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Charles Muiruri,1,2 Isabelle P Sico,1 Julie Schexnayder,3 Allison R Webel,3 Nwora Lance Okeke,4 Christopher T Longenecker,5 Juan Marcos Gonzalez,1 Kelley A Jones,1 Sarah E Gonzales,1 Hayden B Bosworth1 1Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA; 2Duke Global Health Institute, Duke University, Durham, NC, USA; 3Frances Payne Bolton School of Nursing, Case Western Reserve University, Cleveland, OH, USA; 4Department of Medicine, Duke University Medical Center, NC, USA; 5Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, USACorrespondence: Charles Muiruri Email charles.muiruri@duke.eduBackground: After achieving viral suppression, it is critical for persons living with HIV (PLWH) to focus on prevention of non-AIDS comorbidities such as cardiovascular disease (CVD) in order to enhance their quality of life and longevity of life. Despite PLWH elevated risk of developing CVD compared to individuals without HIV, PLWH do not often meet evidence-based treatment goals for CVD prevention; the reasons for PLWH not meeting guideline recommendations are poorly understood. The objective of this study was to identify the factors associated with adherence to CVD medications for PLWH who have achieved viral suppression.Methods: Qualitative data were obtained from formative research conducted to inform the adaptation of a nurse-led intervention trial to improve cardiovascular health at three large academic medical centers in the United States. Transcripts were analyzed using content analysis guided by principles drawn from grounded theory.Results: Fifty-one individuals who had achieved viral suppression (< 200 copies/mL) participated: 37 in 6 focus groups and 14 in individual semi-structured interviews. Mean age was 57 years (SD: 7.8); most were African Americans (n=31) and majority were male (n=34). Three main themes were observed. First, participants reported discordance between their healthcare providers’ recommendations and their own preferred strategies to reduce CVD risk. Second, participants intentionally modified frequency of CVD medication taking which appeared to be related to low CVD risk perception and perceived or experienced side effects with treatment. Finally, participants discussed the impact of long-term experience with HIV care on adherence to CVD medication and motivational factors that enhanced adherence to heart healthy behaviors.Conclusion: Findings suggest that future research should focus on developing interventions to enhance patient–provider communication in order to elicit beliefs, concerns and preferences for CVD prevention strategies. Future research should seek to leverage and adapt established evidence-based practices in HIV care to support CVD medication adherence.Keywords: medication adherence, persons living with HIV, viral suppression, cardiovascular disease, qualitative research

Objectives: Cardiovascular risk is increased in people living with HIV (PLWH). In HIV‐uninfected populations, total absolute monocyte count (AMC) has been shown to be predictive of future cardiovascular events (CVEs). We sought to determine whether AMC predicts CVEs in PLWH independent of established and HIV‐related cardiovascular risk factors. Methods: We identified all PLWH within the Partners HIV Cohort without factors that could confound the monocyte count. CVE was defined as fatal or non‐fatal acute myocardial infarction or ischaemic stroke. Baseline‐measured AMC was defined as the average of all outpatient AMC counts a year before and after the baseline date. Multivariable Cox proportional hazards models were used to assess the association of baseline AMC with CVEs. Results: Our cohort consisted of 1980 patients, with median follow‐up of 10.9 years and 182 CVEs. Mean (± SD) age was 41.9 ± 9.3 years; 73.0% were male. Mean CD4 count was 506.3 ± 307.1 cells/µL, 48% had HIV viral load (VL) < 400 copies/mL, and 87% were on antiretroviral therapy. Mean AMC was 0.38 × 103 ± 0.13 cells/µL. In multivariable modelling adjusted for traditional CV risk factors, CD4 cell count, and HIV VL, AMC quartile 2 (Q2) (HR = 1.01, P = 0.98), Q3 (HR = 1.07, P = 0.76), and Q4 (HR = 0.97, P = 0.89) were not significantly predictive of CVE compared with Q1. Discussion: Baseline AMC was not associated with long‐term CVEs in PLWH. AMC obtained in routine clinical encounters does not appear to enhance CV risk stratification in PLWH. [ABSTRACT FROM AUTHOR]

Objectives HIV-infected adults have heightened monocyte activation and inflammation, at least partially as a consequence of altered gut integrity. The role of dietary factors in microbial translocation and inflammation and their downstream effect on markers of cardiovascular disease (CVD) have not been explored. Our purpose was to describe the longitudinal dietary patterns of HIV-infected adults, and to examine the relationship between dietary intake, gut integrity, inflammation and subclinical markers of CVD in HIV-infected adults. Methods We conducted a secondary analysis of 147 HIV-infected participants in a 96-week randomized clinical trial of rosuvastatin as primary CVD prevention. Dietary intake was assessed using dietary recall; plasma gut integrity, monocyte activation and inflammation markers were measured using an enzyme-linked immunosorbent assay ( ELISA); and CVD risk was assessed using carotid ultrasound and the coronary artery calcium score. Linear mixed models were used to analyse longitudinally measured biomarkers. Results The median age was 45 years and 78% of patients were male. At baseline, participants consumed a mean (standard deviation) of 108 (70) g of fat daily, 19 (15.6) g of fibre, 266 (186) g of carbohydrates and 15.6 (5.9) g of protein; 45% of the sample consumed alcohol. Over time, alcohol consumption was associated with several markers of gut integrity and inflammation (all P < 0.05). Conclusions HIV-infected adults in a contemporary, high-resource setting have poor dietary patterns. Alcohol use was associated with worse gut integrity and increased inflammation, while other aspects of diet (fibre, carbohydrates and fat) were not. These data add to growing evidence illustrating the need for a better understanding of the effect of lifestyle factors on comorbidities in HIV-infected adults. [ABSTRACT FROM AUTHOR]

Objectives HIV-infected patients on antiretroviral therapy ( ART) have an increased cardiovascular disease ( CVD) risk as a result of heightened inflammation and immune activation, despite at times having normal lipids and few traditional risk factors. Biomarkers are needed to identify such patients before a clinical event. Lipoprotein-associated phospholipase A2 ( Lp-PLA2) predicts CVD events in the general population. This study investigated the relationship between Lp-PLA2 and markers of CVD risk, systemic inflammation, immune activation, and coagulation in HIV infection. Methods One hundred subjects on stable ART with normal fasting low-density lipoprotein ( LDL) cholesterol were enrolled in the study. Plasma Lp-PLA2 concentrations were measured by enzyme-linked immunosorbent assay ( ELISA; > 200 ng/mL was considered high CVD risk). Subclinical atherosclerosis, endothelial function, inflammation, immune activation and fasting lipids were also evaluated. Results The median age of the patients was 47 years and 77% were male. Median (range) Lp-PLA2 was 209 (71-402) ng/mL. Fifty-seven per cent of patients had Lp-PLA2 concentrations > 200 ng/mL. Lp-PLA2 was positively correlated with soluble markers of inflammation or immune activation (tumour necrosis factor receptor- II, intercellular and vascular cellular adhesion molecules, and CD14; all R = 0.3; P < 0.01), and negatively correlated with coagulation markers ( D-dimer and fibrinogen; both R = −0.2; P < 0.04). Lp-PLA2 was not correlated with lipids, coronary artery calcium score, or flow-mediated vasodilation, but trended towards a significant correlation with carotid intima-media thickness ( R = 0.2; P = 0.05). Conclusions In this population with stable ART and normal LDL cholesterol, Lp-PLA2 was in the high CVD risk category in the majority of subjects. Lp-PLA2 appears to be associated with inflammation/immune activation, but also with anti-thrombotic effects. Lp-PLA2 may represent a valuable early biomarker of CVD risk in HIV infection before subclinical atherosclerosis can be detected. [ABSTRACT FROM AUTHOR]

Background: Hypertension is a leading risk factor for cardiovascular disease among patients living with HIV (PLWH). Understanding the predictors and patterns of antihypertensive medication prescription and blood pressure (BP) control among PLWH with hypertension (HTN) is important to improve the primary prevention efforts for this high-risk population. We sought to assess important patient-level correlates (eg, race) and inter-facility variations in antihypertension medication prescriptions and BP control among Veterans living with HIV (VLWH) and HTN., Methods: We studied VLWH with a diagnosis of HTN who received care in the Veterans Health Administration (VHA) from January 2018 to December 2019. We evaluated HTN treatment and blood pressure control across demographic variables, including race, and by medical comorbidities. Data were also compared among VHA facilities. Predictors of HTN treatment and control were assessed in 2-level hierarchical multivariate logistic regression models to estimate odds ratios (ORs). The VHA facility random-effects parameters from the hierarchical models were used to calculate the median odds ratios to characterize the variation across the different VHA facilities., Results: A total of 17,468 VLWH with HTN (mean age 61 years, 97% male, 54% Black, 40% White) who received care within the VHA facilities in 2018-2019 were included. 73% were prescribed antihypertension medications with higher prescription rates among Black vs White patients (75% vs 71%) and higher prescription rates among patients with a history of cardiovascular disease, diabetes, and kidney disease (>80%), and those receiving antiretroviral therapy and with controlled HIV viral load (∼75%). Only 27% of VLWH with HTN had optimal BP control of systolic BP <130 mmHg and diastolic BP <80 mmHg, with a lower rate of control among Black vs White patients (24% v. 31%). In multivariate regression, Black patients had a higher likelihood of HTN medication prescription (OR 1.32, 95% CI: 1.22-1.42) but were less likely to have optimal BP control (OR 0.82; 0.76-0.88). Important positive correlates of antihypertensive prescription and optimal BP control included: number of outpatient visits in prior year, and histories of diabetes, coronary artery disease, and heart failure. There was about 10% variability in both antihypertensive prescription and BP control patterns between VHA facilities for patients with similar characteristics. There was increased inter-facility variation in antihypertensive prescription among those with a history of heart failure and those not receiving antiretroviral therapy., Conclusion: In a retrospective analysis of large VHA data, we found that VLWH with HTN have suboptimal antihypertensive medication prescription and BP control. Black VLWH had higher HTN medication prescription rates but lower optimal BP control., Competing Interests: Conflict of interest None reported., (Published by Elsevier Inc.)

Background: People with HIV (PWH) have lower exercise capacity than peers without HIV, which may be explained by chronotropic incompetence, the inability to increase heart rate during exercise., Methods: The Exercise for Healthy Aging Study included adults aged 50 to 75 years with and without HIV. Participants completed 12 weeks of moderate-intensity exercise, before randomization to moderate or high intensity for 12 additional weeks. We compared adjusted heart rate reserve (AHRR; chronotropic incompetence <80%) on cardiopulmonary exercise testing by HIV serostatus and change from baseline to 12 and 24 weeks using mixed effects models., Results: Among 32 PWH and 37 controls (median age, 56 years; 7% female), 28% of PWH vs 11% of controls had chronotropic incompetence at baseline (P = .067). AHRR was lower among PWH (91% vs 101%; difference, 10%; 95% CI, 1.9%-18.9%; P = .02). At week 12, AHRR normalized among PWH (+8%; 95% CI, 4%-11%; P < .001) and was sustained at week 24 (+5%; 95% CI, 1%-9%; P = .008) versus no change among controls (95% CI, -4% to 4%; P = .95; interaction P = .004). After 24 weeks of exercise, 15% of PWH and 10% of controls had chronotropic incompetence (P = .70)., Conclusions: Chronotropic incompetence contributes to reduced exercise capacity among PWH and improves with exercise training., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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: Adults with congenital heart disease (ACHD) are at risk for lower quality of life (QOL) and psychological health. Behavioral interventions to meet their psychosocial needs are lacking. The aim of this study is to evaluate the feasibility of implementing the Promoting Resilience in Stress Management (PRISM) intervention in ACHD and its efficacy in increasing resilience in this population., Methods: We designed a phase II randomized controlled clinical trial of patients with moderate or complex ACHD, physiological stages C or D. Enrolled participants will be randomized to receive PRISM or usual care. PRISM is a manualized, skills-based behavioral intervention comprised of four one-on-one sessions targeting resilience resources (stress-management, goal-setting, cognitive reframing, meaning making), an optional session on advance care planning, and a facilitated family meeting. Participants in both groups will complete study questionnaires at enrollment and 3-months later. The primary aim is to describe feasibility, namely the proportions of patients who a) enroll in the study among those eligible, and b) complete the PRISM intervention among those randomized to that arm. We will also evaluate PRISM's efficacy by using linear regression models to compare changes in mean resilience scores between assigned groups. In exploratory analyses, we will evaluate effects on QOL, psychological distress, perceived competence for health care management, and comfort with advance care planning., Discussion: This study will provide rigorous evidence to determine the feasibility and efficacy of a brief intervention to promote resilience and psychosocial health in ACHD. Findings may guide the development of a future multi-site effectiveness study., Clinical Trial Registration: NCT04738474., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: There is an unmet surgical burden among people living with rheumatic heart disease (RHD) in Uganda. Nevertheless, risk factors associated with time to first intervention and preoperative mortality are poorly understood., Methods: Individuals with RHD who met indications for valve surgery were identified using the Uganda National RHD Registry (January 2010-August 2022). Kaplan-Meier estimates and multivariable Cox proportional hazard models were used., Results: Of the cohort with clinical RHD, 64% (1452 of 2269) met criteria for an index operation. Of those, 13.5% obtained a surgical intervention, whereas 30.6% died before the operation. The estimated likelihood of first operation was 50% at 9.3 years of follow-up (95% CI, 8.1-upper limit not reached). Intervention was more likely in men vs women (hazard ratio [HR], 1.78; 95% CI, 1.21-2.64), those with postsecondary education vs primary school or less (HR, 3.60; 95% CI, 1.88-6.89), and those with a history of atrial fibrillation (HR, 2.78; 95% CI, 1.63-4.76). Surgical intervention was less likely for adults vs those aged <18 years (HR, 0.49; 95% CI, 0.32-0.77) and those with New York Heart Association Functional Class III/IV vs I/II (HR, 0.51; 95% CI, 0.32-0.83). The median preoperative survival time among those awaiting first operation was 4.6 years (95% CI, 3.9-5.7 years). History of infective endocarditis, right ventricular dysfunction, pericardial effusion, atrial fibrillation, and having surgical indications for multiple valves were associated with increased probability of death., Conclusions: Our analysis revealed a prolonged time to first surgical intervention and high preintervention death for RHD in Uganda, with factors such as age, sex, and education level remaining barriers to obtaining surgery., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Despite improvements to the cascade of HIV care in East Africa, access to care for non-communicable disease co-morbidities like hypertension (HTN) remains a persistent problem. The integration of care for these conditions presents an opportunity to achieve efficiencies in delivery as well as decrease overall costs for patients. This study aims to build evidence on the burden of current out-of-pocket costs of care among HIV-HTN co-morbid patients., Methods: We administered a pre-tested, cross-sectional, out-of-pocket cost survey to 94 co-morbid patients receiving HIV care from 10 clinics in the Wakiso and Kampala districts of Uganda from June to November 2021. The survey assessed socio-demographic characteristics, direct medical costs (e.g., medications, consultations), indirect costs (e.g., transport, food, caregiving), and economic costs (i.e., foregone income) associated with seeking HIV and HTN care, as well as possible predictors of monthly care costs. Patients were sampled both during a government-imposed nation-wide full COVID-19 lockdown (n = 30) and after it was partially lifted (n = 64)., Results: Median HIV care costs constitute between 2.7 and 4.0% of median monthly household income, while HTN care costs are between 7.1 to 7.9%. For just under half of our sample, the median monthly cost of HTN care is more than 10% of household income, and more than a quarter of patients report borrowing money or selling assets to cover costs. We observe uniformly lower reported costs of care for both conditions under full COVID-19 lockdown, suggesting that access to care was limited. The main predictors of monthly HIV and HTN care costs varied by disease and costing perspective., Conclusions: Patient out of pocket costs of care for HIV and HTN were substantial, but significantly lower during the 2021 full COVID-19 lockdown in Uganda. New strategies such as service integration need to be explored to reduce these costs., Competing Interests: The authors have declared that no competing interest exist., (Copyright: © 2024 Cameron 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: People with HIV (PWH) are at elevated risk for atherosclerotic cardiovascular disease (ASCVD). Underrepresented racial and ethnic groups (UREGs) with HIV in the southern U.S. are disproportionately affected, yet whether cardiology specialist care for this at-risk group improves blood pressure and lipid control or prevents cardiovascular events is unknown., Methods: We evaluated a cohort of PWH from UREGs at elevated ASCVD risk without known cardiovascular disease who received HIV-related care from 2015-2018 at four academic medical centers in the Southern United States with follow up through 2020. Primary outcomes were blood pressure control (<140/90 mmHg) and lipid control (LDL-C ≤ 100 mg/dl) over 2 years and time to first major adverse cardiovascular (MACE) event. Statistical analyses were adjusted for cohort/site and patient factors including HIV measures and comorbidities., Results: Among 3972 included PWH (median age 47 years old, 32.6% female) without diagnosed cardiovascular disease, 276 (6.9%) had a cardiology clinic visit. Cardiology clinic visits were not significantly associated with subsequent blood pressure control (adjusted OR 0.78, 95% CI 0.49-1.24, p=0.29) or lipid control (adjusted OR 2.25, 95% CI 0.72-7.01, p=0.16). Over a median follow up of 5 years, patients who had a cardiology clinic visit had higher risk of MACE, overall mortality, and falsification endpoints (hospitalization or death from accident/trauma and pneumonia/sepsis) indicating a higher risk group overall, even after adjusting for measured risk factors., Conclusions: Among UREG PWH at elevated cardiovascular risk, a cardiology clinic visit was not associated with improved cardiovascular risk factors or reduced risk of cardiovascular events. Our study suggests that seeing a cardiologist is not alone sufficient to promote cardiovascular health or prevent cardiovascular events among PWH, but with low confidence given the higher risk among those who had a cardiology visit., Competing Interests: Disclosures: CTL is on the advisory board for Theratechnologies outside the scope of this work. None of the other authors have pertinent disclosures or relevant conflicts of interest.

Competing Interests: American Heart Association Awards: 23HERNPRH1150359,23HERNCRH1076858, 878926, 878922, 20SFRN35360185, 20SFRN35380042.

Obesity is a recognized public health epidemic with a prevalence that continues to increase dramatically in nearly all populations, impeding progress in reducing incidence rates of cardiovascular disease. Over the past decade, obesity science has evolved to improve knowledge of its multifactorial causes, identifying important biological causes and sociological determinants of obesity. Treatments for obesity have also continued to develop, with more evidence-based programs for lifestyle modification, new pharmacotherapies, and robust data to support bariatric surgery. Despite these advancements, there continues to be a substantial gap between the scientific evidence and the implementation of research into clinical practice for effective obesity management. Addressing barriers to obesity science implementation requires adopting feasible methodologies and targeting multiple levels (eg, clinician, community, system, policy) to facilitate the delivery of obesity-targeted therapies and maximize the effectiveness of guideline-driven care to at-need patient populations. This scientific statement (1) describes strategies shown to be effective or promising for enhancing translation and clinical application of obesity-based research; (2) identifies key gaps in the implementation of obesity science into clinical practice; and (3) provides guidance and resources for health care professionals, health care systems, and other stakeholders to promote broader implementation and uptake of obesity science for improved population-level obesity management. In addition, advances in implementation science that hold promise to bridge the know-do gap in obesity prevention and treatment are discussed. Last, this scientific statement highlights implications for health research policy and future research to improve patient care models and optimize the delivery and sustainability of equitable obesity-related care.

Background: Africa has a disproportionate burden of HIV-related cardiovascular disease. We aimed to describe physical activity in people living with HIV (PLHIV) and people without HIV (PWOH) in Uganda and characterize its relationship with the presence of computed tomography angiography-detected (CCTA) coronary artery disease (CAD)., Methods: We performed a cross-sectional analysis of the Ugandan Study of HIV Effects on the Myocardium and Atherosclerosis using Computed Tomography (mUTIMA-CT) cohort. From 2017-2019, physical activity in PLHIV and PWOH was assessed by accelerometry over seven days. Participants additionally underwent CCTA. Univariable and multivariable modified Poisson regression was used to analyze the relationship between physical activity and CAD presence., Results: 168 participants were analyzed. The median (IQR) age was 57 (53-58) years old and 64% were female. Males had more moderate-to-vigorous physical activity per week [68 minutes (12-144) vs 15 minutes (0-50), P <0.001] and less light physical activity [788 minutes (497-1,202) vs [1,059 (730-1490), P =0.001] compared to females, but there was no difference by HIV status. After adjusting for age, which accounted for 10% of the variation in steps taken, and sex, no significant associations were found between physical activity and coronary plaque., Conclusion: Objectively measured physical activity was low compared to guideline recommendations, with males being somewhat more active than females and without significant differences by HIV status. Physical activity was not associated with the presence of CAD independently of age and sex., Competing Interests: DISCLOSURES The authors have no relevant conflicts of interest.

The increased incidence of chronic diseases among people with HIV (PWH) is poised to increase the need for specialty care outside of HIV treatment settings. To reduce outcome disparities for HIV-associated comorbidities in the United States, it is critical to optimize access to and the quality of specialty care for underrepresented racial and ethnic minority (URM) individuals with HIV. We explored the experiences of URM individuals with HIV and other comorbidities in the specialty care setting during their initial and follow-up appointments. We conducted qualitative interviews with participants at three large academic medical centers in the United States with comprehensive health care delivery systems between November 2019 and March 2020. The data were analyzed using applied thematic analysis. A total of 27 URM individuals with HIV were interviewed. The majority were Black or African American and were referred to cardiology specialty care. Most of the participants had positive experiences in the specialty care setting. Facilitators of the referral process included their motivation to stay healthy, referral assistance from HIV providers, access to reliable transportation, and proximity to the specialty care health center. Few participants faced individual, interpersonal, and structural barriers, including the perception of individual and facility stigma toward PWH, a lack of transportation, and a lack of rapport with providers. Future case studies are needed for those URM individuals with HIV who face barriers and negative experiences. Interventions that involve PWH and health care providers in specialty care settings with a focus on individual- and structural-level stigma can support the optimal use of specialty care.

Background: Underrepresented racial and ethnic groups (UREGs) with HIV have a higher risk of cardiovascular disease (CVD) compared with the general population. Referral to a cardiovascular specialist improves CVD risk factor management in high-risk individuals. However, patient and provider factors impacting the likelihood of UREGs with HIV to have an encounter with a cardiologist are unknown., Methods: We evaluated a cohort of UREGs with HIV and borderline CVD risk (10-year risk ≥ 5% by the pooled cohort equations or ≥ 7.5% by Framingham risk score). Participants received HIV-related care from 2014-2020 at four academic medical centers in the United States (U.S.). Adjusted Cox proportional hazards regression was used to estimate the association of patient and provider characteristics with time to first ambulatory cardiology encounter., Results: A total of 2,039 people with HIV (PWH) and borderline CVD risk were identified. The median age was 45 years (IQR: 36-50); 52% were female; and 94% were Black. Of these participants, 283 (14%) had an ambulatory visit with a cardiologist (17% of women vs. 11% of men, p < .001). In fully adjusted models, older age, higher body mass index (BMI), atrial fibrillation, multimorbidity, urban residence, and no recent insurance were associated with a greater likelihood of an encounter with a cardiologist., Conclusion: In UREGs with HIV and borderline CVD risk, the strongest determinants of a cardiology encounter were diagnosed CVD, insurance type, and urban residence. Future research is needed to determine the extent to which these encounters impact CVD care practices and outcomes in this population., Trial Registration: ClinicalTrials.gov Identifier: NCT04025125., (© 2023. The Author(s).)

Background: Guideline-directed medical therapies (GDMTs) improve quality of life and health outcomes for patients with heart failure (HF). However, GDMT utilization is suboptimal among patients with HF., Objective: The aims of this study were to engage key stakeholders in semistructured, virtual human-centered design sessions to identify challenges in GDMT optimization posthospitalization and inform the development of a digital toolkit aimed at optimizing HF GDMTs., Methods: For the human-centered design sessions, we recruited ( a ) clinicians who care for patients with HF across 3 hospital systems, ( b ) patients with HF with reduced ejection fraction (ejection fraction ≤ 40%) discharged from the hospital within 30 days of enrollment, and ( c ) caregivers. All participants were 18 years or older, English speaking, with Internet access., Results: A total of 10 clinicians (median age, 37 years [interquartile range, 35-41], 12 years [interquartile range, 10-14] of experience caring for patients with HF, 80% women, 50% White, 50% nurse practitioners) and three patients and one caregiver (median age 57 years [IQR: 53-60], 75% men, 50% Black, 75% married) were included. Five themes emerged from the clinician sessions on challenges to GDMT optimization (eg, barriers to patient buy-in). Six themes on challenges (eg, managing medications), 4 themes on motivators (eg, regaining independence), and 3 themes on facilitators (eg, social support) to HF management arose from the patient and caregiver sessions., Conclusions: The clinician, patient, and caregiver insights identified through human-centered design will inform a digital toolkit aimed at optimizing HF GDMTs, including a patient-facing smartphone application and clinician dashboard. This digital toolkit will be evaluated in a multicenter, clinical trial., Competing Interests: Under a license agreement between Corrie Health and Johns Hopkins University, the university owns equity in Corrie Health. The university, F.A.M. and S.S.M. are entitled to royalty distributions related to Corrie Health. In addition, F.A.M. and S.S.M. are co-founders of and hold equity in Corrie Health. This arrangement has been reviewed and approved by Johns Hopkins University in accordance with its conflict of interest policies. F.A.M. and S.S.M. have also received research and material support from Apple and iHealth. Furthermore, S.S.M. is on the Advisory Board for Care Access and reports personal consulting fees from Amgen, AstraZeneca, Chroma, Kaneka, NewAmsterdam, Novartis, Novo Nordisk, Sanofi, and 89bio. E.M.S. reports personal consulting fees from Corrie Health. A.S. reports consulting fees from Lexicon Pharmaceuticals, Reprieve Cardiovascular, and Cleerly Health. N.A.G. reports consulting fees from Kiniksa Pharmaceuticals. All other authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Adult congenital heart disease (ACHD) can negatively impact quality of life (QOL). Strengthening resilience may improve this and other psychosocial outcomes important for living a meaningful life., Objectives: The purpose of this study was to describe resilience and key psychosocial health outcomes in ACHD and evaluate the associations between resilience and these outcomes., Methods: We conducted a prospective cohort study of outpatients with moderate or complex ACHD between May 2021 and June 2022. Participants completed surveys at baseline and 3 months, evaluating resilience (Connor-Davidson Resilience Scale-10), health-related QOL (EQ5D-3L, linear analog scale), health status (Euroqol visual analog scale), self-competence (Perceived Competence Scale), and psychological symptom burden (Hospital Anxiety and Depression Scale) and distress (Kessler-6)., Results: The mean participant age (N = 138) was 41 ± 14 years, 51% were female, and 83% self-identified as non-Hispanic White. ACHD was moderate for 75%; 57% were physiologic class B. Mean baseline resilience score (Connor-Davidson Resilience Scale-10) was 29.20 ± 7.54. Participants had relatively good health-related QOL, health status, and self-competence, and low psychological symptom burden and distress. Higher baseline resilience was associated with better values of all outcomes at 3 months (eg, 1 point higher resilience was associated with 0.92 higher linear analog scale; 95% CI: 0.52-1.32) with or without adjustment for demographics. After further adjusting for the baseline psychosocial measure, only the association between resilience and QOL measures at 3 months remained statistically significant., Conclusions: Resilience is positively associated with health-related QOL for outpatients with moderate or complex ACHD, though relationships are small in magnitude. Study findings can guide the application of resilience-building interventions to the ACHD population.

In this cohort study, we determined time to blood pressure (BP) control and its predictors among hypertensive PLHIV enrolled in integrated hypertension-HIV care based on the World Health Organization (WHO) HEARTS strategy at Mulago Immunosuppression Clinic in Uganda. From August 2019 to March 2020, we enrolled hypertensive PLHIV aged ≥ 18 years and initiated Amlodipine 5 mg mono-therapy for BP (140-159)/(90-99) mmHg or Amlodipine 5 mg/Valsartan 80 mg duo-therapy for BP ≥ 160/90 mmHg. Patients were followed with a treatment escalation plan until BP control, defined as BP < 140/90 mmHg. We used Cox proportional hazards models to identify predictors of time to BP control. Of 877 PLHIV enrolled (mean age 50.4 years, 62.1% female), 30% received mono-therapy and 70% received duo-therapy. In the monotherapy group, 66%, 88% and 96% attained BP control in the first, second and third months, respectively. For patients on duo-therapy, 56%, 83%, 88% and 90% achieved BP control in the first, second, third, and fourth months, respectively. In adjusted Cox proportional hazard analysis, higher systolic BP (aHR 0.995, 95% CI 0.989-0.999) and baseline ART tenofovir/lamivudine/efavirenz (aHR 0.764, 95% CI 0.637-0.917) were associated with longer time to BP control, while being on ART for >10 years was associated with a shorter time to BP control (aHR 1.456, 95% CI 1.126-1.883). The WHO HEARTS strategy was effective at achieving timely BP control among PLHIV. Additionally, monotherapy anti-hypertensive treatment for stage I hypertension is a viable option to achieve BP control and limit pill burden in resource limited HIV care settings., (© 2024. The Author(s).)

Importance: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately., Objective: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group., Data Sources: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023., Study Selection: Included studies met the following criteria: patients living with HIV and HIV-negative comparator group included, patients presenting with ACS or undergoing PCI included, and longitudinal follow-up data collected after the initial event., Data Extraction and Synthesis: Data extraction was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Clinical outcome data were pooled using a random-effects model meta-analysis., Main Outcome and Measures: The following clinical outcomes were studied: all-cause mortality, major adverse cardiovascular events, cardiovascular death, recurrent ACS, stroke, new heart failure, total lesion revascularization, and total vessel revascularization. The maximally adjusted relative risk (RR) of clinical outcomes on follow-up comparing patients living with HIV with patients in control groups was taken as the main outcome measure., Results: A total of 15 studies including 9499 patients living with HIV (pooled proportion [range], 76.4% [64.3%-100%] male; pooled mean [range] age, 56.2 [47.0-63.0] years) and 1 531 117 patients without HIV in a control group (pooled proportion [range], 61.7% [59.7%-100%] male; pooled mean [range] age, 67.7 [42.0-69.4] years) were included; both populations were predominantly male, but patients living with HIV were younger by approximately 11 years. Patients living with HIV were also significantly more likely to be current smokers (pooled proportion [range], 59.1% [24.0%-75.0%] smokers vs 42.8% [26.0%-64.1%] smokers) and engage in illicit drug use (pooled proportion [range], 31.2% [2.0%-33.7%] drug use vs 6.8% [0%-11.5%] drug use) and had higher triglyceride (pooled mean [range], 233 [167-268] vs 171 [148-220] mg/dL) and lower high-density lipoprotein-cholesterol (pooled mean [range], 40 [26-43] vs 46 [29-46] mg/dL) levels. Populations with and without HIV were followed up for a pooled mean (range) of 16.2 (3.0-60.8) months and 11.9 (3.0-60.8) months, respectively. On postdischarge follow-up, patients living with HIV had lower prevalence of statin (pooled proportion [range], 53.3% [45.8%-96.1%] vs 59.9% [58.4%-99.0%]) and β-blocker (pooled proportion [range], 54.0% [51.3%-90.0%] vs 60.6% [59.6%-93.6%]) prescriptions compared with those in the control group, but these differences were not statistically significant. There was a significantly increased risk among patients living with HIV vs those without HIV for all-cause mortality (RR, 1.64; 95% CI, 1.32-2.04), major adverse cardiovascular events (RR, 1.11; 95% CI, 1.01-1.22), recurrent ACS (RR, 1.83; 95% CI, 1.12-2.97), and admissions for new heart failure (RR, 3.39; 95% CI, 1.73-6.62)., Conclusions and Relevance: These findings suggest the need for attention toward secondary prevention strategies to address poor outcomes of cardiovascular disease among patients living with HIV.

Background: Health-related quality of life (HRQOL) is a critical issue for patients undergoing surgery for congenital heart disease (CHD) but has never been assessed in a low-income country. We conducted a cross-sectional mixed methods study with age-matched healthy siblings serving as controls at the Uganda Heart Institute., Methods: One-hundred fifteen CHD pediatric and young adult patients and sibling control participants were recruited. Health-related quality of life was assessed using the Pediatric Quality of Life Inventory Version 4.0 in participants ages 5-17 and 36-Item Short Form Survey for young adults aged 18-25. A subset of 27 participants completed face-to-face interviews to supplement quantitative findings., Results: Eighty-six pediatric (age 5-17) sibling and parent pairs completed Peds QOL surveys, and 29 young adult (age 18-25) sibling pairs completed SF-36 surveys. One third of patients had surgery in Uganda. Ventricular septal defects and tetralogy of Fallot were the most common diagnoses. Health-related quality of life scores in patients were lower across all domains compared to control participants in children. Reductions in physical and emotional domains of HRQOL were also statistically significant for young adults. Variables associated with lower HRQOL score on multivariate analysis in pediatric patients were younger age in the physical and emotional domains, greater number of surgeries in the physical domain and surgery outside Uganda in the school domain. The only predictor of lower HRQOL score in young adults was surgery outside Uganda in the social domain. Qualitative interviews identified a number of themes that correlated with survey results including abandonment by family, isolation from peers and community, financial hardship and social stigmatization., Conclusion: Health-related quality of life was lower in Ugandan patients after CHD surgery than siblings. Younger patients and those who had surgery outside of Uganda had lower HRQOL. These data have important implications for patients undergoing CHD surgery in LMIC and have potential to inform interventions., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Importance: Despite higher atherosclerotic cardiovascular disease (ASCVD) risk, people with HIV (PWH) experience unique barriers to ASCVD prevention, such as changing models of HIV primary care., Objective: To test whether a multicomponent nurse-led strategy would improve systolic blood pressure (SBP) and non-high-density lipoprotein (HDL) cholesterol level in a diverse population of PWH receiving antiretroviral therapy (ART)., Design, Setting, and Participants: This randomized clinical trial enrolled PWH at 3 academic HIV clinics in the US from September 2019 to January 2022 and conducted follow-up for 12 months until January 2023. Included patients were 18 years or older and had a confirmed HIV diagnosis, an HIV-1 viral load less than 200 copies/mL, and both hypertension and hypercholesterolemia. Participants were stratified by trial site and randomized 1:1 to either the multicomponent EXTRA-CVD (A Nurse-Led Intervention to Extend the HIV Treatment Cascade for Cardiovascular Disease Prevention) intervention group or the control group. Primary analyses were conducted according to the intention-to-treat principle., Intervention: The EXTRA-CVD group received home BP monitoring guidance and BP and cholesterol management from a dedicated prevention nurse at 4 in-person visits (baseline and 4, 8, and 12 months) and frequent telephone check-ins up to every 2 weeks as needed. The control group received general prevention education sessions from the prevention nurse at each of the 4 in-person visits., Main Outcomes and Measures: Study-measured SBP was the primary outcome, and non-HDL cholesterol level was the secondary outcome. Measurements were taken over 12 months and assessed by linear mixed models. Prespecified moderators tested were sex at birth, baseline ASCVD risk, and trial site., Results: A total of 297 PWH were randomized to the EXTRA-CVD arm (n = 149) or control arm (n = 148). Participants had a median (IQR) age of 59.0 (53.0-65.0) years and included 234 males (78.8%). Baseline mean (SD) SBP was 135.0 (18.8) mm Hg and non-HDL cholesterol level was 139.9 (44.6) mg/dL. At 12 months, participants in the EXTRA-CVD arm had a clinically significant 4.2-mm Hg (95% CI, 0.3-8.2 mm Hg; P = .04) lower SBP and 16.9-mg/dL (95% CI, 8.6-25.2 mg/dL; P < .001) lower non-HDL cholesterol level compared with participants in the control arm. There was a clinically meaningful but not statistically significant difference in SBP effect in females compared with males (11.8-mm Hg greater difference at 4 months, 9.6 mm Hg at 8 months, and 5.9 mm Hg at 12 months; overall joint test P = .06)., Conclusions and Relevance: Results of this trial indicate that the EXTRA-CVD strategy effectively reduced BP and cholesterol level over 12 months and should inform future implementation of multifaceted ASCVD prevention programs for PWH., Trial Registration: ClinicalTrials.gov Identifier: NCT03643705.

Background: Atrial fibrillation (AF) is a common complication of rheumatic heart disease (RHD) and is challenging to treat in lower-resourced settings in which RHD remains endemic., Objective: We characterized demographics, treatment outcomes, and factors leading to care retention for participants with RHD and AF in Uganda., Methods: We conducted a retrospective analysis of the Uganda national RHD registry between June 2009 and May 2018. Participants with AF or atrial flutter were included. Demographics, survival, and care metrics were compared with participants without AF. Multivariable logistic regression was used to identify factors associated with retention in care among participants with AF., Results: A total of 1530 participants with RHD were analyzed and 293 (19%) had AF. The median age was 24 (interquartile range 14-38) years. Mortality was similar in both groups (adjusted hazard ratio 1.183, P = .77) over a median follow-up of 203 (interquartile range 98-275) days. A total of 79% of AF participants were prescribed anticoagulation, and 43% were aware of their target international normalized ratio. Retention in care was higher in participants with AF (18% vs 12%, P < .01). Factors associated with decreased retention in care include New York Heart Association functional class III/IV (adjusted odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76) and distance to nearest health center (adjusted OR 0.94, 95% CI 0.90-0.99). Anticoagulation prescription was associated with enhanced care retention (adjusted OR 1.86, 95% CI 1.24-2.79)., Conclusion: Participants with RHD and AF in Uganda do not experience higher mortality than those without AF. Anticoagulation prescription rates are high. Although retention in care is poor among RHD participants, those with concurrent AF are more likely to be retained., (© 2024 Heart Rhythm Society. Published by Elsevier Inc.)

Introduction: The association of physical activity (PA) with subclinical cardiovascular disease (CVD) is unclear. Clarifying this relationship may inform cardiovascular prevention strategies., Methods: We performed a systematic review (CRD42021226089) using Medline, Embase, CINAHL and Cochrane (1 January 2000 to 1 September 2023). Studies published with adult populations exploring the relationship between objectively measured PA and subclinical CVD were included. Subclinical CVD was assessed using: ankle-brachial index (ABI); arterial stiffness; carotid artery disease; coronary artery atherosclerosis; endothelial function; and measures of cardiac structure and function. The Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) and Cochrane Risk of Bias tools were used for quality review., Results: Of 68 included studies, most supported an inverse relationship between PA and subclinical CVD. Arterial stiffness was the most common outcome ( n =40), and 33 studies suggested that less sedentary behaviour (SB), increased PA and/or higher intensity PA was associated with less arterial stiffness. Ten studies of carotid artery disease (total n =18), six of endothelial function ( n =10), two of coronary artery disease ( n =3) and all of ABI ( n =6) suggested that PA or less SB is associated with less subclinical disease. Five studies assessing cardiac structure/function ( n =6) suggested alterations in structure/function with PA., Conclusions: PA reduces the risk of CVD events, and this systematic review demonstrates that some of the benefits may be mediated by an inverse association between PA and subclinical CVD. Interventions to increase PA are important for CVD prevention, so we provide a comprehensive overview of which surrogate outcome measures may be most useful to assess future CVD prevention interventions., Prospero Registration Number: CRD42021226089., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Heart failure disproportionately affects individuals residing in rural areas, leading to worse health outcomes. Digital health interventions have been proposed as a promising approach for improving heart failure management. This systematic review aims to identify randomized trials of digital health interventions for individuals living in underserved rural areas with heart failure., Methods and Results: We conducted a systematic review by searching 6 databases (CINAHL, EMBASE, MEDLINE, Web of Science, Scopus, and PubMed; 2000-2023). A total of 30 426 articles were identified and screened. Inclusion criteria consisted of digital health randomized trials that were conducted in underserved rural areas of the United States based on the US Census Bureau's classification. Two independent reviewers screened the studies using the National Heart, Lung, and Blood Institute tool to evaluate the risk of bias. The review included 5 trials from 6 US states, involving 870 participants (42.9% female). Each of the 5 studies employed telemedicine, 2 studies used remote monitoring, and 1 study used mobile health technology. The studies reported improvement in self-care behaviors in 4 trials, increased knowledge in 2, and decreased cardiovascular mortality in 1 study. However, 3 trials revealed no change or an increase in health care resource use, 2 showed no change in cardiac biomarkers, and 2 demonstrated an increase in anxiety., Conclusions: The results suggest that digital health interventions have the potential to enhance self-care and knowledge of patients with heart failure living in underserved rural areas. However, further research is necessary to evaluate their impact on clinical outcomes, biomarkers, and health care resource use., Registration: URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022366923.

Cardiovascular diseases (CVDs) remain the leading cause of death and disability worldwide. Digital health technologies are important public health interventions for addressing the burden of cardiovascular disease. In this article, we discuss the importance of translating digital innovations in research-funded projects to low-resource settings globally to advance global cardiovascular health equity. We also discuss current global cardiovascular health inequities and the digital health divide within and between countries. We present various considerations for translating digital innovations across different settings across the globe, including reciprocal innovation , a "bidirectional, co-constituted, and iterative exchange of ideas, resources, and innovations to address shared health challenges across diverse global settings." In this case, afferent reciprocal innovations may flow from high-income countries toward low- and middle-income countries, and efferent reciprocal innovations may be exported to high-income countries from low- and middle-income countries with adaptation. Finally, we discuss opportunities for bidirectional learning between local and global institutions and highlight examples of projects funded through the American Heart Association Health and Innovation Strategically Funded Research Network that have been adapted to lower-resource settings or have the potential to be adapted to lower-resource settings.

Inequities in global health research are well documented. For example, training opportunities for US investigators to conduct research in low-income and middle-income countries (LMIC) have exceeded opportunities for LMIC investigators to train and conduct research in high-income countries. Reciprocal innovation addresses these inequities through collaborative research across diverse global settings.The Fogarty International Center of the US National Institutes of Health (NIH) promotes research capacity building in LMICs. Fogarty K-grants for mentored career development in global health are available for both US and LMIC investigators, whereas the D43 is the standard grant to support institutional training programmes in LMIC. Other NIH institutes fund T32 training grants to support biomedical research training in the USA, but very few have any global health component. Most global health training partnerships have historically focused on research conducted solely in LMIC, with few examples of bidirectional training partnerships. Opportunities may exist to promote global health reciprocal innovation (GHRI) research by twinning K-awardees in the USA with those from LMIC or by intentionally creating partnerships between T32 and D43 training programmes.To sustain independent careers in GHRI research, trainees must be supported through the path to independence known as the K (mentored grantee)-to-R (independent grantee) transition. Opportunities to support this transition include comentorship, research training at both LMIC and US institutions and protected time and resources for research. Other opportunities for sustainability include postdoctoral training before and after the K-award period, absorption of trained researchers into home institutions, South-South training initiatives and innovations to mitigate brain drain., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The COVID-19 pandemic's impact on cardiovascular health behaviors including diet, physical activity, medication adherence, and self-care among people living with HIV (PLWH) remains unknown. Using qualitative analyses, we examined the impact of the COVID-19 pandemic on cardiovascular health behaviors among PLWH. Twenty-four PLWH were enrolled in this multisite study from September to October 2020. Individuals participated in semi-structured telephone interviews that were recorded, transcribed, and coded by 4 independent coders. Codes were adjudicated and analyzed for common themes. Participants were, on average, 59.2 years old (+/-9.4), 75% African American ( n  = 18) and 71% male ( n  = 17). The pandemic altered cardiovascular disease health behaviors. PLWH changed diet based on stay-at-home orders and food access. Alterations in physical activity included transitioning from gym and group class exercise to home-based exercise. Antiretroviral adherence was maintained, even when other health behaviors wavered, suggesting resilience in PLWH that may be harnessed to maintain other health behaviors.

Background: Veterans living with HIV have up to twice the risk of atherosclerotic cardiovascular disease (ASCVD) compared to those without HIV. Objective: Our study seeks to test a non-physician led virtual self-management implementation strategy to reduce ASCVD risk among people living with HIV (PWH). We aim to conduct a randomized control trial among PWH ( n  = 300) with a diagnosis of hypertension (HTN) who are enrolled in Veterans Health Administration (VHA) clinics, on suppressive antiretroviral therapy (ART), randomized 1:1 to intervention vs. education control for a 12-month duration. Methods: Using human centered design approach, we have adapted a previous 5-component telehealth focused, non-physician led intervention to a Veteran population. The education control arm receives enhanced education in addition to usual care. The primary outcome is 6 mmHg reduction in systolic BP over 12-month in the intervention arm compared to the control arm. The secondary outcome is a 12-month difference in non-HDL cholesterol. While each component of our intervention has an evidence base, they have not been tested together in an HIV context. Conclusion: The proposed multicomponent intervention has the potential to improve cardiovascular outcomes in PWH using novel virtual care methods in a patient centered care approach.

Background: Chronic valvular heart disease is a well-known, long-term complication of acute rheumatic fever (ARF), which remains a major public health problem in low- and middle-income countries. Access to surgical management remains limited. Outcomes of the minority proportion of patients that access surgery have not been described in Uganda., Objectives: To describe the volume and type of rheumatic heart disease (RHD) valvular interventions and the outcomes of operated patients in the Uganda RHD registry., Methods: We performed a retrospective cohort study of all valve surgery procedures identified in the Uganda RHD registry through December 2021., Results: Three hundred and sixty-seven surgical procedures were performed among 359 patients. More than half were among young (55.9% were ≤20 years of age), female (59.9%) patients. All patients were censored at 15 years. The median (IQR) follow up period was 43 (22,79) months. Nearly half of surgeries (46.9%) included interventions on multiple valves, and most valvular operations were replacements with mechanical prostheses (96.6%). Over 70% of the procedures were sponsored by charity organizations. The overall mortality of patients who underwent surgery was 13% (47/359), with over half of the mortalities occurring within the first year following surgery (27/47; 57.4%). Fifteen-year survival or freedom from re-operation was not significantly different between those receiving valve replacements and those receiving valve repair (log-rank p = 0.76)., Conclusions: There has been increasing access to valve surgery among Ugandan patients with RHD. Post-operative survival is similar to regionally reported rates. The growing cohort of patients living with prosthetic valves necessitates national expansion and decentralization of post-operative care services. Major reliance on charity funding of surgery is unsustainable, thus calling for locally generated and controlled support mechanisms such as a national health insurance scheme. The central illustration (Figure 1) provides a summary of our findings and recommendations., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2023 The Author(s).)

Introduction: Rheumatic heart disease (RHD) affects over 39 million people worldwide, the majority in low-income and middle-income countries. Secondary antibiotic prophylaxis (SAP), given every 3-4 weeks can improve outcomes, provided more than 80% of doses are received. Poor adherence is strongly correlated with the distance travelled to receive prophylaxis. Decentralising RHD care has the potential to bridge these gaps and at least maintain or potentially increase RHD prophylaxis uptake. A package of implementation strategies was developed with the aim of reducing barriers to optimum SAP uptake., Methods and Analysis: A hybrid implementation-effectiveness study type III was designed to evaluate the effectiveness of a package of implementation strategies including a digital, cloud-based application to support decentralised RHD care, integrated into the public healthcare system in Uganda. Our overarching hypothesis is that secondary prophylaxis adherence can be maintained or improved via a decentralisation strategy, compared with the centralised delivery strategy, by increasing retention in care. To evaluate this, eligible patients with RHD irrespective of their age enrolled at Lira and Gulu hospital registry sites will be consented for decentralised care at their nearest participating health centre. We estimated a sample size of 150-200 registrants. The primary outcome will be adherence to secondary prophylaxis while detailed implementation measures will be collected to understand barriers and facilitators to decentralisation, digital application tool adoption and ultimately its use and scale-up in the public healthcare system., Ethics and Dissemination: This study was approved by the Institutional Review Board (IRB) at Cincinnati Children's Hospital Medical Center (IRB 2021-0160) and Makerere University School of Medicine Research Ethics Committee (Mak-SOMREC-2021-61). Participation will be voluntary and informed consent or assent (>8 but <18) will be obtained prior to participation. At completion, study findings will be communicated to the public, key stakeholders and submitted for publication., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Most rheumatic heart disease (RHD) registries are static and centralized, collecting epidemiological and clinical data without providing tools to improve care. We developed a dynamic cloud-based RHD case management application with the goal of improving care for patients with RHD in Uganda., Methods: The Active Community Case Management Tool (ACT) was designed to improve community-based case management for chronic disease, with RHD as the first test case. Global and local partner consultation informed selection of critical data fields and prioritization of application functionality. Multiple stages of review and revision culminated in user testing of the application at the Uganda Heart Institute., Results: Global and local partners provided feedback of the application via survey and interview. The application was well received, and top considerations included avenues to import existing patient data, considering a minimum data entry form, and performing a situation assessment to tailor ACT to the health system setup for each new country. Test users completed a postuse survey. Responses were favorable regarding ease of use, desire to use the application in regular practice, and ability of the application to improve RHD care in Uganda. Concerns included appropriate technical skills and supports and potential disruption of workflow., Conclusion: Creating the ACT application was a dynamic process, incorporating iterative feedback from local and global partners. Results of the user testing will help refine and optimize the application. The ACT application showed potential for utility and integration into existing care models in Uganda., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: While understanding the impact of mental health on health perception improves patient-centered care, this relationship is not well-established in patients with cardiovascular disease (CVD). We examined the relationship between psychological distress and health perception in patients with a previous myocardial infarction (MI) and/or stroke., Methods: We extracted data for patients with a previous MI and/or stroke from the 2019 National Health Interview Survey (NHIS). Health perception was self-reported. Presence and severity of anxiety and depression were estimated using the Generalized Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-8 (PHQ-8). Binary analyses of anxiety/depression, multivariable logistic regressions controlling for confounders, and univariable analyses of confounders and anxiety/depression severity were performed., Results: Of 31,948 individuals for whom data on MI/stroke was available, 1235 reported a previous MI and 1203 a previous stroke. The odds of positive perceived health status were lower for individuals with anxiety/depression compared to those without anxiety/depression in both post-MI (anxiety OR 0.52, 95% CI = 0.32-0.85, P < 0.001; depression OR 0.45, 95% CI = 0.29-0.7, P < 0.001) and post-stroke groups (anxiety OR 0.61, 95% CI = 0.39-0.97, P < 0.001; depression OR 0.37, 95% CI = 0.25-0.55, P < 0.001) upon multivariable analyses. Increasing severity of anxiety/depression was also associated with worse perception of health status upon univariable analysis., Conclusion: Among patients with a previous acute CVD event, those with psychological distress have worse perception of their health status. Understanding the range of patient health perceptions can help physicians provide more patient-centered care and encourage patient behaviors that may improve both CVD and mental health outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: World Health Organization (WHO) HEARTS packages are increasingly used to control hypertension. However, their feasibility in persons living with HIV (PLHIV) is unknown. We studied the effectiveness and implementation of a WHO HEARTS intervention to integrate the management of hypertension into HIV care., Methods: This was a mixed methods study at Uganda's largest HIV clinic. Components of the adapted WHO HEARTS intervention were lifestyle counseling, free hypertension medications, hypertension treatment protocol, task shifting, and monitoring tools. We determined the effectiveness of the intervention among PLHIV by comparing hypertension and HIV outcomes at baseline and 21 months. The RE-AIM framework was used to evaluate the implementation outcomes of the intervention at 21 months. We conducted four focus group discussions with PLHIV (n = 42), in-depth interviews with PLHIV (n = 9), healthcare providers (n = 15), and Ministry of Health (MoH) policymakers (n = 2)., Results: Reach: Among the 15,953 adult PLHIV in the clinic, of whom 3892 (24%) had been diagnosed with hypertension, 1133(29%) initiated integrated hypertension-HIV treatment compared to 39 (1%) at baseline. Among the enrolled patients, the mean age was 51.5 ± 9.7 years and 679 (62.6%) were female., Effectiveness: Among the treated patients, hypertension control improved from 9 to 72% (p < 0.001), mean systolic blood pressure (BP) from 153.2 ± 21.4 to 129.2 ± 15.2 mmHg (p < 0.001), and mean diastolic BP from 98.5 ± 13.5 to 85.1 ± 9.7 mmHg (p < 0.001). Overall, 1087 (95.9%) of patients were retained by month 21. HIV viral suppression remained high, 99.3 to 99.5% (p = 0.694). Patients who received integrated hypertension-HIV care felt healthy and saved more money. Adoption: All 48 (100%) healthcare providers in the clinic were trained and adopted the intervention. Training healthcare providers on WHO HEARTS, task shifting, and synchronizing clinic appointments for hypertension and HIV promoted adoption., Implementation: WHO HEARTS intervention was feasible and implemented with fidelity. Maintenance: Leveraging HIV program resources and adopting WHO HEARTS protocols into national guidelines will promote sustainability., Conclusions: The WHO HEARTS intervention promoted the integration of hypertension management into HIV care in the real-world setting. It was acceptable, feasible, and effective in controlling hypertension and maintaining optimal viral suppression among PLHIV. Integrating this intervention into national guidelines will promote sustainability., (© 2023. BioMed Central Ltd.)

Background: People with human immunodeficiency virus (PWH) are at increased risk for comorbidities, and plasma interleukin 6 (IL-6) levels are among the most robust predictors of these outcomes. Tocilizumab (TCZ) blocks the receptor for IL-6, inhibiting functions of this cytokine., Methods: This was a 40-week, placebo-controlled, crossover trial (NCT02049437) where PWH on stable antiretroviral therapy (ART) were randomized to receive 3 monthly doses of TCZ or matching placebo intravenously. Following a 10-week treatment period and a 12-week washout, participants were switched to the opposite treatment. The primary endpoints were safety and posttreatment levels of C-reactive protein (CRP) and CD4+ T-cell cycling. Secondary endpoints included changes in inflammatory indices and lipid levels., Results: There were 9 treatment-related toxicities of grade 2 or greater during TCZ administration (mostly neutropenia) and 2 during placebo administration. Thirty-one of 34 participants completed the study and were included in a modified intent-to-treat analysis. TCZ reduced levels of CRP (median decrease, 1819.9 ng/mL, P < .0001; effect size, 0.87) and reduced inflammatory markers in PWH, including D-dimer, soluble CD14, and tumor necrosis factor receptors. T-cell cycling tended to decrease in all maturation subsets after TCZ administration, but was only significant among naive CD4 T cells. Lipid levels, including lipid classes that have been related to cardiovascular disease risk, increased during TCZ treatment., Conclusions: TCZ is safe and decreases inflammation in PWH; IL-6 is a key driver of the inflammatory environment that predicts morbidity and mortality in ART-treated PWH. The clinical significance of lipid elevations during TCZ treatment requires further study. Clinical Trials Registration. NCT02049437., Competing Interests: Potential conflicts of interest. N. T. F. reports grants or contracts from the NIH and Gilead, and has served as a consultant for Gilead. C. T. L. has received research grants from Gilead Sciences and Medtronic Foundation and has served on an advisory board for Esperion Therapeutics. A. L. has served as a consultant to Abbott. G. A. M. reports grants or contracts from Pfizer, Astellas, Roche, Genentech, Redhill, Cognivue, Vanda, and Tetraphase; served as scientific advisor and consultant for Gilead, Merck, Janssen, Theratechnologies, and GSK/ViiV; and received payment for expert testimony from Gilead. M. M. L. has received competitive grant funding from Gilead and has served as consultant for Merck. C. F. reports serving as a paid consultant for Gilead, Janssen, Merck, American Gene Technologies, Thera Technologies, Shinogi, and ViiV Healthcare; payment or honoraria for speaking engagements from International AIDS Society–USA and Virology Education; payment for expert testimony from Gilead Sciences; 3 issued or pending patents related to long-acting delivery of antiretroviral drugs; and participation on the scientific advisory board for Navigen Corporation and data and safety monitoring board (DSMB) or advisory board for Watermark, LLC. L. H. C. reports consulting fees from Sanofi Genzyme, Genetech, GSK, BMS, Galvani, and UCB; payment or honoraria for nonbranded speaking engagements from Sanofi and AstraZeneca. E. V. C. reports participation on a Melinta Pharmaceuticals data and safety monitoring board for a pediatric antibacterial study. D. D. A. reports a grant from the Department of Defense (grant number 12935153). C. L. S. reports a VA Merit Award and VA Career Development Award. B. R. has received payment or honoraria from Gilead Sciences, ViiV Healthcare, and Theratechnologies (paid to author). All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Phenotypes and mechanisms of cardiovascular disease (CVD) may differ across global populations. In sub-Saharan Africa (SSA), distinct environmental determinants may influence development and progression of atherosclerotic coronary artery disease (CAD)., Methods: We investigated associations between 6 established markers of myocardial stress and subsequent subclinical CAD (sCAD), defined as presence of any atherosclerosis on coronary CT angiography (CCTA) in a 2-year prospective cohort of Ugandan adults enriched for cardiometabolic risk factors (RFs) and HIV. Six plasma biomarkers were measured baseline among 200 participants (50% with HIV) aged ≥ 45 years with ≥ 1 cardiovascular RF. At 2-year follow-up, 132 participants (52% with HIV) who returned underwent coronary CCTA., Results: In logistic regression models adjusted for cardiovascular RFs (age, diabetes, hypertension, hyperlipidemia, smoking, obesity) and non-traditional RFs (HIV, chronic kidney disease), only NT-proBNP predicted subsequent subclinical CAD (p < 0.008, Bonferroni correction for multiple testing). In sensitivity analyses adjusted for ASCVD risk category (instead of individual RFs) in the baseline cohort with multiple imputation applied to missing year 2 CCTA data (n = 200), NT-proBNP remained significantly associated with subsequent CAD (p < 0.008)., Conclusions: NT-proBNP consistently predicted subclinical CAD in Uganda in the absence of such an association among other markers of myocardial stress, suggesting a role for NT-proBNP in atherosclerosis independently of coronary microvascular dysfunction., (© 2023. The Author(s).)

Background: Inflammation and thrombosis are often linked mechanistically and are associated with adverse events after transcatheter aortic valve replacement (TAVR). High residual platelet reactivity (HRPR) is especially common when clopidogrel is used in this setting, but its relevance to immune activation is unknown. We sought to determine whether residual activity at the purinergic receptor P2Y12 (P2Y12) promotes prothrombotic immune activation in the setting of TAVR., Methods: This was a randomized trial of 60 patients (enrolled July 2015 through December 2018) assigned to clopidogrel (300mg load, 75mg daily) or ticagrelor (180mg load, 90 mg twice daily) before and for 30 days following TAVR. Co-primary endpoints were P2Y12-dependent platelet activity (Platelet Reactivity Units; VerifyNow) and the proportion of inflammatory (cluster of differentiation [CD] 14+/CD16+) monocytes 1 day after TAVR., Results: Compared to clopidogrel, those randomized to ticagrelor had greater platelet inhibition (median Platelet Reactivity Unit [interquartile range]: (234 [170.0-282.3] vs. 128.5 [86.5-156.5], p < 0.001), but similar inflammatory monocyte proportions (22.2% [18.0%-30.2%] vs. 25.1% [22.1%-31.0%], p = 0.201) 1 day after TAVR. Circulating monocyte-platelet aggregates, soluble CD14 levels, interleukin 6 and 8 levels, and D-dimers were also similar across treatment groups. HRPR was observed in 63% of the clopidogrel arm and was associated with higher inflammatory monocyte proportions. Major bleeding events, pacemaker placement, and mortality did not differ by treatment assignment., Conclusions: Residual P2Y12 activity after TAVR is common in those treated with clopidogrel but ticagrelor does not significantly alter biomarkers of prothrombotic immune activation. HRPR appears to be an indicator (not a cause) of innate immune activation in this setting., Competing Interests: David A. Zidar reports research grant support from AstraZeneca, honoraria from GSK/Pfizer and Medtronic. Steven Filby is a consultant for Boston Scientific. Nicholas T. Funderburg is a consultant for Gilead. Mehdi Shishebhor is a consultant for Abbott Vascular, Medtronic, Terumo, Philips, and Boston Scientific. Sahil A. Parikh serves on the advisory Board of Abbott, Boston Scientific, Medtronic, Philips, Janssen, Cordis, Efemoral, and Advanced Nanotechnologies; receives research support from Abbott, Boston Scientific, surmodics, shockwave, and trireme; and is a consultant for Inari, Penumbra, Abiomed, and Terumo. Guilherme Attizzani is a consultant and advisory board member of Medtronic and Abbott Vascular. Daniel I. Simon reports honoraria from Medtronic.

Statins are cholesterol-lowering drugs commonly used among people with HIV, associated with an increased risk of myopathies. Considering that cardiovascular disease, statin therapy, and sarcopenia are independently prevalent in people with HIV, clarity on the potential benefits or harms of statin therapy on muscle health is useful to provide insight into ways to maximize skeletal muscle health and minimize CVD risk in this population. We aimed to study the effects of statin therapy on strength, muscle mass, and physical function parameters in people with HIV. This was a pilot cross-sectional study. People with HIV on continuous statin therapy (n = 52) were paired 1:1 according to age (people with HIV 53.9 ± 8.2 and people with HIV on statins 53.9 ± 8.4 years), sex, body mass index (Body mass index, people with HIV 28.6 ± 5.3 and people with HIV on statins 28.8 ± 6.3 kg/m 2 ), and race with people with HIV not using statin (n = 52). Participants were evaluated for muscle strength (i.e. handgrip strength), lean and fat body mass (using bioelectric impedance analysis), and physical function (i.e. Short Physical Performance Battery-SPPB). Isokinetic strength and appendicular lean mass (using dual-energy X-ray absorptiometry), more accurate strength and body composition measures, were determined in 38% of the participants. Overall, statin usage does not exacerbated loss of muscle strength (32.2 ± 11.5 vs. 30.3 ± 9.6 kg, p > 0.05) muscle mass (7.6 ± 1.8 vs. 7.7 ± 1.1 kg/m 2 , p > 0.05), and impaired physical performance (10.1 ± 1.8 vs. 9.7 ± 2.1 points, p > 0.05) of PLWH. When analyzed by sex, men living with HIV on statins usage presented higher appendicular muscle mass (28.4 ± 3.1 vs. 26.2 ± 4.9 kg, p < 0.05) handgrip strength (42.1 ± 8.8 vs. 37.1 ± 8.3 kg, p < 0.05) and physical function through SPPB score (10.9 ± 1.3 vs. 9.5 ± 2.1, p < 0.05) than men living with HIV not on statins treatment. The same protection was not observed in women. This data was demonstrated when muscle mass and strength were determined clinically (i.e. handgrip strength and electrical impedance) and when more precise laboratory measurements of muscle mass and strength were conducted (i.e. isokinetic strength and DXA scans). Statin does not exacerbate muscle wasting, strength loss, or muscle dysfunction among people with HIV. Indeed, statins may protect men, but not woman with HIV against HIV and antiretroviral therapy-induced loss of muscle mass and strength., (© 2023. The Author(s).)

Objective: Inflammation is key in the pathogenesis of atherosclerotic coronary artery disease (CAD). Distinct sex-specific inflammatory mechanisms may contribute to CAD in sub-Saharan Africa (SSA), where environmental and biological determinants of systemic inflammation may differ from those in high-income settings., Approach and Results: We investigated sex differences in inflammatory markers and CAD in a 2-year prospective cohort of Ugandan adults enriched for cardiometabolic risk factors (RFs) and HIV. Seven plasma biomarkers were quantified at the baseline visit among 125 females and 75 males (50% with HIV) at least 45 years old at enrollment with one or more major cardiovascular RF. In year 2, coronary CT angiography (CCTA) was performed in 82 females and 50 males returning for follow-up (52% with HIV). In sex-specific models adjusted for cardiovascular RFs and HIV, tumor necrosis factor-alpha (TNF-α) RII and sCD163 predicted subsequent CAD in females, while only fibrinogen was predictive in males ( P  < 0.05). Interleukin-6 (IL-6) and sCD14 were inversely associated with CAD in males ( P  < 0.05). Sex modified the associations of TNF-α RII, sCD14, and sCD163 with CAD ( P  < 0.05 for interaction). In multivariable multiple imputation models applied to missing year 2 CCTA data to test associations between serum biomarkers in the baseline cohort ( n  = 200) and subsequent CAD, higher sCD163 was predictive in females only ( P  < 0.05)., Conclusions: The positive link between inflammation and subclinical CAD was stronger among females than males in Uganda. Mechanisms by which sex modulates the relationship between inflammation and CAD should be further investigated in SSA., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Prospective investigations on the risk of cardiovascular disease among youth with perinatally acquired human immunodeficiency virus (PHIV) in sub-Saharan Africa are lacking., Methods: A prospective observational cohort study was performed in 101 youth (aged 10-18 years) with PHIV and 97 who were human immunodeficiency virus (HIV) uninfected (HIV-), from 2017 to 2021 at the Joint Clinical Research Center in Uganda. Participants with PHIV were receiving antiretroviral therapy (ART) and had HIV-1 RNA levels ≤400 copies/mL. The common carotid artery intima-media thickness (IMT) and pulse wave velocity (PWV) were evaluated at baseline and at 96 weeks. Groups were compared using unpaired t-test, and potential predictors of IMT and PWV were assessed using quantile regression., Results: Of the 198 participants recruited at baseline, 168 (89 with PHIV, 79 HIV-) had measurements at 96 weeks. The median age (interquartile range) age was 13 (11-15) years; 52% were female, and 85% had viral loads <50 copies/mL that remained undetectable at week 96. The baseline mean common carotid artery IMT was slightly higher in participants with PHIV compared with controls (P < .01), and PWV did not differ between groups (P = .08). At week 96, IMT decreased and PWV increased in the PHIV group (P ≤ .03); IMT increased in the HIV- group (P = .03), with no change in PWV (P = .92). In longitudinal analyses in those with PHIV, longer ART duration was associated with lower PWV (β = .008 [95% confidence interval, -.008 to .003]), and abacavir use with greater IMT (β = .043 [.012-.074])., Conclusions: In healthy Ugandan youth with PHIV, virally suppressed by ART, the common carotid artery IMT did not progress over 2 years. Prolonged and early ART may prevent progression of subclinical vascular disease, while prolonged use of abacavir may increase it., Competing Interests: Potential conflicts of interest. C. K. reports grants or contracts from the NIH. C. T. L. reports grants or contracts from Gilead Sciences and participation on a data safety monitoring board or advisory board for Esperion Therapeutics. N. F. reports grants or contracts from the NIH and Gilead. G. A. M. served as a scientific consultant for Gilead, ViiV, Merck, Theratechnologies and Janssen and has received grant support from Astellas, Tetraphase, Roche, Redhill, Pfizer, and Genentech and consulting fees from Janssen, Theratechnologies, Gilead, Merck, and ViiV. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)