Kidney Function, Cognitive Impairment, and Trajectories: A Longitudinal Biracial Study.

Background: Chronic kidney disease (CKD) is associated with incident cognitive impairment (ICI) and disproportionately affects older adults and Black persons.

Objective: To determine (1) whether age or race differences exist in the association of CKD and ICI and (2) whether cognitive trajectories differ in people with and without CKD.

Design: Nationwide cohort study.

Air pollution is associated with increased risk of venous thromboembolism: the Multi-Ethnic Study of Atherosclerosis.

Air pollution exposure may induce procoagulant effects, and chronic exposure may be linked to greater risk of venous thromboembolism (VTE). We tested the hypothesis that air pollution is associated with increased VTE risk in the prospective Multi-Ethnic Study of Atherosclerosis (MESA), which has well-characterized air pollution measures and information on potential confounding factors. We included 6,651 participants recruited in 2000-2002 (baseline age range: 45-84 yrs; 53% female).

Plasma Biomarkers of Kidney Health and Mortality in Diabetes and Chronic Kidney Disease in the REGARDS Study.

Key Points: In diabetes and CKD, creatinine- and cystatin C–based eGFR has a strong inverse correlation with plasma TNF receptor 1, TNF receptor 2, and soluble urokinase-type plasminogen activator receptor. Higher plasma soluble TNF receptors 1 and 2 and soluble urokinase-type plasminogen activator receptor were each individually associated with mortality, independent of baseline kidney measures.

Background: Several plasma biomarkers of kidney health have been associated with CKD progression in persons with diabetes, but their associations with mortality risk have been largely unexplored.

Association of Duration of Recognized Hypertension and Stroke Risk: The REGARDS Study.

Background: The focus for reducing hypertension-related cardiovascular disease is the management of blood pressure. Limited data are available on the potential benefit of delaying the onset of hypertension.

Methods: Stroke-free Black and White participants from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke; recruited 2003-2007) were followed through 2022 for incident stroke events.

Lead-In Parenteral Anticoagulation Prior to Direct Oral Anticoagulation for Cerebral Venous Thrombosis.

Background: Growing evidence suggests that direct oral anticoagulants (DOACs) may be suitable for cerebral venous thrombosis (CVT). The optimal strategy regarding lead-in parenteral anticoagulation (PA) prior to DOAC is unknown.

Methods: In this post hoc analysis of the retrospective ACTION-CVT study, we compared patients treated with DOACs as part of routine care: those given "very early" DOAC (no PA), "early" (<5 days PA) and "delayed" (5-21 days PA).

Diagnosis of Incident Cancer After Cryptogenic Stroke: An Exploratory Analysis of the ARCADIA Randomized Trial.

Objectives: The objective of this study was to estimate the incidence, timing, and type of new cancer diagnosis among patients with cryptogenic stroke.

Methods: We used data from the ARCADIA trial, which enrolled patients with cryptogenic stroke and atrial cardiopathy. Participants were prospectively followed, and serious adverse events were assessed every 3 months or sooner if investigators were alerted between visits to an event.

Lessons Learned from National Heart, Lung, and Blood Institute Covid-19 Clinical Trials.

AbstractIn response to the Covid-19 pandemic, the National Heart, Lung, and Blood Institute launched five multisite clinical trials testing candidate host tissue-directed medical interventions to hasten recovery, improve function, and reduce morbidity and mortality. Speed, flexibility, and collaboration were essential. This article from the Steering and Executive committees describes the Collaborating Network of Networks for Evaluating Covid-19 and Therapeutic Strategies (CONNECTS) research program that enrolled 6690 participants and evaluated 18 intervention strategies using 10 molecular agents across the care continuum (outpatient, inpatient, and post discharge), and reports lessons learned from this initiative.

The association of leptin and incident hypertension in the reasons for geographic and racial differences in stroke (REGARDS) cohort.

Leptin is an adipokine associated with obesity and with hypertension in animal models. Whether leptin is associated with hypertension independent of obesity is unclear. Relative to White adults, Black adults have higher circulating leptin concentration.

Effect of sodium-glucose co-transporter-2 inhibitors on survival free of organ support in patients hospitalised for COVID-19 (ACTIV-4a): a pragmatic, multicentre, open-label, randomised, controlled, platform trial.

Background: Patients hospitalised for COVID-19 are at risk for multiorgan failure and death. Sodium-glucose co-transporter-2 (SGLT2) inhibitors provide cardiovascular and kidney protection in patients with cardiometabolic conditions and could provide organ protection during COVID-19. We aimed to investigate whether SGLT2 inhibitors can reduce the need for organ support in patients hospitalised for COVID-19.

Endothelial Dysfunction Biomarkers and CKD Incidence in the REGARDS Cohort.

Introduction: Chronic kidney disease (CKD) is only partly caused by traditional risk factors. Endothelial dysfunction is common in CKD and may contribute to CKD incidence. We studied the association of circulating biomarkers reflecting endothelial dysfunction with incident CKD.

Heparin Dose Intensity and Organ Support-Free Days in Patients Hospitalized for COVID-19.

Background: Clinical trials suggest that therapeutic-dose heparin may prevent critical illness and vascular complications due to COVID-19, but knowledge gaps exist regarding the efficacy of therapeutic heparin including its comparative effect relative to intermediate-dose anticoagulation.

Objectives: The authors performed 2 complementary secondary analyses of a completed randomized clinical trial: 1) a prespecified per-protocol analysis; and 2) an exploratory dose-based analysis to compare the effect of therapeutic-dose heparin with low- and intermediate-dose heparin.

Methods: Patients who received initial anticoagulation dosed consistently with randomization were included.

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

Importance: Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden.

Objective: To determine time to recovery following SARS-CoV-2 infection and identify factors associated with recovery by 90 days.

Design, Setting, And Participants: For this prospective cohort study, standardized ascertainment of SARS-CoV-2 infection was conducted starting in April 1, 2020, across 14 ongoing National Institutes of Health-funded cohorts that have enrolled and followed participants since 1971.

Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies.

Rationale & Objective: Tubulointerstitial 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 Design: Prospective cohort (Atherosclerosis Risk in Communities [ARIC]) and case-cohort (Multi-Ethnic Study of Atherosclerosis [MESA] and Reasons for Geographic and Racial Differences in Stroke [REGARDS]).

Soluble CD14 and Incident Diabetes Risk: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Context: Soluble CD14 (sCD14) is an inflammation biomarker with higher concentrations in White than Black adults. Higher sCD14 is seen in insulin resistance and diabetes. There are limited data on the relationship between sCD14 and incident diabetes.

Direct oral anticoagulants for treatment of venous thrombosis: illustrated review of appropriate use.

Direct oral anticoagulants (DOACs) have become the preferred option for treatment of venous thromboembolism due to their favorable profile compared with other agents such as vitamin K antagonists or low-molecular-weight heparin. However, findings from randomized controlled trials suggest efficacy and/or safety concerns with DOAC use in some clinical contexts. This illustrated review will summarize indications where DOACs have proven efficacy and safety, situations where they fall short, and situations where uncertainty remains compared with other treatments for venous thromboembolism.

Proneurotensin/Neuromedin N and Risk of Incident CKD and Other Kidney Outcomes in Community-Living Individuals: The REGARDS Study.

Rationale & Objective: Plasma proneurotensin/neuromedin N (pro-NT/NMN) is a precursor of neurotensin, a tridecapeptide linked with type 2 diabetes mellitus and other comorbid conditions associated with kidney disease. Whether pro-NT/NMN is directly associated with incident chronic kidney disease (CKD), and whether that association differs by race, is uncertain. We evaluated whether pro-NT/NMN levels were associated with increased risk of kidney outcomes.

N-Terminal Pro-B-Type Natriuretic Peptide and Risk for Diabetes Mellitus and Metabolic Syndrome.

Context: Natriuretic peptide concentrations are inversely associated with risk of diabetes mellitus and may be protective from metabolic dysfunction.

Objective: We studied associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes, metabolic syndrome (MetS), and MetS components.

Design/setting/participants: 2,899 participants with baseline (2003-2007) and follow-up (2013-2016) examinations and baseline NT-proBNP measurement in the REasons for Geographic And Racial Differences in Stroke study.

Sex-Associated Metabolites and Incident Stroke, Incident Coronary Heart Disease, Hypertension, and Chronic Kidney Disease in the REGARDS Cohort.

Background: Sex disparities exist in cardiometabolic diseases. Metabolomic profiling offers insight into disease mechanisms, as the metabolome is influenced by environmental and genetic factors. We identified metabolites associated with sex and determined if sex-associated metabolites are associated with incident stoke, incident coronary heart disease, prevalent hypertension, and prevalent chronic kidney disease.

Omega-3 Fatty Acids and Risk of Ischemic Stroke in REGARDS.

We examined associations between lipidomic profiles and incident ischemic stroke in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. Plasma lipids (n = 195) were measured from baseline blood samples, and lipids were consolidated into underlying factors using exploratory factor analysis. Cox proportional hazards models were used to test associations between lipid factors and incident stroke, linear regressions to determine associations between dietary intake and lipid factors, and the inverse odds ratio weighting (IORW) approach to test mediation.

Design, Synthesis, and Investigation of the Pharmacokinetics and Anticancer Activities of Indenoisoquinoline Derivatives That Stabilize the G-Quadruplex in the Promoter and Inhibit Topoisomerase I.

G-quadruplexes are noncanonical four-stranded DNA secondary structures. is a master oncogene and the G-quadruplex formed in the promoter functions as a transcriptional silencer and can be stabilized by small molecules. We have previously revealed a novel mechanism of action for indenoisoquinoline anticancer drugs, dual-downregulation of MYC and inhibition of topoisomerase I.

Factor VIII and Incident Hypertension in Black and White Adults: The REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort.

Background: Nearly half of all Americans have hypertension, and Black adults experience a disproportionate burden. Hypercoagulability may relate to hypertension risk, and higher levels of factor VIII increase thrombosis risk. Black adults have higher factor VIII and more hypertension than other groups.

Methylation patterns associated with C-reactive protein in racially and ethnically diverse populations.

Systemic low-grade inflammation is a feature of chronic disease. C-reactive protein (CRP) is a common biomarker of inflammation and used as an indicator of disease risk; however, the role of inflammation in disease is not completely understood. Methylation is an epigenetic modification in the DNA which plays a pivotal role in gene expression.