HIV/AIDS and air pollution as emerging cardiovascular risk factors in Cape Town populations : is endothelial function a marker of effect

Everson, Frans Pieter (2020-03)

Thesis (PhD)--Stellenbosch University, 2020.

Thesis

ENGLISH ABSTRACT: Background: HIV and antiretroviral therapy (ART) are associated with cardiovascular disease (CVD). Concomitantly,air pollution is a global health concern and associated with CVD. Although South Africa (SA) has the largest HIV population, ART roll-out programme and also one of the most carbon-intensive economies in world, the effects of these emerging cardiovascular risk factors remain under investigated. Aim: The current study aimed to investigate whether endothelial function (an early marker of cardiovascular risk/disease) is a marker of effect of HIV, ART and air pollution in a study cohort residing in the Cape Town region. Methods: Volunteering participants were recruited from health-care clinics in Worcester and Cape Town. A health questionnaire was completed (demographic, lifestyle, and socioeconomic information), anthropometric measurements taken (BMI and blood pressure) and fasting blood and urine samples collected from each participant for chemical pathology and biomarker analyses. Sub-study 1 followed a repeated measures design (baseline and 18-month follow-up visit) to investigate the effects of HIV (viral load) and ART (pre- vs. post-ART treatment and an 18-month ART treatment period) on markers of endothelial function. Sub-study 2 investigated the effects of personal air pollution exposure (NO2 and BTEX via passive diffusion samplers) in a repeated measures design (baseline and 6-month follow-up visit) on markers of endothelial function. Markers of endothelial function for both sub-studies included: tumor necrosis factor-alpha (TNF-α), high sensitivity C-reactive protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1),vascular cellular adhesion molecule-1 (VCAM-1), e-selectin, p-selectin, vascular endothelial growth factor (VEGF), plasminogen activator inhibitor-1 (PAI-1), retinalmicrovascular calibres (including central retinal arteriolar/venular equivalent (CRAE; CRVE), CRAE/CRVE ratio (AVR)) and flow-mediated dilation (FMD). Results: Sub-study 1: Each interquartile range (IQR) increment increase in viral load (1300 copies mRNA/ml) was associated with CRVE (9.29 μm), AVR (-0.016) and %FMD (-2.13%). Compared to baseline, initiating ART was associated with VCAM-1 (-148 ng/ml), VEGF (40.6%), PAI-1 (14.12 ng/ml) and CRVE (-6.42 μm). An 18-month ART treatment period was associated with TNF-α (-1.22 pg/ml), ICAM-1 (-45%), e-selectin (-5.57 ng/ml) CRVE (–7.00 μm) and % FMD (-9.8%). Sub-study 2: Each IQR increment increase in NO2 (7.0 μg/m³) was associated with VEGF (-18.9%), CRVE (-2.93 μm) and baseline brachial artery diameter (-0.29 μm). Benzene (IQR: 3.3 μg/m³) was associated with p-selectin (-5.8 pg/ml), toluene (IQR: 30.0 μg/m³) was associated with PA1-1 (7.2 ng/ml). Ethyl-benzene (IQR: 3.8 μg/m³) was associated with VCAM-1 (-4.9%) and PA1-1 (9.1 ng/ml). m+p-Xylene and o-Xylene (IQR 3.8 μg/m³ respectively) were associated with VCAM-1 (-1.47% and -4.5%) and PA1 (3.08 ng/ml and 11.7 ng/ml). 3+4MHA (1380 ng/ml) was associated with %FMD (-0.40%). Discussion and Conclusion: The study showed that endothelial function is a marker of effect of HIV, ART and air pollutants (NO2 and BTEX) in the current study population, and that HIV and air pollution contribute to an increased cardiovascular risk profile while ART exhibited varying effects. This study underscores the relevance of these emerging cardiovascular risk factors in South Africa and the greater sub-Saharan Africa region. This study strongly supports the need for further investigation, also in study populations beyond the Western Cape.

AFRIKAANSE OPSOMMING: Inleiding: MIV en anti-retrovirale terapie (ART) is geassosieer met kardiovaskulêre siekte (KVS). Terselfdertyd isdaar wêreldwye kommer oor die gesondheidsimpak van lugbesoedeling met lg. wat ook met KVS geassosieer word. Alhoewel Suid-Afrika (SA) die grootste MIV populasie, die grootste ART voorsieningsprogram en ook een van die mees koolstof-intensiewe ekonomieë ter wêreld het, word daar min navorsing oor die effekte van hierdie ontluikende kardiovaskulêre risikofaktore onderneem. Doelstelling: Die huidige studie het ten doel gehad om vas te stel of endoteelfunksie (‘n vroeë merker van kardiovaskulêre risko/siekte) ‘n merker van die effekte van MIV, ART en lugbesoedeling is in ‘n studie-populasie in die Kaapstad omgewing. Metodes: Vrywillige deelnemers was by gesondheidsklinieke in Worcester en Kaapstad gewerf. ‘n Gesondheidsvraelys is voltooi (demografiese, leefstyl en sosioekonomiese inligting), antropometriese afmetings (liggaam-massa indeks en bloeddruk) is ingesamel en vastende bloed- en urinemonsters is van elke deelnermer verkry vir chemiese patologie en biomerker analises. Sub-studie 1 het ‘n herhaalde-metings-ontwerp gevolg (basislyn en ‘n 18-maande opvolg) om die effekte van MIV (virale lading) en ART (pre- vs. post-ART behandeling en ‘n 18-maande ART behandelingsperiode) op merkers van endoteelfunksie te bepaal. Sub-studie 2 het ook via ‘n heraalde metings-ontwerp (basislyn en ‘n 6-maande opvolg besoek) die effekte van persoonlike lugbesoedeling blootstelling (NO2 en BTEX m.b.v. passiewe duffusie toestelle) op ‘n reeks merkers van endoteelfunksie bepaal. Die volgende merkers van endoteelfunksie is vir beide sub-studies in ag geneem: tumor nekrose faktor-alfa (TNF-α), hoë sensitiwiteits C-reaktiewe proteïen (hsCRP), intersellulêre adhesiemolekule-1 (ICAM-1), vaskulêre adhesie molekule-1 (VCAM-1), e-selectin, p-selectin, vaskulêre endoteel groeifaktor (VEGF), plasminogeen aktiveerder inhibitor-1 (PAI-1), retinale mikrovaskulêre afmetings (insluitende sentrale retinale arteriolêre / venulêre ekwivalent (CRAE; CRVE), CRAE/CRCE verhouding (AVR) en vloei-gemedieerde dilatasie (FMD). Resultate: Sub-studie 1: Elke inkrementele interkwartielreikwydte (IKR) verhoging in virale lading (1300 kopieë mRNS/ml) was geassosieer met CRVE (9.29 μm), AVR (-0.016) and % FMD (-2.13%). In vergelyking met basislyn, was die inisiëring van ART geassosieer met VCAM-1 (-148 ng/ml), VEGF (40.6%), PAI-1 (14.12 ng/ml) en CRVE (-6.42 μm). ‘n 18-maande ART behandelingsperiode was geassosieer met TNF-α (-1.22 pg/ml), ICAM-1 (-45%), e-selectin (-5.57 ng/ml) CRVE (–7.00 μm) en % FMD (-9.8%). Sub-studie 2: Elke inkrementele IKR verhoging in NO2 (7.0 μg/m³) was geassosieer met VEGF (-18.9%), CRVE (-2.93 μm) en basislyn brachiale arterie deursnee (-0.29 μm). Benseen (IKR: 3.3 μg/m³) was geassosieer met p-selectin (-5.8 pg/ml) en tolueen (IKR: 30.0 μg/m³) met PA1-1 (7.2 ng/ml). Etiel-benseen (IKR: 3.8 μg/m³) was geassosieer met VCAM-1 (-4.9%) en PA1-1 (9.1 ng/ml). m+p-Xileen and o-Xileene (IKR: 3.8 μg/m³ onderskeidelik) was geassosieer met VCAM-1 (-1.47% en -4.5%) en PAI-1 (3.08 ng/ml en 11.7 ng/ml). 3+4MHA (1380 ng/ml) was gesosieer met % FMD (-0.40%). Gevolgtrekking: Die studie het aangetoon dat endoteelfunksie ‘n merker van die effekte van MIV, ART en verskeie lugbesoedelingstowwe (NO2 en BTEX) in die huidige studie-populasie is. Die resultate toon dat MIV en lugbesoedeling bydra tot ‘n verhoogde kardiovaskulêre risiko profiel terwyl ART wisselende effekte getoon het. Die studie beklemtoon verder die relevansie van hierdie ontluikende kardiovaskulêre risikofaktore in Suid-Afrika en die groter sub-Sahara Afrika streek. Laastens beklemtoon die studie die behoefte aan verdere navorsing, ook in populasies buite die Wes-Kaap.

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