The relationship between carotid intima-media thickness, serum biomarkers of cardiovascular disease, and HIV-infection in a South African study population

Date
2021-03
Journal Title
Journal ISSN
Volume Title
Publisher
Stellenbosch : Stellenbosch University
Abstract
Background: Brachial artery flow-mediated dilatation (FMD) and carotid artery intima-media thickness(IMT)are measures of vascular endothelial function and subclinical atherosclerosis respectively. Both endothelial dysfunction and subclinical atherosclerosis have been linked with HIV and antiretroviral therapy (ART) in the developed world. Furthermore, known biomarkers of inflammation and endothelial dysfunction can be measured to predict cardiovascular outcomes in HIV-infected individuals. The exact link between endothelial dysfunction, atherosclerosis, HIV, ART and the biomarkers remains inconclusive, particularly in South African and Western Cape populations.Aims: To investigate the putative relationship between subclinical atherosclerosis, endothelial dysfunction, biomarkers of cardiovascular disease (CVD), and HIV-infection in a Western Cape study population. Methods:Two different epidemiological studies were performed: a cross-sectional main study (HIV-infected, n= 204 of whom on ART n=188and without ART n= 16;and HIV-free, n= 143), and a longitudinal sub-study to assess the 12-month temporal progression of selected CVD outcomes (HIV-free, n= 57). For both studies, participants were recruited from health clinics in Cape Town and Worcester between 2017 and 2018. Lifestyle and health data were collected, and vascular (FMD%and IMT by ultrasound technology), anthropometric (body-mass-index [BMI]; waist circumference [WC]), cardiovascular (lipid profile; blood pressure [BP]; plasma glucose), renal (creatinine; urine albumin creatinine ratio [ACR]), liver (gamma-glutamyl-transferase [GGT]) and HIV-related (viral load; CD4, duration of HIV, duration of treatment) measures were obtained. Serum biomarkers were analyzed using Luminex technology, including C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1) and adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cellular adhesion molecule-1 [VCAM-1], e-selectin, p-selectin). Results: In the longitudinal study (mean age: 45 years), WC, plasma glucose, BP, and hypertension, increased at 12-months follow-up. In the cross-sectional study (mean age: 41 years), the HIV-infected group showed a lower BMI, WC, BP,hypertension and PAI-1 versus the HIV-free group (p<0.05), whereas anaemia, ACR, creatinine, GGT and VCAM-1 were increased in the HIV-infected group (p<0.05). Additionally, viral load and VCAM-1 levels were higher in the HIV-infected without ART group versus the ART treated group (p<0.05). CD4 count, total cholesterol, HDL, LDL, hemoglobin, GGT, creatinine levels were higher in the ART group compared to the ART naïve group (p<0.05). Flow mediated dilatation (FMD)was higher and IMT was lower in the ART group versus ART naïve group (p<0.05). Furthermore, no significant correlations were found between biomarkers and FMD and IMT. With regards to independent associations, in the HIV-infected group, age positively associated with IMT (p<0.001), while in the HIV-free group, age, high systolic BP, obesity and LDL cholesterol positively associated with IMT (p<0.05). In the HIV-infected group, ART positively associated, while viral load inversely associated with FMD%. In the HIV-free group, creatinine inversely associated with FMD% (p<0.05).Discussion and conclusion: Overall, our study showed a higher presence and progression of cardiovascular risk parameters in the HIV-free population. In the HIV context, ART showed a morecardioprotective and immune-protective effect, where it was associated with reduced subclinical atherosclerosis and improved endothelial function. Our study confirmed that age is an independent predictor of subclinical atherosclerosis while viral load is an independent, inverse predictor of endothelial function.
Agtergrond: Bragiale arterie vloei-gemedieerde dilatasie (FMD) en karotis arterie intima-media dikte (IMD) verteenwoordig die meting van vaskulêre endoteelfunksie en subkliniese aterosklerose onderskeidelik. Voorheen het studies in ontwikkelde lande aangetoon. Daar is voorheen tudies in ontwikkelde lande aangetoon dat beide endoteeldisfunksie en subkliniese aterosklerose ‘n verband met MIV en antiretrovirale terapie (ART) toon. Verder kan verskeie inflammatoriese en endoteeldisfunksie biomerkers gemeet word om kardiovaskulêre uitkomste in MIV-geïnfekteerde populasies te voorspel. Die presiese verband tussen endoteeldisfunksie, aterosklerose, MIV, ART en die biomerkers is nog nie heeltemal verklaar of duidelik nie nie, veral nie in Suid-Afrikaanse en Wes-Kaapse bevolkings nie.Doelstelling: Om die potensiele vermoedelike verband tussen subkliniese aterosklerose, endoteeldisfunksie, kardiovaskulêre biomerkers en MIV-infeksie in ‘n Wes-Kaapse studiebevolking te ondersoek. Metodiek: Twee verskillende epidemiologiese studies was onderneem: ‘n deuranit hoofstudie (MIV-geïnfekteer, n= 204 waarvan n=188 op ART was, en n=16 ART sonder; MIV negatief is, n= 143), en ‘n longitudinale sub-studie om die 12-maande progressie van geselekteerde kardiovaskulêre uitkomste te ondersoek (MIV negatief, n= 57). Deelnemers was by gesondheidsklinieke in Kaapstad en Worcester tussen 2017 en 2018 gewerf. Lewenstyl-en gesondheidsinligting was ingesamel, asook vaskulêre (FMD en IMD met behulp van ultraklank tegnologie), antropometriese (liggaamsmassa-indeks [LMI]; middelomtrek [MO]), kardiovaskulêre (lipiedprofiel; bloeddruk [BP]; plasma glukose), nier (kreatinien; urien albumien-kreatinienverhouding [ACR]), lewer (gamma glutamieltransferase [GGT]) en MIV-verwante (virale lading; CD4, duur van MIV-infeksie, duur van behandeling) metings was ingesamel. Serum biomerkers was met behulp van Luminex tegnologie geanaliseer, insluitende C-reaktiewe proteïen (CRP), tumor nekrose faktor-alfa (TNF-α), vaskulêre endoteel groeifaktor (VEGF), plasminogeen-aktiveerder-inhibeerder-1 (PAI-1), en aanhegtingsmolekules (intersellulêre adhesiemolekule-1 [ICAM-1], vaskulêre sellulêre adhesiemolekule-1 [VCAM-1], e-selektien, p-selektien). Resultate: In die longitudinale studie (gemiddelde ouderdom: 45 jaar), het WC, plasma glukose, BP, en hipertensie toegeneem na 12 maande. In die deursnitstudie (gemiddelde ouderdom: 41 jaar), was BMI, WC, BP, hipertensie en PAI-1 laer in die MIV-geïnfekteerde groep in vergelyking met die geen MIV groep (p<0.05), terwyl anemie, ACR, kreatinien, GGT and VCAM-1 verhoog was in die MIV-geïnfekteerde groep (p<0.05). Verder was die virale lading en VCAM-1 vlakke hoër in die onbehandelde MIV-geïnfekteerdegroep in vergelyking met die ART groep (p<0.05). CD4 telling,totale cholesterol, HDL, LDL, hemoglobien, GGT en kreatinien vlakke was hoër in die ART groep (p<0.05 vs onbehandeld). FMD was hoër en IMT laer in die ART groep (p<0.05 vs. onbehandeld). Verderkon geen betekenisvolle korrelasies tussen die biomerkers, FMD en IMT aangetoon word nie. Wat onafhanklike assosiasies betref, het ouderdom positief geassosieer met IMT in die MIV-geïnfekteerde groep (p<0.001), terwyl ouderdom, hoë sistoliese bloeddruk, vetsug en LDL cholesterol positief met IMT geassosieer was in die kontrole groep (p<0.05). In die MIV-geïnfekteerde groep het ART positief geassosieer met FMD%, terwyl virale lading omgekeerd geassosieer met FMD%. In die geen MIV groep, was kreatinien omgekeerd geassosieer met FMD% (p<0.05).Bespreking en gevolgtrekking: Oor die algemeen het ons studie ‘n hoër teenwoordigheid en progressie van kardiovaskulêre risikofaktore in die geen MIV groep getoon. In die geval van die MIV-geïnfekteerde deelnemers, het ART behandeling meer kardio-en immuunbeskermende effekte getoon, waar dit met verlaagde subkliniese atereosklerose en beter endoteelfunksie geassosieer was. Die studie het ook bevestig dat ouderdom ‘n onfhanklike voorspeller van subkliniese aterosklerose is, terwyl virale lading ‘n onafhanklike, omgekeerde voorspeller van endoteelfunksie is.
Description
Thesis (PhD)--Stellenbosch University, 2021.
Keywords
HIV, Cardiovascular diseases, Endothelial function, Endothelial cells, Atherosclerosis, Cardiovascular risk factors, Carotid intima-media thickness, Antiretroviral therapy, UCTD
Citation