Josef Coresh, MD, PhD

Purpose The Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study is a randomized clinical trial designed to determine the effects of a best-practice hearing intervention versus a successful aging health education control intervention on cognitive decline among community-dwelling older adults with untreated mild-to-moderate hearing loss. We describe the baseline audiologic characteristics of the ACHIEVE participants. Method Participants aged 70–84 years (N = 977; Mage = 76.8) were enrolled at four U.S. sites through two recruitment routes: (a) an ongoing longitudinal study and (b) de novo through the community. Participants underwent diagnostic evaluation including otoscopy, tympanometry, pure-tone and speech audiometry, speech-in-noise testing, and provided self-reported hearing abilities. Baseline characteristics are reported as frequencies (percentages) for categorical variables or …

Background Limited data exist regarding risk factors for aortic stenosis (AS). The plasma proteome is a promising phenotype for discovery of novel biomarkers and potentially causative mechanisms. Objectives The aim of this study was to discover novel biomarkers with potentially causal associations with AS. Methods We measured 4,877 plasma proteins (SomaScan aptamer-affinity assay) among ARIC (Atherosclerosis Risk In Communities) study participants in mid-life (visit 3 [V3]; n = 11,430; age 60 ± 6 years) and in late-life (V5; n = 4,899; age 76 ± 5 years). We identified proteins cross-sectionally associated with aortic valve (AV) peak velocity (AVmax) and dimensionless index by echocardiography at V5 and with incident AV-related hospitalization after V3 with the use of multivariable linear and Cox proportional hazard regression. We assessed associations of candidate proteins with changes in AVmax over …

This study investigates correlates of anti-S1 antibody response following COVID-19 vaccination in a U.S. population-based meta-cohort of adults participating in longstanding NIH-funded cohort studies. Anti-S1 antibodies were measured from dried blood spots collected between February 2021-August 2022 using Luminex-based microsphere immunoassays. Of 6245 participants, mean age was 73 years (range, 21-100), 58% were female, and 76% were non-Hispanic White. Nearly 52% of participants received the BNT162b2 vaccine and 48% received the mRNA-1273 vaccine. Lower anti-S1 antibody levels are associated with age of 65 years or older, male sex, higher body mass index, smoking, diabetes, COPD and receipt of BNT16b2 vaccine (vs mRNA-1273). Participants with a prior infection, particularly those with a history of hospitalized illness, have higher anti-S1 antibody levels. These results suggest that …

BackgroundPre-pregnancy obesity, diabetes and hypertension are prevalent among reproductive-age women in the US and are associated with adverse maternal and neonatal outcomes. While prenatal care mitigates these risks, many individuals do not receive adequate prenatal care. We evaluated the incidence and timing of prenatal care initiation among women with pre-pregnancy cardiometabolic risk factors.MethodsUsing data from the National Vital Statistics System between 2017-2019 (n= 13,460,936), we compared timing of prenatal care among self-reported race/ethnicity groups, stratified by maternal cardiometabolic risk factors.ResultsPrevalence of pre-pregnancy obesity, diabetes, and hypertension were 28.0%, 0.9%, and 1.9%, respectively. Most individuals initiated prenatal care in the first trimester. Individuals who identified as Non-Hispanic Native Hawaiian and Other Pacific Islander (NHOPI) and …

Background: Plasma proteins, directly secreted from tumor cells or a result of the body’s response to a tumor, may have utility for early detection. We aimed to identify plasma protein combinations that predict prediagnostic cancers in a prospective study. Methods: We sampled from 8,186 ARIC study participants without a cancer diagnosis at blood draw and with 4,877 log2-transformed proteins measured by SomaScan. We selected as cases those diagnosed within 5 years after blood draw and were registry/medical record confirmed. We selected as controls those who never had a cancer history by 2015 and did not die of cancer. Participants with possible liver, kidney, or inflammatory conditions were excluded (eGFR-cr<30, top 1% of plasma AST, ALT, CRP). Highly correlated proteins (r>±0.75), abundant or known markers (albumin, CRP, PSA), and proteins with wide log2-transformed distributions (SD>1 and >10 …

Rationale & ObjectiveTubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD.Study DesignProspective cohort (ARIC) and case-cohort (MESA and REGARDS).Setting & ParticipantsAdults with eGFR ≥60 mL/min/1.73m2 and without diabetes in the ARIC, REGARDS, and MESA studies.ExposureBaseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1 (KIM-1), epidermal growth factor (EGF), and chitinase-3-like protein 1 (YKL-40).OutcomeIncident CKD or ESKD (end-stage kidney disease).Analytical ApproachMultivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all three cohorts.Results872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 …

Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer's disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole genome sequencing of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European American (EA) ancestry group compared to those of Hispanic American (HA), African American (AA), and East Asian (EAS) ancestry. Further, we identified two genes (CFHR1 and LRP6) that harbor multiple rare, putatively deleterious variants associated with mLOY susceptibility, show that subsets of human hematopoietic stem cells are enriched for activity of mLOY susceptibility variants, and that certain alleles on chromosome Y are more likely to be lost than others.

Background Hearing loss is linked to loneliness and social isolation, but evidence is typically based on self-reported hearing. This study quantifies the associations of objective and subjective hearing loss with loneliness and social network characteristics among older adults with untreated hearing loss. Methods This study uses baseline data (N = 933) from the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study. Hearing loss was quantified by the better ear, speech-frequency pure tone average (PTA), Quick Speech-in-Noise test, and hearing-related quality of life. Outcomes were validated measures of loneliness and social network characteristics. Associations were assessed by Poisson, negative binomial, and linear regression adjusted for demographic, health, and study design characteristics. Results Participants were mean of 76.8 (4.0 …