Women with HIV (WHIV) on anti-retroviral therapy (ART) are living longer but facing heightened vulnerability to heart failure.
We investigated metabolic/hormonal/immune parameters relating to ...diastolic dysfunction-a precursor to heart failure-among WHIV without known cardiovascular disease (CVD).
Nineteen ART-treated WHIV and 11 non-HIV-infected women without known CVD enrolled and successfully completed relevant study procedures cardiac magnetic resonance spectroscopy (MRS) and cardiac MRI. Groups were matched on age and body mass index. Primary outcome measures included intramyocardial triglyceride content (cardiac MRS) and diastolic function (cardiac MRI). Relationships between intramyocardial triglyceride content and clinical parameters were also assessed.
Among WHIV (vs non-HIV-infected women), intramyocardial triglyceride content was threefold higher 1.2 (0.4, 3.1) vs 0.4 (0.1, 0.5)%, P = 0.01, and diastolic function was reduced (left atrial passive ejection fraction: 27.2 ± 9.6 vs 35.9 ± 6.4%, P = 0.007). There was a strong inverse relationship between intramyocardial triglyceride content and diastolic function (ρ = -0.62, P = 0.004). Among the whole group, intramyocardial triglyceride content did not relate to chronologic age but did increase across the reproductive aging spectrum (P = 0.02). HIV status and reproductive aging status remained independent predictors of intramyocardial triglyceride content after adjusting for relevant cardiometabolic parameters (overall model R2 = 0.56, P = 0.003; HIV status P = 0.01, reproductive aging status P = 0.02).
For asymptomatic WHIV, increased intramyocardial triglyceride content is associated with diastolic dysfunction. Moreover, relationships between intramyocardial triglyceride accumulation and women's reproductive aging are noted.
Abstract
Background
People with human immunodeficiency virus (PWH) demonstrate increased atherosclerotic cardiovascular disease (ASCVD). Statins are being studied to prevent ASCVD in human ...immunodeficiency virus (HIV), but little is known regarding the effects of statins on a broad range of inflammatory and cardiovascular proteins in this population.
Methods
We used a highly specific discovery proteomic approach (Protein Extension Assay), to determine statin effects on over 350 plasma proteins in relevant ASCVD pathways among HIV and non-HIV groups. Responses to pitavastatin calcium were assessed in 89 PWH in the INTREPID trial and 46 non-HIV participants with features of central adiposity and insulin resistance. History of cardiovascular disease was exclusionary for both studies.
Results
Among participants with HIV, PCOLCE (enzymatic cleavage of type I procollagen) significantly increased after pitavastatin therapy and PLA2G7 (systemic marker of arterial inflammation) decreased. Among participants without HIV, integrin subunit alpha M (integrin adhesive function) and defensin alpha-1 (neutrophil function) increased after pitavastatin therapy and PLA2G7 decreased. At baseline, comparing participants with and without HIV, differentially expressed proteins included proteins involved in platelet and endothelial function and immune activation.
Conclusions
Pitavastatin affected proteins important to platelet and endothelial function and immune activation, and effects differed to a degree within PWH and participants without HIV.
We assessed the effects of pitavastatin on a broad array of proteins using a highly specific proximity extension assay (PEA) in HIV and metabolic syndrome non-HIV patients. Our results highlight effects on key inflammatory, collagen, neutrophil, and integrin functions.
Background. The ability to noninvasively assess arterial CD206⁺ macrophages may lead to improved understanding of human immunodeficiency virus (HIV)–associated cardiovascular disease. Methods. We ...trialed a novel macrophage-specific arterial imaging technique. Results. We demonstrated colocalization between technetium Tc 99m tilmanocept (⁹⁹ᵐTc-tilmanocept) and CD206⁺ macrophages ex vivo. In vivo application of ⁹⁹ᵐTc-tilmanocept single-photon emission computed tomography/computed tomography revealed high-level ⁹⁹ᵐTc-tilmanocept uptake across 20.4% of the aortic surface volume among HIV-infected subjects, compared with 4.3% among non–HIV-infected subjects (P = .009). Among all subjects, aortic high-level ⁹⁹ᵐTc-tilmanocept uptake was related to noncalcified aortic plaque volume (r = 0.87; P = .003) on computed tomographic angiography, and this relationship held when we controlled for HIV status. Conclusion. These first-in-human data introduce a novel macrophage-specific arterial imaging technique in HIV. Clinical Trials Registration. NCT02542371
Research shows that a diverse faculty improves academic, clinical, and research outcomes in higher education. Despite that, persons in minority groups, usually categorized by race or ethnicity, are ...underrepresented in academia (URiA). The Nutrition Obesity Research Centers (NORCs), supported by the NIDDK, hosted workshops on five separate days in September and October 2020. NORCs convened these workshops to identify barriers and facilitators for diversity, equity, and inclusion (DEI) and provide specific recommendations to improve DEI within obesity and nutrition for individuals from URiA groups. Recognized experts on DEI presented each day, after which the NORCs conducted breakout sessions with key stakeholders who engage in nutrition and obesity research. The breakout session groups included early-career investigators, professional societies, and academic leadership. The consensus from the breakout sessions was that glaring inequities affect URiA in nutrition and obesity, particularly related to recruitment, retention, and advancement. Recommendations from the breakout sessions to improve DEI across the academe focused on six themes: (1) recruitment, (2) retention, (3) advancement, (4) intersectionality of multiple challenges (e.g., being Black and a woman), (5) funding agencies, and (6) implementation of strategies to address problems related to DEI.
What is already known?Achieving diversity, equity, and inclusion remains a significant challenge in academiaWhat does this study add?This paper adds recommendations for academic universities, professional societies, and funding agencies to correct the underrepresentation in academia of marginalized or minority researchers and faculty.How might these results change the direction of research?These recommendations could improve diversity, equality, and inclusion efforts in the fields of nutrition and obesity.
BACKGROUND:In high-resource settings, the HIV-attributable risk of myocardial infarction (MI) is higher among women than among men. The extent to which unique mechanisms contribute to MI risk among ...women vs. men with HIV remains unclear.
METHODS:Subclinical coronary atherosclerotic plaque characteristics—including high-risk morphology plaque features—were compared among 48 HIV-infected women 48 (41, 54) years and 97 HIV-infected men 48 (42, 52) years on stable antiretroviral therapy (ART) without known cardiovascular disease. These individuals had previously completed coronary computed tomography angiography and metabolic/immune phenotyping as part of a prospective study.
RESULTS:Extending previous analyses, now focusing exclusively on ART-treated participants, we found that HIV-infected women had a lower prevalence of any subclinical coronary atherosclerotic plaque (35% vs. 62%, P = 0.003) and a lower number of segments with plaque (P = 0.01), compared with HIV-infected men. We also report for the first time that ART-treated HIV-infected women had a lower prevalence of high-risk positively remodeled plaque (25% vs. 51%, P = 0.003) and a lower number of positively remodeled plaque segments (P = 0.002). In models adjusting for cardiovascular risk factors, we further showed that male sex remained associated with any coronary plaque odds ratio 3.8, 95% confidence interval(1.4 to 11.4) and with positively remodeled plaque odds ratio 3.7, 95% confidence interval(1.4, 10.9).
CONCLUSIONS:ART-treated HIV-infected women (vs. HIV-infected men) had a lower prevalence and burden of subclinical coronary plaque and high-risk morphology plaque. Thus, unique sex-specific mechanisms beyond subclinical plaque may drive the higher HIV-attributable risk of MI among women vs. men.
Abstract
Background
People with human immunodeficiency virus (PWH) face increased risks for heart failure and adverse heart failure outcomes. Myocardial steatosis predisposes to diastolic ...dysfunction, a heart failure precursor. We aimed to characterize myocardial steatosis and associated potential risk factors among a subset of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) participants.
Methods
Eighty-two PWH without known heart failure successfully underwent cardiovascular magnetic resonance spectroscopy, yielding data on intramyocardial triglyceride (IMTG) content (a continuous marker for myocardial steatosis extent). Logistic regression models were applied to investigate associations between select clinical characteristics and odds of increased or markedly increased IMTG content.
Results
Median (Q1, Q3) IMTG content was 0.59% (0.28%, 1.15%). IMTG content was increased (> 0.5%) among 52% and markedly increased (> 1.5%) among 22% of participants. Parameters associated with increased IMTG content included age (P = .013), body mass index (BMI) ≥ 25 kg/m2 (P = .055), history of intravenous drug use (IVDU) (P = .033), and nadir CD4 count < 350 cells/mm³ (P = .055). Age and BMI ≥ 25 kg/m2 were additionally associated with increased odds of markedly increased IMTG content (P = .049 and P = .046, respectively).
Conclusions
A substantial proportion of antiretroviral therapy–treated PWH exhibited myocardial steatosis. Age, BMI ≥ 25 kg/m2, low nadir CD4 count, and history of IVDU emerged as possible risk factors for myocardial steatosis in this group.
Clinical Trials Registration
NCT02344290; NCT03238755.
Abstract The intrauterine environment plays a critical role in shaping chronic disease risk over the life course. We prospectively evaluated cardiometabolic outcomes in toddlers born to mothers with ...versus without prenatal severe acute respiratory syndrome coronavirus 2 infection. Children with in utero severe acute respiratory syndrome coronavirus 2 exposure had higher left ventricular mass in association with altered maternal immunologic indices.
Abstract
Context
In the general population, high-density lipoprotein (HDL) cholesterol efflux capacity (HCEC) relates inversely to incident cardiovascular events. Previous studies have suggested that ...HCEC is decreased in HIV and that antiretroviral therapy (ART) initiation might improve HCEC.
Objective
To evaluate HCEC in the context of ART initiation and immune activation in HIV.
Design and Outcome Measures
Baseline HCEC from 10 ART-naive HIV-infected males and 12 prospectively matched non–HIV-infected males were analyzed. In the HIV cohort, HCEC 6 months after elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) therapy was evaluated. HCEC served as the primary outcome and was measured by the ability of J774 mouse macrophages to efflux cholesterol. Our ex vivo assay used two cholesterol acceptors apolipoprotein B (apoB)-depleted sera or purified HDL and modulation of cellular efflux pathways using a liver X receptor (LXR) agonist.
Results
The median age was 34 years interquartile range (IQR), 27 to 51, and baseline HDL was 46 mg/dL (IQR, 38 to 61). HCEC was significantly greater in the non–HIV-infected subjects than in the HIV-infected subjects at baseline. HCEC, assessed using apoB-depleted sera, significantly increased after ART (no LXR agonist, baseline: median, 8.1%; IQR, 7.0% to 11.9%; after ART: median, 12.9%; IQR, 10.4% to 21.1%; P = 0.006; LXR agonist, baseline, 1.3% ± 1.3%; after ART, 2.5% ± 1.0%; P = 0.02), although not to the levels in the non–HIV-infected subjects (no LXR agonist: median, 14.9%; IQR, 11.5% to 19.1%; LXR agonist: 5.8% ± 1.3%). HCEC, assessed using purified HDL, did not significantly increase after ART. The change in HCEC with ART related inversely to the change in the percentage of CD14−CD16+ (nonclassical) monocytes (ρ = −0.74, P = 0.04) and directly to the change in the percentage of CD14+CD16− (classical) monocytes (ρ = 0.72, P = 0.045).
Conclusions
Our data suggest improvement of HCEC with E/C/F/TDF and a relationship between the ART-induced decrease in immune activation and ART-induced improvement in HCEC.
HCEC was measured in HIV-infected subjects before and after 6 months of ART. HCEC improved with ART but not to the level of controls. Changes in HCEC related to changes in monocyte subpopulations.
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