Adapting an Intervention to Improve Acute Myocardial Infarction Care in Tanzania: Co-Design of the MIMIC Intervention.

Background: Uptake of evidence-based care for acute myocardial infarction (AMI) is suboptimal in Tanzania, but there are currently no published interventions to improve AMI care in sub-Saharan Africa. Objectives: Co-design a quality improvement intervention for AMI care tailored to local contextual factors. Methods: An interdisciplinary design team consisting of 20 physicians, nurses, implementation scientists, and administrators met from June 2022 through August 2023. Half of the design team consisted of representatives from the target audience, emergency department physicians and nurses at a referral hospital in northern Tanzania. The design team reviewed multiple published quality improvement interventions focusing on ED-based AMI care. After selecting a multicomponent intervention to improve AMI care in Brazil (BRIDGE-ACS), the design team used the ADAPT-ITT framework to adapt the intervention to the local context. Findings: The design team audited current AMI care processes at the study hospital and reviewed qualitative data regarding barriers to care. Multiple adaptations were made to the original BRIDGE-ACS intervention to suit the local context, including re-designing the physician reminder system and adding patient educational materials. Additional feedback was sought from topical experts, including patients with AMI. Draft intervention materials were iteratively refined in response to feedback from experts and the design team. The finalized intervention, Multicomponent Intervention to Improve Myocardial Infarction Care in Tanzania (MIMIC), consisted of five core components: physician reminders, pocket cards, champions, provider training, and patient education. Conclusion: MIMIC is the first locally tailored intervention to improve AMI care in sub-Saharan Africa. Future studies will evaluate implementation outcomes and efficacy.

Diffuse myocardial fibrosis is uncommon in people with perinatally acquired human immunodeficiency virus infection.

BACKGROUND: Cardiovascular disease (CVD) remains a leading cause of death in people living with HIV. Myocardial fibrosis is well-described in HIV infection acquired in adulthood. We evaluate the burden of fibrosis by cardiac magnetic resonance in people with perinatal HIV infection. METHODS: Individuals with perinatally acquired HIV (pnHIV) diagnosed before 10 years-old and on antiretroviral treatment for ≥ 6 months were matched with uninfected controls. Patients with significant cardiometabolic co-morbidities and pregnancy were excluded. Diffuse fibrosis was assessed by cardiac magnetic resonance (CMR) with native T1 mapping for calculation of extracellular volume fraction (ECV). Viability was assessed with late gadolinium enhancement. The normality of fibrosis was assessed using the Komogrov-Smirnov test. Fibrosis between the groups was analyzed using a Mann-Whitney U test, as the data was not normally distributed. Statistical significance was defined as a p-valve < 0.05. RESULTS: Fourteen adults with pnHIV group and 26 controls (71% female and 86% Black race) were assessed. The average (± standard deviation) age in the study group was 29 (± 4.3) years-old. All pnHIV had been on ART for decades. Demographic data, CMR functional/volumetric data, and pre-contrast T1 mapping values were similar between groups. Diastolic function was normal in 50% of pnHIV patients and indeterminate in most of the remainder (42%). There was no statistically significant difference in ECV between groups; p = 0.24. CONCLUSION: Perinatally-acquired HIV was not associated with diffuse myocardial fibrosis. Larger prospective studies with serial examinations are needed to determine whether pnHIV patients develop abnormal structure or function more often than unaffected controls.

Nurse-Led Strategy to Improve Blood Pressure and Cholesterol Level Among People With HIV: A Randomized Clinical Trial.

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.

Closing the Last Mile Gap in Access to Multimodality Imaging in Rural Settings: Design of the Imaging Core of the Risk Underlying Rural Areas Longitudinal Study.

Achieving optimal cardiovascular health in rural populations can be challenging for several reasons including decreased access to care with limited availability of imaging modalities, specialist physicians, and other important health care team members. Therefore, innovative solutions are needed to optimize health care and address cardiovascular health disparities in rural areas. Mobile examination units can bring imaging technology to underserved or remote communities with limited access to health care services. Mobile examination units can be equipped with a wide array of assessment tools and multiple imaging modalities such as computed tomography scanning and echocardiography. The detailed structural assessment of cardiovascular and lung pathology, as well as the detection of extracardiac pathology afforded by computed tomography imaging combined with the functional and hemodynamic assessments acquired by echocardiography, yield deep phenotyping of heart and lung disease for populations historically underrepresented in epidemiological studies. Moreover, by bringing the mobile examination unit to local communities, innovative approaches are now possible including engagement with local professionals to perform these imaging assessments, thereby augmenting local expertise and experience. However, several challenges exist before mobile examination unit-based examinations can be effectively integrated into the rural health care setting including standardizing acquisition protocols, maintaining consistent image quality, and addressing ethical and privacy considerations. Herein, we discuss the potential importance of cardiac multimodality imaging to improve cardiovascular health in rural regions, outline the emerging experience in this field, highlight important current challenges, and offer solutions based on our experience in the RURAL (Risk Underlying Rural Areas Longitudinal) cohort study.

Effects of Pitavastatin on Coronary Artery Disease and Inflammatory Biomarkers in HIV: Mechanistic Substudy of the REPRIEVE Randomized Clinical Trial.

Importance: Cardiovascular disease (CVD) is increased in people with HIV (PWH) and is characterized by premature noncalcified coronary plaque. In the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE), pitavastatin reduced major adverse cardiovascular events (MACE) by 35% over a median of 5.1 years. Objective: To investigate the effects of pitavastatin on noncalcified coronary artery plaque by coronary computed tomography angiography (CTA) and on inflammatory biomarkers as potential mechanisms for MACE prevention. Design, Setting, and Participants: This double-blind, placebo-controlled randomized clinical trial enrolled participants from April 2015 to February 2018 at 31 US clinical research sites. PWH without known CVD who were taking antiretroviral therapy and had low to moderate 10-year CVD risk were included. Data were analyzed from April to November 2023. Intervention: Oral pitavastatin calcium, 4 mg per day. Main Outcomes and Measures: Coronary CTA and inflammatory biomarkers at baseline and 24 months. The primary outcomes were change in noncalcified coronary plaque volume and progression of noncalcified plaque. Results: Of 804 enrolled persons, 774 had at least 1 evaluable CTA. Plaque changes were assessed in 611 who completed both CT scans. Of 611 analyzed participants, 513 (84.0%) were male, the mean (SD) age was 51 (6) years, and the median (IQR) 10-year CVD risk was 4.5% (2.6-7.0). A total of 302 were included in the pitavastatin arm and 309 in the placebo arm. The mean noncalcified plaque volume decreased with pitavastatin compared with placebo (mean [SD] change, -1.7 [25.2] mm3 vs 2.6 [27.1] mm3; baseline adjusted difference, -4.3 mm3; 95% CI, -8.6 to -0.1; P = .04; 7% [95% CI, 1-12] greater reduction relative to placebo). A larger effect size was seen among the subgroup with plaque at baseline (-8.8 mm3 [95% CI, -17.9 to 0.4]). Progression of noncalcified plaque was 33% less likely with pitavastatin compared with placebo (relative risk, 0.67; 95% CI, 0.52-0.88; P = .003). Compared with placebo, the mean low-density lipoprotein cholesterol decreased with pitavastatin (mean change: pitavastatin, -28.5 mg/dL; 95% CI, -31.9 to -25.1; placebo, -0.8; 95% CI, -3.8 to 2.2). The pitavastatin arm had a reduction in both oxidized low-density lipoprotein (-29% [95% CI, -32 to -26] vs -13% [95% CI, -17 to -9]; P < .001) and lipoprotein-associated phospholipase A2 (-7% [95% CI, -11 to -4] vs 14% [95% CI, 10-18]; P < .001) compared with placebo at 24 months. Conclusions and Relevance: In PWH at low to moderate CVD risk, 24 months of pitavastatin reduced noncalcified plaque volume and progression as well as markers of lipid oxidation and arterial inflammation. These changes may contribute to the observed MACE reduction in REPRIEVE. Trial Registration: ClinicalTrials.gov Identifier: NCT02344290.

Risk factors for clonal hematopoiesis of indeterminate potential in people with HIV: a report from the REPRIEVE trial.

ABSTRACT: Clonal hematopoiesis of indeterminate potential (CHIP), the clonal expansion of myeloid cells with leukemogenic mutations, results in increased coronary artery disease (CAD) risk. CHIP is more prevalent among people with HIV (PWH), but the risk factors are unknown. CHIP was identified among PWH in REPRIEVE (Randomized Trial to Prevent Vascular Events in HIV) using whole-exome sequencing. Logistic regression was used to associate sociodemographic factors and HIV-specific factors with CHIP adjusting for age, sex, and smoking status. In the studied global cohort of 4486 PWH, mean age was 49.9 (standard deviation [SD], 6.4) years; 1650 (36.8%) were female; and 3418 (76.2%) were non-White. CHIP was identified in 223 of 4486 (4.97%) and in 38 of 373 (10.2%) among those aged ≥60 years. Age (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.05-1.09; P < .0001) and smoking (OR, 1.37; 95% CI, 1.14-1.66; P < .001) associated with increased odds of CHIP. Globally, participants outside of North America had lower odds of CHIP including sub-Saharan Africa (OR, 0.57; 95% CI, 0.4-0.81; P = .0019), South Asia (OR, 0.45; 95% CI, 0.23-0.80; P = .01), and Latin America/Caribbean (OR, 0.56; 95% CI, 0.34-0.87; P = .014). Hispanic/Latino ethnicity (OR, 0.38; 95% CI, 0.23-0.54; P = .002) associated with significantly lower odds of CHIP. Among HIV-specific factors, CD4 nadir <50 cells/mm3 associated with a 1.9-fold (95%CI, 1.21-3.05; P = .006) increased odds of CHIP, with the effect being significantly stronger among individuals with short duration of antiretroviral therapy (ART; OR, 4.15; 95% CI, 1.51-11.1; P = .005) (Pinteraction= .0492). Among PWH at low-to-moderate CAD risk on stable ART, smoking, CD4 nadir, North American origin, and non-Hispanic ethnicity associated with increased odds of CHIP. This trial was registered at www.ClinicalTrials.gov as NCT02344290.

Six month incidence of major adverse cardiovascular events among adults with HIV in northern Tanzania: a prospective observational study.

OBJECTIVES: We aimed to prospectively describe incident cardiovascular events among people living with HIV (PLWH) in northern Tanzania. Secondary aims of this study were to understand non-communicable disease care-seeking behaviour and patient preferences for cardiovascular care and education. DESIGN: A prospective observational study. SETTING: This study was conducted at the Majengo HIV Care and Treatment Clinic, an outpatient government-funded clinic in Moshi, Tanzania PARTICIPANTS: Adult patients presenting to an HIV clinic for routine care in northern Tanzania were enrolled from 1 September 2020 to 1 March 2021. INTERVENTIONS: At enrolment, participants completed a survey and a resting 12-lead ECG was obtained. At 6 month follow-up, a repeat survey regarding interim health events and repeat ECG was obtained. PRIMARY AND SECONDARY OUTCOME MEASURES: Interim major adverse cardiovascular events (MACE) were defined by: self-reported interim stroke, self-reported hospitalisation for heart failure, self-reported interim myocardial infarction, interim myocardial infarction by ECG criteria (new pathologic Q waves in two contiguous leads) or death due to cardiovascular disease (CVD). RESULTS: Of 500 enrolled participants, 477 (95.4%) completed 6 month follow-up and 3 (0.6%) died. Over the 6 month follow-up period, 11 MACE occurred (3 strokes, 6 myocardial infarctions, 1 heart failure hospitalisation and 1 cardiovascular death), resulting in an incidence rate of 4.58 MACE per 100 person-years. Of participants completing 6 month follow-up, 31 (6.5%) reported a new non-communicable disease diagnosis, including 23 (4.8%) with a new hypertension diagnosis. CONCLUSIONS: The incidence of MACE among PLWH in Tanzania is high. These findings are an important preliminary step in understanding the landscape of CVD among PLWH in Tanzania and highlight the need for interventions to reduce cardiovascular risk in this population.

Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus.

Plasma vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NRP-1) had the largest association with coronary plaque in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) proteomics analysis. With little known about NRP-1 in people with human immunodeficiency virus (PWH), we explored its relation to other proteins in REPRIEVE and validated our findings through a Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) case-cohort study by assessing its relation to host factors and incident cardiovascular disease and cancer. Within REPRIEVE, NRP-1 was associated with proteins involved in angiogenesis, signal transduction, immunoregulation, and cell migration/adhesion. Within CNICS, NRP-1 was associated with key host factors, including older age and male sex. NRP-1 was associated with an increased hazard of multiple cancers but a decreased prostate cancer risk. Finally, NRP-1 was most strongly associated with mortality and type 2 myocardial infarction. These data suggest that NRP-1 is part of a clinically relevant immunoregulatory pathway related to multiple comorbidities in PWH. Clinical Trials Registration. NCT02344290.

Longitudinal ECG changes among adults with HIV in Tanzania: A prospective cohort study.

The prevalence of cardiovascular disease (CVD) is rising among people with HIV (PWH) in sub-Saharan Africa (SSA). Despite the utility of the electrocardiogram (ECG) in screening for CVD, there is limited data regarding longitudinal ECG changes among PWH in SSA. In this study, we aimed to describe ECG changes over a 6-month period in a cohort of PWH in northern Tanzania. Between September 2020 and March 2021, adult PWH were recruited from Majengo HIV Care and Treatment Clinic (MCTC) in Moshi, Tanzania. Trained research assistants surveyed participants and obtained a baseline ECG. Participants then returned to MCTC for a 6-month follow-up, where another ECG was obtained. Two independent physician adjudicators interpreted baseline and follow-up ECGs for rhythm, left ventricular hypertrophy (LVH), bundle branch blocks, ST-segment changes, and T-wave inversion, using standardized criteria. New ECG abnormalities were defined as those that were absent in a patient's baseline ECG but present in their 6-month follow-up ECG. Of 500 enrolled participants, 476 (95.2%) completed follow-up. The mean (± SD) age of participants was 45.7 (± 11.0) years, 351 (73.7%) were female, and 495 (99.8%) were taking antiretroviral therapy. At baseline, 248 (52.1%) participants had one or more ECG abnormalities, the most common of which were LVH (n = 108, 22.7%) and T-wave inversion (n = 89, 18.7%). At six months, 112 (23.5%) participants developed new ECG abnormalities, including 40 (8.0%) cases of new T-wave inversion, 22 (4.6%) cases of new LVH, 12 (2.5%) cases of new ST elevation, and 11 (2.3%) cases of new prolonged QTc. Therefore, new ECG changes were common over a relatively short 6-month period, which suggests that subclinical CVD may develop rapidly in PWH in Tanzania. These data highlight the need for additional studies on CVD in PWH in SSA and the importance of routine CVD screening in this high-risk population.

Diffuse Myocardial Fibrosis is Uncommon in People with Perinatally Acquired Human Immunodeficiency Virus Infection.

Background: Cardiovascular disease (CVD) remains a leading cause of death in people living with HIV. Myocardial fibrosis is well-described in HIV infection acquired in adulthood. We evaluate the burden of fibrosis by cardiac magnetic resonance in people with perinatal HIV infection. Methods: Individuals with perinatally acquired HIV (pnHIV) diagnosed before 10 years-old and on antiretroviral treatment for ≥ 6 months were matched with uninfected controls. Patients with significant cardiometabolic co-morbidities and pregnancy were excluded. Diffuse fibrosis was assessed by cardiac magnetic resonance (CMR). with native T1 mapping for calculation of extracellular volume fraction (ECV). Viability was assessed with late gadolinium enhancement. The normality of fibrosis was assessed using the Komogrov-Smirnov test. Fibrosis between the groups was analyzed using a Mann-Whitney U test, as the data was not normally distributed. Statistical significance was defined as a p-valve < 0.05. Results: Fourteen adults with pnHIV group and 26 controls (71% female and 86% Black race) were assessed. The average (± standard deviation) age in the study group was 29 (± 4.3) years-old. All pnHIV had been on ART for decades. Demographic data, CMR functional/volumetric data, and pre-contrast T1 mapping values were similar between groups. Diastolic function was normal in 50% of pnHIV patients and indeterminate in most of the remainder (42%). There was no statistically significant difference in ECV between groups; p = 0.24. Conclusion: Perinatally-acquired HIV was not associated with diffuse myocardial fibrosis. Early exposure to ART may be cardioprotective against development of myocardial fibrosis in patients with perinatal HIV.

Pericoronary Adipose Tissue Density, Inflammation, and Subclinical Coronary Artery Disease Among People With HIV in the REPRIEVE Cohort.

BACKGROUND: Pericoronary adipose tissue (PCAT) may influence plaque development through inflammatory mechanisms. We assessed PCAT density, as a measure of pericoronary inflammation, in relationship to coronary plaque among people with human immunodeficiency virus (HIV [PWH]) and to a matched control population. METHODS: In this baseline analysis of 727 participants of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) Mechanistic Substudy, we related computed tomography-derived PCAT density to presence and extent (Leaman score) of coronary artery disease (CAD), noncalcified plaque, coronary artery calcium (CAC), and vulnerable plaque features using multivariable logistic regression analyses. We further compared the PCAT density between PWH and age, sex, body mass index, CAC score, and statin use-matched controls from the community-based Framingham Heart Study (N = 464), adjusting for relevant clinical covariates. RESULTS: Among 727 REPRIEVE participants (age 50.8 ± 5.8 years; 83.6% [608/727] male), PCAT density was higher in those with (vs without) coronary plaque, noncalcified plaque, CAC >0, vulnerable plaque, and high CAD burden (Leaman score >5) (P < .001 for each comparison). PCAT density related to prevalent coronary plaque (adjusted odds ratio [per 10 HU]: 1.44; 95% confidence interval, 1.22-1.70; P < .001), adjusted for clinical cardiovascular risk factors, body mass index, and systemic immune/inflammatory biomarkers. Similarly, PCAT density related to CAC >0, noncalcified plaque, vulnerable plaque, and Leaman score >5 (all P ≤ .002). PCAT density was greater among REPRIEVE participants versus Framingham Heart Study (-88.2 ± 0.5 HU versus -90.6 ± 0.4 HU; P < .001). CONCLUSIONS: Among PWH in REPRIEVE, a large primary cardiovascular disease prevention cohort, increased PCAT density independently associated with prevalence and severity of coronary plaque, linking increased coronary inflammation to CAD in PWH.

Pitavastatin to Prevent Cardiovascular Disease in HIV Infection.

BACKGROUND: The risk of cardiovascular disease is increased among persons with human immunodeficiency virus (HIV) infection, so data regarding primary prevention strategies in this population are needed. METHODS: In this phase 3 trial, we randomly assigned 7769 participants with HIV infection with a low-to-moderate risk of cardiovascular disease who were receiving antiretroviral therapy to receive daily pitavastatin calcium (at a dose of 4 mg) or placebo. The primary outcome was the occurrence of a major adverse cardiovascular event, which was defined as a composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, stroke, transient ischemic attack, peripheral arterial ischemia, revascularization, or death from an undetermined cause. RESULTS: The median age of the participants was 50 years (interquartile range, 45 to 55); the median CD4 count was 621 cells per cubic millimeter (interquartile range, 448 to 827), and the HIV RNA value was below quantification in 5250 of 5997 participants (87.5%) with available data. The trial was stopped early for efficacy after a median follow-up of 5.1 years (interquartile range, 4.3 to 5.9). The incidence of a major adverse cardiovascular event was 4.81 per 1000 person-years in the pitavastatin group and 7.32 per 1000 person-years in the placebo group (hazard ratio, 0.65; 95% confidence interval [CI], 0.48 to 0.90; P = 0.002). Muscle-related symptoms occurred in 91 participants (2.3%) in the pitavastatin group and in 53 (1.4%) in the placebo group; diabetes mellitus occurred in 206 participants (5.3%) and in 155 (4.0%), respectively. CONCLUSIONS: Participants with HIV infection who received pitavastatin had a lower risk of a major adverse cardiovascular event than those who received placebo over a median follow-up of 5.1 years. (Funded by the National Institutes of Health and others; REPRIEVE ClinicalTrials.gov number, NCT02344290.).

Cardiology Encounters for Underrepresented Racial and Ethnic Groups with Human Immunodeficiency Virus and Borderline Cardiovascular Disease Risk.

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.

Clinical and Echocardiographic Diversity Associated With Physical Fitness in the Project Baseline Health Study: Implications for Heart Failure Staging.

BACKGROUND: Clinical and echocardiographic features may carry diverse information about the development of heart failure (HF). Therefore, we determined heterogeneity in clinical and echocardiographic phenotypes and its association with exercise capacity. METHODS: In 2036 community-dwelling individuals, we defined echocardiographic profiles of left and right heart remodeling and dysfunction. We subdivided the cohort based on presence (+) or absence (-) of HF risk factors (RFs) and echocardiographic abnormalities (RF-/Echo-, RF-/Echo+, RF+/Echo-, RF+/Echo+). Multivariable-adjusted associations between subgroups and physical performance metrics from 6-minute walk and treadmill exercise testing were assessed. RESULTS: The prevalence was 35.3% for RF-/Echo-, 4.7% for RF-/Echo+, 39.3% for RF+/Echo-, and 20.6% for RF+/Echo+. We observed large diversity in echocardiographic profiles in the Echo+ group. Participants with RF-/Echo+ (18.6% of Echo+) had predominantly echocardiographic abnormalities other than left ventricular (LV) diastolic dysfunction, hypertrophy and reduced ejection fraction, whereas their physical performance was similar to RF-/Echo-. In contrast, participants with RF+/Echo+ presented primarily with LV hypertrophy or dysfunction, features that related to lower 6-minute walking distance and lower exercise capacity. CONCLUSIONS: Subclinical echocardiographic abnormalities suggest HF pathogenesis, but the presence of HF risk factors and type of echo abnormality should be considered so as to distinguish adverse from benign adaptation and to stratify HF risk.

Sex Differences in Subclinical Atherosclerosis and Systemic Immune Activation/Inflammation Among People With Human Immunodeficiency Virus in the United States.

BACKGROUND: Among people with HIV (PWH), sex differences in presentations of atherosclerotic cardiovascular disease (ASCVD) may be influenced by differences in coronary plaque parameters, immune/inflammatory biomarkers, or relationships therein. METHODS: REPRIEVE, a primary ASCVD prevention trial, enrolled antiretroviral therapy (ART)-treated PWH. At entry, a subset of US participants underwent coronary computed tomography angiography (CTA) and immune phenotyping (n = 755 CTA; n = 725 CTA + immune). We characterized sex differences in coronary plaque and immune/inflammatory biomarkers and compared immune-plaque relationships by sex. Unless noted otherwise, analyses adjust for ASCVD risk score. RESULTS: The primary analysis cohort included 631 males and 124 females. ASCVD risk was higher among males (median: 4.9% vs 2.1%), while obesity rates were higher among females (48% vs 21%). Prevalence of any plaque and of plaque with either ≥1 visible noncalcified portion or vulnerable features (NC/V-P) was lower among females overall and controlling for relevant risk factors (RR [95% CI] for any plaque: .67 [.50, .92]; RR for NC/V-P: .71 [.51, 1.00] [adjusted for ASCVD risk score and body mass index]). Females showed higher levels of IL-6, hs-CRP, and D-dimer and lower levels of Lp-PLA2 (P < .001 for all). Higher levels of Lp-PLA2, MCP-1, and oxLDL were associated with higher plaque (P < .02) and NC/V-P prevalence, with no differences by sex. Among females but not males, D-dimer was associated with higher prevalence of NC/V-P (interaction P = .055). CONCLUSIONS: Among US PWH, females had a lower prevalence of plaque and NC/V-P, as well as differences in key immune/inflammatory biomarkers. Immune-plaque relationships differed by sex for D-dimer but not other tested parameters. Clinical Trial Registration. ClinicalTrials.gov; identifier: NCT0234429 (date of initial registration: 22 January 2015).

Cytomegalovirus Immunoglobulin G (IgG) Titer and Coronary Artery Disease in People With Human Immunodeficiency Virus (HIV).

BACKGROUND: Cytomegalovirus (CMV) infection is thought to result in increased immune activation in people with human immunodeficiency virus (HIV, PWH). Although some data have linked asymptomatic CMV infection to cardiovascular disease among PWH, it remains unknown whether CMV is associated with increased or high-risk coronary plaque. METHODS: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40-75 years on stable antiretroviral therapy (ART) with low-to-moderate atherosclerotic cardiovascular disease (ASCVD) risk. Among a subset of US REPRIEVE participants, coronary plaque was assessed by coronary computed tomography angiography. Here, we assessed the relationship between CMV immunoglobulin G (IgG) titer and (1) levels of immune activation, (2) inflammatory biomarkers, and (3) coronary plaque phenotypes at study entry. RESULTS: Of 672 participants, mean age was 51 years, 83% were men, median ASCVD risk score was 4.5%, and 66% had current CD4+ T-cell count ≥500 cells/mm3. Higher CMV IgG quartile group was associated with older age and lower current and nadir CD4+ T-cell counts. CMV IgG titer was associated with specific inflammatory biomarkers (sCD163, MCP-1, interleukin [IL]-6, hsCRP) in univariate analysis, but not after controlling for HIV-specific factors. In contrast, CMV IgG titer was not associated with coronary artery disease indexes, including presence of plaque, coronary artery calcium (CAC) score >0, vulnerable plaque presence, or Leaman score >5. CONCLUSIONS: No meaningful association was seen between CMV IgG titer and coronary artery disease indexes among ART-treated PWH at study enrollment. Longitudinal assessments in REPRIEVE will determine the relationship of CMV IgG titer to plaque progression and cardiovascular events. CLINICAL TRIALS REGISTRATION: NCT02344290.

Ideal cardiovascular health, biomarkers, and coronary artery disease in persons with HIV.

OBJECTIVE: To investigate relationships between Life's Simple 7 (LS7), an assessment of cardiovascular health (CVH), and coronary plaque among people with HIV (PWH). DESIGN: Cross-sectional. METHODS: Coronary computed tomography angiography, immune/inflammatory biomarkers, and characterization of LS7 were collected among a subset of ART-treated PWH enrolled in REPRIEVE, a primary prevention trial. Analyses adjusted for cardiovascular disease risk (ASCVD score). RESULTS: Median age of the 735 participants was 51(±6) years, 16% female, and median (Q1-Q3) CVD risk was 4.5% (2.6-6.9). Forty percent had poor (≤2 ideal components), 51% had intermediate (three or four ideal components), and only 9% had ideal CVH (≥5). Coronary plaque was present in 357 (49%); 167 (23%) had one or more vulnerable plaque features, 293 (40%) had noncalcified plaque, and 242 (35%) had a coronary artery calcium score >0. All three phenotypes were increasingly more prevalent with poorer CVH and these relationships remained after adjusting for ASCVD risk. Poor CVH was associated with higher high-sensitivity C-reactive protein, oxidized low-density cholesterol, and interleukin-6. The relationship of LS7 to plaque remained after adjusting for these biomarkers. CONCLUSIONS: Among PWH, poor CVH as measured by LS7 was associated with coronary plaque presence, vulnerable features, and calcification. LS7 was also associated with selected biomarkers; adjustment for these and ASCVD score reduced but did not eliminate LS7's association with plaque, suggesting the possibility of additional protective mechanisms against atherogenesis and plaque remodeling. Clinical use of LS7 and further exploration of its relationships with coronary artery disease may enhance efforts to reduce cardiovascular morbidity and mortality in PWH. CLINICAL TRIALS REGISTRATION: NCT02344290.

Performance of Cardiovascular Risk Prediction Models Among People Living With HIV: A Systematic Review and Meta-analysis.

Importance: Extant data on the performance of cardiovascular disease (CVD) risk score models in people living with HIV have not been synthesized. Objective: To synthesize available data on the performance of the various CVD risk scores in people living with HIV. Data Sources: PubMed and Embase were searched from inception through January 31, 2021. Study Selection: Selected studies (1) were chosen based on cohort design, (2) included adults with a diagnosis of HIV, (3) assessed CVD outcomes, and (4) had available data on a minimum of 1 CVD risk score. Data Extraction and Synthesis: Relevant data related to study characteristics, CVD outcome, and risk prediction models were extracted in duplicate. Measures of calibration and discrimination are presented in tables and qualitatively summarized. Additionally, where possible, estimates of discrimination and calibration measures were combined and stratified by type of risk model. Main Outcomes and Measures: Measures of calibration and discrimination. Results: Nine unique observational studies involving 75 304 people (weighted average age, 42 years; 59 490 male individuals [79%]) living with HIV were included. In the studies reporting these data, 86% were receiving antiretroviral therapy and had a weighted average CD4+ count of 449 cells/µL. Included in the study were current smokers (50%), patients with diabetes (5%), and patients with hypertension (25%). Ten risk prediction scores (6 in the general population and 4 in the HIV-specific population) were analyzed. Most risk scores had a moderate performance in discrimination (C statistic: 0.7-0.8), without a significant difference in performance between the risk scores of the general and HIV-specific populations. One of the HIV-specific risk models (Data Collection on Adverse Effects of Anti-HIV Drugs Cohort 2016) and 2 of the general population risk models (Framingham Risk Score [FRS] and Pooled Cohort Equation [PCE] 10 year) had the highest performance in discrimination. In general, models tended to underpredict CVD risk, except for FRS and PCE 10-year scores, which were better calibrated. There was substantial heterogeneity across the studies, with only a few studies contributing data for each risk score. Conclusions and Relevance: Results of this systematic review and meta-analysis suggest that general population and HIV-specific CVD risk models had comparable, moderate discrimination ability in people living with HIV, with a general tendency to underpredict risk. These results reinforce the current recommendations provided by the American College of Cardiology/American Heart Association guidelines to consider HIV as a risk-enhancing factor when estimating CVD risk.