Race, Social Determinants of Health, and Comorbidity Patterns Among Participants with Heart Failure in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

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.

The Association Between Experienced Discrimination and Pain in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

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.

Polypharmacy and Guideline-Directed Medical Therapy Initiation Among Adults Hospitalized With Heart Failure.

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.

Trajectory of Cognitive Decline After Incident Heart Failure Hospitalization: Findings From the REGARDS Study.

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.

Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

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 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) 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 HbA1c 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.

Reductions in renin-angiotensin system inhibitors following hospitalization for heart failure.

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.

Association of Integrase Strand Transfer Inhibitor-Based Antiretroviral Therapy with Blood Pressure and Sustained Hypertension in People with HIV.

BACKGROUND: Integrase strand transfer inhibitors (INSTI) 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 mmHg or DBP≥80 mmHg on AOBP, sustained hypertension was defined as awake SBP≥130 mmHg or DBP≥80 mmHg. RESULTS: Mean SBP and DBP was higher among participants taking INSTI-based versus non-INSTI-based ART (AOBP-SBP/DBP: 144.7/83.8 versus 135.3/79.3 mmHg; awake-SBP/DBP: 143.2/80.9 versus 133.4/76.3 mmHg; asleep-SBP/DBP: 133.3/72.9 versus 120.3/65.4 mmHg; 24-hour-SBP/DBP: 140.4/78.7 versus 130.0/73.7 mmHg). After multivariable adjustment, AOBP, awake, asleep and 24-hour SBP was 12.5 (95%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) mmHg higher among those taking INSTI-based versus non-INSTI-based ART, respectively. AOBP, awake, asleep and 24-hour DBP was 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) mmHg higher among those taking INSTI-based versus non-INSTI-based ART after multivariable adjustment. All participants had SBP ≥130 mmHg or DBP≥80 mmHg on AOBP and 97.9% and 65.7% of participants taking INSTI-based and non-INSTI-based ART had sustained hypertension, respectively. CONCLUSION: INSTI-based ART was associated with higher SBP and DBP than non-INSTI-based ART.

Awareness, treatment, and control of hypertension among women at risk or living with HIV in the US South.

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.

Development and validation of mortality prediction models based on the social determinants of health.

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.

Cardiovascular Burden of the V142I Transthyretin Variant.

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.

Cardiometabolic Disease Staging and Major Adverse Cardiovascular Event Prediction in 2 Prospective Cohorts.

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.

Why location matters: associations between county-level characteristics and availability of National Cancer Oncology Research Program and National Cancer Institute sites.

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.

Regional and rural-urban patterns in the prevalence of diagnosed hypertension among older U.S. adults with diabetes, 2005-2017.

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.

Population-average mediation analysis for zero-inflated count outcomes.

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.

Characteristics and determinants of pulmonary long COVID.

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.

Impact of Chronic HIV Infection on Acute Immune Responses to SARS-CoV-2.

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.

Association Between Pharmacy Proximity With Cardiovascular Medication Use and Risk Factor Control in the United States.

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.

Characteristics and Determinants of Pulmonary Long COVID.

RATIONALE: Persistent cough and dyspnea are prominent features of post-acute sequelae of SARS-CoV-2 (termed 'Long COVID'); however, physiologic measures and clinical features associated with these pulmonary symptoms remain poorly defined. OBJECTIVES: Using longitudinal pulmonary function testing (PFTs) and CT imaging, this study aimed to identify the characteristics and determinants of pulmonary Long COVID. METHODS: The University of Alabama at Birmingham Pulmonary Long COVID cohort was utilized to characterize lung defects in patients with persistent pulmonary symptoms after resolution primary COVID infection. Longitudinal PFTs including total lung capacity (TLC) and diffusion limitation of carbon monoxide (DLCO) were used to evaluate restriction and diffusion impairment over time in this cohort. Analysis of chest CT imaging was used to phenotype the pulmonary Long COVID pathology. Risk factors linked to development of pulmonary Long COVID were estimated using univariate and multivariate logistic regression models. MEASUREMENTS AND MAIN RESULTS: Longitudinal evaluation 929 patients with post-COVID pulmonary symptoms revealed diffusion impairment (DLCO ≤80%) and restriction (TLC ≤80%) in 51% of the cohort (n=479). In multivariable logistic regression analysis (adjusted odds ratio; aOR, 95% confidence interval [CI]), invasive mechanical ventilation during primary infection conferred the greatest increased odds of developing pulmonary Long COVID with diffusion impaired restriction (aOR=10.9 [4.09-28.6]). Finally, a sub-analysis of CT imaging identified evidence of fibrosis in this population. CONCLUSIONS: Persistent diffusion impaired restriction was identified as a key feature of pulmonary Long COVID. Subsequent clinical trials should leverage combined symptomatic and quantitative PFT measurements for more targeted enrollment of pulmonary Long COVID patients.

Neighborhood Disadvantage and Risk of Heart Failure: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

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.