Healthy Aging In Neighborhoods of Diversity Across the Life Span (HANDLS)

National Institute On Aging

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Abstract

The HANDLS study is an epidemiologic, interdisciplinary, longitudinal study of a baseline representative sample of African Americans and whites between 30-64 years of age recruited as a fixed cohort of participants by household screenings from an area probability sample of twelve census segments in Baltimore City. The HANDLS design is an area probability sample of Baltimore based on the 2000 Census. Using this methodology, working with survey statisticians we chose 12 neighborhoods to meet race by SES by age distribution of the prospective cohort because they were likely to yield representative distributions of Baltimore City with sufficient individuals to fill the sampling design based. Within the 13 neighborhoods, housing units were selected with a known non-zero chance of selection. The addresses were screened for individuals who meet the age-gender-race-poverty sample size, and those were chosen to be included in the sample using a probability sampling method. From these probabilities, we can compute weights to adjust for unequal probabilities of selection. These weights will be needed to compute estimates that combine subjects across any of the age-gender-race-poverty group. The poverty status delimiter is 125% poverty based on 125% of the 2004 Health and Human Services Poverty Guidelines. In the initial examination and recruitment study data was collected in two parts. The first part consisted of an in-home interview that included questionnaires about the participants health status, health service utilization, psychosocial factors, nutrition, neighborhood characteristics, and demographics. The second part was collected on the medical research vehicles and included medical history and physical examination, dietary recall, cognitive evaluation, psychophysiology assessments including heart rate variability, arterial thickness, carotid ultrasonography, assessments of muscle strength and bone density, and laboratory measurements (blood chemistries, hematology, and biomaterials). Using mobile medical research vehicles, we visit each census tract for 4 months and we will re-visit every census tract in a 3.5-year cycle. HANDLS completed its baseline examination wave in March 2009 with a final total accrual of 3720 participants. The cohort is comprised of African American (59%) and Whites (41%). Approximately 41% of the cohort reported a household income below the 125% poverty status delimiter. Of those below the 125% poverty delimiter, 13% were white and 28% African American. Of those above the 125% poverty delimiter, 28% were white and 31% African American. The mean age of the sample was 47.7 years at baseline. There were no significant age differences associated with sex or race. Participants below the 125% poverty delimiter were slightly younger than those above the delimiter. HANDLS medical examination rate was 75.2% comparable to the 75% examination rate for the National Health and Nutrition Examination Study (NHANES). Wave 3 examinations started in July 2009 and was completed in June 2013 with a show rate of 91%. The Wave 3 protocol in keeping with the longitudinal study design maintained many of the same study domains as the baseline wave 1 examination including: cognition, cardiovascular disease, nutrition, physical performance, psychology, health services, genomics (genetics and epigenetics), and molecular biomarkers of disease. This protocol also included new areas of study particularly focused on renal function, neuroanatomy, financial and health literacy. Wave 4 conducted from September 2013 through July 2017. The Wave 4 protocol included the addition of the EndoPAT as a measure of endothelial dysfunction, longitudinal assessment of carotid intimal thickness as well and the cognitive domain uses measures that are less dependent on literacy to assess executive function. The Home Visit Protocol developed to prevent the bias resulting from missing data from participants who have become home-bound over the course of the study is ongoing. Wave 5 will begin in September 2017 with new additions to the protocol including sensory testing (olfaction, vision, fundal imaging), microbiome and environmental exposure biomaterial collection. Notable findings this year include studies on differential gene expression by race in systemic arterial hypertension in women and the effect of perceived discrimination on renal function. African Americans (AAs) are disproportionately affected by hypertension and the incidence, prevalence, and severity of hypertension is highest among AA women. Previous data suggests that differential gene expression influences individual susceptibility to selected diseases. We hypothesized that this may affect health disparities in hypertension. We profiled mRNA expression levels in peripheral blood mononuclear cells (PBMCs) isolated from AA or white, normotensive or hypertensive females and identified thousands of mRNAs significantly and differentially-expressed by race and hypertension status. Profound gene expression differences were observed in AA hypertensive females compared with all other groups. AA hypertensive females have significantly elevated expression of inflammatory genes and pathways when compared to AA normotensive controls or white hypertensives. We next sought to understand the mechanism that contributes to differential gene expression patterns in AA hypertensive females. Considering microRNAs play important roles in modulating mRNA expression levels, we profiled global microRNA expression and observed 36 microRNAs that were significantly and differentially-expressed by race and hypertension status. We performed bioinformatic microRNA target prediction analyses to identify novel mRNA-microRNA pairs involved with inflammation-related pathways and which were also differentially-expressed by race. We identified several novel pairs, including MCL1/miR-20a-5p, APOL3/miR-4763-5p, PLD1/miR-4717-3p, and PLD1/miR-4709-3p, never associated with hypertension and we validated our predicted mRNA-microRNA interactions in primary endothelial cells. Altogether, we identified significant gene expression differences between AA and white hypertensive females and pinpointed novel mRNA-microRNA pairs differentially-expressed by hypertension and race. These novel findings enhance our understanding of hypertension in AA females and provide potential new avenues for therapeutic intervention. Perceived discrimination has been associated with psychosocial distress and adverse health outcomes. We examined associations of perceived discrimination measures with changes in kidney function in 1,620 HANDLS participants with preserved baseline kidney function (estimated glomerular filtration rate (eGFR) 60 ml/min/1.73m2) (662 Whites and 958 African-Americans (AA), aged 30-64 years). Self-reported perceived racial discrimination (PRD) and perceived gender discrimination (PGD) and a general measure of experience of discrimination (EOD) were examined in relation to baseline, follow-up and annual rate of change in eGFR. Perceived gender discrimination High vs. Low PGD was associated with a lower baseline eGFR in all models. Among White women, High EOD was associated with lower baseline eGFR, an effect that was strengthened in the full model. Overall, High vs. Low PGD was associated with lower follow-up eGFR. Among AA women, both PRD and PGD were linked to lower follow-up kidney function, an effect that was attenuated with covariate adjustment, indicating mediation through health-related, psychosocial and lifestyle factors. In contrast, EOD was not linked to follow-up eGFR in any of the sex by race groups. Perceived racial and gender discrimination are associated with poor kidney function assessed by glomerular filtration rate and the strength of associations differ by sex and race groups.