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Favel L Mondesir,1 Emily B Levitan,2 Gargya Malla,2 Reshmi Mukerji,3 April P Carson,2 Monika M Safford,4 Janet M Turan5 1Division of Cardiovascular Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA; 2Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USA; 3School of Medicine, Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA; 4Department of Medicine, Weill Cornell Medicine, New York, NY, USA; 5Department of Health Care Organization and Policy, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, USACorrespondence: Favel L MondesirDivision of Cardiovascular Medicine, School of Medicine, University of Utah, Room 4A100, 30 N 1900 E, Salt Lake City, UT 84132, USATel +1-801-587-9048Email favel.mondesir@hsc.utah.eduBackground: Few qualitative studies have explored factors influencing medication adherence among people with coronary heart disease (CHD) or CHD risk factors. We explored how factors related to the patient (e.g. self-efficacy), social/economic conditions (e.g. social support and cost of medications), therapy (e.g. side effects), health condition (e.g. comorbidities), and the healthcare system/healthcare team (e.g. support from healthcare providers and pharmacy access) influence medication adherence, based on the World Health Organization Multidimensional Adherence Model (WHO-MAM).Methods: We conducted 18 in-depth qualitative interviews from April to July 2018 with ambulatory care patients aged ≥45 years (8 black men, 5 black women, 2 white men, and 3 white women) who were using medications for diabetes, hypertension, dyslipidemia and/or CHD. We used thematic analysis to analyze the data, and sub-themes emerged within each WHO-MAM dimension.Findings: Patient-related factors included beliefs about medications as important for self and faith; the desire to follow the advice of family, friends, and influential others; and self-efficacy. Social/economic factors included observations of social network members and information received from them; social support for medication adherence and pharmacy utilization; and economic influences. Therapy-related barriers included side effects and medicine schedules. Only a few participants mentioned condition-related factors. Healthcare system/healthcare team-related factors included support from doctors and pharmacists; and ease of pharmacy access and utilization.Conclusion: These results underscore the need for multidimensional interventions aimed at improving medication adherence and overall health of patients with CHD and CHD risk factors.Keywords: medication adherence, qualitative research, coronary heart disease, diabetes, hypertension, dyslipidemia

Emily B Levitan,1 Christopher Gamboa,1 Monika M Safford,2 Dana V Rizk,3 Todd M Brown,4 Elsayed Z Soliman,5 Paul Muntner11Department of Epidemiology, 2Division of Preventive Medicine, 3Division of Nephrology, 4Division of Cardiology, University of Alabama at Birmingham, Birmingham, AL, USA; 5Epidemiological Cardiology Research Center, Wake Forest University School of Medicine, Winston Salem, NC, USABackground: Individuals with unrecognized myocardial infarction (UMI) have similar risks for cardiovascular events and mortality as those with recognized myocardial infarction (RMI). The prevalence of cardioprotective medication use and blood pressure and low-density lipoprotein cholesterol control among individuals with UMI is unknown.Methods: Participants from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who were recruited between May 2004 and October 2007 received baseline twelve-lead electrocardiograms (n = 21,036). Myocardial infarction (MI) status was characterized as no MI, UMI (electrocardiogram abnormalities consistent with MI without self-reported history; n = 949; 4.5%), and RMI (self-reported history of MI; n = 1574; 7.5%).Results: For participants with no MI, UMI, and RMI, prevalence of use was 38.4%, 44.4%, and 75.7% for aspirin; 18.0%, 25.8%, and 57.2% for beta blockers; 31.7%, 38.7%, and 55.0% for angiotensin converting enzyme inhibitors or angiotensin receptor blockers; and 28.1%, 33.9%, and 64.1% for statins, respectively. Participants with RMI were 35% more likely to have low-density lipoprotein cholesterol < 100 mg/dL than participants with UMI (prevalence ratio = 1.35, 95% confidence interval 1.19–1.52). Blood pressure control (

Background/objectives: Marine omega-3 fatty acids have beneficial effects on cardiovascular risk factors. Consumption of fatty fish and marine omega-3 has been associated with lower rates of cardiovascular diseases. We examined the association of fatty fish and marine omega-3 with heart failure (HF) in a population of middle-aged and older women.Subjects/methods: Participants in the Swedish Mammography Cohort aged 48-83 years completed 96-item food-frequency questionnaires. Women without any history of HF, myocardial infarction or diabetes at baseline (n=36,234) were followed from 1 January 1998 until 31 December 2006 for HF hospitalization or mortality through Swedish inpatient and cause-of-death registers; 651 women experienced HF events. Cox proportional hazards models accounting for age and other confounders were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CI).Results: Compared with women who did not eat fatty fish, RR were 0.86 (95% CI: 0.67, 1.10) for <1 serving per week, 0.80 (95% CI: 0.63, 1.01) for 1 serving per week, 0.70 (95% CI: 0.53, 0.94) for 2 servings per week and 0.91 (95% CI: 0.59, 1.40) for >or=3 servings per week (P(trend)=0.049). RR across quintiles of marine omega-3 fatty acids were 1 (reference), 0.85 (95% CI: 0.67, 1.07), 0.79 (95% CI: 0.61, 1.02), 0.83 (95% CI 0.65, 1.06) and 0.75 (95% CI: 0.58, 0.96) (P(trend)=0.04).Conclusion: Moderate consumption of fatty fish (1-2 servings per week) and marine omega-3 fatty acids were associated with a lower rate of first HF hospitalization or death in this population. [ABSTRACT FROM AUTHOR]

On the surface electrocardiogram, an abnormally wide QRS|T angle reflects changes in the regional action potential duration profiles and in the direction of the repolarization sequence, which is thought to increase the risk of ventricular arrhythmia. We investigated the relation between an abnormal QRS|T angle and mortality in a nationally representative sample of subjects without clinically evident heart disease. We studied 7,052 participants ≥40 years old in the third National Health and Nutrition Examination Survey with 12-lead electrocardiograms. Those with self-reported or electrocardiographic evidence of a previous myocardial infarction, QRS duration of ≥120 ms, or history of heart failure were excluded. Borderline and abnormal spatial QRS|T angles were defined according to gender-specific 75th and 95th percentiles of frequency distributions. All-cause (1,093 women and 1,191 men) and cardiovascular (462 women and 455 men) mortality during the 14-year period was assessed through linkage with the National Death Index. On multivariate analyses, an abnormal spatial QRS|T angle was associated with an increased hazard ratio (HR) for cardiovascular mortality in women (HR 1.82, 95% confidence interval 1.05 to 3.14) and men (HR 2.21, 95% confidence interval 1.32 to 3.68). Also, the multivariate adjusted HR for all-cause mortality associated with an abnormal QRS|T angle was 1.30 (95% confidence interval 0.95 to 1.78) for women and 1.87 (95% confidence interval 1.29 to 2.7) for men. A borderline QRS|T angle was not associated with an increased risk of all-cause or cardiovascular mortality. In conclusion, an abnormal QRS|T angle, as measured on a 12-lead electrocardiogram, was associated with an increased risk of cardiovascular and all-cause mortality in this population-based sample without known heart disease. [ABSTRACT FROM AUTHOR]

Importance: Classification of persons with long COVID (LC) or post-COVID-19 condition must encompass the complexity and heterogeneity of the condition. Iterative refinement of the classification index for research is needed to incorporate newly available data as the field rapidly evolves., Objective: To update the 2023 research index for adults with LC using additional participant data from the Researching COVID to Enhance Recovery (RECOVER-Adult) study and an expanded symptom list based on input from patient communities., Design, Setting, and Participants: Prospective, observational cohort study including adults 18 years or older with or without known prior SARS-CoV-2 infection who were enrolled at 83 sites in the US and Puerto Rico. Included participants had at least 1 study visit taking place 4.5 months after first SARS-CoV-2 infection or later, and not within 30 days of a reinfection. The study visits took place between October 2021 and March 2024., Exposure: SARS-CoV-2 infection., Main Outcomes and Measures: Presence of LC and participant-reported symptoms., Results: A total of 13 647 participants (11 743 with known SARS-CoV-2 infection and 1904 without known prior SARS-CoV-2 infection; median age, 45 years [IQR, 34-69 years]; and 73% were female) were included. Using the least absolute shrinkage and selection operator analysis regression approach from the 2023 model, symptoms contributing to the updated 2024 index included postexertional malaise, fatigue, brain fog, dizziness, palpitations, change in smell or taste, thirst, chronic cough, chest pain, shortness of breath, and sleep apnea. For the 2024 LC research index, the optimal threshold to identify participants with highly symptomatic LC was a score of 11 or greater. The 2024 index classified 20% of participants with known prior SARS-CoV-2 infection and 4% of those without known prior SARS-CoV-2 infection as having likely LC (vs 21% and 5%, respectively, using the 2023 index) and 39% of participants with known prior SARS-CoV-2 infection as having possible LC, which is a new category for the 2024 model. Cluster analysis identified 5 LC subtypes that tracked quality-of-life measures., Conclusions and Relevance: The 2024 LC research index for adults builds on the 2023 index with additional data and symptoms to help researchers classify symptomatic LC and its symptom subtypes. Continued future refinement of the index will be needed as the understanding of LC evolves.

Rationale: Robust COVID-19 outcomes classification is important for ongoing epidemiology research on acute and post-acute COVID-19 conditions. Protocolized medical record review is an established method to validate endpoints for clinical trials and cardiovascular epidemiology cohorts; however, a protocol to adjudicate hospitalizations for COVID-19 among epidemiology cohorts was lacking., Objectives: We developed a protocol to ascertain and adjudicate hospitalized COVID-19 across a meta-cohort of 14 US prospective cohort studies. This report describes the first three years of protocol implementation (October 1, 2020-October 1, 2023) and evaluates its repeatability and performance compared to classification by administrative codes., Methods: The protocol was adapted from cohort approaches to clinical cardiovascular events ascertainment and adjudication. Potential COVID-19 hospitalizations and deaths were identified by self-/proxy-report and, in some cases, active surveillance. Medical records were requested from hospitals and adjudicated for COVID-19 outcomes by clinically trained personnel according to a standardized rubric. Inter-rater agreement was assessed. The sensitivity and specificity of discharge diagnosis codes was compared to adjudicated diagnoses., Measurements and Main Results: The study obtained medical records for 1,167 potential COVID-19 hospitalizations, which underwent protocolized adjudication. Adjudication confirmed COVID-19 infection was present for 1,030 (88%) events, of which COVID-19 was not the cause of hospitalization for 78 (8%). Of 952 hospitalizations determined by adjudicators to be caused by COVID-19, 319 (34%) participants were critically ill and 210 (22%) died. Pneumonia was confirmed in 822 (86%) and acute kidney injury in 350 (37%); other cardiovascular and thrombotic complications were rare (2-5%). Interrater reliability among adjudicators was high (kappa = 0.85-1.00) except for myocardial infarction (kappa = 0.60). Compared to adjudication, sensitivity of discharge diagnosis codes was higher for pneumonia (84%) and pulmonary embolism (81%) than for other complications (48-70%)., Conclusions: Protocolized adjudication confirmed four out of five COVID-19 hospitalizations in a US meta-cohort and confirmed cases of pneumonia, pulmonary embolism, and other conditions that were not indicated by discharge diagnosis codes. These results highlight the importance of validating health outcomes for use in research on COVID-19 and post-COVID-19 conditions, and some limitations of claims-based data., Competing Interests: A Krishnaswamy left Columbia University and joined Merck (Epidemiology) as a project manager following completion of her work on this paper. Mitchell Elkind receives royalties from UpToDate for a chapter on neurological complications of COVID-19; receives study drug in kind from the BMS-Pfizer Alliance for Eliquis and ancillary funding from Roche, both for an NIH-funded trial of stroke prevention. E B Levitan receives research funding from Amgen (to UAB) unrelated to the current work and personal fees for serving on a DSMB from University of Pittsburgh for an NIH funded trial. David Schwartz is founder and chief scientific officer of Eleven P15, a company dedicated to the diagnosis, prevention, and treatment of early presentations of pulmonary fibrosis. Joyce Lee serves as a consultant for Eleven P15. Sally Wenzel receives funding for consulting and clinical trials from AstraZeneca, GSK, Sanofi-Genzyme, Novartis, Knopp; she also receives research support from Pieris and Regeneron. PG Woodruff has served as a consultant for Roche, Sanofi, Amegne and Astra Zeneca outside the context of this paper. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2025 Oelsner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Increased burden of socially determined vulnerabilities (SDV), which include nonmedical conditions that contribute to patient health, is associated with incident heart failure (HF). Mediators of this association have not been examined. We aimed to determine if a healthy lifestyle mediates the association between SDV and HF., Methods: We included adults aged 45 to 64 years old across the United States from the REGARDS cohort study (Reasons for Geographic and Racial Differences in Stroke) without evidence of HF at baseline. The primary exposure was a count of SDV based on the Healthy People 2030 framework. The primary outcome was incident HF. We assessed the role of a healthy behavior score (HBS range, 0-8) and its components (adherence to a Mediterranean diet, physical activity, lack of sedentary lifestyle, and smoking abstinence) as potential mediators of the association between SDV and incident HF., Results: We included 13 on 525 participants. The median HBS was 4, with 16% with low HBS (0-2), 55% with moderate HBS (3-5), and 29% with high HBS (6-8). Increasing burden of SDV was associated with a stepwise increase in incident HF (adjusted hazard ratio, 1.84 [95% CI, 1.32-2.52] for 1 SDV, 2.59 [95% CI, 1.87-3.60] for 2 SDV, and 4.20 [95% CI, 3.08-5.73] for ≥3 SDV). There was no statistically significant mediation of HBS for the association of SDV count of 1 and incident HF. HBS score mediated 10.6% of the association between SDV count of 2 and incident HF and 11.1% of the association for those with ≥3 SDV. This increased to 10.8% and 18.3%, respectively, in the complete case analysis. Regarding individual components of HBS as mediators, only avoidance of a sedentary lifestyle was statistically significant (8.6% mediation) for the association of SDV count of 2 and incident HF., Conclusions: A healthy lifestyle plays a small role in mediating the association between high SDV count and incident HF.

Background: Inflammation plays a key role in the development of heart failure (HF), and diet is a known modifiable factor that modulates systemic inflammation. The dietary inflammatory score (DIS) is a tool that quantifies the inflammatory components of diet. We sought to determine whether the DIS is associated with incident HF events., Methods: We examined a total of 17,975 participants without HF at baseline who were in the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort. The main exposure variable was the DIS quartile, which was derived from the Food Frequency Questionnaire obtained at baseline study enrollment. The main outcome was an incident HF event, defined as hospitalization due to HF or death. To examine the association between the DIS and incident HF events, we conducted Cox proportional hazard regression modeling, adjusting for total energy intake, sociodemographic factors and pro-inflammatory lifestyle behaviors., Results: The sample mean age was 64 + 9.2 years, 55.8% were female, and 32.3% were Black. Over a median follow-up of 11.1 years, we observed 900 incident HF events, including 752 hospitalizations and 148 deaths due to HF. In an adjusted model, the highest DIS quartile (Q4) was associated with incident HF (HR 1.26 95% CI 1.03-1.54). Of note, these findings remained, even after adjusting for comorbid conditions and physiological parameters. In an age-stratified analysis, the association was present only in those aged < 65 years (Q4: HR 1.65 95% CI 1.08-2.51). Moreover, the association was present for heart failure with reserved ejection fraction (Q4: HR 1.44 95% CI 1.07-1.94) but not for heart failure with preserved ejection fraction., Conclusion: The highest DIS quartile was associated with incident HF events. These findings indicate the potential value of specific dietary patterns to prevent HF., Competing Interests: Disclosures PG receives personal fees for medicolegal consulting related to heart failure, has received honoraria from Akcea Therapeutics and Bionest and is also supported by National Institute on Aging, grant K76AG064428. MMS is a founder of MedExplain, a patient-education company. All other authors report no conflicts., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Introduction: Medication regimen complexity may be an important risk factor for adverse outcomes in older adults with heart failure. However, increasing complexity is often necessary when prescribing guideline-directed medical therapy at the time of a heart failure hospitalization. We sought to determine whether increased medication regimen complexity following a heart failure hospitalization was associated with worse post-hospitalization outcomes., Methods: This retrospective cohort study included Reasons for Geographic and Racial Differences in Stroke (REGARDS) participants aged at least 65 years hospitalized for heart failure between 2003 and 2014. We calculated changes between hospital admission and discharge in medication count (Δcount) and in the validated Medication Regimen Complexity Index (ΔMRCI), which incorporates each medication's dosage formulation, frequency, timing, and special instructions. The primary outcome was a composite of 90-day all-cause readmission and all-cause mortality post-discharge. We calculated ΔMRCI and Δcount, identified their predictors, and examined their association with the primary outcome., Results: Among 725 patients hospitalized for heart failure, the mean (SD) age was 77 (7.2) years, 46% were female, and 35% were Black. At discharge, nearly 75% had an increase in their medication regimen complexity and 60% had an increase in their medication count. Patients with the highest ΔMRCI and Δcount were more likely to be female and Black. Predictors of the highest ΔMRCI included Charlson comorbidity index and not being discharged home; predictors of the highest Δcount included intensive care unit stay. Approximately 48% of patients experienced a 90-day readmission or death. Neither ΔMRCI (highest versus lowest tertile; HR 1.14, 95% CI 0.86, 1.50) nor Δcount (HR 0.97, 95% CI 0.73, 1.27) were associated with 90-day outcomes., Conclusion: Following a heart failure hospitalization, increased medication regimen complexity was common but was not associated with 90-day post-hospitalization outcomes. These are reassuring data, suggesting that it is reasonable for clinicians to focus on optimizing medication regimens for patients with heart failure even if it increases regimen complexity., Competing Interests: Declarations. Funding: This research project is supported by cooperative agreement U01 NS041588 co-funded by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging (NIA), National Institutes of Health, Department of Health and Human Service. Additional funding was provided by National Heart, Lung, and Blood Institute (NHLBI) grant R01HL080477 and NIA grant R03AG056446. Conflict of Interest: P.G. is supported by National Institute on Aging grants K76AG064428, R21AG077092, and R01AG085420; was a member of the Junior Investigator Intensive Program of the US Deprescribing Research Network and is supported by a US Deprescribing Research Pilot Grant funded by the National Institute on Aging (R24AG064025); reports personal fees from Agepha Pharma, Akros Pharma, Axon therapies, and Sensorum Health; and has received personal fees for medicolegal consulting and expert testimony related to HF. A.P.A. has received relevant research support through grants to his institution from the National Heart, Lung, and Blood Institute (K23HL150159), the American Heart Association (2nd 305 Century Early Faculty Independence Award), The Permanente Medical Group, Northern California Community Benefits Programs, Garfield Memorial Fund, Abbott Laboratories, Amarin Pharma, Inc., Edwards Lifesciences LLC, Esperion Therapeutics, Inc., and Novartis. E.B.L. has received research funding from Amgen, Inc, and personal fees from University of Pittsburgh for serving on a data safety and monitoring board. Aayush Visaria, William McDonald, John Mancini, Min Ji Kwak, Ashkan Hashemi, Mark S. Lachs, and Andrew R. Zullo declare that they have no potential conflicts of interest that might be relevant to this work. Ethical Approval: This retrospective study was approved by the Weill Cornell Institutional Review Board. Consent to Participate: All participants provided written informed consent. Consent for Publication: Not applicable. Data Availability: The data that support the findings of this study are available from the REGARDS-MI substudy (Parent REGARDS Study Data Access: https://www.uab.edu/soph/regardsstudy/researchers , REGARDS-MI: https://careinnovation.weill.cornell.edu/research-studies/reasons-geographic-and-racial-differences-stroke-%E2%80%93-myocardial-infarction-regards-mi ), but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are, however, available from the authors upon reasonable request and with permission of the corresponding author. Code Availability: Not applicable. Author Contributions: A.V.: analysis, data curation, methodology, software, visualization, writing, reviewing and editing; W.M.: analysis, visualization, writing, reviewing and editing; J.M.: conceptualization, validation, reviewing and editing; A.A.: validation, reviewing and editing, investigation; M.J.K.: analysis, investigation, methodology, reviewing and editing; A.H.: data curation, analysis, project administration, reviewing and editing; M.L.: conceptualization, methodology, reviewing and editing; A.Z.: methodology, validation, reviewing and editing; M.S.: funding acquisition, methodology, resources, supervision, reviewing and editing; E.L.: methodology, resources, supervision, reviewing and editing; and P.G.: conceptualization, data curation, funding acquisition, investigation, methodology, resources, writing, reviewing and editing., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Social risk factors are linked to adverse health outcomes, but their total impact on long-term quality of life is obscure. We hypothesized that a higher burden of social risk factors is associated with greater decline in quality of life over 10 years., Methods: We examined associations between social risk factors count and decline >5 points in (i) physical component summary, and (ii) mental component summary scores from the Short Form-12 among Black and White participants in the Reasons for Geographic and Racial Differences in Stroke study (n = 14 401)., Results: For physical component summary, White participants with 1 social risk factor had relative risk (RR) for decline of 1.14 [95% confidence intervals (CI): 1.07-1.12]. Those with ≥2 social risk factors had RR of 1.26 [95% CI: 1.17-1.35], after adjusting for baseline demographics, health behaviors, medical conditions, medications, and physiological variables. Black participants with 1 social risk factor had RR of 1.03 [95% CI: 0.93-1.15]. Those with ≥2 social risk factors had RR of 1.24 [95% CI: 1.13-1.36]. For mental component summary, White participants with 1 social risk factor had RR for decline of 1.19 [95% CI: 1.04-1.37]. Those with ≥2 social risk factors had RR of 1.47 [95% CI: 1.28-1.68]. Black participants with 1 social risk factor had RR of 1.18 [95% CI: 0.96-1.45]. Those with ≥2 social risk factors had RR of 1.38 [95% CI: 1.14-1.66]., Conclusions: More social risk factors increased the risk of decline of quality of life for Black and White individuals, especially impacting mental health., (© The Author(s) 2025. Published by Oxford University Press on behalf of the Gerontological Society of America.)

Aims: Limited data are available that evaluate the efficacy of renin-angiotensin system inhibitor (RASI) dose-reduction in older adults with heart failure with reduced ejection fraction following a heart failure hospitalization., Methods and Results: We examined a 5% random sample of Medicare beneficiaries with prescription coverage who were discharged to home following a hospitalization for heart failure with reduced ejection fraction between 1 January 2007 and 30 June 2018 and were treated with RASI prior to hospitalization. We classified patients into three mutually exclusive groups based on RASI dosage before (prescription fills up to 90 days prior to) and after a hospitalization (prescription fills up to 365 days that were most proximate to the discharge date as possible)-same/increased dose, dose-reduction, and discontinuation. We examined associations between RASI prescribing patterns and outcomes (mortality and all-cause readmission at 30 days and 1 year) using Cox proportional hazards models. Among 12 794 unique older adults, 36.8% experienced a RASI reduction following their hospitalization for HFrEF-15.7% had a dose-reduction and 21.1% had a discontinuation. Neither dose-reduction nor discontinuation was associated with 30-day mortality. Discontinuation was associated 1-year mortality, 30-day all-cause readmission, and 1-year all-cause readmission, whereas dose-reduction was not., Conclusion: RASI dose-reduction occurs in 1 out of 7 HF hospitalizations. In contrast to RASI discontinuation, RASI dose-reduction was not associated with adverse short or long-term outcomes. These findings indicate that RASI dose-reduction is preferred over RASI discontinuation in selected situations where RASI reduction is needed., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Importance: Structural racism in the US is evidenced in the discriminatory practice of historical racial redlining when neighborhoods were valued, in part, based on the community's racial and ethnic compositions. However, the influence of these systemic practices in the context of the HIV epidemic is not well understood., Objective: To assess the effect of redlining on time to viral suppression among people newly diagnosed with HIV., Design, Setting, and Participants: Observational study that included individuals diagnosed with HIV from January 1, 2011, to December 31, 2019, in New Orleans, Louisiana. At the time of their HIV diagnosis, these individuals lived in neighborhoods historically mapped by the Home Owners' Loan Corporation (HOLC). The HOLC lending risk maps classified neighborhoods into 1 of 4 color-coded grades: A (best), B (still desirable), C (definitely declining), and D (hazardous)., Main Outcome and Measures: The primary outcome of interest was time to viral suppression (estimated as the time from the diagnosis date to the date of the first recorded viral load that was <200 copies/mL). Individual-level demographic factors were used to evaluate time to viral suppression along with a neighborhood measure of gentrification (based on US census tract-level characteristics for educational attainment, housing development and value, and household income) and a Cox gamma frailty model with census tract used as the frailty term., Results: Of 1132 individuals newly diagnosed with HIV, 871 (76.9%) were men and 620 (54.8%) were 25 to 44 years of age. Of the 697 individuals living in historically redlined neighborhoods (HOLC grade D), 100 (14.6%) were living in neighborhoods that were gentrifying. The median time to viral suppression was 193 days (95% CI, 167-223 days) for persons with HIV living in redlined neighborhoods compared with 164 days (95% CI, 143-185 days) for the 435 persons with HIV living in HOLC grade A, B, or C (nonredlined) neighborhoods. Among persons with HIV living in gentrifying neighborhoods, those living in redlined neighborhoods had a longer time to viral suppression compared with persons living in nonredlined neighborhoods (hazard ratio, 0.54 [95% CI, 0.36-0.82])., Conclusions and Relevance: These findings suggest the enduring effects of systemic racism on present-day health outcomes among persons with HIV. Regardless of their neighborhood's contemporary level of gentrification, individuals diagnosed with HIV while living in historically redlined neighborhoods may experience a significantly longer time to viral suppression.

Purpose: Many adults with atherosclerotic cardiovascular disease (ASCVD) who are recommended to take a statin, ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) by the 2018 American Heart Association/American College of Cardiology cholesterol guideline do not receive these medications. We estimated the percentage of recurrent ASCVD events potentially prevented with guideline-recommended cholesterol-lowering therapy following a myocardial infarction (MI) hospitalization., Methods: We conducted simulations using data from US adults with government health insurance through Medicare or commercial health insurance in the MarketScan database. We used data from patients with an MI hospitalization in 2018-2019 to estimate the percentage receiving guideline-recommended therapy. We used data from patients with an MI hospitalization in 2013-2016 to estimate the 3-year cumulative incidence of recurrent ASCVD events (i.e., MI, coronary revascularization or ischemic stroke). The low-density lipoprotein cholesterol (LDL-C) reduction with guideline-recommended therapy was derived from trials of statins, ezetimibe and PCSK9i, and the associated ASCVD risk reduction was estimated from a meta-analysis by the Cholesterol-Lowering Treatment Trialists Collaboration., Results: Among 279,395 patients with an MI hospitalization in 2018-2019 (mean age 75 years, mean LDL-C 92 mg/dL), 27.3% were receiving guideline-recommended cholesterol-lowering therapy. With current cholesterol-lowering therapy use, 25.3% (95%CI: 25.2%-25.4%) of patients had an ASCVD event over 3 years. If all patients were to receive guideline-recommended therapy, 19.8% (95%CI: 19.5%-19.9%) were estimated to have an ASCVD event over 3 years, representing a 21.6% (95%CI: 20.5%-23.6%) relative risk reduction., Conclusion: Implementation of guideline-recommended cholesterol-lowering therapy could prevent a substantial percentage of recurrent ASCVD events., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Integrase strand transfer inhibitors (INSTIs) are a commonly used antiretroviral therapy (ART) class in people with human immunodeficiency virus (HIV) and associated with weight gain. We studied the association of INSTI-based ART with systolic and diastolic blood pressure (SBP and DBP)., Methods: We recruited 50 people taking INSTI-based ART and 40 people taking non-INSTI-based ART with HIV and hypertension from the University of Alabama at Birmingham HIV clinic. Office BP was measured unattended using an automated (AOBP) device. Awake, asleep, and 24-hour BP were measured through ambulatory BP monitoring. Among participants with SBP ≥130 mm Hg or DBP ≥80 mm Hg on AOBP, sustained hypertension was defined as awake SBP ≥130 mm Hg or DBP ≥80 mm Hg., Results: Mean SBP and DBP were higher among participants taking INSTI- vs. non-INSTI-based ART (AOBP-SBP/DBP: 144.7/83.8 vs. 135.3/79.3 mm Hg; awake-SBP/DBP: 143.2/80.9 vs. 133.4/76.3 mm Hg; asleep-SBP/DBP: 133.3/72.9 vs. 120.3/65.4 mm Hg; 24-hour-SBP/DBP: 140.4/78.7 vs. 130.0/73.7 mm Hg). After multivariable adjustment, AOBP, awake, asleep, and 24-hour SBP were 12.5 (95% confidence interval [CI] 5.0-20.1), 9.8 (95% CI 3.6-16.0), 10.4 (95% CI 2.0-18.9), and 9.8 (95% CI 4.2-15.4) mm Hg higher among those taking INSTI- vs. non-INSTI-based ART, respectively. AOBP, awake, asleep, and 24-hour DBP were 7.5 (95% CI 0.3-14.6), 6.1 (95% CI 0.3-11.8), 7.5 (95% CI 1.4-13.6), and 6.1 (95% CI 0.9-11.3) mm Hg higher among those taking INSTI- vs. non-INSTI-based ART after multivariable adjustment. All participants had SBP ≥130 mm Hg or DBP ≥80 mm Hg on AOBP and 97.9% and 65.7% of participants taking INSTI- and non-INSTI-based ART had sustained hypertension, respectively., Conclusions: INSTI-based ART was associated with higher SBP and DBP than non-INSTI-based ART., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Cognitive impairment is common among adults with heart failure (HF) and associated with poor outcomes. However, less is known about the trajectory of cognitive decline after a first HF hospitalization. We examined the rate of cognitive decline among adults with incident HF hospitalization compared with those without HF hospitalization., Methods and Results: The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective longitudinal study of 23 894 participants aged ≥45 years free of HF at baseline. HF hospitalization was expert adjudicated. Changes in global cognitive function (primary outcome) were assessed with the Six-Item Screener (range, 0-6). Secondary outcomes included change in Word List Learning (range, 0-30), Word List Delayed Recall (WLD; range, 0-10), and Animal Fluency Test (range, 0+). Segmented linear mixed-effects regression models were used. Over 5 years, mean scores across all 4 cognitive tests declined for all participants regardless of HF status. Those with incident HF hospitalization experienced faster declines in the Six-Item Screener versus those who were HF free (difference, -0.031 [95% CI, -0.047 to -0.016]; P <0.001), a finding that persisted in fully adjusted models. Those with incident HF hospitalization did not experience faster declines in Word List Learning, Word List Delayed Recall, or Animal Fluency Test scores compared with those without HF hospitalization. Participants with hospitalization for HF with preserved, compared with reduced, ejection fraction had faster decline in Animal Fluency Test., Conclusions: Global cognitive decline occurred faster among adults with incident HF hospitalization compared with those who remained free of HF hospitalization. This pattern was not seen for the other cognitive domains.

Background: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC)., Objective: To investigate clinical laboratory markers of SARS-CoV-2 and PASC., Design: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024)., Setting: 83 enrolling sites., Participants: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection., Measurements: Participants completed questionnaires and standard clinical laboratory tests., Results: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 10 9 cells/L [95% CI, 264.5 to 267.4 × 10 9 cells/L]) than participants without known prior infection (275.2 × 10 9 cells/L [CI, 268.5 to 282.0 × 10 9 cells/L]), as well as higher mean hemoglobin A 1c (HbA 1c ) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA 1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero., Limitation: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined., Conclusion: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC., Primary Funding Source: National Institutes of Health., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0737.

Objectives: Timely control of hypertension is vital to prevent comorbidities. We evaluated the association of race/ethnicity and HIV infection with incident hypertension outcomes, including awareness, treatment, and control., Design: We evaluated cisgender women living with HIV and sociodemographically matched women living without HIV recruited into four Southern sites of the Women's Interagency HIV Study (WIHS) (2013-2019)., Methods: We calculated measurements of the time to four events or censoring: incident hypertension, hypertension awareness, hypertension treatment, and hypertension control. Hazard ratios for race/ethnicity and HIV status were calculated for each outcome using Cox proportional-hazards models adjusted for sociodemographic, behavioral, and clinical risk factors., Results: Among 712 women, 56% were hypertensive at baseline. Forty-five percentage of the remaining women who were normotensive at baseline developed incident hypertension during follow-up. Non-Hispanic white and Hispanic women had faster time to hypertension control compared with non-Hispanic black women ( P  = 0.01). In fully adjusted models, women living with HIV who were normotensive at baseline had faster time to treatment compared with normotensive women living without HIV ( P  = 0.04)., Conclusion: In our study of women in the US South, non-Hispanic black women became aware of their hypertension diagnosis more quickly than non-Hispanic white and Hispanic women but were slower to control their hypertension. Additionally, women living with HIV more quickly treated and controlled their hypertension compared with women living without HIV., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The relationship between experienced discrimination and its effects on pain interference and management among racial disparities is not well explored. This research investigated these associations among Black and White U.S. adults., Methods: The analysis involved 9369 Black and White adults in the REasons for Geographic and Racial Differences in Stroke (REGARDS), assessing experiences of discrimination, pain interference (SF-12), and pain treatment, incorporating factors like demographics, comorbidities, and stress., Results: Black participants experiencing moderate discrimination were found to have a 41% increased likelihood of pain interference (aOR 1.41, 95% CI 1.02-1.95), similaritythose facing high levels of discrimination also showed a 41% increase (aOR 1.41, 95% CI 1.06-1.86) compared to those without such experiences. White individuals reporting moderate discrimination also faced a heightened risk, with a 21% greater chance of pain interference (aOR 1.21, 95% CI 1.01-1.45). Notably, the presence of moderate discrimination among Black participants correlated with a 12% reduced probability of receiving pain treatment (aOR 0.88, 95% CI 0.56-1.37). Furthermore, Black, and White individuals who reported discrimination when seeking employment had a 33% (aOR 0.67, 95% CI 0.45-0.98) and 32% (aOR 0.68, 95% CI 0.48-0.96) lower likelihood, respectively, of receiving treated pain., Conclusion: The study elucidates how discrimination exacerbates pain interference and restricts access to treatment, affecting Black and White individuals differently. These findings underscore an urgent need for strategies to counteract discrimination's negative effects on healthcare outcomes. Addressing these disparities is crucial for advancing health equity and improving the overall quality of care., (© 2024. W. Montague Cobb-NMA Health Institute.)

Background: Underprescribing of guideline-directed medical therapy (GDMT) for heart failure (HF) persists., Objectives: The purpose of this study was to assess polypharmacy as a barrier to GDMT., Methods: We examined participants hospitalized for HF with reduced ejection fraction and HF with mildly reduced ejection fraction between 2003 and 2017 from the Reasons for Geographic and Racial Differences in Stroke study. Participants were stratified by admission medication count-0 to 4, 5 to 9, and ≥10 medications. We examined GDMT use at admission, GDMT contraindications, and initiation of eligible indicated GDMT by medication count. We conducted a multivariable Poisson regression with robust standard errors to examine the association between medication count and GDMT initiation. GDMT included agents for HF with reduced ejection fraction/HF with mildly reduced ejection fraction, antiplatelet agents and statins for coronary artery disease, and anticoagulants for atrial fibrillation., Results: Among 545 participants with HF, 34% were not taking a beta-blocker, 39% were not taking an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, or hydralazine-isosorbide dinitrate, and 90% were not taking a mineralocorticoid receptor antagonist at admission; among participants with coronary artery disease, 36% were not taking an antiplatelet agent, and 38% were not taking a statin; and among participants with atrial fibrillation, 49% were not taking an anticoagulant. Polypharmacy was inversely associated with initiation of at least one indicated medication (5-9 medications: relative risk [RR]: 0.67; 95% CI: 0.56-0.82; P  < 0.001; ≥10 medications: RR: 0.50; 95% CI: 0.39-0.64; P  < 0.001) and initiation of at least half of indicated medications (5-9 medications: RR: 0.64; 95% CI: 0.51-0.81; P  < 0.001; ≥10 medications: RR: 0.50; 95% CI: 0.38-0.67; P  < 0.001)., Conclusions: Polypharmacy is an important barrier to GDMT., Competing Interests: This research project is supported by cooperative agreement U01 NS041588, co-funded by the 10.13039/100000065National Institute of Neurological Disorders and Stroke (NINDS) and the 10.13039/100000049National Institute on Aging (NIA), the 10.13039/100000002National Institutes of Health, and the 10.13039/100000016Department of Health and Human Services. Additional funding was provided by 10.13039/100000050National Heart, Lung, and Blood Institute (NHLBI) grant R01HL080477 (Dr Safford) and 10.13039/100000049NIA grant R03AG056446 (Dr Goyal). Representatives from the 10.13039/100000050NHLBI did not have any role in the design and conduct of the study, the collection, management, analysis, and interpretation of the data, or the preparation or approval of the manuscript. Dr Goyal is supported by 10.13039/100000968American Heart Association grant 20CDA35310455, 10.13039/100000049National Institute on Aging grant K76AG064428; has received personal fees for medicolegal consulting related to heart failure; has received consulting fees from Sensorum Health; and has received honoraria from Akcea Therapeutics, Inc. Dr Ambrosy is supported by a Mentored Patient-Oriented Research Career Development Award (K23HL150159) through the 10.13039/100000050National Heart, Lung, and Blood Institute and has received relevant research support through grants to his institution from 10.13039/100000046Abbott, 10.13039/100014389Amarin Pharma, 10.13039/100006520Edwards Lifesciences, 10.13039/501100022336Esperion, Lexicon, and 10.13039/100008272Novartis. Dr Levitan has received research funding from 10.13039/100002429Amgen, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: There is no standardised approach to screening adults for social risk factors. The goal of this study was to develop mortality risk prediction models based on the social determinants of health (SDoH) for clinical risk stratification., Methods: Data were used from REasons for Geographic And Racial Differences in Stroke (REGARDS) study, a national, population-based, longitudinal cohort of black and white Americans aged ≥45 recruited between 2003 and 2007. Analysis was limited to participants with available SDoH and mortality data (n=20 843). All-cause mortality, available through 31 December 2018, was modelled using Cox proportional hazards with baseline individual, area-level and business-level SDoH as predictors. The area-level Social Vulnerability Index (SVI) was included for comparison. All models were adjusted for age, sex and sampling region and underwent internal split-sample validation., Results: The baseline prediction model including only age, sex and REGARDS sampling region had a c-statistic of 0.699. An individual-level SDoH model (Model 1) had a higher c-statistic than the SVI (0.723 vs 0.708, p<0.001) in the testing set. Sequentially adding area-level SDoH (c-statistic 0.723) and business-level SDoH (c-statistics 0.723) to Model 1 had minimal improvement in model discrimination. Structural racism variables were associated with all-cause mortality for black participants but did not improve model discrimination compared with Model 1 (p=0.175)., Conclusion: In conclusion, SDoH can improve mortality prediction over 10 years relative to a baseline model and have the potential to identify high-risk patients for further evaluation or intervention if validated externally., Competing Interests: Competing interests: MMS is the founder and owner of MedExplain, a medical education company. EBL receives research support from Amgen (to her institution, not to her directly). The other authors declare that they have no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Mediation analysis is an increasingly popular statistical method for explaining causal pathways to inform intervention. While methods have increased, there is still a dearth of robust mediation methods for count outcomes with excess zeroes. Current mediation methods addressing this issue are computationally intensive, biased, or challenging to interpret. To overcome these limitations, we propose a new mediation methodology for zero-inflated count outcomes using the marginalized zero-inflated Poisson (MZIP) model and the counterfactual approach to mediation. This novel work gives population-average mediation effects whose variance can be estimated rapidly via delta method. This methodology is extended to cases with exposure-mediator interactions. We apply this novel methodology to explore if diabetes diagnosis can explain BMI differences in healthcare utilization and test model performance via simulations comparing the proposed MZIP method to existing zero-inflated and Poisson methods. We find that our proposed method minimizes bias and computation time compared to alternative approaches while allowing for straight-forward interpretations., (© 2024 John Wiley & Sons Ltd.)

Importance: Individual cohort studies concur that the amyloidogenic V142I variant of the transthyretin (TTR) gene, present in 3% to 4% of US Black individuals, increases heart failure (HF) and mortality risk. Precisely defining carrier risk across relevant clinical outcomes and estimating population burden of disease are important given established and emerging targeted treatments., Objectives: To better define the natural history of disease in carriers across mid to late life, assess variant modifiers, and estimate cardiovascular burden to the US population., Design, Setting, and Participants: A total of 23 338 self-reported Black participants initially free from HF were included in 4 large observational studies across the US (mean [SD], 15.5 [8.2] years of follow-up). Data analysis was performed between May 2023 and February 2024., Exposure: V142I carrier status (n = 754, 3.2%)., Main Outcomes and Measures: Hospitalizations for HF (including subtypes of reduced and preserved ejection fraction) and all-cause mortality. Outcomes were analyzed by generating 10-year hazard ratios for each age between 50 and 90 years. Using actuarial methods, mean survival by carrier status was estimated and applied to the 2022 US population using US Census data., Results: Among the 23 338 participants, the mean (SD) age at baseline was 62 (9) years and 76.7% were women. Ten-year carrier risk increased for HF hospitalization by age 63 years, predominantly driven by HF with reduced ejection fraction, and 10-year all-cause mortality risk increased by age 72 years. Only age (but not sex or other select variables) modified risk with the variant, with estimated reductions in longevity ranging from 1.9 years (95% CI, 0.6-3.1) at age 50 to 2.8 years (95% CI, 2.0-3.6) at age 81. Based on these data, 435 851 estimated US Black carriers between ages 50 and 95 years are projected to cumulatively lose 957 505 years of life (95% CI, 534 475-1 380 535) due to the variant., Conclusions and Relevance: Among self-reported Black individuals, male and female V142I carriers faced similar and substantial risk for HF hospitalization, predominantly with reduced ejection fraction, and death, with steep age-dependent penetrance. Delineating the individual contributions of, and complex interplay among, the V142I variant, ancestry, the social construct of race, and biological or social determinants of health to cardiovascular disease merits further investigation.

Background: Hypertension prevalence among the overall US adult population has been relatively stable during the last two decades. However, whether this stabilization has occurred across rural-urban communities and across different geographic regions is unknown, particularly among older adults with diabetes who are likely to have concomitant cardiovascular risk factors., Methods: This serial cross-sectional analysis used the 5% national sample of Medicare administrative claims data (n = 3,516,541) to examine temporal trends (2005-2017) in diagnosed hypertension among older adults with diabetes, across urban-rural communities and US census regions (Northeast, Midwest, South, and West). Joinpoint regression was used to obtain annual percent change (APC) in hypertension prevalence across rural-urban communities and geographic regions, and multivariable adjusted regression was used to assess associations between rural-urban communities and hypertension prevalence., Results: The APC in the prevalence of hypertension was higher during 2005-2010, and there was a slowdown in the increase during 2011-2017 across all regions, with significant variations across rural-urban communities within each of the regions. In the regression analysis, in the adjusted model, older adults living in non-core (most rural) areas in the Midwest (PR = 0.988, 95% CI: 0.981-0.995) and West (PR = 0.935, 95% CI: 0.923-0.946) had lower hypertension prevalence than their regional counterparts living in large central metro areas., Conclusions: Although the magnitudes of these associations are small, differences in hypertension prevalence across rural-urban areas and geographic regions may have implications for targeted interventions to improve chronic disease prevention and management., (© 2024. The Author(s).)

Abstract: There is mounting evidence that HIV infection is a risk factor for severe presentations of COVID-19. We hypothesized that the persistent immune activation associated with chronic HIV infection contributes to worsened outcomes during acute COVID-19. The goals of this study were to provide an in-depth analysis of immune response to acute COVID-19 and investigate relationships between immune responses and clinical outcomes in an unvaccinated, sex- and race-matched cohort of people with HIV (PWH, n = 20) and people without HIV (PWOH, n = 41). We performed flow cytometric analyses on peripheral blood mononuclear cells from PWH and PWOH experiencing acute COVID-19 (≤21-day postsymptom onset). PWH were younger (median 52 vs 65 years) and had milder COVID-19 (40% vs 88% hospitalized) compared with PWOH. Flow cytometry panels included surface markers for immune cell populations, activation and exhaustion surface markers (with and without SARS-CoV-2-specific antigen stimulation), and intracellular cytokine staining. We observed that PWH had increased expression of activation (eg, CD137 and OX40) and exhaustion (eg, PD1 and TIGIT) markers as compared to PWOH during acute COVID-19. When analyzing the impact of COVID-19 severity, we found that hospitalized PWH had lower nonclassical (CD16 + ) monocyte frequencies, decreased expression of TIM3 on CD4 + T cells, and increased expression of PDL1 and CD69 on CD8 + T cells. Our findings demonstrate that PWH have increased immune activation and exhaustion as compared to a cohort of predominately older, hospitalized PWOH and raises questions on how chronic immune activation affects acute disease and the development of postacute sequelae., Competing Interests: E.B.L. research funding unrelated to the current work, Amgen Inc. N.E. intellectual property, “Human neutralizing antibodies against SARS-CoV-2/COVID-19” licensed to the Plantform Corp. The remaining authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The majority of patients with cancer seek care at community oncology sites; however, most clinical trials are available at National Cancer Institute (NCI)-designated sites. Although the NCI National Cancer Oncology Research Program (NCORP) was designed to address this problem, little is known about the county-level characteristics of NCORP site locations., Methods: This cross-sectional analysis determined the association between availability of NCORP or NCI sites and county-level characteristic theme percentile scores from the Center for Disease Control and Prevention's Social Vulnerability Index themes. Health Resources and Services Administration's Area Health Resource Files were used to determine contiguous counties. We estimated risk ratios and 95% confidence intervals (CIs) using modified Poisson regression models to evaluate the association between county-level characteristics and site availability within singular and singular and contiguous counties., Results: Of 3141 included counties, 14% had an NCORP, 2% had an NCI, and 1% had both sites. Among singular counties, for a standard deviation increase in the racial and ethnic theme score, there was a 22% higher likelihood of NCORP site availability (95% CI = 1.10 to 1.36); for a standard deviation increase in the socioeconomic status theme score, there was a 24% lower likelihood of NCORP site availability (95% CI = 0.67 to 0.87). Associations were of smaller magnitude when including contiguous counties. NCI sites were located in more vulnerable counties., Conclusions: NCORP sites were more often in racially diverse counties and less often in socioeconomically vulnerable counties. Research is needed to understand how clinical trial representation will increase if NCORP sites strategically increase their locations in more vulnerable counties., (© The Author(s) 2024. Published by Oxford University Press.)

BACKGROUNDPersistent cough and dyspnea are prominent features of postacute sequelae of SARS-CoV-2 (also termed "long COVID"); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined. Using longitudinal pulmonary function testing (PFT) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary long COVID.METHODSThis single-center retrospective study included 1,097 patients with clinically defined long COVID characterized by persistent pulmonary symptoms (dyspnea, cough, and chest discomfort) lasting for 1 or more months after resolution of primary COVID infection.RESULTSAfter exclusion, a total of 929 patients with post-COVID pulmonary symptoms and PFTs were stratified as diffusion impairment and pulmonary restriction, as measured by percentage predicted diffusion capacity for carbon monoxide (DLCO) and total lung capacity (TLC). Longitudinal evaluation revealed diffusion impairment (DLCO ≤ 80%) and pulmonary restriction (TLC ≤ 80%) in 51% of the cohort overall (n = 479). In multivariable modeling regression analysis, invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary long COVID with diffusion impairment and restriction (adjusted odds ratio [aOR] = 9.89, 95% CI 3.62-26.9]). Finally, a subanalysis of CT imaging identified radiographic evidence of fibrosis in this patient population.CONCLUSIONLongitudinal PFTs revealed persistent diffusion-impaired restriction as a key feature of pulmonary long COVID. These results emphasize the importance of incorporating PFTs into routine clinical practice for evaluation of long COVID patients with prolonged pulmonary symptoms. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary long COVID patients.FUNDINGNational Institute of Allergy and Infectious Diseases (AI156898, K08AI129705), National Heart, Lung, and Blood Institute (HL153113, OTA21-015E, HL149944), and the COVID-19 Urgent Research Response Fund at the University of Alabama at Birmingham.

Background: Cardiometabolic risk prediction models that incorporate metabolic syndrome traits to predict cardiovascular outcomes may help identify high-risk populations early in the progression of cardiometabolic disease., Objectives: The purpose of this study was to examine whether a modified cardiometabolic disease staging (CMDS) system, a validated diabetes prediction model, predicts major adverse cardiovascular events (MACE)., Methods: We developed a predictive model using data accessible in clinical practice [fasting glucose, blood pressure, body mass index, cholesterol, triglycerides, smoking status, diabetes status, hypertension medication use] from the REGARDS (REasons for Geographic And Racial Differences in Stroke) study to predict MACE [cardiovascular death, nonfatal myocardial infarction, and/or nonfatal stroke]. Predictive performance was assessed using receiver operating characteristic curves, mean squared errors, misclassification, and area under the curve (AUC) statistics., Results: Among 20,234 REGARDS participants with no history of stroke or myocardial infarction (mean age 64 ± 9.3 years, 58% female, 41% non-Hispanic Black, and 18% diabetes), 2,695 developed incident MACE (13.3%) during a median 10-year follow-up. The CMDS development model in REGARDS for MACE had an AUC of 0.721. Our CMDS model performed similarly to both the ACC/AHA 10-year risk estimate (AUC 0.721 vs 0.716) and the Framingham risk score (AUC 0.673)., Conclusions: The CMDS predicted the onset of MACE with good predictive ability and performed similarly or better than 2 commonly known cardiovascular disease prediction risk tools. These data underscore the importance of insulin resistance as a cardiovascular disease risk factor and that CMDS can be used to identify individuals at high risk for progression to cardiovascular disease.

Background: Life's Simple 7 (LS7) is an easily calculated and interpreted metric of cardiovascular health based on 7 domains: smoking, diet, physical activity, body mass index, blood pressure, cholesterol, and fasting glucose. The Life's Essential 8 (LE8) metric was subsequently introduced, adding sleep metrics and revisions of the previous 7 domains. Although calculating LE8 requires additional information, we hypothesized that it would be a more reliable index of cardiovascular health., Methods: Both the LS7 and LE8 metrics yield scores with higher values indicating lower risk. These were calculated among 11 609 Black and White participants free of baseline cardiovascular disease (CVD) in the Reasons for Geographic and Racial Differences in Stroke study, enrolled in 2003 to 2007, and followed for a median of 13 years. Differences in 10-year risk of incident CVD (coronary heart disease or stroke) were calculated as a function LS7, and LE8 scores were calculated using Kaplan-Meier and proportional hazards analyses. Differences in incident CVD discrimination were quantified by difference in the c-statistic., Results: For both LS7 and LE8, the 10-year risk was approximately 5% for participants around the 99th percentile of scores, and a 4× higher 20% risk for participants around the first percentile. Comparing LS7 to LE8, 10-year risk was nearly identical for individuals at the same relative position in score distribution. For example, the "cluster" of 2013 participants with an LS7 score of 7 was at the 35.8th percentile in distribution of LS7 scores, and had an estimated 10-year CVD risk of 8.4% (95% CI, 7.2%-9.8%). In a similar location in the LE8 distribution, the 1457 participants with an LE8 score of 60±2.5 at the 39.4th percentile of LE8 scores had a 10-year risk of CVD of 8.5% (95% CI, 7.1%-10.1%), similar to the cluster defined by LS7. The age-race-sex adjusted c-statistic of the LS7 model was 0.691 (95% CI, 0.667-0.705), and 0.695 for LE8 (95% CI, 0.681-0.709) ( P for difference, 0.12)., Conclusions: Both LS7 and LE8 were associated with incident CVD, with discrimination of the 2 indices practically indistinguishable. As a simpler metric, LS7 may be favored for use by the general population and clinicians., Competing Interests: None.

Background: Poor neighborhood-level access to health care, including community pharmacies, contributes to cardiovascular disparities in the United States. The authors quantified the association between pharmacy proximity, antihypertensive and statin use, and blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) among a large, diverse US cohort., Methods and Results: A cross-sectional analysis of Black and White participants in the REGARDS (Reasons for Geographic and Racial Differences in Stroke) study during 2013 to 2016 was conducted. The authors designated pharmacy proximity by census tract using road network analysis with population-weighted centroids within a 10-minute drive time, with 5- and 20-minute sensitivity analyses. Pill bottle review measured medication use, and BP and LDL-C were assessed using standard methods. Poisson regression was used to quantify the association between pharmacy proximity with medication use and BP control, and linear regression for LDL-C. Among 16 150 REGARDS participants between 2013 and 2016, 8319 (51.5%) and 8569 (53.1%) had an indication for antihypertensive and statin medication, respectively, and pharmacy proximity data. The authors did not find a consistent association between living in a census tract with higher pharmacy proximity and antihypertensive medication use, BP control, or statin medication use and LDL-C levels, regardless of whether the area was rural, suburban, or urban. Results were similar among the 5- and 20-minute drive-time analyses., Conclusions: Living in a low pharmacy proximity census tract may be associated with antihypertensive and statin medication use, or with BP control and LDL-C levels. Although, in this US cohort, outcomes were similar for adults living in high or low pharmacy proximity census tracts.

Background: Heart failure (HF) affects >6 million US adults, with recent increases in HF hospitalizations. We aimed to investigate the association between neighborhood disadvantage and incident HF events and potential differences by diabetes status., Methods: We included 23 645 participants from the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), a prospective cohort of Black and White adults aged ≥45 years living in the continental United States (baseline 2005-2007). Neighborhood disadvantage was assessed using a Z score of 6 census tract variables (2000 US Census) and categorized as quartiles. Incident HF hospitalizations or HF-related deaths through 2017 were adjudicated. Multivariable-adjusted Cox regression was used to examine the association between neighborhood disadvantage and incident HF. Heterogeneity by diabetes was assessed using an interaction term., Results: The mean age was 64.4 years, 39.5% were Black adults, 54.9% females, and 18.8% had diabetes. During a median follow-up of 10.7 years, there were 1125 incident HF events with an incidence rate of 3.3 (quartile 1), 4.7 (quartile 2), 5.2 (quartile 3), and 6.0 (quartile 4) per 1000 person-years. Compared to adults living in the most advantaged neighborhoods (quartile 1), those living in neighborhoods in quartiles 2, 3, and 4 (most disadvantaged) had 1.30 (95% CI, 1.06-1.60), 1.36 (95% CI, 1.11-1.66), and 1.45 (95% CI, 1.18-1.79) times greater hazard of incident HF even after accounting for known confounders. This association did not significantly differ by diabetes status (interaction P =0.59). For adults with diabetes, the adjusted incident HF hazards comparing those in quartile 4 versus quartile 1 was 1.34 (95% CI, 0.92-1.96), and it was 1.50 (95% CI, 1.16-1.94) for adults without diabetes., Conclusions: In this large contemporaneous prospective cohort, neighborhood disadvantage was associated with an increased risk of incident HF events. This increase in HF risk did not differ by diabetes status. Addressing social, economic, and structural factors at the neighborhood level may impact HF prevention., Competing Interests: Disclosures Drs Safford and Carson receive investigator-initiated research support from Amgen Inc. Dr Goyal has received personal fees for medicolegal consulting on heart failure and has received honoraria from Akcea Inc and Bionest Inc. The other authors report no conflicts.

Background: Among individuals with heart failure (HF), racial differences in comorbidities may be mediated by social determinants of health (SDOH)., Methods: Black and White US community-dwelling participants in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study aged ≥ 45 years with an adjudicated HF hospitalization between 2003 and 2017 were included in this cross-sectional analysis. We assessed whether higher prevalence of comorbidities in Black participants compared to White participants were mediated by SDOH in socioeconomic, environment/housing, social support, and healthcare access domains, using the inverse odds weighting method., Results: Black (n = 240) compared to White (n = 293) participants with HF with preserved ejection fraction (HFpEF) had higher prevalence of diabetes [1.38 (95% CI: 1.18 - 1.61)], chronic kidney disease [1.21 (95% CI: 1.01 - 1.45)], and anemia [1.33 (95% CI: 1.02 - 1.75)] and lower prevalence of atrial fibrillation [0.80 (95% CI: (0.65 - 0.98)]. Black (n = 314) compared to White (n = 367) participants with HF with reduced ejection fraction (HFrEF) had higher prevalence of hypertension [1.04 (95% CI: 1.02 - 1.07)] and diabetes [1.26 (95% CI: 1.09 - 1.45)] and lower prevalence of coronary artery disease [0.86 (95% CI: 0.78 - 0.94)] and atrial fibrillation [0.70 (95% CI: 0.58 - 0.83)]. Socioeconomic status explained 14.5%, 26.5% and 40% of excess diabetes, anemia, and chronic kidney disease among Black adults with HFpEF; however; mediation was not statistically significant and no other SDOH substantially mediated differences in comorbidity prevalence., Conclusions: Socioeconomic status partially mediated excess diabetes, anemia, and chronic kidney disease experienced by Black adults with HFpEF, but differences in other comorbidities were not explained by other SDOH examined., Competing Interests: Dr. Emily B. Levitan receives funding from Amgen Inc.

Mediation analysis has become increasingly popular over the last decade as researchers are interested in assessing mechanistic pathways for intervention. Although available methods have increased, there are still limited options for mediation analysis with zero-inflated count variables where the distribution of response has a "cluster" of data at the zero value (i.e. distribution of number of cigarettes smoked per day, where nonsmokers cluster at zero cigarettes). The currently available methods do not obtain unbiased population average effects of mediation effects. In this paper, we propose an extension of the counterfactual approach to mediation with direct and indirect effects to scenarios where the mediator is a count variable with excess zeroes by utilizing the Marginalized Zero-Inflated Poisson Model (MZIP) for the mediator model. We derive direct and indirect effects for continuous, binary, and count outcomes, as well as adapt to allow mediator-exposure interactions. Our proposed work allows straightforward calculation of direct and indirect effects for the overall population mean values of the mediator, for scenarios in which researchers are interested in generalizing direct and indirect effects to the population. We apply this novel methodology to an application observing how alcohol consumption may explain sex differences in cholesterol and assess model performance via a simulation study comparing the proposed MZIP mediator framework to existing methods for marginal mediator effects., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: End-stage kidney disease (ESKD) is an established risk factor for chronic limb-threatening ischemia (CLTI). Procedural location for ESKD patients has not been well described. This study aims to examine variation in index procedural location in ESKD versus non-ESKD patients undergoing peripheral vascular intervention for CLTI and identify preoperative risk factors for tibial interventions., Methods: Chronic limb-threatening ischemia (CLTI) patients were identified in the Vascular Quality Initiative (VQI) peripheral vascular intervention dataset. Patient demographics and comorbidities were compared between patients with and without ESKD and those undergoing index tibial versus nontibial interventions. A multivariable logistic regression evaluating risk factors for tibial intervention was conducted., Results: A total of 23,480 procedures were performed on CLTI patients with 13.6% (n = 3154) with ESKD. End-stage kidney disease (ESKD) patients were younger (66.56 ± 11.68 versus 71.66 ± 12.09 y old, P = 0.019), more often Black (40.6 versus 18.6%, P < 0.001), male (61.2 versus 56.5%, P < 0.001), and diabetic (81.8 versus 60.0%, P < 0.001) than non-ESKD patients. Patients undergoing index tibial interventions had higher rates of ESKD (19.4 versus 10.6%, P < 0.001) and diabetes (73.4 versus 57.5%, P < 0.001) and lower rates of smoking (49.9 versus 73.0%, P < 0.001) than patients with nontibial interventions. ESKD (odds ratio (OR) 1.67, 95% confidence interval (CI) 1.52-1.86, P < 0.001), Black race (OR 1.19, 95% CI 1.09-1.30, P < 0.001), and diabetes (OR 1.82, 95% CI 1.71-2.00, P < 0.001) were risk factors for tibial intervention., Conclusions: Patients with ESKD and CLTI have higher rates of diabetes and tibial disease and lower rates of smoking than non-ESKD patients. Tibial disease was associated with ESKD, diabetes, and Black race., (Published by Elsevier Inc.)

Background: Hypertension-related diseases are major causes of morbidity among women living with HIV. We evaluated cross-sectional associations of race/ethnicity and HIV infection with hypertension prevalence, awareness, treatment, and control., Methods: Among women recruited into Southern sites of the Women's Interagency HIV Study (2013-2015), hypertension was defined as (1) systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg according to clinical guidelines when data were collected, (2) self-report of hypertension, or (3) use of antihypertensive medication. Awareness was defined as self-report of hypertension, and treatment was self-report of any antihypertensive medication use. Blood pressure control was defined as <140/90 mm Hg at baseline. Prevalence ratios for each hypertension outcome were estimated through Poisson regression models with robust variance estimators adjusted for sociodemographic, behavioral, and clinical risk factors., Results: Among 712 women, 56% had hypertension and 83% were aware of their diagnosis. Of those aware, 83% were using antihypertensive medication, and 63% of those treated had controlled hypertension. In adjusted analyses, non-Hispanic White and Hispanic women had 31% and 48% lower prevalence of hypertension than non-Hispanic Black women, respectively. Women living with HIV who had hypertension were 19% ( P = .04) more likely to be taking antihypertension medication when compared with women living without HIV., Conclusions: In this study population of women living with and without HIV in the US South, the prevalence of hypertension was lowest among Hispanic women and highest among non-Hispanic Black women. Despite similar hypertension prevalence, women living with HIV were more likely to be taking antihypertensive medication when compared with women living without HIV., Competing Interests: Potential conflicts of interest. E. B. L. receives research funding from Amgen unrelated to the current work. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Aim: We evaluated patient-level factors associated with receipt of hemoglobin A1c (HbA1c) testing among Alabama Medicaid beneficiaries with type 2 diabetes., Methods: We conducted a retrospective analysis of person-year observations from Medicaid claims data from 2011 to 2020. Adults aged 19-64 years with type 2 diabetes and continuous enrollment in Medicaid for study year and year prior were included. Primary outcomes were ≥ 1 and ≥ 2 HbA1c test(s) per year. We conducted multivariable Poisson regression stratified by Medicaid eligibility reason (disability, poverty) examining the association of study year, demographics, clinical factors, and healthcare utilization with HbA1c testing., Results: We analyzed 288,379 observations, 51% with disability-based, 49% poverty-based eligibility. Overall, 57% observations had ≥ 1 HbA1c, 35% had ≥ 2 HbA1c tests. More observations with disability-based than poverty-based eligibility had ≥ 1 (76% vs. 38%) and ≥ 2 HbA1c tests (49% vs. 20%). Patient-level factors were associated with a higher likelihood of having ≥ 1 HbA1c: Black race and older age (disability-based eligibility); year after 2011, female sex, and younger age (poverty-based eligibility); and rurality, insulin use, endocrinology care, diabetes complications, and ambulatory care visits (both groups)., Conclusions: Just over one-third of adult Alabama Medicaid beneficiaries with diabetes had ≥ 2 HbA1c tests per year; testing frequency differed by Medicaid eligibility., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Objective: Age is the strongest contributor to 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk. Some older adults have a predicted ASCVD risk ≥7.5 %, without established risk factors. We sought to compare ASCVD incidence among adults with predicted ASCVD risk ≥7.5 %, with and without established ASCVD risk factors, to adults with predicted risk <7.5 %., Methods: We analyzed data from REasons for Geographic and Racial Differences in Stroke study participants, 45-79 years old, without ASCVD or diabetes, not taking statins and with low-density lipoprotein cholesterol 70-189 mg/dL. Participants were categorized into 3 groups based on their 10-year predicted ASCVD risk and presence of established risk factors: <7.5 %, ≥7.5 % with established risk factors and ≥7.5 % without established risk factors. Established risk factors included smoking, systolic blood pressure ≥130 mmHg or antihypertensive medication use, total cholesterol ≥200 mg/dL, or high-density lipoprotein cholesterol <50 mg/dL for women (<40 mg/dL for men). Participants were followed for ASCVD events., Results: Among 11,115 participants, 911 incident ASCVD events occurred over a median of 11.1 years. ASCVD incidence rates were 3.6, 12.8, and 9.8 per 1,000 person-years for participants with predicted risk <7.5 %, predicted risk ≥7.5 % with established risk factors and predicted risk ≥7.5 % without established risk factors, respectively. Compared to adults with predicted risk <7.5 %, hazard ratios for incident ASCVD in participants with risk ≥7.5 % with and without established risk factors were 3.58 (95 %CI 3.03 - 4.21) and 2.72 (95 %CI 1.91-3.88), respectively., Conclusions: Adults with a 10-year predicted ASCVD risk ≥7.5 % but without established risk factors had a high ASCVD incidence., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mary Cushman reports financial support was provided by 10.13039/100000065National Institute of Neurological Disorders and Stroke and the 10.13039/100000049National Institute on Aging (NIA), 10.13039/100000002National Institutes of Health, 10.13039/100022173Department of Health and Human Service. Lisandro Colantonio, Paul Muntner, Emily Levitan reports a relationship with Amgen Inc that includes: funding grants., (© 2023 The Authors. Published by Elsevier B.V.)

Importance: Involvement of a cardiologist in the care of adults during a hospitalization for heart failure (HF) is associated with reduced rates of in-hospital mortality and hospital readmission. However, not all patients see a cardiologist when they are hospitalized for HF., Objective: To determine whether social determinants of health (SDOH) are associated with cardiologist involvement in the management of adults hospitalized for HF., Design, Setting, and Participants: This retrospective cohort study used data from the Reasons for Geographic and Racial Difference in Stroke (REGARDS) cohort. Participants included adults who experienced an adjudicated hospitalization for HF between 2009 and 2017 in all 48 contiguous states in the US. Data analysis was performed from November 2022 to January 2023., Exposures: A total of 9 candidate SDOH, aligned with the Healthy People 2030 conceptual model, were examined: Black race, social isolation, social network and/or caregiver availability, educational attainment less than high school, annual household income less than $35 000, living in rural area, living in a zip code with high poverty, living in a Health Professional Shortage Area, and living in a state with poor public health infrastructure., Main Outcomes and Measures: The primary outcome was cardiologist involvement, defined as involvement of a cardiologist as the primary responsible clinician or as a consultant. Bivariate associations between each SDOH and cardiologist involvement were examined using Poisson regression with robust SEs., Results: The study included 1000 participants (median [IQR] age, 77.8 [71.5-84.0] years; 479 women [47.9%]; 414 Black individuals [41.4%]; and 492 of 876 with low income [56.2%]) hospitalized at 549 unique US hospitals. Low annual household income (<$35 000) was the only SDOH with a statistically significant association with cardiologist involvement (relative risk, 0.88; 95% CI, 0.82-0.95). In a multivariable analysis adjusting for age, race, sex, HF characteristics, comorbidities, and hospital characteristics, low income remained inversely associated with cardiologist involvement (relative risk, 0.89; 95% CI, 0.82-0.97)., Conclusions and Relevance: This cohort study found that adults with low household income were 11% less likely than adults with higher incomes to have a cardiologist involved in their care during a hospitalization for HF. These findings suggest that socioeconomic status may bias the care provided to patients hospitalized for HF.

Introduction: Despite advances in diabetes management, only one-quarter of people with diabetes in the US achieve optimal targets for glycated hemoglobin A 1c (HbA 1c ), blood pressure, and cholesterol. We sought to evaluate temporal trends and predictors of achieving glycemic control among adults with type 2 diabetes covered by Alabama Medicaid from 2011 through 2019., Methods: We completed a retrospective analysis of Medicaid claims and laboratory data, using person-years as the unit of analysis. Inclusion criteria were being aged 19 to 64 years, having a diabetes diagnosis, being continuously enrolled in Medicaid for a calendar year and preceding 12 months, and having at least 1 HbA 1c result during the study year. Primary outcomes were HbA 1c thresholds of <7% and <8%. Primary exposure was study year. We conducted separate multivariable-adjusted logistic regressions to evaluate relationships between study year and HbA 1c thresholds., Results: We included 43,997 person-year observations. Mean (SD) age was 51.0 (9.9) years; 69.4% were women; 48.1% were Black, 42.9% White, and 0.4% Hispanic. Overall, 49.1% had an HbA 1c level of <7% and 64.6% <8%. Later study years and poverty-based eligibility were associated with lower probability of reaching target HbA 1c levels of <7% or <8%. Sex, race, ethnicity, and geography were not associated with likelihood of reaching HbA 1c <7% or <8% in any model., Conclusion: Later study years were associated with lower likelihood of meeting target HbA 1c levels compared with 2011, after adjusting for covariates. With approximately 35% not meeting an HbA 1c target of <8%, more work is needed to improve outcomes of low-income adults with type 2 diabetes.