Premorbid physical activity and prognosis after incident myocardial infarction: the Atherosclerosis Risk in Communities Study.

BACKGROUND: High to moderate levels of physical activity (PA) are associated with low risk of incident cardiovascular disease. However, it is unclear whether the benefits of PA in midlife extend to cardiovascular health following myocardial infarction (MI) in later life. METHODS: Among 1,111 ARIC participants with incident MI during ARIC follow-up (mean age 73 [SD 9] years at MI, 54% men, 21% Black), PA on average 11.9 (SD 6.9) years prior to incident MI (premorbid PA) was evaluated as the average score of PA between visit 1 (1987-89) and visit 3 (1993-95) using a modified Baecke questionnaire. Total and domain-specific PA (sport, non-sport leisure, and work PA) was analyzed for associations with composite and individual outcomes of mortality, recurrent MI, and stroke after index MI using multivariable Cox models. RESULTS: During a median follow-up of 4.6 (IQI 1.0-10.5) years after incident MI, 823 participants (74%) developed a composite outcome. The 10-year cumulative incidence of the composite outcome was lower in the highest, as compared to the lowest tertile of premorbid total PA (56% vs. 70%, respectively). This association remained statistically significant even after adjusting for potential confounders (adjusted hazard ratio [aHR] 0.80 [0.67-0.96] for the highest vs. lowest tertile). For individual outcomes, high premorbid total PA was associated with a low risk of recurrent MI (corresponding aHR 0.64 [0.44, 0.93]). When domain-specific PA was analyzed, similar results were seen for sport and work PA. The association was strongest in the first year following MI (e.g., aHR of composite outcome 0.66 [95% CI 0.47, 0.91] for the highest vs. lowest tertile of total PA). CONCLUSIONS: Premorbid PA was associated positively with post-MI cardiovascular health. Our results demonstrate the additional prognostic advantages of PA beyond reducing the risk of incident MI.

Prevalence and Disparities in Telehealth Use Among US Adults Following the COVID-19 Pandemic: National Cross-Sectional Survey.

BACKGROUND: Telemedicine expanded during the COVID-19 pandemic, though use differed by age, sex, race or ethnicity, educational attainment, income, and location. It is unclear if high telehealth use or inequities persisted late into the pandemic. OBJECTIVE: This study aims to evaluate the prevalence of, inequities in, and primary reasons for telehealth visits a year after telemedicine expansion. METHODS: We used cross-sectional data from the 2022 Health Information National Trends Survey (HINTS 6), the first cycle with data on telemedicine. In total, 4830 English- and Spanish-speaking US adults (aged ≥18 years) were included in this study. The primary outcomes were telehealth visit attendance in the 12 months before March 7, 2022, to November 8, 2022, and the primary reason for the most recent telehealth visit. We evaluated sociodemographic and clinical predictors of telehealth visit attendance and the primary reason for the most recent telehealth visit through Poisson regression. Analyses were weighted according to HINTS 6 standards. RESULTS: We included 4830 participants (mean age 48.3, SD 17.5 years; 50.28% women; 65.21% White). Among US adults, 38.78% reported having a telehealth visit in the previous year. Telehealth visit attendance rates were similar across age, race or ethnicity, income, and urban versus rural location. However, individuals with a telehealth visit were less likely to live in the Midwest (adjusted prevalence ratio [aPR] 0.65, 95% CI 0.54-0.77), and more likely to be women (aPR 1.21, 95% CI 1.06-1.38), college graduates or postgraduates (aPR 1.24, 95% CI 1.05-1.46), covered by health insurance (aPR 1.56, 95% CI 1.08-2.26), and married or cohabitating (aPR 1.17, 95% CI 1.03-1.32), adjusting for sociodemographic characteristics, frequency of health care visits, and comorbidities. Among participants with a telehealth visit in the past year, the primary reasons for their most recent visit were minor or acute illness (32.15%), chronic disease management (21%), mental health or substance abuse (16.94%), and an annual exam (16.22%). Older adults were more likely to report that the primary reason for their most recent telehealth visit was for chronic disease management (aPR 2.08, 95% CI 1.33-3.23), but less likely to report that it was for a mental health or substance abuse issue (aPR 0.19, 95% CI 0.10-0.35), adjusting for sociodemographic characteristics and frequency of health care visits. CONCLUSIONS: Among US adults, telehealth visit attendance was high more than a year after telemedicine expansion and did not differ by age, race or ethnicity, income, or urban versus rural location. Telehealth could continue to be leveraged following COVID-19 to improve access to care and health equity.

Longitudinal plasma metabolome patterns and relation to kidney function and proteinuria in pediatric chronic kidney disease.

INTRODUCTION: Understanding plasma metabolome patterns in relation to changing kidney function in pediatric chronic kidney disease (CKD) is important for continued research for identifying novel biomarkers, characterizing biochemical pathophysiology, and developing targeted interventions. There is a limited number of studies of longitudinal metabolomics, and virtually none in pediatric CKD. METHODS: The Chronic Kidney Disease in Children (CKiD) study is a multi-institutional, prospective cohort that enrolled children aged six-months to 16-years with estimated glomerular filtration rate (eGFR) 30-90ml/min/1.73m2. Untargeted metabolomics profiling was performed on plasma samples from the baseline, two-, and four-year study visits. There were technologic updates in the metabolomic profiling platform used between the baseline and follow-up assays. Statistical approaches were adopted to avoid direct comparison of baseline and follow-up measurements.To identify metabolite associations with eGFR or urine protein:creatinine (UPCR) among all three timepoints, we applied linear mixed effects (LME) models. To identify metabolites associated with time, we applied LME models to the two- and four-year follow-up data. We applied linear regression analysis to examine associations between change in metabolite level over time (∆level) and change in eGFR (∆eGFR) and UPCR (∆UPCR). We reported significance based on both the False Discovery Rate (FDR) <0.05 and p<0.05. RESULTS: There were 1156 person-visits (N: baseline=626, 2-year=254, 4-year=276) included. There were 622 metabolites with standardized measurements at all three timepoints. In LME modeling, 406 and 343 metabolites associated with eGFR and UPCR at FDR<0.05 respectively. Among 530 follow-up person-visits, 158 metabolites showed differences over time at FDR<0.05. For participants with complete data at both follow-up visits (N=123), we report 35 metabolites with ∆level∼∆eGFR associations significant at FDR<0.05. There were no metabolites with significant ∆level∼∆UPCR associations at FDR<0.05. We report 16 metabolites with ∆level∼∆UPCR associations at p<0.05 and associations with UPCR in LME modeling at FDR<0.05. CONCLUSION: We characterized longitudinal plasma metabolomic patterns associated with eGFR and UPCR in a large pediatric CKD population. Many of these metabolite signals have been associated with CKD progression, etiology, and proteinuria in previous CKD Biomarkers Consortium studies. There were also novel metabolite associations with eGFR and proteinuria detected.

Hearing Impairment and Physical Activity and Physical Functioning in Older Adults: Baseline Results from the ACHIEVE Trial.

BACKGROUND: Hearing loss is associated with restricted physical activity (PA) and impaired physical functioning, yet the relationship between severity of hearing impairment (HI) and novel PA measures in older adults with untreated HI is not well understood. METHODS: Analyses included 845 participants aged ≥70 years (mean=76.6y) with a better-hearing ear pure-tone average (PTA) ≥30 and <70 dB in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study who wore an ActiGraph accelerometer for 7 days. Physical functioning measures included grip strength and the Short Physical Performance Battery (SPPB). Linear regression models estimated the association by HI level (moderate or greater [PTA≥40 dB] vs. mild [PTA<40 dB]) and continuous hearing with total daily activity counts, active minutes/day, activity fragmentation, grip strength, and gait speed. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) of poor performance on the SPPB (≤6) and its subtests (≤2). Mixed-effects models estimated differences by HI level in activity by time of day. RESULTS: Participants with moderate or greater HI had poorer physical functioning, particularly balance (OR=2.17, 95% CI=1.29-3.67), vs. those with mild impairment. There was no association of HI level with activity quantities or fragmentation. For diurnal patterns of activity, participants with moderate or greater HI had fewer activity counts in the afternoon (12:00pm-05:59pm). CONCLUSIONS: Older adults with worse hearing had shifted diurnal patterns and poorer balance performance. Exercise programs should be tailored to older adults with different levels of HI to maintain PA and physical functioning, particularly balance control.

Head Injury and Risk of Incident Ischemic Stroke in Community-Dwelling Adults.

BACKGROUND: While stroke is a recognized short-term sequela of traumatic brain injury, evidence about long-term ischemic stroke risk after traumatic brain injury remains limited. METHODS: The Atherosclerosis Risk in Communities Study is an ongoing prospective cohort comprised of US community-dwelling adults enrolled in 1987 to 1989 followed through 2019. Head injury was defined using self-report and hospital-based diagnostic codes and was analyzed as a time-varying exposure. Incident ischemic stroke events were physician-adjudicated. We used Cox regression adjusted for sociodemographic and cardiovascular risk factors to estimate the hazard of ischemic stroke as a function of head injury. Secondary analyses explored the number and severity of head injuries; the mechanism and severity of incident ischemic stroke; and heterogeneity within subgroups defined by race, sex, and age. RESULTS: Our analysis included 12 813 participants with no prior head injury or stroke. The median follow-up age was 27.1 years (25th-75th percentile=21.1-30.5). Participants were of median age 54 years (25th-75th percentile=49-59) at baseline; 57.7% were female and 27.8% were Black. There were 2158 (16.8%) participants with at least 1 head injury and 1141 (8.9%) participants with an incident ischemic stroke during follow-up. For those with head injuries, the median age to ischemic stroke was 7.5 years (25th-75th percentile=2.2-14.0). In adjusted models, head injury was associated with an increased hazard of incident ischemic stroke (hazard ratio [HR], 1.34 [95% CI, 1.12-1.60]). We observed evidence of dose-response for the number of head injuries (1: HR, 1.16 [95% CI, 0.97-1.40]; ≥2: HR, 1.94 [95% CI, 1.39-2.71]) but not for injury severity. We observed evidence of stronger associations between head injury and more severe stroke (National Institutes of Health Stroke Scale score ≤5: HR, 1.31 [95% CI, 1.04-1.64]; National Institutes of Health Stroke Scale score 6-10: HR, 1.64 [95% CI, 1.06-2.52]; National Institutes of Health Stroke Scale score ≥11: HR, 1.80 [95% CI, 1.18-2.76]). Results were similar across stroke mechanism and within strata of race, sex, and age. CONCLUSIONS: In this community-based cohort, head injury was associated with subsequent ischemic stroke. These results suggest the importance of public health interventions aimed at preventing head injuries and primary stroke prevention among individuals with prior traumatic brain injuries.

Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.

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.

Cross-Sectional Associations of Peripheral Hearing, Brain Imaging, and Cognitive Performance With Speech-in-Noise Performance: The Aging and Cognitive Health Evaluation in Elders Brain Magnetic Resonance Imaging Ancillary Study.

PURPOSE: Population-based evidence in the interrelationships among hearing, brain structure, and cognition is limited. This study aims to investigate the cross-sectional associations of peripheral hearing, brain imaging measures, and cognitive function with speech-in-noise performance among older adults. METHOD: We studied 602 participants in the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) brain magnetic resonance imaging (MRI) ancillary study, including 427 ACHIEVE baseline (2018-2020) participants with hearing loss and 175 Atherosclerosis Risk in Communities Neurocognitive Study Visit 6/7 (2016-2017/2018-2019) participants with normal hearing. Speech-in-noise performance, as outcome of interest, was assessed by the Quick Speech-in-Noise (QuickSIN) test (range: 0-30; higher = better). Predictors of interest included (a) peripheral hearing assessed by pure-tone audiometry; (b) brain imaging measures: structural MRI measures, white matter hyperintensities, and diffusion tensor imaging measures; and (c) cognitive performance assessed by a battery of 10 cognitive tests. All predictors were standardized to z scores. We estimated the differences in QuickSIN associated with every standard deviation (SD) worse in each predictor (peripheral hearing, brain imaging, and cognition) using multivariable-adjusted linear regression, adjusting for demographic variables, lifestyle, and disease factors (Model 1), and, additionally, for other predictors to assess independent associations (Model 2). RESULTS: Participants were aged 70-84 years, 56% female, and 17% Black. Every SD worse in better-ear 4-frequency pure-tone average was associated with worse QuickSIN (-4.89, 95% confidence interval, CI [-5.57, -4.21]) when participants had peripheral hearing loss, independent of other predictors. Smaller temporal lobe volume was associated with worse QuickSIN, but the association was not independent of other predictors (-0.30, 95% CI [-0.86, 0.26]). Every SD worse in global cognitive performance was independently associated with worse QuickSIN (-0.90, 95% CI [-1.30, -0.50]). CONCLUSIONS: Peripheral hearing and cognitive performance are independently associated with speech-in-noise performance among dementia-free older adults. The ongoing ACHIEVE trial will elucidate the effect of a hearing intervention that includes amplification and auditory rehabilitation on speech-in-noise understanding in older adults. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25733679.

Glucose Color Index: Development and Validation of a Novel Measure of the Shape of Glycemic Variability.

BACKGROUND: Standard continuous glucose monitoring (CGM) metrics: mean glucose, standard deviation, coefficient of variation, and time in range, fail to capture the shape of variability in the CGM time series. This information could facilitate improved diabetes management. METHODS: We analyzed CGM data from 141 adults with type 2 diabetes in the Hyperglycemic Profiles in Obstructive Sleep Apnea (HYPNOS) trial. Participants in HYPNOS wore CGM sensors for up to two weeks at two time points, three months apart. We calculated the log-periodogram for each time period, summarizing using disjoint linear models. These summaries were combined into a single value, termed the Glucose Color Index (GCI), using canonical correlation analysis. We compared the between-wear correlation of GCI with those of standard CGM metrics and assessed associations between GCI and diabetes comorbidities in 398 older adults with type 2 diabetes from the Atherosclerosis Risk in Communities (ARIC) study. RESULTS: The GCI achieved a test-retest correlation of R = .75. Adjusting for standard CGM metrics, the GCI test-retest correlation was R = .55. Glucose Color Index was significantly associated (p < .05) with impaired physical functioning, frailty/pre-frailty, cardiovascular disease, chronic kidney disease, and dementia/mild cognitive impairment after adjustment for confounders. CONCLUSION: We developed and validated the GCI, a novel CGM metric that captures the shape of glucose variability using the periodogram signal decomposition. Glucose Color Index was reliable within participants over a three-month period and associated with diabetes comorbidities. The GCI suggests a promising avenue toward the development of CGM metrics which more fully incorporate time series information.

Self-Rated Health in Middle Age and Risk of Hospitalizations and Death: Recurrent Event Analysis of the ARIC Study.

BACKGROUND: Self-rated health is a simple measure that may identify individuals who are at a higher risk for hospitalization or death. OBJECTIVE: To quantify the association between a single measure of self-rated health and future risk of recurrent hospitalizations or death. PARTICIPANTS: Atherosclerosis Risk in Communities (ARIC) study, a community-based prospective cohort study of middle-aged men and women with follow-up beginning from 1987 to 1989. MAIN MEASURES: We quantified the associations between initial self-rated health with risk of recurrent hospitalizations and of death using a recurrent events survival model that allowed for dependency between the rates of hospitalization and hazards of death, adjusted for demographic and clinical factors. KEY RESULTS: Of the 14,937 ARIC cohort individuals with available self-rated health and covariate information, 34% of individuals reported "excellent" health, 47% "good," 16% "fair," and 3% "poor" at study baseline. After a median follow-up of 27.7 years, 1955 (39%), 3569 (51%), 1626 (67%), and 402 (83%) individuals with "excellent," "good," "fair," and "poor" health, respectively, had died. After adjusting for demographic factors and medical history, a less favorable self-rated health status was associated with increased rates of hospitalization and death. As compared to those reporting "excellent" health, adults with "good," "fair," and "poor" health had 1.22 (1.07 to 1.40), 2.01 (1.63 to 2.47), and 3.13 (2.39 to 4.09) times the rate of hospitalizations, respectively. The hazards of death also increased with worsening categories of self-rated health, with "good," "fair," and "poor" health individuals experiencing 1.30 (1.12 to 1.51), 2.15 (1.71 to 2.69), and 3.40 (2.54 to 4.56) times the hazard of death compared to "excellent," respectively. CONCLUSIONS: Even after adjusting for demographic and clinical factors, having a less favorable response on a single measure of self-rated health taken in middle age is a potent marker of future hospitalizations and death.

Plasma Proteins associated with Chronic Histopathologic Lesions on Kidney Biopsy.

BACKGROUND: The severity of chronic histopathologic lesions on kidney biopsy is independently associated with higher risk of progressive chronic kidney disease (CKD). Because kidney biopsies are invasive, identification of blood markers that report on underlying kidney histopathology has the potential to enhance CKD care. METHODS: We examined the association between 6592 plasma protein levels measured by aptamers and the severity of interstitial fibrosis and tubular atrophy (IFTA), glomerulosclerosis, arteriolar sclerosis, and arterial sclerosis among 434 participants of the Boston Kidney Biopsy Cohort. For proteins significantly associated with at least one histologic lesion, we assessed renal arteriovenous protein gradients among 21 individuals who had undergone invasive catheterization and assessed the expression of the cognate gene among 47 individuals with single cell RNA sequencing data in the Kidney Precision Medicine Project. RESULTS: In models adjusted for estimated glomerular filtration rate (eGFR), proteinuria, and demographic factors, we identified 35 proteins associated with one or more chronic histologic lesions, including 20 specific for IFTA, 8 specific for glomerulosclerosis, and 1 specific for arteriolar sclerosis. In general, higher levels of these proteins were associated with more severe histologic score and lower eGFR. Exceptions included testican-2 and NELL1, which were associated with less glomerulosclerosis and IFTA, respectively, and higher eGFR; notably, both of these proteins demonstrated significantly higher levels from artery to renal vein, demonstrating net kidney release. In the Kidney Precision Medicine Project, 13 of the 35 protein hits had cognate gene expression enriched in one or more cell types in the kidney, including podocyte expression of select glomerulosclerosis markers (including testican-2) and tubular expression of several IFTA markers (including NELL1). CONCLUSIONS: Proteomic analysis identified circulating proteins associated with chronic histopathologic lesions, some of which have concordant site-specific expression within the kidney.

Maintenance of Normal Blood Pressure From Middle to Older Age: Results From the Atherosclerosis Risk in Communities Study.

BACKGROUND: It is unknown whether maintaining normal blood pressure (BP) from middle to older age is associated with improved health outcomes. METHODS: We estimated the proportion of Atherosclerosis Risk in Communities study participants who maintained normal BP from 1987 to 1989 (visit 1) through 1996 to 1998 and 2011 to 2013 (over 4 and 5 visits, respectively). Normal BP was defined as systolic BP <120 mm Hg and diastolic BP <80 mm Hg, without antihypertensive medication. We estimated the risk of cardiovascular disease, dementia, and poor physical functioning after visit 5. In exploratory analyses, we examined participant characteristics associated with maintaining normal BP. RESULTS: Among 2699 participants with normal BP at baseline (mean age 51.3 years), 47.1% and 15.0% maintained normal BP through visits 4 and 5, respectively. The hazard ratios comparing participants who maintained normal BP through visit 4 but not visit 5 and through visit 5 versus those who did not maintain normal BP through visit 4 were 0.80 (95% CI, 0.63-1.03) and 0.60 (95% CI, 0.42-0.86), respectively, for cardiovascular disease, and 0.85 (95% CI, 0.71-1.01) and 0.69 (95% CI, 0.54-0.90), respectively, for poor physical functioning. Maintaining normal BP through visit 5 was more common among participants with normal body mass index versus obesity at visit 1, those with normal body mass index at visits 1 and 5, and those with overweight at visit 1 and overweight or normal body mass index at visit 5, compared with those with obesity at visits 1 and 5. CONCLUSIONS: Maintaining normal BP was associated with a lower risk of cardiovascular disease and poor physical functioning.

Integrated Proteomic and Metabolomic Modules associated with Risk of Kidney Disease Progression.

BACKGROUND: Proteins and metabolites play crucial roles in various biological functions and are frequently interconnected through enzymatic or transport processes. METHODS: We present an integrated analysis of 4,091 proteins and 630 metabolites in the Chronic Renal Insufficiency Cohort Study (N=1,708; average follow-up for kidney failure [KF], 9.5 years, with 537 events). Proteins and metabolites were integrated using an unsupervised clustering method and we assessed associations between clusters and CKD progression and kidney failure using Cox proportional hazards models. Analyses were adjusted for demographics and risk factors including the estimated glomerular filtration rate (eGFR) and urine protein-creatinine ratio. Associations were identified in a discovery sample (random two-thirds, N=1139) and then evaluated in a replication sample (one-third, N=569). RESULTS: We identified 139 modules of correlated proteins and metabolites, which were represented by their principal components (PC). Modules and PC loadings were projected onto the replication sample which demonstrated a consistent network structure. Two modules, representing a total of 236 proteins and 82 metabolites, were robustly associated with both CKD progression and kidney failure in both discovery and validation samples. Using gene set enrichment, several transmembrane related terms were identified as over-represented in these modules. Transmembrane-ephrin receptor activity displayed the largest odds (OR = 13.2, P-value = 5.5×10 -5 ). A module containing CRIM1 and NPNT expressed in podocytes demonstrated particularly strong associations with kidney failure (P-value = 2.6×10 -5 ). CONCLUSIONS: This study demonstrates that integration of the proteome and metabolome can identify functions of pathophysiologic importance in kidney disease.

Satisfaction with Telehealth Care in the United States: Cross-Sectional Survey.

Background: Telehealth use remains high following the COVID-19 pandemic, but patient satisfaction with telehealth care is unclear. Methods: We used cross-sectional data from the Health Information National Trends Survey (HINTS 6). 2,058 English and Spanish-speaking U.S. adults (≥18 years) with a telehealth visit in the 12 months before March-November 2022 were included in this study. The primary outcomes were telehealth visit modality and satisfaction in the 12 months before HINTS 6. We evaluated sociodemographic predictors of telehealth visit modality and satisfaction via Poisson regression. Analyses were weighted according to HINTS standards. Results: We included 2,058 participants (48.4 ± 16.8 years; 57% women; 66% White), of which 70% had an audio-video and 30% an audio-only telehealth visit. Adults with an audio-video visit were more likely to have health insurance (adjusted prevalence ratio [aPR]: 1.55, 95% confidence interval [CI]: 1.18-2.04) and have an annual household income of ≥$75,000 (aPR: 1.18, 95% CI: 1.00-1.39) and less likely to be ≥65 years (aPR: 0.79, 95% CI: 0.70-0.89), adjusting for sociodemographic characteristics. No further inequities were noted by telehealth modality. Seventy-five percent of participants felt that their telehealth visits were as good as in-person care. No significant differences in telehealth satisfaction were observed across sociodemographic characteristics, telehealth modality, or the participants' primary reason for their most recent telehealth visit in adjusted analysis. Conclusions: Among U.S. adults with a telehealth visit, the majority had an audio-video visit and were satisfied with their care. Telehealth should continue, being offered following COVID-19, as it is uniformly valued by patients.

Association of Sevelamer Initiation with Gastrointestinal Bleeding Hospitalization in Individuals Requiring Hemodialysis.

Introduction Case reports have suggested a causative role between sevelamer use and subsequent gastrointestinal bleeding (GIB), but no large observational studies have evaluated this association. Methods Using the United States Renal Data System database from 2015 to 2019, we examined the association between initiation of sevelamer (versus non-sevelamer containing phosphate binders) and GIB hospitalization as well as all-cause mortality among individuals on hemodialysis. We emulated a target trial using Cox regression models and inverse probability of treatment weights to estimate the adjusted hazard ratios (HR) across outcomes and subgroups. Results Among 21,354 new users of phosphate binders (11,276 sevelamer and 10,078 non-sevelamer) with baseline lab data (calcium, phosphorus, hemoglobin, and albumin), there were 2,811 GIB hospitalizations and 5,920 deaths after a median follow-up of 1.3 years. Compared with the initiation of non-sevelamer binders, sevelamer was not associated with an increased risk of GIB hospitalization (89 vs. 90 events per 1000 person-years; IPTW-HR 0.98, 95% CI 0.91 - 1.06) or all-cause mortality (220 vs. 224 events per 1000 person-years; IPTW-HR 0.98 95% CI 0.93 - 1.03). Subgroup analyses (such as diabetes and anti-coagulation use) were generally consistent, and there was no association between sevelamer dose and GIB hospitalization. Conclusion Among patients requiring hemodialysis, sevelamer (vs non-sevelamer) containing phosphate binders was not associated with increased risk of GIB hospitalization.

Galectin-3, Metabolic Risk, and Incident Heart Failure: The ARIC Study.

BACKGROUND: It is unclear how metabolic syndrome (MetS) and diabetes affect Gal-3 (galectin 3) levels and the resulting implications for heart failure (HF) risk. We assessed relationships of MetS and diabetes with Gal-3, and their joint associations with incident HF. METHODS AND RESULTS: We included 8445 participants without HF (mean age, 63 years; 59% men; 16% Black race) at ARIC (Atherosclerosis Risk in Communities) study visit 4 (1996-1999). We categorized participants as having MetS only, MetS with diabetes, or neither, and by quartiles of MetS severity Z score. We assessed cross-sectional associations of metabolic risk categories with high Gal-3 level (≥75th percentile) using logistic regression. We used Cox regression to evaluate combined associations of metabolic risk categories and Gal-3 quartiles with HF. In cross-sectional analyses, compared with no MetS and no diabetes, MetS only (odds ratio [OR], 1.24 [95% CI, 1.10-1.41]) and MetS with diabetes (OR, 1.59 [95% CI, 1.32-1.92]) were associated with elevated Gal-3. Over a median follow-up of 20.5 years, there were 1749 HF events. Compared with individuals with neither diabetes nor MetS and with Gal-3 in the lowest quartile, the combination of MetS with diabetes and Gal-3 ≥75th percentile was associated with a 4-fold higher HF risk (hazard ratio, 4.35 [95% CI, 3.30-5.73]). Gal-3 provided HF prognostic information above and beyond MetS, NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity cardiac troponin T, and CRP (C-reactive protein) (ΔC statistic for models with versus without Gal-3: 0.003; P=0.004). CONCLUSIONS: MetS and diabetes are associated with elevated Gal-3. The HF risk significantly increased with the combination of greater metabolic risk and higher Gal-3.

Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury.

Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI. In three population-based epidemiology cohorts, we found that CHIP was associated with a greater risk of incident AKI, which was more pronounced in patients with AKI requiring dialysis and in individuals with somatic mutations in genes other than DNMT3A, including mutations in TET2 and JAK2. Mendelian randomization analyses supported a causal role for CHIP in promoting AKI. Non-DNMT3A-CHIP was also associated with a nonresolving pattern of injury in patients with AKI. To gain mechanistic insight, we evaluated the role of Tet2-CHIP and Jak2V617F-CHIP in two mouse models of AKI. In both models, CHIP was associated with more severe AKI, greater renal proinflammatory macrophage infiltration and greater post-AKI kidney fibrosis. In summary, this work establishes CHIP as a genetic mechanism conferring impaired kidney function recovery after AKI via an aberrant inflammatory response mediated by renal macrophages.

Four high sensitivity troponin assays and mortality in US adults with cardiovascular disease: The national health and nutrition examination survey, 1999-2004.

Objective: High sensitivity cardiac troponin (hs-cTn) may be useful to monitor residual risk in secondary prevention. Our objective was to study the correlations and comparative associations with mortality of four hs-cTn assays in US adults with known cardiovascular disease (CVD). Methods: We studied 1,211 adults with a history of CVD who participated in the National Health and Nutrition Examination Survey (NHANES) 1999-2004. Using stored samples, we measured hs-cTnT (Roche) and three hs-cTnI assays (Abbott, Siemens, and Ortho). Outcomes were all-cause and CVD mortality, with follow-up through December 31, 2019. Results: Mean age was 64 years, 48 % were female, and 80 % identified as non-Hispanic White. Pearson's correlation coefficients between hs-cTn assays ranged from 0.67 to 0.85. There were 848 deaths (365 from CVD). Among adults with a history of prior non-fatal CVD, each hs-cTn assay (log-transformed, per 1-SD) was independently associated with CVD death (HRs ranging from 1.55 to 2.16 per 1-SD, all p-values <0.05) and with all-cause death (HRs ranging from 1.31 to 1.62 per 1-SD, all p-values <0.05). Associations of hs-cTnT and all-cause and CVD death remained significant after adjusting for hs-cTnI (and vice versa). Associations between hs-cTnI and CVD death remained significant after mutually adjusting for other individual hs-cTnI assays: e.g., HR 2.21 (95 % CI 1.60, 3.05) for Ortho (hs-cTnI) after adjustment for Siemens (hs-cTnI) and HR 1.81 (95 % CI 1.35, 2.43) for Ortho (hs-cTnI) after adjustment for Abbott (hs-cTnI). Conclusion: In US adults with a history of CVD, we found modest correlations between 4 hs-cTn assays. All assays were associated with all-cause and CVD mortality. The hs-cTnT assay was associated with mortality independent of the hs-cTnI assays. Hs-cTnI assays also appeared to be independent of each other. Thus, hs-cTn assays may provide distinct information for residual risk in secondary prevention adults.

Demographic and Clinical Factors Associated With SARS-CoV-2 Spike 1 Antibody Response Among Vaccinated US Adults: the C4R Study.

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 adults with certain socio-demographic and clinical characteristics may have less robust antibody responses to COVID-19 vaccination and could be prioritized for more frequent re-vaccination.

Validation of a Zio XT Patch Accelerometer for the Objective Assessment of Physical Activity in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Combination devices to monitor heart rate/rhythms and physical activity are becoming increasingly popular in research and clinical settings. The Zio XT Patch (iRhythm Technologies, San Francisco, CA, USA) is US Food and Drug Administration (FDA)-approved for monitoring heart rhythms, but the validity of its accelerometer for assessing physical activity is unknown. OBJECTIVE: To validate the accelerometer in the Zio XT Patch for measuring physical activity against the widely-used ActiGraph GT3X. METHODS: The Zio XT and ActiGraph wGT3X-BT (Actigraph, Pensacola, FL, USA) were worn simultaneously in two separately-funded ancillary studies to Visit 6 of the Atherosclerosis Risk in Communities (ARIC) Study (2016-2017). Zio XT was worn on the chest and ActiGraph was worn on the hip. Raw accelerometer data were summarized using mean absolute deviation (MAD) for six different epoch lengths (1-min, 5-min, 10-min, 30-min, 1-h, and 2-h). Participants who had ≥3 days of at least 10 h of valid data between 7 a.m-11 p.m were included. Agreement of epoch-level MAD between the two devices was evaluated using correlation and mean squared error (MSE). RESULTS: Among 257 participants (average age: 78.5 ± 4.7 years; 59.1% female), there were strong correlations between MAD values from Zio XT and ActiGraph (average r: 1-min: 0.66, 5-min: 0.90, 10-min: 0.93, 30-min: 0.93, 1-h: 0.89, 2-h: 0.82), with relatively low error values (Average MSE × 106: 1-min: 349.37 g, 5-min: 86.25 g, 10-min: 56.80 g, 30-min: 45.46 g, 1-h: 52.56 g, 2-h: 54.58 g). CONCLUSIONS: These findings suggest that Zio XT accelerometry is valid for measuring duration, frequency, and intensity of physical activity within time epochs of 5-min to 2-h.