividual standard deviation of lipid measurements over 20 years of young adulthood (1985-2005). Cognitive tests were administered in 2010. Brain scans were performed in 2010 on 714 participants. To facilitate comparison, cognitive tests and brain metrics were z-scored.ResultsMean age at baseline was 25.4 years. Higher 20-year LDL variability was associated with worse verbal memory in midlife (β = -0.25, 95% CI: -0.42, -0.08), adjusted for important covariates. Higher 20-year HDL variability was associated with worse processing speed in midlife (β = -0.80, 95% CI: -1.18, -0.41) and brain integrity, for example, smaller total brain volume (β = -0.58, 95% CI: -0.82, -0.34) and worse total brain fractional anisotropy (β = -1.13, 95% CI: -1.87, -0.39).ConclusionsHigher long-term lipid variability in adulthood was associated with worse cognition and brain integrity in midlife, in a relatively young cohort.

In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS is selected by optimizing the coefficient of variation (CV) across estimated effect sizes from multiple potential PRS using the same GWAS, after which the 3 trait-specific PRSs are combined via an unweighted sum called "PRSsum", forming the HTN-PRS. The HTN-PRS is associated with both prevalent and incident hypertension at 4-6 years of follow up. This association is further confirmed in age-stratified analysis. In an independent biobank of 40,201 individuals, the HTN-PRS is confirmed to be predictive of increased risk for coronary artery disease, ischemic stroke, type 2 diabetes, and chronic kidney disease.

ObjectiveIncome volatility presents a growing public health threat. To our knowledge, no previous study examined the relationship among income volatility, cognitive function, and brain integrity.MethodsWe studied 3,287 participants aged 23-35 years in 1990 from the Coronary Artery Risk Development in Young Adults prospective cohort study. Income volatility data were created using income data collected from 1990 to 2010 and defined as SD of percent change in income and number of income drops ≥25% (categorized as 0, 1, or 2+). In 2010, cognitive tests (n = 3,287) and brain scans (n = 716) were obtained.ResultsAfter covariate adjustment, higher income volatility was associated with worse performance on processing speed (β = -1.09, 95% confidence interval [CI] -1.73 to -0.44) and executive functioning (β = 2.53, 95% CI 0.60-4.50) but not on verbal memory (β = -0.02, 95% CI -0.16 to 0.11). Similarly, additional income drops were associated with worse performance on processing speed and executive functioning. Higher income volatility and more income drops were also associated with worse microstructural integrity of total brain and total white matter. All findings were similar when restricted to those with high education, suggesting reverse causation may not explain these findings.ConclusionIncome volatility over a 20-year period of formative earning years was associated with worse cognitive function and brain integrity in midlife.

Objectives:To examine the association between diabetes and cognitive function within U.S. Hispanics/Latinos of Central American, Cuban, Dominican, Mexican, Puerto Rican, and South American background. Method: This cross-sectional study included 9,609 men and women (mean age = 56.5 years), who are members of the Hispanic Community Health Study/Study of Latinos. We classified participants as having diabetes, prediabetes, or normal glucose regulation. Participants underwent a neurocognitive battery consisting of tests of verbal fluency, delayed recall, and processing speed. Analyses were stratified by Hispanic/Latino subgroup. Results: From fully adjusted linear regression models, compared with having normal glucose regulation, having diabetes was associated with worse processing speed among Cubans (β = -1.99; 95% CI [confidence interval] = [-3.80, -0.19]) and Mexicans (β = -2.26; 95% CI = [-4.02, -0.51]). Compared with having normal glucose regulation, having prediabetes or diabetes was associated with worse delayed recall only among Mexicans (prediabetes: β = -0.34; 95% CI = [-0.63, -0.05] and diabetes: β = -0.41; 95% CI = [-0.79, -0.04]). No associations with verbal fluency. Discussion: The relationship between diabetes and cognitive function varied across Hispanic/Latino subgroup.

Background Despite the high burden of anxiety and hypertension in Hispanic/Latino adults, little is known about their association in this population. Purpose To examine the associations of anxiety symptoms with 6-year changes in blood pressure (BP) and incident hypertension in Hispanic/Latino adults. Methods We examined data from a probability sample of 10,881 Hispanic/Latino persons aged 18–74 who attended visits 1 (V1; 2008–2011) and 2 (V2; 2014–2017) of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a prospective cohort study. Anxiety symptoms were assessed at V1 using the 10-item Spielberger Trait Anxiety Scale (M = 17.1; Range = 10–40) and dichotomized using a cut-point of 20, the highest quartile in this cohort. BP was measured at both visits using a standardized protocol. Results Adults with elevated anxiety symptoms had a 1.02 mm Hg greater increase in systolic (p  = .02) and a 0.75 mm Hg greater increase in diastolic BP (p  = .02) over 6.1 years than those with lower symptoms, after adjusting for sociodemographic and clinical covariates. These associations differed by sex. Elevated anxiety was associated with a greater increase in systolic and diastolic BP in men only. Among persons without hypertension at V1 (N = 7,412), those with elevated anxiety symptoms at V1 had a 22% higher incidence of hypertension (p  = .02) 6.1 years later. Conclusions Our findings underscore the importance of screening for and treating elevated anxiety symptoms to help prevent hypertension. Further research on the role of sex and underlying mechanisms is warranted. [ABSTRACT FROM AUTHOR]

ObjectiveWe examined whether greater depressive symptoms were associated with domain-specific cognitive performance, change in cognition, and MRI markers of brain atrophy and subclinical cerebrovascular disease in a diverse sample of older adults from the Northern Manhattan Study.MethodsData were analyzed from the Northern Manhattan Study, a prospective cohort study of mostly Caribbean Hispanic, stroke-free, older adults. A total of 1,111 participants had baseline measures of depressive symptoms, measured as the Center of Epidemiological Studies-Depression Scale, MRI markers, and cognitive function. A Center of Epidemiological Studies-Depression score ≥16 was considered indicative of greater depressive symptoms. Multivariable linear and logistic regression models were used to examine the associations of interest.ResultsAt baseline, 22% of participants had greater depressive symptoms. Greater depressive symptoms were significantly associated with worse baseline episodic memory in models adjusted for sociodemographic, vascular risk factor, behavioral, and antidepressive medication variables (β [95% confidence interval] = -0.21 [-0.33 to -0.10], p = 0.0003). Greater depressive symptoms were also associated with smaller cerebral parenchymal fraction (β [95% confidence interval] = -0.56 [-1.05 to -0.07], p = 0.02) and increased odds of subclinical brain infarcts (odds ratio [95% confidence interval] = 1.55 [1.00-2.42], p = 0.05), after adjustment for sociodemographic, behavioral, and vascular risk factor variables. Greater depressive symptoms were not significantly associated with white matter hyperintensity volume, hippocampal volume, or change in cognition over an average of 5 years. Results were unchanged when stabilized inverse probability weights were applied to address selective attrition during the study period.ConclusionsIn this sample of mostly Caribbean Hispanic, stroke-free, older adults, greater depressive symptoms were associated with worse episodic memory, smaller cerebral volume, and silent infarcts.

BackgroundLow heart rate variability (HRV), a marker of cardiac autonomic dysfunction, has been associated with major risk factors of cognitive impairment. Yet, the direct association of HRV with cognitive function remains relatively unexplored, particularly in midlife.MethodsIn 2005, 2 measures of short-term HRV, the SD of normal-to-normal intervals (SDNN) and the root mean square of successive differences (RMSSD), were calculated for participants of the Coronary Artery Risk Development in Young Adults study, and then categorized into quartiles. Five years later, 3 cognitive tests were administered for verbal memory ("Rey Auditory-Verbal Learning Test", RAVLT, range 0-15), processing speed ("Digit Symbol Substitution Test", DSST, range 0-133), and executive function ("Stroop interference").ResultsTwo thousand one hundred and eighteen participants (57.7% female, 42.2% Black) with a mean baseline age of 45.3 years were included in this analysis. In demographic-adjusted models, compared to participants with quartile 1 SDNN (lowest quartile), participants in the upper quartiles of SDNN scored better on the DSST (quartile 4: β = 1.83 points better, P = 0.03; and quartile 3: β = 1.95 points better, P = 0.03) and on the stroop (quartile 3: β = 1.19 points better, P < 0.05; and quartile2: β = 1.44 points better, P = 0.02). After adjusting for behavioral and cardiovascular risk factors, higher quartile SDNN remained significantly associated with better stroop score (quartile 3: β = 1.21 points better, P = 0.04; and quartile 2: β = 1.72 points better, P < 0.01) but not with DSST. There was no association between quartile of RMSSD and cognitive function, from fully adjusted models.ConclusionsOur findings suggest that higher quartile SDDN is associated with better executive function in midlife, above, and beyond cardiovascular risk factors.

BackgroundWalking speed is associated with functional status and all-cause mortality. Yet the relationship between walking speed and stroke, also a leading cause of disability, remains poorly understood, especially in older Latino adults who suffer from a significant burden of stroke.MethodsA total of 1,486 stroke-free participants from the Sacramento Area Latino Study on Aging, aged 60 and older at baseline in 1998-1999, were followed annually through 2010. Participants reported their usual walking speed outdoors which was classified into slow, medium, or fast. We also assessed timed tandem walk ability (unable or eight or more errors vs less than eight errors). We ascertained three incident stroke endpoints: total stroke, nonfatal stroke, and fatal stroke. Using Cox proportional hazards models, we estimated hazard ratios (HRs) for stroke at different walking speed and timed tandem walk categories.ResultsOver an average of 6 years of follow-up (SD = 2.8), the incidence rate of total strokes was 23.2/1,000 person-years for slow walkers compared to 15.6/1,000 person-years for medium walkers, and 7.6/1,000 person-years for fast walkers. In Cox models adjusted for sociodemographics, cardiovascular risk, cognition and functional status, and self-rated health, the hazard of total stroke was 31% lower for medium walkers (HR: 0.69, 95% confidence interval [CI]: 0.47, 1.02) and 56% lower for fast walkers (HR: 0.44, 95% CI: 0.24, 0.82) compared with slow walkers. We found similar associations with timed tandem walk ability (fully adjusted HR: 0.66, 95% CI: 0.45, 0.98).ConclusionsOur findings suggest perceived walking speed captures more than self-rated health alone and is a strong risk factor for stroke risk in Latino older adults.

IntroductionThe relationship between low income and worse health outcomes is evident, yet its association with cognitive outcomes is less explored. Most studies have measured income at one time and none have examined how sustained exposure to low income influences cognition in a relatively young cohort. This study examined the effect of sustained poverty and perceived financial difficulty on cognitive function in midlife.MethodsIncome data were collected six times between 1985 and 2010 for 3,383 adults from the Coronary Artery Risk Development in Young Adults prospective cohort study. Sustained poverty was defined by the percentage of time participants' household income was

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Longitudinal change in income is crucial in explaining cardiovascular health inequalities. However, there is limited evidence for cardiovascular disease (CVD) risk associated with income dynamics over time among individuals with type 2 diabetes (T2D). Methods: Using a nationally representative sample from the Korean National Health Insurance Service database, 1 528 108 adults aged 30–64 with T2D and no history of CVD were included from 2009 to 2012 (mean follow-up of 7.3 years). Using monthly health insurance premium information, income levels were assessed annually for the baseline year and the four preceding years. Income variability was defined as the intraindividual standard deviation of the percent change in income over 5 years. The primary outcome was a composite event of incident fatal and nonfatal CVD (myocardial infarction, heart failure, and stroke) using insurance claims. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated after adjusting for potential confounders. Results: High-income variability was associated with increased CVD risk (HRhighest vs. lowest quartile 1.25, 95% CI 1.22–1.27; Ptrend <.001). Individuals who experienced an income decline (4 years ago vs. baseline) had increased CVD risk, which was particularly notable when the income decreased to the lowest level (i.e. Medical Aid beneficiaries), regardless of their initial income status. Sustained low income (i.e. lowest income quartile) over 5 years was associated with increased CVD risk (HRn = 5 years vs. n = 0 years 1.38, 95% CI 1.35–1.41; Ptrend <.0001), whereas sustained high income (i.e. highest income quartile) was associated with decreased CVD risk (HRn = 5 years vs. n = 0 years 0.71, 95% CI 0.70–0.72; Ptrend <.0001). Sensitivity analyses, exploring potential mediators, such as lifestyle-related factors and obesity, supported the main results. Conclusions: Higher income variability, income declines, and sustained low income were associated with increased CVD risk. Our findings highlight the need to better understand the mechanisms by which income dynamics impact CVD risk among individuals with T2D. Structured Graphical Abstract This study investigates the association between income dynamics over five years and incident composite cardiovascular outcomes in non-elderly individuals with type 2 diabetes. Our graphical abstract highlights significant associations between cardiovascular risk and income metrics, including income variability (standard deviation of percent change), changes in income status (rise and decline), and cumulative number of years in low- or high-income status. [ABSTRACT FROM AUTHOR]

Purpose: To determine whether high-sensitivity C-reactive protein (hsCRP) is associated with incident Metabolic Syndrome (MetS) among U.S. Hispanic/Latino adults. Patients and Methods: The Hispanic Community Health Study/Study of Latinos is a longitudinal observational cohort assessing cardiovascular health among diverse U.S. Hispanic/Latino adults. hsCRP was measured at visit 1 (2008–2011) and classified as low, moderate, or high, based on the Centers for Disease Control and Prevention and American Heart Association (CDC/AHA) guidelines. All MetS components [abdominal obesity, triglycerides, high-density lipoprotein (HDL) cholesterol, blood pressure, and fasting glucose] were measured at visit 1 and visit 2 (2014–2017). MetS was defined as the presence of three or more components based on the 2005 definition from the modified Third Report of the National Cholesterol Education Program Adult Treatment Panel (modified NCEP ATP III). Participants free of MetS at visit 1 and with complete data on hsCRP and all MetS components were included (n = 6121 participants). We used Poisson regression analysis to determine whether hsCRP was associated with incident MetS after adjusting for demographic, behavioral, and clinical factors. All analyses accounted for the complex survey design of the study. Results: In fully adjusted models, moderate versus low hsCRP was associated with a 33% increased risk of MetS [incidence rate ratio (IRR): 1.33, 95% confidence interval (CI): 1.10–1.61], while high versus low hsCRP was associated with a 89% increased risk of MetS (IRR: 1.89, 95% CI: 1.58–2.25). Conclusions: Greater levels of hsCRP were associated with new onset of MetS in a diverse sample of U.S. Hispanic/Latino adults. Results suggest that hsCRP may be an independent risk factor for MetS. [ABSTRACT FROM AUTHOR]

ObjectiveTo examine the influence of neighbourhood socioeconomic position (NSEP) on development of diabetes over time.DesignA longitudinal cohort study.SettingThe data reported were from the Sacramento Area Latino Study on Aging, a longitudinal study of the health of 1789 older Latinos.ParticipantsCommunity-dwelling older Mexican Americans residing in the Sacramento Metropolitan Statistical Area.Main outcomeMultistate Markov regression were used to model transitions through four possible states over time: 1=normal; 2=pre-diabetic; 3=diabetic; and 4=death without diabetes.ResultsAt baseline, nearly 50% were non-diabetic, 17.5% were pre-diabetic and nearly 33% were diabetic. At the end of follow-up, there were a total of 824 people with type 2 diabetes. In a fully adjusted MSM regression model, among non-diabetics, higher NSEP was not associated with a transition to pre-diabetes. Among non-diabetics, higher NSEP was associated with an increased risk of diabetes (HR=1.66, 95% CI 1.14 to 2.42) and decreased risk of death without diabetes (HR: 0.56, 95% CI 0.33 to 0.96). Among pre-diabetics, higher NSEP was significantly associated with a transition to non-diabetic status (HR: 1.22, 95% CI 0.99 to 1.50). Adjusting for BMI, age, education, physical activity, smoking, alcohol consumption, medical insurance and nativity did not affect this relationship.ConclusionsOur findings show that high NSEP poses higher risk of progression from normal to diabetes compared with a lower risk of death without diabetes. This work presents a possibility that these associations are modified by nativity or culture.

Using data from the National Health and Nutrition Examination Survey (2001–2018; N = 19,602), this study examined whether ultra-processed food (UPF) consumption is associated with cardiometabolic health (obesity, hypertension, high cholesterol, and diabetes), among White, Black, Hispanic, and Asian Americans (AA) US adults 50 or older. Diet was assessed using 24 hour dietary recall. NOVA dietary classification system was used to calculate the percentage of caloric intake derived from UPFs. Cardiometabolic information was assessed through physical examination, blood tests, and self-reported medication information. A median of 54% (IQR: 40%, 68%) of caloric intake was attributed to UPFs and was lowest for AAs (34%, IQR: 20%, 49%) and highest for White adults (56%; IQR: 42, 69%). In multivariable adjusted models, UPF consumption was associated with greater odds of obesity, high cholesterol, and diabetes. UPF consumption is associated with poor cardiometabolic health among all US older adults. For AAs, UPFs may be particularly obesogenic. [ABSTRACT FROM AUTHOR]