Abstract MP16: Perivascular Adipose Tissue Inflammation Impairs Microvascular Endothelial Function In People Living With HIV

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Dan Wang ◽  
Cheng Wang ◽  
Seble Kassaye ◽  
Princy Kurmar ◽  
Jennifer Verbesey ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Ros Generation ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Perivascular Adipose Tissue ◽  
Microvascular Endothelial ◽  
Adipose Inflammation ◽  
Living With Hiv ◽  
Endothelium Dependent Relaxation ◽  
Microvascular Endothelial Function

Introduction and hypothesis: We had reported that people living with HIV (PLWH) have microvascular endothelial dysfunction and increased ROS. We now tested the hypothesis that perivascular adipose tissue (PVAT) could enhance oxidative stress and inflammation and impair the function of subcutaneous microarterioles (SMAs) in PLWH. Methods: SMAs were obtained from young, virally-suppressed HIV-infected subjects (n=11) or matched controls (n=11). Subjects were without associated CVD risk factors. Microvascular reactivity and PVAT function were accessed by myograph from isolated subcutaneous vessels with or without PVAT of skin biopsy. Results: The HIV-infected group had significantly (P<0.05) increased adipose MDA, TNFα, IL-1α, leptin and reduced adiponectin. The PVAT-denuded SMAs from the HIV group had significantly (P<0.05) impaired acetylcholine-induced endothelium-dependent relaxation factor (EDRF, 26±4 vs 38±3%) and NO activity (0.35±0.03 vs 0.58± 0.07 Δfluoresence unit) and significantly (P<0.05) increased contraction to U-46,619 (200±8 vs 141±7%) and endothelin 1 (ET1, 167±12 vs 118±17%) and ROS generation (0.32 ± 0.06 vs 0.1 ± 0.03 (E/DHE fluoresce unit). PVAT enhanced EDRF (50±4 vs 38±3 %) and NO (0.84 ±0.1 vs 0.58±0.07 Δfluoresence unit ) only in controls (P<0.05). The reduction of U46,619 anti-contractivity by PVAT is decreased in HIV (48±7 vs 85±9%, P<0.05). Conclusion: HIV-infected individuals have intrinsic vascular defects from ROS augmented by extrinsic vascular defects from adipose inflammation that impairs the beneficial microvascular PVAT signaling. Therefore, targets for potential prevention of cardiovascular morbidity in PLWH should include the elimination of ROS and inflammation in both microvessels themselves and the surrounding extravascular PVAT.

Abstract P623: Endothelial Dysfunction and Abnormal Perivascular Adipose Tissue Signaling in Subcutaneous Vessels from HIV-infected individuals

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Dan Wang ◽  
Cheng Wang ◽  
Cuiwei Wang ◽  
Chenglong Liu ◽  
Jennifer Verbesey ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Endothelial Dysfunction ◽  
Vascular Dysfunction ◽  
Ros Generation ◽  
Vascular Endothelial ◽  
Cvd Risk ◽  
Vascular Effects ◽  
Perivascular Adipose Tissue ◽  
Substrate Inhibitor ◽  
Endothelium Dependent Relaxation

Objective: Perivascular adipose tissue (PVAT) normally promotes vascular endothelial function, whereas is impaired by reactive oxygen species (ROS) in CVD. But PVAT effects on microvessels in HIV are unexplored. We previously reported endothelial dysfunction in living subcutaneous microvascular arterioles (SMAs) dissected from a gluteal biopsy in HIV infected individuals. We test hypothesis that HIV increases microvascular ROS and asymmetric dimethylarginine (ADMA) leading to impair microvascular function and PVAT signaling. Methods: Isolated SMAs with or without PVAT were prepared from young African American HIV-infected (n=8) and matched HIV-uninfected women (n=6) enrolled in the DC Women’s Interagency HIV Study (DC-WIHS). HIV-infected participants were virally suppressed on HAART without identified CVD risk factors (except obesity). SMA’s acetylcholine (ACh)-induced endothelium dependent relaxation (EDR), nitric oxide (NO) activity (DAF-FM), ACh-induced endothelium dependent contractions (EDC) and ROS generation (temp-9AC), plasma L-arginine, ADMA and adipose adipokines and malondialdehyde (MDA) were measured. Results: HIV-infected participants had significantly ( p <0.05) reduced plasma ratio of L-arginine : ADMA (99 ± 13 vs 182 ± 32 μmol/μmol), increased adipose MDA (15.1 ± 2.5 vs 10.9 ± 2.6 ng/mg protein) and leptin (40 ± 9 vs 28 ± 7 ng/mg protein); and reduced adiponectin in plasma (14 ± 2 vs 23 ± 2 ng/ml) and in adipose (2.1 ± 0.3 vs 4.6 ± 1.3 ng/mg protein). ACh-induced EDR (57 ± 4 vs 71± 4%) and NO (0.20 ± 0.03 vs 0.58 ± 0.07 Δfluoresce unit) were significantly attenuated (p<0.05) in vessels from HIV-infected participants, whereas EDC (22 ± 2 vs 7 ± 2%) and O 2 - (0.17 ± 0.02 vs 0.09 ± 0.02 Δfluoresce unit) were significantly increased ( p <0.05) . PVAT significantly increased ( p <0.05) EDR (87 ± 3 vs 72 ± 4%) and NO (0.84 ± 0.09 vs 0.58 ± 0.08 Δfluoresce unit) only in control vessels. Conclusion: HIV-infected individuals have reductions in NO synthase substrate: inhibitor ratio (L-arginine:ADMA) and consequent increased intrinsic vascular effects of ROS leading to disruption of the beneficial microvascular PVAT signaling pathway. Therapeutic targets for vascular dysfunction in HIV should include ROS and its extravascular actions on ADMA and PVAT.

Imaging modalities for cardiovascular phenotyping in asymptomatic people living with HIV

2021 ◽  
pp. 1358863X2097870
Author(s):  
Maria Bonou ◽  
Chris J Kapelios ◽  
Eleni Athanasiadi ◽  
Sophie I Mavrogeni ◽  
Mina Psichogiou ◽  
...  
Keyword(s):  
Cardiac Computed Tomography ◽  
Imaging Modalities ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Improve Risk Stratification ◽  
Positron Emission ◽  
Pet Ct ◽  
Living With Hiv ◽  
Subclinical Cvd ◽  
Related Mortality

Cardiovascular disease (CVD) has emerged as a leading cause of non-HIV-related mortality among people living with HIV (PLWH). Despite the growing CVD burden in PLWH, there is concern that general population risk score models may underestimate CVD risk in these patients. Imaging modalities have received mounting attention lately to better understand the pathophysiology of subclinical CVD and provide improved risk assessment in this population. To date, traditional and well-established techniques such as echocardiography, pulse wave velocity, and carotid intima thickness continue to be the basis for the diagnosis and subsequent monitoring of vascular atherosclerosis and heart failure. Furthermore, novel imaging tools such as cardiac computed tomography (CT) and cardiac CT angiography (CCTA), positron emission tomography/CT (PET/CT), and cardiac magnetic resonance (CMR) have provided new insights into accelerated cardiovascular abnormalities in PLWH and are currently evaluated with regards to their potential to improve risk stratification.

scholarly journals Limited Utility of Cardiovascular Risk Scores for People Living with HIV in Malawi

2020 ◽  
Author(s):  
Chia Goh ◽  
Henry Mwandumba ◽  
Alicja Rapala ◽  
Willard Tingao ◽  
Irene Sheha ◽  
...  
Keyword(s):  
Risk Score ◽  
Low Income ◽  
Intima Media Thickness ◽  
Risk Groups ◽  
Carotid Intima Media Thickness ◽  
Endothelial Damage ◽  
Risk Scores ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Living With Hiv

HIV is associated with increased cardiovascular disease (CVD) risk. Despite the high prevalence of HIV in low income subSaharan Africa, there are few data on the assessment of CVD risk in the region. In this study, we aimed to compare the utility of existing CVD risk scores in a cohort of Malawian adults, and assess to what extent they correlate with established markers of endothelial damage: carotid intima media thickness (IMT) and pulse wave velocity (PWV). WHO/ISH, SCORE, FRS, ASCVD, QRISK2 and D:A:D scores were calculated for 279 Malawian adults presenting with HIV and low CD4. Correlation of the calculated 10year CVD risk score with IMT and PWV was assessed using Spearmans rho. The median (IQR) age of patients was 37 (31 to 43) years and 122 (44%) were female. Median (IQR) blood pressure was 120/73mmHg (108/68 to 128/80) and 88 (32%) study participants had a new diagnosis of hypertension. The FRS and QRISK2 scores included the largest number of participants in this cohort (96% and 100% respectively). D:A:D, a risk score specific for people living with HIV, identified more patients in moderate and high risk groups. Although all scores correlated well with physiological markers of endothelial damage, FRS and QRISK2 correlated most closely with both IMT [r2 0.51, p<0.0001 and r2 0.47, p<0.0001 respectively] and PWV [r2 0.47, p<0.0001 and r2 0.5, p<0.0001 respectively]. Larger cohort studies are required to adapt and validate risk prediction scores in this region, so that limited healthcare resources can be effectively targeted.

scholarly journals Increased mitochondrial ROS generation mediates the loss of the anti-contractile effects of perivascular adipose tissue in high-fat diet obese mice

2017 ◽  
Vol 174 (20) ◽  
pp. 3527-3541 ◽  
Author(s):  
Rafael Menezes da Costa ◽  
Rafael S Fais ◽  
Carlos R P Dechandt ◽  
Paulo Louzada-Junior ◽  
Luciane C Alberici ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Ros Generation ◽  
Obese Mice ◽  
High Fat ◽  
Perivascular Adipose Tissue ◽  
Mitochondrial Ros

scholarly journals Long-lasting alterations in adipose tissue density and adiponectin production in people living with HIV after thymidine analogues exposure

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Marco Gelpi ◽  
◽  
Andreas Dehlbæk Knudsen ◽  
Karoline Brostrup Larsen ◽  
Amanda Mocroft ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
People Living With Hiv ◽  
Tissue Density ◽  
Living With Hiv

scholarly journals Treatment of early hypertension among persons living with HIV in Haiti: Protocol for a randomized controlled trial

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0254740
Author(s):  
Lily D. Yan ◽  
Vanessa Rouzier ◽  
Eliezer Dade ◽  
Collette Guiteau ◽  
Jean Lookens Pierre ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Randomized Controlled Trial ◽  
Antihypertensive Treatment ◽  
Viral Suppression ◽  
Controlled Trial ◽  
Standard Of Care ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Randomized Controlled ◽  
Living With Hiv

Background People living with HIV (PLWH) are at increased risk of cardiovascular disease (CVD) and death, with greater burdens of both HIV and CVD in lower-middle income countries. Treating prehypertension in PLWH may reduce progression to hypertension, CVD risk and potentially mortality. However, no trial has evaluated earlier blood pressure treatment for PLWH. We propose a randomized controlled trial to assess the feasibility, benefits, and risks of initiating antihypertensive treatment among PLWH with prehypertension, comparing prehypertension treatment to standard of care following current WHO guidelines. Methods A total of 250 adults 18–65 years and living with HIV (PLWH) with viral suppression in the past 12 months, who have prehypertension will be randomized to prehypertension treatment versus standard of care. Prehypertension is defined as having a systolic blood pressure (SBP) 120–139 mmHg or diastolic blood pressure (DBP) 80–89 mmHg. In the prehypertension treatment arm, participants will initiate amlodipine 5 mg daily immediately. In the standard of care arm, participants will initiate amlodipine only if they develop hypertension defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg. The primary outcome is the difference in mean change of SBP from enrollment to 12 months. Secondary outcomes include feasibility, acceptability, adverse effects, HIV viral suppression, and medication adherence. Qualitative in-depth interviews with providers and participants will explore attitudes about initiating amlodipine, satisfaction, perceived CVD risk, and implementation challenges. Discussion PLWH have a higher CVD risk and may benefit from a lower BP threshold for initiation of antihypertensive treatment. Trial registration Clinicaltrials.gov registration number NCT04692467, registration date December 15, 2020, protocol ID 20–03021735.

scholarly journals Associations between subcutaneous fat density and systemic inflammation differ by HIV serostatus and are independent of fat quantity

2019 ◽  
Vol 181 (4) ◽  
pp. 451-459 ◽  
Author(s):  
J E Lake ◽  
P Debroy ◽  
D Ng ◽  
K M Erlandson ◽  
L A Kingsley ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Systemic Inflammation ◽  
Disease Risk ◽  
Subcutaneous Fat ◽  
Density Measurement ◽  
Metabolic Parameter ◽  
People Living With Hiv ◽  
Linear Regression Models ◽  
Hiv Serostatus ◽  
Living With Hiv

Objectives Adipose tissue (AT) density measurement may provide information about AT quality among people living with HIV. We assessed AT density and evaluated relationships between AT density and immunometabolic biomarker concentrations in men with HIV. Design Cross-sectional analysis of men enrolled in the Multicenter AIDS Cohort Study. Methods Abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) density (Hounsfield units, HU; less negative = more dense) were quantified from computed tomography (CT) scans. Multivariate linear regression models described relationships between abdominal AT density and circulating biomarker concentrations. Results HIV+ men had denser SAT (−95 vs −98 HU HIV−, P < 0.001), whereas VAT density was equivalent by HIV serostatus men (382 HIV−, 462 HIV+). Historical thymidine analog nucleoside reverse transcriptase inhibitor (tNRTI) use was associated with denser SAT but not VAT. In adjusted models, a 1 s.d. greater SAT or VAT density was associated with higher levels of adiponectin, leptin, HOMA-IR and triglyceride:HDL cholesterol ratio and lower hs-CRP concentrations in HIV− men. Conversely, in HIV+ men, each s.d. greater SAT density was not associated with metabolic parameter improvements and was significantly (P < 0.05) associated with higher systemic inflammation. Trends toward higher inflammatory biomarker concentrations per 1 s.d. greater VAT density were also observed among HIV+ men. Conclusions Among men living with HIV, greater SAT density was associated with greater systemic inflammation independent of SAT area. AT density measurement provides additional insight into AT density beyond measurement of AT quantity alone, and may have implications for metabolic disease risk.

scholarly journals Echocardiographic Assessment of Asymptomatic US Air Force Members with Early HIV Infection

2019 ◽  
Author(s):  
Gadiel Rafael Alvarado ◽  
Courtney Usry ◽  
Rosco Gore ◽  
James Watts ◽  
Jason Okulicz
Keyword(s):  
Hiv Infection ◽  
Air Force ◽  
Global Longitudinal Strain ◽  
People Living With Hiv ◽  
Hiv Diagnosis ◽  
Cvd Risk ◽  
Us Air Force ◽  
Increased Risk ◽  
Hiv Acquisition ◽  
Living With Hiv

Abstract Objective People living with HIV (PLHIV) are at increased risk for cardiovascular disease (CVD) and development of subclinical echocardiographic abnormalities. The pathogenicity of HIV induced cardiotoxicity has been described however the time to development of echocardiographic abnormalities after HIV acquisition remains unclear. In this study we describe the echocardiographic evaluations of asymptomatic US Air Force members who were diagnosed with HIV infection. Results Patients (n=50) were predominantly male (96%), mostly black (60%), with a mean age of 28 years. At HIV diagnosis, the mean viral load was 112,585 copies/mL and CD4 count was 551 cells/uL; 2 patients were diagnosed with AIDS. All were found to have normal systolic ejection fraction (EF) and global longitudinal strain (GLS) however evidence of right ventricular dilatation and cardiac remodeling was observed in 7 (14%) and 13 (26%) patients, respectively. Subgroup analyses showed no significant differences in echocardiographic findings by HIV disease severity or CVD risk factors (p >0.05 for all). This study suggests that untreated HIV may have a low impact on the development of echocardiographic abnormalities shortly after seroconversion. Longitudinal studies are warranted to determine the optimal CVD risk assessment strategies for PLHIV.

scholarly journals Factors affecting statin uptake among people living with HIV: primary care provider perspectives

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Allison J. Ober ◽  
Sae Takada ◽  
Deborah Zajdman ◽  
Ivy Todd ◽  
Tamara Horwich ◽  
...  
Keyword(s):  
Risk Assessment ◽  
Primary Care ◽  
Community Health ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Standard Practice ◽  
Risk Threshold ◽  
Health Clinics ◽  
Community Health Clinics ◽  
Living With Hiv

Abstract Background Cardiovascular disease (CVD) is a major cause of morbidity and mortality among people living with HIV (PLWH), but statin therapy, safe and effective for PLWH, is under-prescribed. This study examined clinic leadership and provider perceptions of factors associated with statin prescribing for PLWH receiving care in eight community health clinics across Los Angeles, California. Methods We conducted semi-structured telephone interviews with clinic leadership and providers across community health clinics participating in a larger study (INSPIRE) aimed at improving statin prescribing through education and feedback. Clinics included federally qualified health centers (N = 5), community clinics (N = 1) and county-run ambulatory care clinics (N = 2). Leadership and providers enrolled in INSPIRE (N = 39) were invited to participate in an interview. We used the Consolidated Framework for Implementation Research (CFIR) to structure our interview guide and analysis. We used standard qualitative content analysis methods to identify themes within CFIR categories; we also assessed current CVD risk assessment and statin-prescribing practices. Results Participants were clinic leaders (n = 6), primary care physicians with and without an HIV specialization (N = 6, N = 6, respectively), infectious diseases specialists (N = 12), nurse practitioners, physician assistants and registered nurses (N = 7). Ninety-five percent of providers from INSPIRE participated in an interview. We found that CVD risk assessment for PLWH is standard practice but that there is variation in risk assessment practices and that providers are unsure whether or how to adjust the risk threshold to account for HIV. Time, clinic and patient priorities impede ability to conduct CVD risk assessment with PLWH. Conclusions Providers desire more data and standard practice guidance on prescribing statins for PLWH, including estimates of the effect of HIV on CVD, how to adjust the CVD risk threshold to account for HIV, which statins are best for people on antiretroviral therapy and on shared decision-making around prescribing statins to PLWH. While CVD risk assessment and statin prescribing fits within the mission and workflow of primary care, clinics may need to emphasize CVD risk assessment and statins as priorities in order to improve uptake.

scholarly journals 963. Non-Invasive Detection of Cardiovascular Risk in People Living with HIV in Miami

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S511-S512
Author(s):  
Douglas Salguero ◽  
Jason Galo ◽  
Jornan Rodriguez ◽  
Mollie Pester ◽  
Alejandro Chedebau ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Arterial Stiffness ◽  
Augmentation Index ◽  
Linear Regression Analysis ◽  
People Living With Hiv ◽  
Cvd Risk ◽  
Non Invasive ◽  
Early Markers ◽  
The Mean ◽  
Living With Hiv

Abstract Background HIV is a risk factor for Cardiovascular Disease (CVD), and CVD is the leading cause of mortality among Hispanics (H). Hispanics in the US are disproportionately affected by HIV with higher rates of HIV related morbidity and mortality, as well as adverse CVD outcomes. This study sought to identify early markers of CVD risk among Hispanics living with HIV. Methods Interim analysis of 38 H and non-Hispanics (NH) people living with HIV (PLWH), stable on antiretroviral regimen, 30-50 years of age, without previously detected CVD. Demographics, CD4 T cells, HIV RNA viral load, traditional early markers of CVD risk were collected. CVD risk markers were obtained with non-invasive tools: epicardial adipose tissue (EAT) thickness was assessed by echocardiogram; arterial stiffness was assessed by applanation tonometry sequentially at the carotid, femoral and radial arteries (including central augmentation index - AI, peripheral AI, radial pulse wave velocity - PWV, and femoral PWV). The Framingham Coronary Event Risk Score (FCER) was calculated for each subject. Descriptive and linear regression analysis for predictors of FCER measures were age adjusted. Results Among the 38 participants enrolled the mean age was 42 years, 80% male, H 76%, NH 24%, Black 16%, with mean BMI of 26.7. 45% met clinical criteria for metabolic syndrome: high waist girth 24%, high blood pressure 18%, high Fasting Glucose 16%, high total cholesterol 21%, high triglycerides 26%, low HDL 45%, high LDL 18%, high TC/HDL ratio 68%. The mean EAT was 3.8 mm, mean central AI 20.2 %, mean peripheral AI 73%, mean femoral PWV 28.8 m/s, mean radial PWV 8.7 m/s. Older age was associated with greater central AI (r = 0.37, p =.01) and peripheral AI (r = 0.38, p =.01) but not with increased EAT. Regression analysis predicting FCER relationships showed radial PWV as an independent predictor of increased FCER (r = 0.36, p &lt; .05). Conclusion Risk factors leading to CVD are common among this group of PLWH and radial PWV is a moderate predictor of increased FCER. Although measures of arterial stiffness are available, they are not routinely used to assess CVD risk. Further studies should evaluate the use of noninvasive methods for diverse PLWH, to prevent the development of CVD. Disclosures All Authors: No reported disclosures

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